Tumour progression and survival in patients with T1G3 bladder tumours: 15-year outcome. Defining early morbidity of radical cystectomy for patients with bladder cancer using a standardized reporting methodology. Combined treatment of invasive bladder carcinoma with transurethral resection, induction chemotherapy, and radical radiotherapy plus concomitant protracted infusion of cisplatin and 5‐fluorouracil Potential impact of postoperative early complications on the timing of adjuvant chemotherapy in patients undergoing radical cystectomy: a high-volume tertiary cancer center experience. Efficacy and tolerability of concurrent weekly low dose cisplatin during radiation treatment of localised muscle invasive bladder transitional cell carcinoma: a report of two sequential Phase II studies from the Trans Tasman Radiation Oncology Group. Radical radiotherapy for muscle invasive transitional cell carcinoma of the bladder: failure analysis. Combined-modality therapy with gemcitabine and radiation therapy as a bladder preservation strategy: long-term results of a phase I trial. MRE11 expression is predictive of cause-specific survival following radical radiotherapy for muscle-invasive bladder cancer. Treatment of invasive bladder cancer by cisplatin and radiation in patients unsuited for surgery. Retinoblastoma protein expression is an independent predictor of both radiation response and survival in muscle-invasive bladder cancer The initial results in muscle-invading bladder cancer of RTOG 95-06: phase I/II trial of transurethral surgery plus radiation therapy with concurrent cisplatin and 5-fluorouracil followed by selective bladder preservation or cystectomy depending on the initial response. Prognostic factors in invasive bladder carcinoma in a prospective trial of preoperative adjuvant chemotherapy and radiotherapy. Effective bladder sparing therapy with intra-arterial cisplatin and radiotherapy for localized bladder cancer. Long-term results of a phase II study of synchronous chemoradiotherapy in advanced muscle invasive bladder cancer Long-term outcomes of selective bladder preservation by combined-modality therapy for invasive bladder cancer: the MGH experience. Conservative treatment of invasive bladder carcinoma by transurethral resection, protracted intravenous infusion chemotherapy, and hyperfractionated radiotherapy Distressful symptoms after radical radiotherapy for urinary bladder cancer. RTOG 97-06: initial report of a phase I-II trial of selective bladder conservation using TURBT, twice-daily accelerated irradiation sensitized with cisplatin, and adjuvant MCV combination chemotherapy. Selective bladder preservation by combined modality protocol treatment: long-term outcomes of 190 patients with invasive bladder cancer. Phase II study of radiochemotherapy with vinblastine in invasive bladder cancer. Apoptosis, proliferation and p53, cyclin D1, and retinoblastoma gene expression in relation to radiation response in transitional cell carcinoma of the bladder. Phase III trial of neoadjuvant chemotherapy in patients with invasive bladder cancer treated with selective bladder preservation by combined radiation therapy and chemotherapy: initial results of Radiation Therapy Oncology Group 89-03. A randomised trial of accelerated radiotherapy for localised invasive bladder cancer. Combined radiation and chemotherapy for invasive transitional-cell carcinoma of the bladder: a prospective study. Combination cisplatin, 5-fluorouracil and radiation therapy for locally advanced unresectable or medically unfit bladder cancer cases: a Southwest Oncology Group Study. Chemoradiotherapy for muscle invading bladder carcinoma. Final report of a single institutional organ-sparing program. Organ-sparing treatment of advanced bladder cancer: a 10-year experience. Phase I study of gemcitabine and radiotherapy plus cisplatin after transurethral resection as conservative treatment for infiltrating bladder cancer. Concurrent cisplatin and radiotherapy for patients with muscle invasive bladder cancer who are not candidates for radical cystectomy. Prospective quality-of-life assessment in patients receiving concurrent gemcitabine and radiotherapy as a bladder preservation strategy. Methotrexate, vinblastine, doxorubicin and cisplatin chemotherapy and cystectomy for unresectable bladder cancer. Concurrent platinum and docetaxel chemotherapy and external radical radiotherapy in patients with invasive transitional cell bladder carcinoma. A preliminary report of tolerance and local control. Combination transurethral resection, systemic chemotherapy, and pelvic radiotherapy for invasive (T2-T4) bladder cancer unsuitable for cystectomy: a phase I/II Southwestern Oncology Group study. A phase I/II trial of transurethral surgery combined with concurrent cisplatin, 5-fluorouracil and twice daily radiation followed by selective bladder preservation in operable patients with muscle invading bladder cancer. Combined chemotherapy and radiation with selective organ preservation for muscle-invasive bladder carcinoma. A single-institution phase II study. Muscle-invasive bladder cancer treated with external beam radiotherapy: pretreatment prognostic factors and the predictive value of cystoscopic re-evaluation during treatment. Transurethral surgery and twice-daily radiation plus paclitaxel-cisplatin or fluorouracil-cisplatin with selective bladder preservation and adjuvant chemotherapy for patients with muscle invasive bladder cancer (RTOG 0233): a randomised multicentre phase 2 trial. Quality of life assessment after concurrent chemoradiation for invasive bladder cancer: results of a multicenter prospective study (GETUG 97-015). Improved local control of invasive bladder cancer by concurrent cisplatin and preoperative or definitive radiation. The National Cancer Institute of Canada Clinical Trials Group. Concurrent cisplatin, 5-fluorouracil, leucovorin, and radiotherapy for invasive bladder cancer. Combined modality treatment with bladder preservation for muscle invasive bladder cancer. Conservative treatment with transurethral resection, neoadjuvant chemotherapy followed by radiochemotherapy in stage T2-3 transitional bladder cancer Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer. Neoadjuvant combined modality program with selective organ preservation for invasive bladder cancer: results of Radiation Therapy Oncology Group phase II trial 8802. Phase II study of conformal hypofractionated radiotherapy with concurrent gemcitabine in muscle-invasive bladder cancer. Radiotherapy with or without chemotherapy in muscle-invasive bladder cancer. Whole-pelvis or bladder-only chemoradiation for lymph node-negative invasive bladder cancer: single-institution experience. Randomized Noninferiority Trial of Reduced High-Dose Volume Versus Standard Volume Radiation Therapy for Muscle-Invasive Bladder Cancer: Results of the BC2001 Trial (CRUK/01/004) LIFE AND DEATH OF SPARE (SELECTIVE BLADDER PRESERVATION AGAINST RADICAL EXCISION): REFLECTIONS ON WHY THE SPARE TRIAL CLOSED Phase I-II RTOG study (99-06) of patients with muscle-invasive bladder cancer undergoing transurethral surgery, paclitaxel, cisplatin, and twice-daily radiotherapy followed by selective bladder preservation or radical cystectomy and adjuvant chemotherapy. Long-term results of two prospective bladder-sparing trimodality approaches for invasive bladder cancer: neoadjuvant chemotherapy and concurrent radio-chemotherapy. Radical cystectomy versus bladder-preserving therapy for muscle-invasive urothelial carcinoma: examining confounding and misclassification biasin cancer observational comparative effectiveness research. Radiotherapy with concurrent carbogen and nicotinamide in bladder carcinoma. Radical cystectomy for urothelial carcinoma of the bladder without neoadjuvant or adjuvant therapy: long-term results in 1100 patients. Bladder preservation in selected patients with muscle-invasive bladder cancer by complete transurethral resection of the bladder plus systemic chemotherapy: long-term follow-up of a phase 2 nonrandomized comparative trial with radical cystectomy.
OBJECTIVE To evaluate tumour progression and survival of patients with T1G3 bladder tumours who were followed for 15 years . PATIENTS AND METHODS A subset of 48 patients with T1G3 bladder tumours was entered into a r and omized trial of transurethral resection ( TUR ) or TUR plus bacille Calmette-Guèrin ( BCG ) therapy and followed for a minimum of 15 years . Thirty-nine ( 81 % ) patients received one or more courses of BCG . The endpoints of the study were stage progression ( defined as muscle invasion of metastasis ) and disease-specific survival . RESULTS Of the 48 patients , 25 ( 52 % ) progressed and 15 ( 31 % ) died from the disease ; 33 patients ( 69 % ) survived , including 24 ( 50 % ) with an intact bladder . The median progression-free survival time was 151 months . Tumour progression occurred in 35 % of the patients within the first 5 years , in 16 % after 5 - 10 years and in 12 % of those followed for 10 - 15 years . Deaths from cancer occurred in 25 % of the patients in the first 5 years and in 10 % of patients at risk from 5 to 15 years . CONCLUSIONS Patients with T1G3 bladder tumours who are treated conservatively are at life-long risk of having a muscle-invasive tumour and dying from bladder cancer BACKGROUND Reporting methodology is highly variable and nonst and ardized , yet surgical outcomes are utilized in clinical trial design and evaluation of healthcare provider performance . OBJECTIVE We sought to define the type , incidence , and severity of early postoperative morbidities following  radical cystectomy ( RC )  using a st and ardized reporting methodology . DESIGN , SETTING , AND PARTICIPANTS Between 1995 and 2005 , 1142 consecutive RCs were entered into a prospect i ve complication data base and retrospectively review ed for accuracy . All patients underwent RC/urinary diversion by high-volume fellowship-trained urologic oncologists . MEASUREMENTS All complications within 90 d of surgery were analyzed and grade d according to the Memorial Sloan-Kettering Cancer Center complication grading system . Complications were defined and stratified into 11 specific categories . Univariate and multivariate regression models were used to define predictors of complications . RESULTS AND LIMITATIONS Sixty-four percent ( 735/1142 ) of patients experienced a complication within 90 d of surgery . Among patients experiencing a complication , 67 % experienced a complication during the operative hospital admission and 58 % following discharge . Overall , the highest grade of complication was grade 0 in 36 % ( n=407 ) , grade 1 - 2 in 51 % ( n=582 ) , and grade 3 - 5 in 13 % ( n=153 ) . Gastrointestinal complications were most common ( 29 % ) , followed by infectious complications ( 25 % ) and wound-related complications ( 15 % ) . The 30-d mortality rate was 1.5 % . CONCLUSIONS Surgical morbidity following RC is significant and , when strict reporting guidelines are incorporated , higher than previously published . Accurate reporting of postoperative complications after RC is essential for counseling patients , combined modality treatment planning , clinical trial design , and assessment of surgical success The aim of this study was to define the maximum tolerated doses ( MTDs ) of cisplatin ( CDDP ) and 5‐fluorouracil ( 5‐FU ) administered as protracted intravenous infusion ( PVI ) during hyperfractionated radiotherapy ( HFRT ) administered with organ‐sparing intent to patients with infiltrating transitional cell carcinoma of the bladder ( TCCB ) BACKGROUND Perioperative cisplatin combination chemotherapy is associated with a survival benefit in patients with invasive bladder cancer ( BCa ) . However , in a recent report from the National Cancer Data base ( NCDB ) , only 11.6 % of stage III BCa patients received perioperative chemotherapy , the majority in the adjuvant setting . OBJECTIVE We explore the impact of postoperative complications on the timing of adjuvant chemotherapy . DESIGN , SETTING , AND PARTICIPANTS An independent review board approved the review of 1142 consecutive radical cystectomies ( RC ) , and data from these cases were entered into a prospect i ve complication data base ( 1995 - 2005 ) which was utilized and retrospectively review ed for accuracy at a single , academic , tertiary cancer center . INTERVENTIONS All patients underwent RC/urinary diversion by high-volume , fellowship-trained , urologic oncologists . MEASUREMENTS All complications within 90 d of surgery were defined and grade d using a five- grade modification of the original Clavien system utilized at Memorial Sloan-Kettering Cancer Center and stratified into 11 categories . Grade 2 - 5 complications typically prohibit starting adjuvant chemotherapy . Univariate and multivariable logistic regression were used to evaluate variables associated with complications . RESULTS AND LIMITATIONS Overall , 64 % ( 735 of 1142 patients ) experienced one or more complications , of which 83 % ( 611 of 735 ) were grade 2 - 5 . Furthermore , 57 % of grade 2 - 5 complications ( 347 of 611 ) occurred between discharge and 90 d , 38 % ( 233 of 611 ) within 6 wk , and 19 % ( 114 of 611 ) between 6 wk and 12 wk , the general time frame for adjuvant chemotherapy . Overall , 26 % ( 298 of 1142 patients ) required readmission . Surgical morbidity at a high-volume tertiary cancer center may not reflect the case mix or surgical experience seen in the community setting . CONCLUSION This series demonstrates that 30 % of patients ( 347 of 1142 ) undergoing RC may not have been able to receive adjuvant chemotherapy due to postoperative complications . This information should be taken into consideration when planning multimodal therapy and further supports the use of perioperative chemotherapy in the neoadjuvant setting BACKGROUND AND PURPOSE To determine the feasibility , toxicity , and clinical effectiveness of concurrent weekly cisplatin chemotherapy in conjunction with definitive radiation in the treatment of localised muscle invasive bladder cancer . PATIENTS AND METHODS In January 1997 the Trans Tasman Radiation Oncology Group embarked on a Phase II study ( TROG 97.01 ) of weekly cisplatin ( 35 mg/m(2 ) x 7 doses ) plus radiation to a dose of 63 Gy over 7 weeks . Following an interim toxicity analysis , the dose intensity of cisplatin was reduced to 6 cycles and the radiation schedule changed to 64 Gy over 6.5 weeks leading to the second study ( TROG 99.06 ) . A total of 113 patients were enrolled . RESULTS Acute grade 3 urinary toxicity occurred in 23 % of the patients . Acute grade 4 pelvic toxicity was not seen . Thirty-eight patients ( 33 % ) experienced grade 3 or 4 cisplatin related toxicities with 15 patients ( 12 % ) requiring significant dose modification . The reduced dose intensity in Study 99.06 improved tolerability . Incidence of significant late morbidity was low ( 6 % ) . Seventy-nine patients ( 70 % ) achieved complete remission at the 6 month cystoscopic assessment . Local invasive recurrence was seen in 11 of the 79 patients ( 14 % ) . In 18 patients ( 16 % ) isolated superficial TCC/CIS were detected ( 6 months and beyond ) . The local control rate was 45 % with a functional bladder being retained in 69 of the 113 patients ( 61 % ) . RFS and DSS at 5 years were 33 % and 50 % , respectively . CONCLUSION Our two sequential Phase II studies have shown that concurrent chemoradiation using weekly cisplatin in the management of localised invasive bladder TCC is feasible and reasonably well tolerated . This approach is currently being investigated further in a r and omised study Patients with muscle invasive carcinoma of the bladder treated with radical radiation  were prospect ively documented and followed in an attempt to identify prognostic factors predictive of the response to treatment . Data on 121 consecutive patients treated with radical radiation between 1981 and 1985 are presented . Over-all actuarial survival of the patient population ( median age 70 years ) was 31.6 % at 5 years and cause-specific survival was 44.8 % . At analysis 33 of 121 patients ( 27.3 % ) were alive with preserved bladder function . Independent prognostic factors for cause-specific survival and for complete response with radical radiation were tumor configuration , hemoglobin level and clinical stage . The rate free of local relapse was significantly influenced by stage and presence of coexistent carcinoma in situ . The study suggests that factors other than stage and grade influence prognosis in invasive bladder cancer and should be considered in interpreting treatment results PURPOSE A Phase I trial of twice-weekly gemcitabine and concurrent radiation therapy ( RT ) was performed in patients with muscle-invasive bladder cancer . We present the final analysis of bladder-intact survival ( BIS ) , disease-specific survival ( DSS ) , and overall survival ( OS ) . METHODS AND MATERIAL S Eligible patients had muscle-invasive transitional cell carcinoma ( cT2 - 3 ) and were c and i date s for cystectomy . Patients underwent maximal transurethral resection of bladder tumor followed by twice-weekly gemcitabine with concurrent RT to the bladder ( total of 60 Gy over 6 weeks ) . Gemcitabine doses ranged from 10 to 33 mg/m(2 ) . RESULTS Median follow-up was 5.6 years ( range , 0.6 - 9.5 years ) . Twenty-three of 24 patients were evaluable for response . All patients were clinical stage T2 . Locoregional failure occurred in seven patients ( 30 % ) , which were successfully salvaged by radical cystectomy ( n = 5 ) or intravesical therapy ( n = 2 ) . Four local failures occurred > 5 years after therapy . Most local failures were noninvasive tumors ( Ta or Tis , n = 6 ) . Ten patients ( 43 % ) experienced optimal outcome ( no failures and bladder intact ) . The 5-year actuarial estimates of survival are BIS 62 % , OS 76 % , and DSS 82 % . CONCLUSION Twice-weekly gemcitabine with concurrent RT is well tolerated and provides rates of survival and bladder preservation that are comparable to the existing literature . All locoregional failures were successfully salvaged by either radical cystectomy or intravesical therapy . Given the high proportion of late local failures , we recommend long-term monitoring when using this regimen . Future studies comparing the safety and efficacy of gemcitabine- vs. platinum-based bladder preservation protocol s are pending Radical radiotherapy and surgery achieve similar cure rates in muscle-invasive bladder cancer , but the choice of which treatment would be most beneficial can not currently be predicted for individual patients . The primary aim of this study was to assess whether expression of any of a panel of DNA damage signaling proteins in tumor sample s taken before irradiation could be used as a predictive marker of radiotherapy response , or rather was prognostic . Protein expression of MRE11 , RAD50 , NBS1 , ATM , and H2AX was studied by immunohistochemistry in pretreatment tumor specimens from two cohorts of bladder cancer patients ( validation cohort prospect ively acquired ) treated with radical radiotherapy and one cohort of cystectomy patients .  In the radiotherapy test cohort ( n = 86 ) , low tumor MRE11 expression was associated with worse cancer-specific survival compared with high expression [ 43.1 % versus 68.7 % 3-year cause-specific survival ( CSS ) , P = 0.012 ] by Kaplan-Meier analysis . This was confirmed in the radiotherapy validation cohort ( n = 93 ; 43.0 % versus 71.2 % , P = 0.020 ) . However , in the cystectomy cohort ( n = 88 ) , MRE11 expression was not associated with cancer-specific survival , commensurate with MRE11 being a predictive marker . High MRE11 expression in the combined radiotherapy cohort had a significantly better cancer-specific survival compared with the high-expression cystectomy cohort ( 69.9 % versus 53.8 % 3-year CSS , P = 0.021 ) . In this vali date d immunohistochemistry study , MRE11 protein expression was shown and confirmed as a predictive factor associated with survival following bladder cancer radiotherapy , justifying its inclusion in subsequent trial design s. MRE11 expression may ultimately allow patient selection for radiotherapy or cystectomy , thus improving overall cure rates Seventy patients with muscle-invading bladder carcinoma ( clinical stages T2 to T4 ) who were not c and i date s for cystectomy were treated with combined cisplatin and full-dose external-beam radiation on a multi-institutional prospect i ve protocol from 1980 through 1985 . Thirty-six patients are alive , all but three without evidence of cancer . The complete response rate is 77 % in the 62 patients completing planned irradiation and 70 % for all patients . Among the complete responders , 73 % are currently maintained , and this group has a significantly higher four-year survival than those not having a complete response and those with recurrence of disease--57 % vs 11 % . The observed high complete response rates in patients in all stages and the high survival rates suggest irradiation plus cisplatin therapy offers an important therapeutic gain over radiation therapy alone for invasive cancer of the bladder . These results encourage further evaluation of combining cisplatin-based , multidrug chemotherapy with irradiation in patients with locally very-advanced bladder tumors who are not suited for surgery The objective of the study was to investigate the predictive value of various clinical , biochemical , and histopathological parameters , with special emphasis on the expression of the retinoblastoma protein ( pRB ) , on the radiation response in bladder cancer . In order to obtain a truly objective response measure , patients receiving preoperative radiotherapy followed by cystectomy  were studied . Pretreatment tumour sample s and clinical data from 108 consecutive patients were collected . End points were complete response ( CR ) to radiotherapy , relapse-free survival time and overall survival time . Expression of pRB was assessed by immunohistochemical staining as present or absent . Complete response to radiotherapy  was obtained in 42 of 106 evaluable patients ( 40 % ) . Predictive for CR to radiotherapy , in univariate analysis , was transurethral resection ( as opposed to biopsy ) , B-haemoglobin , no upper urinary retention , and loss of pRB staining . Loss of pRB staining was the strongest independent predictor of radiation response in multivariate logistic regression analysis and absence of upper urinary retention was the only other significant factor . Loss of pRB was the only parameter showing statistically significant , independent association with relapse-free survival , whereas B-haemoglobin was also independently associated with overall survival . Loss of pRB expression seems to indicate a phenotype displaying enhanced radiosensivity and may be of benefit by denoting patients who would selectively benefit from a treatment schedule containing radiotherapy PURPOSE To assess the safety , tolerance , and efficacy of transurethral surgery plus concomitant cisplatin , 5-fluorouracil ( 5-FU ) , and radiation therapy in conjunction with selective bladder preservation in patients with muscle-invading bladder cancer . Patients and Methods . Thirty-four eligible patients with clinical stage T2-T4a , Nx M0 bladder cancer without hydronephrosis were entered into a protocol aim ed at selective bladder preservation . Treatment began with as complete a transurethral resection as possible followed by induction chemoradiation . This consisted of cisplatin 15 mg/m(2 ) i.v . and 5-fluorouracil ( 5-FU ) 400 mg/m(2 ) i.v . in the mornings on d 1 , 2 , 3 , 15 , 16 , and 17 . On d 1 , 3 , 15 , and 17 , radiation was given immediately following the chemotherapy using twice-a-day 3 Gy per fraction cores to the pelvis for a total radiation dose of 24 Gy . Response was evaluated by cystoscopy , cytology , and rebiopsy four weeks later . Patients with a complete response received consolidation therapy with the same drugs and doses on d 1 , 2 , 3 , 15 , 16 , and 17 combined with twice-daily radiation therapy to the bladder and bladder tumor volume of 2.5 Gy per fraction for a total consolidation dose of 20 Gy and a total induction plus consolidation dose to the bladder and bladder tumor of 44 Gy . Patients who did not achieve a complete response were advised to undergo prompt cystectomy , as were those with a subsequent invasive recurrence . The median follow up is 29 months . RESULTS Of the 34 eligible patients , 26 had a visibly complete transurethral resection . One patient did not complete induction treatment due to acute hematologic toxicity . After induction treatment , 22 ( 67 % ) of the 33 patients had no tumor detectable on urine cytology or rebiopsy . Of the 11 patients who still had detectable tumor , six underwent radical cystectomy and five underwent consolidation chemoradiation ( one because of refusal to have the recommended cystectomy and four because the treating institutions erroneously assigned them to receive consolidation chemoradiation rather than cystectomy ) . No patient has required a cystectomy for radiation toxicity . Six patients have died of bladder cancer . The actuarial overall survival at three years is 83 % . The probability of surviving with an intact bladder is 66 % at three years . A total of seven patients ( 21 % ) developed grade 3 or grade 4 hematologic toxicity in conjunction with this treatment . CONCLUSION This aggressive protocol comprising local surgery plus concurrent 5-FU , cisplatin , and high-dose hypofractionated radiation has been associated with moderately severe hematologic toxicity . Longer follow-up will be necessary to assess efficacy . Both the 67 % complete response rate to induction therapy and the 66 % three-year survival with an intact bladder are encouraging Clinical and pathologic factors were analyzed in 40 patients with localized muscle-invasive bladder carcinoma treated in a prospect i ve bladder-preserving program consisting of  transurethral tumor resection , neoadjuvant chemotherapy ( methotrexate , cisplatin , and vinblastine [ MCV ] ) , and 4,000 cGy radiotherapy with concurrent cisplatin .  Patients with biopsy-proven complete response after chemotherapy and 4,000 cGy radiation received  full-dose radiotherapy ( 6,480 cGy ) with cisplatin . Cystectomy was recommended to patients with residual disease . Distant metastasis rate was associated with tumor stage and size : 0 % in T2 patients , 39 % in T3 - 4 patients ( P = .035 ) , 6 % for tumors less than 5 cm , and 59 % for tumors greater than or equal to 5 cm ( P = .002 ) . Risk of bladder tumor recurrence was higher in patients with tumor-associated carcinoma in situ ( CIS ; 40 % ) than those without CIS ( 6 % ; P = .075 ) . Papillary tumors and solid tumors both had similar treatment outcomes . By multivariate analysis , tumor stage T2 ( P = .04 ) and absence of CIS ( P = .03 ) were significant predictors of complete response ; CIS was predictive of local bladder recurrence ( P = .07 ) ; and tumor size ( P = .03 ) , response after chemoradiotherapy ( P = .02 ) , and vascular invasion ( P = .08 ) were associated with distant metastasis . Six of eight local bladder tumor recurrences were superficial tumors . The low actuarial distant metastasis rate of T2 patients ( 0 % at 3 years ) , the 3-year actuarial overall survival rates for T2 ( 89 % ) and T3 - 4 ( 50 % ) patients , and the similar treatment outcomes for papillary versus solid tumors are encouraging when compared with published historical controls . These results provide preliminary evidence ( median follow-up , 30 months ) that the current chemoradiotherapy regimen may have beneficial effects in the treatment of muscle-invasive bladder carcinoma . The true efficacy of neoadjuvant chemotherapy remains to be proven by ongoing r and omized trials PURPOSE We evaluated the feasibility and efficacy of the organ preserving strategy of intra-arterial cisplatin and concurrent radiotherapy for localized bladder cancer . MATERIAL S AND METHODS Bladder preservation has been pursued over the decades in treatment regimens featuring radiotherapy alone or in conjunction with single or multiagent chemotherapy . The chemotherapy has consisted almost exclusively of intravenously administered drugs . There are theoretical and clinical data demonstrating a higher concentration of cisplatin within tumors following intra-arterial as opposed to intravenous delivery . This study was performed to evaluate whether this increased concentration would enhance radiosensitization and thereby increase the success of bladder preservation . RESULTS We report on our prospect ively collected experience during 15 years of treating 200 patients with localized bladder cancer using this regimen of 3 courses of intra-arterial cisplatin integrated with pelvic radiotherapy  and reserving cystectomy for salvage as required . We report on the efficacy in terms of complete response rate , ultimate tumor-free bladder preservation , overall survival and patterns of failure . We detail the acute and chronic toxicity observed to date . CONCLUSIONS This strategy has result ed in a durable high complete response rate and overall tumor-free bladder preservation rate of 75 % while maintaining a survival comparable to that achieved with cystectomy . These results corroborate the hypothesis that intra-arterial administration of cisplatin enhances radiosensitization during pelvic radiotherapy We conducted a phase I/II study investigating synchronous chemoradiotherapy with mitomycin C and infusional 5-fluorouracil ( 5-FU ) in muscle invasive bladder cancer . Early dose escalation results were previously published . We report the long-term toxicity and efficacy results with the optimised regimen . Patients with muscle invasive bladder cancer with glomerular filtration rate > 25 ml min−1 were eligible .  Mitomycin ( 12 mg m−2 on day 1 only ) and infusional 5-FU ( 500 mg m−2 day−1 ) for 5 days were administered during weeks 1 and 4 of radiotherapy of 55 Gy in 20 fractions . A total of 41 patients were enrolled , median age was 68 years , 33 were male and eight female patients . Out of the 41 patients , 20 ( 49 % ) had hydronephrosis at presentation and 25 ( 62 % ) had T3b or T4 disease . Four patients experienced Grade III thrombocytopenia and three patients had Grade III neutropenia . There were no episodes of febrile neutropenia . Four patients experienced Grade III diarrhoea and 1 Grade III urgency and dysuria . Six patients did not undergo cystoscopic evaluation due to early metastatic spread although there was no clinical suggestion of bladder failure . In all , out of 35 evaluable patients , 25 ( 71 % ) had macroscopic complete response at 3-month cystoscopy , and biopsy confirmed in 24 out of 25 . A total of 16 ( 39 % ) patients remain alive with a median follow-up of 50.7 ( range 23.5–68.8 ) months , 14 with a functioning bladder with no reported long-term treatment-related bladder or bowel toxicity . Five out of 41 patients have undergone salvage cystectomy : two for persistent CIS , two T1 and one muscle invasive recurrence . Four patients have received intravesical chemotherapy , of whom two remain alive with a functioning bladder . Overall 12- , 24- and 60-month ( m ) survival rates were 68 , 49 and 36 % . Local and distant progression free rates were 82 and 86 % at 12-m and 79 and 75 % at 24-m . Organ preservation using multimodality therapy is feasible and safe , even in patients with poor renal reserve , and does not compromise salvage therapies . A national phase III trial BC2001 ( www.bc2001.org.uk ) exploring the effects of synchronous chemoradiotherapy with this regimen is currently recruiting BACKGROUND Whether organ-conserving treatment by combined-modality therapy ( CMT ) achieves comparable long-term survival to radical cystectomy ( RC ) for muscle-invasive bladder cancer ( BCa ) is largely unknown . OBJECTIVE Report long-term outcomes of patients with muscle-invasive BCa treated by CMT .  DESIGN , SETTING , AND PARTICIPANTS We conducted an analysis of successive prospect i ve protocol s at the Massachusetts General Hospital ( MGH ) treating 348 patients with cT2 - 4a disease between 1986 and 2006 . Median follow-up for surviving patients was 7.7 yr . INTERVENTIONS Patients underwent concurrent cisplatin-based chemotherapy and radiation therapy ( RT ) after maximal transurethral resection of bladder tumor ( TURBT ) plus neoadjuvant or adjuvant chemotherapy . Repeat biopsy was performed after 40 Gy , with initial tumor response guiding subsequent therapy . Those patients showing complete response ( CR ) received boost chemotherapy and RT . One hundred two patients ( 29 % ) underwent RC-60 for less than CR and 42 for recurrent invasive tumors . MEASUREMENTS Disease-specific survival ( DSS ) and overall survival ( OS ) were evaluated using the Kaplan-Meier method . RESULTS AND LIMITATIONS Seventy-two percent of patients ( 78 % with stage T2 ) had CR to induction therapy . Five- , 10- , and 15-yr DSS rates were 64 % , 59 % , and 57 % ( T2=74 % , 67 % , and 63 % ; T3 - 4=53 % , 49 % , and 49 % ) , respectively . Five- , 10- , and 15-yr OS rates were 52 % , 35 % , and 22 % ( T2 : 61 % , 43 % , and 28 % ; T3 - 4=41 % , 27 % , and 16 % ) , respectively . Among patients showing CR , 10-yr rates of noninvasive , invasive , pelvic , and distant recurrences were 29 % , 16 % , 11 % , and 32 % , respectively . Among patients undergoing visibly complete TURBT , only 22 % required cystectomy ( vs 42 % with incomplete TURBT ; log-rank p<0.001 ) . In multivariate analyses , clinical T-stage and CR were significantly associated with improved DSS and OS . Use of neoadjuvant chemotherapy did not improve outcomes . No patient required cystectomy for treatment-related toxicity . CONCLUSIONS CMT achieves a CR and preserves the native bladder in > 70 % of patients while offering long-term survival rates comparable to contemporary cystectomy series . These results support modern bladder-sparing therapy as a proven alternative for selected patients Organ preservation has been investigated in patients with muscle‐invasive bladder carcinoma over the past decades as an alternative to radical cystectomy . The majority of studies reported that trimodal schedules , including transurethral resection of bladder tumor ( TURB ) , radiotherapy ( RT ) , and chemotherapy , are a feasible and safe organ‐sparing approach without deferring the survival probability . However , to the authors ' knowledge the best combination of RT and chemotherapy has yet to be well defined . The current study evaluated the long‐term results of a schedule of concurrent cisplatin and 5‐fluorouracil ( 5‐FU ) administered as protracted intravenous infusions ( PVI ) during hyperfractionated radiotherapy ( HFRT ) with organ‐sparing intent in patients with infiltrating transitional cell carcinoma of the bladder ( TCCB ) BACKGROUND Radical radiotherapy for muscle-invasive urinary bladder cancer can sterilize the tumour with preserved organ function . Here we studied symptoms , symptom distress and trade-off among long-term survivors and compared figures to those of population controls and patients who had undergone cystectomy .  MATERIAL S AND METHODS We identified 71 patients who had had urinary bladder cancer treated with radical radiotherapy before 1995 . For comparison , 325 patients treated with radical cystectomy and urostomy , continent or non-continent , during the same period and 460 individuals r and omly selected from the general population were included . Information was collected by means of an anonymously answered postal question naire to avoid investigator-related bias . RESULTS Answers were obtained from 58 ( 82 % ) radiated patients , 251 ( 85 % ) cystectomized patients and 310 ( 71 % ) population controls . Of the radiated patients , 74 % reported little or no distress from symptoms from the urinary tract , 38 % had had intercourse the previous month and 57 % ( men ) reported they had ejaculated . Among the cystectomized patients , 13 % had had intercourse and 0 % ( men ) had ejaculated . Moderate or much distress from symptoms from the gastrointestinal tract was reported by 32 % of the radiated patients , 24 % of the cystectomized patients and 9 % of the population controls . After radical radiotherapy , 46 % of the patients were willing to accept some risk of decreased survival to become symptom-free . CONCLUSIONS About 3/4 of these long-term survivors after radical radiotherapy for bladder cancer had a functioning urinary bladder with little or no distress from the urinary tract . The prevalence of sexual dysfunction was lower than after cystectomy and the prevalence of distress from the gastrointestinal tract was comparable To examine combination cisplatin and twice-daily accelerated irradiation ( RT ) after aggressive transurethral resection of bladder tumor ( TURBT ) in an attempt to preserve the bladder and to determine the likelihood that patients who complete this regimen could then complete three cycles of methotrexate , cisplatin , vinblastine ( MCV ) chemotherapy .  Between 1998 and 2000 , 52 patients with Stage T2-T4aN0M0 disease , from 17 institutions , were entered into the trial . Forty-seven patients were deemed eligible ; the planned accrual was 40 . Of the 46 patients , 68 % were > 60 years old , 70 % were men , and 96 % had a Karnofsky score > /=90 . The clinical T stage was T2 in 66 % , T3a in 25 % , and T3b in 9 % . The median follow-up at the time of analysis was 26 months . The protocol required TURBT within 6 weeks of the initiation of induction therapy . Induction treatment involved 13 days of concomitant boost RT , 1.8 Gy to the pelvis in the morning followed by 1.6 Gy to the tumor 4 - 6 h later . For sensitization , cisplatin ( 20 mg/m(2 ) ) was given on the first 3 days of each treatment week . Three to four weeks after induction , patients were evaluated cystoscopically for residual disease . Patients whose biopsies and cytologic evaluations showed no disease completed consolidation chemoirradiation . Patients with residual tumor went on to cystectomy . After either consolidation or cystectomy , patients were to complete three cycles of MCV chemotherapy . Of the 47 patients , 45 % completed all phases of the protocol treatment with minor , or no , deviations . Five patients refused either the postinduction evaluation or cystectomy and 6 refused adjuvant chemotherapy . The CR rate after induction therapy was 74 % . For 2 patients , residual disease after induction was limited to positive cytologic findings , and for 8 patients , biopsy of the primary site revealed persistence . Of the 8 cystectomy patients , 2 had no evidence of disease in the bladder at pathologic review of the surgery specimen . Grade 3 toxicity related to chemotherapy was observed in 11 % of patients during both induction and consolidation , and in 41 % during adjuvant chemotherapy . A total of 8 patients ( 36 % of those receiving adjuvant chemotherapy ) went on to develop Grade 4 neutropenia or thrombocytopenia during additional adjuvant chemotherapy .  Grade 3 toxicity due to RT was seen in 4 % and 0 % of patients during induction and consolidation , respectively . One patient developed Grade 4 hydronephrosis during consolidation . The projected 36-month value for locoregional failure , distant metastasis , overall survival , and bladder-intact survival was 27 % , 29 % , 61 % , and 48 % , respectively . After aggressive TURBT , twice-daily accelerated RT initiated in concomitant-boost format is well tolerated and results in a rate of complete response ( 74 % ) similar to that in previous bladder-sparing trials . The projected 2-year values for locoregional control , bladder-intact survival , and overall survival were also consistent with previously reported trials of bladder-sparing treatment . With only 45 % of patients completing three cycles of MCV , this form of adjuvant chemotherapy appears to be poorly tolerated by most patients OBJECTIVES To evaluate the outcomes of patients with muscle-invasive Stage T2 - 4a bladder carcinoma managed by transurethral surgery and concurrent chemoradiation .  METHODS A total of 190 patients were treated on institutional prospect i ve protocol s using concurrent cisplatin-containing chemotherapy and radiotherapy after rigorous transurethral resection of the bladder tumor . Patients were re-evaluated by repeated biopsy and urine cytologic analysis after 40 Gy , with the initial tumor response guiding subsequent therapy . One hundred twenty-one patients with a complete response by cytologic and histologic examination and those medically unfit for cystectomy received  boost chemoradiation to 64 to 65 Gy . Those patients without a complete response were advised to undergo radical cystectomy . A total of 66 patients ( 35 % ) ultimately underwent radical cystectomy ; 41 for less than a complete response and an additional 25 for recurrent invasive tumors . The median follow-up was 6.7 years for all surviving patients . RESULTS The 5 and 10-year actuarial overall survival rate was 54 % and 36 % , respectively ( Stage T2 , 62 % and 41 % ; Stage T3-T4a , 47 % and 31 % , respectively ) . The 5 and 10-year disease-specific survival rate was 63 % and 59 % ( Stage T2 , 74 % and 66 % ; Stage T3-T4a , 53 % and 52 % ) , respectively . The 5 and 10-year disease-specific survival rate for patients with an intact bladder was 46 % and 45 % ( Stage T2 , 57 % and 50 % ; Stage T3-T4a , 35 % and 34 % ) , respectively . The pelvic failure rate was 8.4 % . No patient required cystectomy because of bladder morbidity . CONCLUSIONS The 10-year overall survival and disease-specific survival rates are comparable with the results reported for contemporary radical cystectomy for patients of similar clinical and pathologic stage . One third of patients treated on protocol with the goal of bladder sparing ultimately required a cystectomy . A trimodality approach with bladder preservation based on the initial tumor response is , therefore , safe , with most long-term survivors retaining functional bladders Concurrent vinablastine-based radiochemotherapy was evaluated in 84 bladder-cancer patients . It was effective in more than half : tumour-specific survival ( 51 % 9-year ) , local control rate ( 55 % 9-year ) . The drawback was the impaired function of the bladder ( 9-year prevalence SOMA G3 - 4 symptoms : 66 % ) , indicating the need for treatment aim ed at reducing chronic morbidity PURPOSE To determine whether the apoptotic index , the Ki67 index , and the expression of the p53 , cyclin D1 , and retinoblastoma genes correlate with local control , overall survival , and time to distant metastases in invasive bladder cancer treated with external beam radiation .  METHODS AND MATERIAL S Paraffin-embedded pretreatment biopsies from 83 patients with invasive transitional cell carcinoma of the bladder were scored morphologically for apoptosis and immunohistochemically for Ki67 , p53 , cyclin D1 , and retinoblastoma gene expression . Survival analysis methods were used to assess overall survival , local control , and freedom from distant metastases . A multiple proportional hazard ( PH ) regression analysis was performed to study the prognostic value of the abovementioned biologic parameters ( all divided into two categories , except Ki67 ) in addition to classical prognostic factors such as T stage , histologic grade , multifocality of the tumor , and completeness of transurethral resection . All patients were treated with external beam radiation as sole treatment . Median follow-up for the 19 patients still living was 7.5 years . RESULTS Apoptotic index varied from 0 % to 3.4 % with a mean of 0.8 % and a median of 0.6 % . Ki67 index varied from 0 % to 60 % with a mean of 14 % and a median of 12 % . P53 protein was detectable in 61 % of the tumors . Overexpression of cyclin D1 was observed in 39 % of the tumors and loss of retinoblastoma protein in 23 % of the tumors . High Ki67 index was found to be significantly associated with p53 expression ( p = 0.04 ) and cyclin D1 overexpression ( p = 0.023 ) . Cyclin D1 overexpression was found more often in Rb-positive tumors than in Rb-negative tumors ( p = 0.006 ) . Other associations between the markers are less clear . Biologic markers were not correlated with T stage or grade . In the PH analysis local control was found to be significantly better for tumors with wild-type p53 ( p = 0.028 ) . Also , tumors with an apoptotic index above the median value ( 0.6 % ) had a significantly better local control rate ( p = 0.035 ) . Ki67 index ( p = 0.35 ) , retinoblastoma gene expression ( p = 0.30 ) and cyclin D1 overexpression ( p = 0.61 ) were not found to have an additional predictive value regarding local tumor control . None of the tested biologic parameters were found to be associated with overall survival . Time to distant metastases was significantly shorter for tumors with high Ki67 index ( p = 0.01 ) and tumors with an apoptotic index less than median ( p = 0.009 ) . CONCLUSIONS The results of our study provide evidence for a prognostic value of p53 expression and apoptotic index with respect to the radiation response in bladder cancer in addition to more conventional prognosticators . The value of these parameters as a predictive assay for radiation response warrants confirmation in larger and prospect i ve studies PURPOSE To assess the efficacy of neoadjuvant methotrexate , cisplatin , and vinblastine ( MCV ) chemotherapy in patients with muscle-invading bladder cancer treated with selective bladder preservation . PATIENTS AND METHODS One hundred twenty-three eligible patients with tumor , node , metastasis system clinical stage T2 to T4aNXMO bladder cancer were r and omized to receive ( arm 1 , n=61 ) two cycles of MCV before 39.6-Gy pelvic irradiation with concurrent cisplatin 100 mg/m2 for two courses 3 weeks apart . Patients assigned to arm 2 ( n=62 ) did not receive MCV before concurrent cisplatin and radiation therapy . Tumor response was scored as a clinical complete response ( CR ) when the cystoscopic tumor-site biopsy and urine cytology results were negative . The CR patients were treated with an additional 25.2 Gy to a total of 64.8 Gy and one additional dose of cisplatin . Those with less than a CR underwent cystectomy . The median follow-up of all patients who survived is 60 months . RESULTS Seventy-four percent of the patients completed the protocol with , at most , minor deviations ; 67 % on arm 1 and 81 % on arm 2 . The actuarial 5-year overall survival rate was 49 % ; 48 % in arm 1 and 49 % in arm 2 . Thirty-five percent of the patients had evidence of distant metastases at 5 years ; 33 % in arm 1 and 39 % in arm 2 . The 5-year survival rate with a functioning bladder was 38 % , 36 % in arm 1 and 40 % in arm 2 . None of these differences are statistically significant . CONCLUSION Two cycles of MCV neoadjuvant chemotherapy were not shown to increase the rate of CR over that achieved with our st and ard induction therapy or to increase freedom from metastatic disease . There was no impact on 5-year overall survival BACKGROUND AND PURPOSE To evaluate the efficacy and toxicity of an accelerated fractionation regimen to treat localised muscle invasive bladder cancer . PATIENTS AND METHODS A prospect i ve r and omised trial was undertaken in 229 patients r and omised between 1988 and 1998 comparing accelerated fractionation ( AF ) to a dose of 60.8 Gy in 32 fractions over 26 days with conventional fractionation ( CF ) treating to 64 Gy in 32 fractions over 45 days . Accelerated fractionation was delivered using two fractions per day with a 6h gap between fractions and with the first daily fraction size being 1.8 Gy and the second daily fraction size being 2.0 Gy . There was a 1 week treatment gap after the first 12 fractions . Conventional fractionation was one fraction per day , 5 days per week . Eligible patients had clinical stage T2 or T3 , N0 or N1 , M0 transitional cell carcinoma . The primary endpoint of the trial was local control and the trial was powered to detect a 20 % difference ( alpha 0.05 , power 90 % ) . Secondary endpoints were toxicity and survival . RESULTS In the initial phase of the trial , r and omisation was unequal such that in total 129 patients were r and omised to accelerated fractionation and 100 to conventional fractionation . Acute toxicity was evaluable in 121 patients treated with AF and 96 patients treated with CF . RTOG grade 2 or 3 bowel toxicity was noted in 44 % of AF patients compared to 26 % of CF patients ( P trend = 0.001 ) . Acute grade 2 or 3 bladder toxicity was seen in 35 % of AF patients compared to 36 % of CF patients ( P=0.99 ) . Late radiation toxicity was evaluated in patients surviving free from local recurrence at 2 years post treatment . Late radiation toxicity equivalent to RTOG grade 2 or more had occurred in 44 % ( 95 % CI 34 - 55 % ) of AF patients and in 38 % ( 95 % CI 26 - 49 % ) of CF patients ( logrank over 5 years follow-up P=0.23 ) . There was no significant difference in analysis of time to loss of local tumour control comparing the two treatment arms ; local recurrence was recorded in 29 of the 100 patients treated with CF and in 41 of 129 patients treated with AF ( logrank P=0.86 ) . There was also no significant difference between the treatment arms comparing disease-free survival and overall survival . The overall survival figures at 3 years were for AF 54 % ( 95 % CI 45 - 63 % ) and for CF 47 % ( 95 % CI 36 - 57 % ) . By 5 years the overall survival was 37 % for AF and 40 % for CF . There were two treatment related deaths , both on the AF arm of the trial . CONCLUSIONS This accelerated fractionation schedule did not improve on the efficacy of conventional fractionation for patients with T2 and T3 bladder cancer and accelerated fractionation was associated with increased acute bowel reactions PURPOSE To improve the results obtained by cystectomy alone and to determine the possibilities of conservative treatment in invasive bladder cancer , we design ed a prospect i ve study using a combination of fluorouracil ( 5-FU ) plus cisplatin and concomitant radiation therapy , followed by either cystectomy or additional chemoradiotherapy . PATIENTS AND METHODS Fifty-four patients with stage T2 to T4 operable untreated invasive bladder cancer were entered onto the study . Treatment was begun in all patients by transurethral resection ( TUR ) and followed by the 5-FU-cisplatin combination with concomitant bifractionated split-course radiation therapy . A control cystoscopy was performed 6 weeks after completion of the neoadjuvant program . Patients with persistent tumor underwent cystectomy . Complete responders were treated by either additional chemoradiotherapy ( group A ) or cystectomy ( group B ) . RESULTS At control cystoscopy , 40 of 54 patients ( 74 % ) had a histologically documented complete response . Four responders developed recurrent pelvic disease after a mean follow-up time of 27 + /- 12 months ( three in group A and one in group B ) . Metastatic disease , which developed in 16 patients , occurred more frequently in the nonresponders ( 71 % ) than in responders ( 15 % ) . The disease-free survival rate at 3 years was 62 % ; it was significantly better in responders ( 77 % ) than in nonresponders ( 23 % ) . There was no difference in survival between groups A and B. CONCLUSION This neoadjuvant chemoradiotherapy combination , easy to implement and well tolerated even in elderly patients , provides a high complete response rate . It may prove to be effective in inoperable patients and may be proposed as conservative treatment in patients with a complete response to the initial course of chemoradiation PURPOSE Patients with locally advanced bladder cancer or who are not medically fit for surgery are a therapeutic dilemma . Radiotherapy with or without single agent cisplatin has been the major therapeutic modality . A phase II Southwest Oncology Group trial investigated the efficacy and feasibility of 5-fluorouracil , cisplatin and radiation in this patient subset . MATERIAL S AND METHODS Eligible patients had muscle invasive bladder cancer ( clinical stages T2-T4 ) with nodal involvement at or below the level of bifurcation of the iliac vessels , were medically or surgically inoperable , or refused cystectomy . Patients underwent pretreatment cystoscopy and detailed tumor mapping , and were treated with 75 mg . /m.2 cisplatin on day 1 and 1 gm./m.2 daily , 5-fluorouracil on days 1 to 4 and definitive radiotherapy . Chemotherapy was repeated every 28 days , twice during and twice after radiation . RESULTS From October 1993 to April 1998 , 60 patients were enrolled in study . Of the 56 eligible patients 34 % had unresectable tumors , 21 % were not medically fit for surgery and 45 % refused cystectomy . Overall , 68 % of the patients had clinical T3 tumors or greater and 22 % had nodal metastasis . Treatment was completed as planned in 32 of 56 ( 57 % ) patients . The most frequent grade 3 or 4 toxicities were neutropenia , stomatitis or mucositis , diarrhea , neuropathy and nausea . There were 53 patients who were evaluable for response , although response was not determined for 18 . The overall response rate was 51 % ( 95 % confidence interval [ CI ] 37 to 65 ) based on intent to treat with a complete response rate of 49 % ( 95 % CI 35 to 63 ) . Estimated median survival of the 56 patients was 27 months ( 95 % CI 21 to 40 months ) with an overall 5-year survival of 32 % . The 5-year survival of the 25 patients who refused surgery was 45 % . CONCLUSIONS Concurrent 5-fluorouracil , cisplatin and radiation therapy is feasible . Despite a promising complete response rate , the overall 5-year survival suggests the need for more effective systemic therapy . The 5-year survival of patients who refused cystectomy suggests that this combined modality may provide another alternative to cystectomy for these patients PURPOSE Chemoradiotherapy is becoming an alternative to radical cystectomy among patients with muscle invading bladder cancer . We began a prospect i ve study in 1988 to determine the possibilities of conservative treatment and aim ing to improve the results obtained by cystectomy alone in invasive bladder cancer . A combination of methotrexate , vinblastine , adriamycin , and cisplatin ( M-VAC ) , followed by radiotherapy and concomitant cisplatin was used . METHODS Fifty patients with good performance status and with stages T2 to T4 operable untreated invasive bladder cancer were entered in the study . Treatment protocol was as follows : ( i ) cytoreductive transurethral resection ; ( ii ) two cycles of M-VAC chemotherapy ; ( iii ) radiotherapy , 45 Gy on pelvic volume and , at the same time , 20 mg/m(2 ) cisplatin on days 1 to 5 . Cystoscopic evaluation : if there was a complete response , radiotherapy was completed up to 65 Gy ; if there was not a complete response , a cystectomy was performed . Median follow-up of the series was 73 months ( 18 - 180 m ) . RESULTS Tumor response was as follows : 34 complete responses ( 68 % ) , 9 partial responses ( 18 % ) , and 7 nonresponses ( 14 % ) were observed . The 5-year overall survival and local control were 48 % and 47 % , respectively . For the complete responder patient , 5-year survival and local control were 65 % and 70 % , respectively . Severe toxicity was uncommon . The most frequent were leucopenia and cystitis . No treatment-related deaths occurred with either treatment protocol . CONCLUSIONS Conservative combination treatment may be an acceptable alternative to immediate cystectomy in selected patients with bladder cancer , although a r and omized clinical trial would be required to produce definitive results PURPOSE Radical cystectomy is considered as st and ard therapy for muscle-invasive bladder cancer . We present 10-year results of bladder-sparing treatment by conservative surgery and radiotherapy + /- chemotherapy . METHODS AND MATERIAL S From 1982 through 1991 , 245 consecutive patients , mean age 66 years , with invasive bladder cancer ( T2 - 3 or poor prognostic T1 , no distant metastases ) entered a prospect i ve protocol with the objective of bladder preservation . Treatment consisted of transurethral resection ( complete , if possible ) and definitive radiotherapy with 56 Gy maximum dose ( 50.4 Gy minimum target dose ) in 28 fractions . Since 1985 , 139 patients received a simultaneous chemotherapy  on 5 days in the first and fifth treatment week with either 25 mg/m2 cisplatin daily ( 79 patients ) or 65 mg/m2 carboplatin ( 60 patients ) . Cystectomy was performed as salvage treatment for residual or recurrent invasive disease . The median follow-up at the date of analysis ( 12 - 31 - 92 ) was 5.9 years . RESULTS The overall survival was 47 % after 5 years and 26 % after 10 years . The 5-year survival according to the initial T-category was 60 % for T1 ( 44 patients ) , 64 % for T2 ( 47 patients ) , 43 % for T3 ( 127 patients ) , and 16 % for T4 ( 23 patients ) . The most important single prognostic factor was the amount of residual tumor after TUR ( 5-year survival 80 % after R0 , 53 % after R1 , and 31 % after R2 resection , p < 0.01 ) . Chemotherapy increased the rate of complete remission , but had no impact on 5-year survival ( 52 % vs. 50 % ) . Fifty-three salvage cystectomies were performed , all without severe complications , and 192 patients ( 79 % ) maintained a normal functioning bladder . The bladder preservation rate in 5-year survivors was 83 % . CONCLUSIONS Organ-sparing treatment of advanced bladder cancer by transurethral surgery and definitive radiotherapy or radiochemotherapy is feasible and effective . The survival in this series is as good as in any comparable cystectomy series . Eighty-three percent of long-term survivors maintained their functioning bladders PURPOSE Although the use of radical transurethral resection followed by concurrent radiochemotherapy leads to a similar survival rate to that achieved after cystectomy , the number of long-term survivors is low in both cases . An improvement may be obtained by adding a new drug , such as gemcitabine , which is active in bladder cancer and acts as a radiosensitizer . However , because gemcitabine may be very toxic when associated with radiotherapy , we design ed this dose-finding study in an attempt to find the dose that can be safely added to radiotherapy and concurrent cisplatin in patients treated with transurethral resection for infiltrating bladder cancer . PATIENTS AND METHODS After undergoing macroscopically complete transurethral resections for transitional carcinoma of the bladder , patients staged pT2 or higher and without distant metastases concurrently received 54 Gy of fractionated radiotherapy over 6 weeks with cisplatin ( 100 mg/m(2 ) q.3 w ) , starting on Day 1 of radiotherapy . Concomitant gemcitabine was administered on Days 1 , 8 , and 15 q.3 w for 2 cycles at a dose of 200 mg/m(2 ) , escalated to 500 mg/m(2 ) , with a 100 mg/m(2 ) increase at each dose level . The maximum tolerated dose was defined as the dose of gemcitabine associated with dose-limiting toxic effects ( febrile neutropenia , Grade 4 thrombocytopenia , Grade 3 or 4 enteric toxicity , or Grade 4 nonhematologic toxicity ) in 33 % of the patients treated at that dose level . Six to 8 weeks after completing the therapy , the patients underwent cystoscopic reevaluation with multiple biopsies of the initial tumor site . RESULTS Of our consecutive series of 16 patients , 5 received a gemcitabine dose of 200 mg/m(2)/week , 3 a dose of 300 mg/m(2)/week , 3 a dose of 400 mg/m(2)/week , and 5 a dose of 500 mg/m(2)/week for 6 weeks . No dose-limiting toxicity was observed at doses of up to 400 mg/m(2)/week . At the dose 500 mg/m(2)/week , 1 patient experienced an intestinal perforation that recovered after surgery , and another suddenly died after developing Grade 3 untreated diarrhea in the last treatment week . All of the 15 evaluable patients were microscopically disease free at the cystoscopic reevaluation ; furthermore , the posttreatment computed tomography scans did not reveal any distant metastases . CONCLUSIONS After transurethral resection for the conservative treatment of infiltrating bladder cancer , gemcitabine doses of up to 400 mg/m(2)/week seem to be safe in combination with cisplatin and radiotherapy in organ-sparing management . On the basis of the promising results of this Phase I study , we are currently conducting a Phase II trial to verify the possible improvement in local control result ing from the addition of gemcitabine PURPOSE We assessed the results and prognostic factors in patients with bladder cancer treated conservatively with concurrent cisplatin and radiotherapy .  MATERIAL S AND METHODS A total of 109 patients with localized muscle invasive bladder cancer who were not c and i date s for radical cystectomy underwent concomitant chemotherapy and radiation . Median patient age was 70 years . Of the patients 36 % had stages T3B and 4 tumors , and 37 % had benefited from prior macroscopically complete transurethral resection .  Pelvic irradiation consisted of 40 to 45 Gy . , and was followed by a boost to the bladder to a total dose of 55 to 60 Gy . Continuous infusion cisplatin ( 20 to 25 mg./m.2 daily for 5 days ) was delivered during weeks 2 and 5 of radiation therapy . RESULTS Median followup was 54.8 months . The projected 4-year locoregional control rate was 47.6 % for the 109 patients and 61.2 % for 76 with a complete response . Projected overall 4-year survival was 41.9 % for all patients and 51.4 % for complete responders . Univariate analysis of prognostic factors was done for local control and survival . Local control was statistically better in patients with a good performance status , stages T2 and 3A disease , complete initial transurethral resection and without hydronephrosis . In terms of overall survival 4 factors were significant : 1 ) performance status , 2 ) T stage , 3 ) absence of hydronephrosis and 4 ) complete response . By multivariate analysis performance status , hydronephrosis and T stage were significant factors for local control , while T stage and complete response were the strongest determinants for survival . CONCLUSIONS Concurrent cisplatin and radiation therapy is a potentially curative and conservative treatment for patients with localized muscle invasive bladder cancer who are not c and i date s for radical surgery , particularly those with intravesical stages T2 and T3A tumors OBJECTIVES To assess , in a Phase I study , whether bladder preservation with concurrent gemcitabine and radiotherapy ( RT ) influenced patient-reported quality of life ( QOL ) as determined by the Functional Assessment of Cancer Therapy-Bladder ( FACT-BL ) . METHODS Between January 1998 and March 2002 , 24 patients with urothelial carcinoma of the bladder were enrolled , and 23 patients underwent transuretheral resection of bladder tumor , followed by twice-weekly gemcitabine with concurrent RT .  The initial dose was 10 mg/m2 given twice weekly and increased as tolerated . To assess treatment-related QOL , patients completed the FACT-BL question naire . RESULTS Of the 24 patients enrolled , 23 ( 96 % ) were assessed for toxicity and response . The FACT-generic ( G ) QOL assessment was obtained from 22 ( 92 % ) of 23 patients . No statistically significant difference was found in the FACT-G or FACT-BL or the combination before , during , or after treatment . The FACT-BL values were lower in patients who received higher doses of gemcitabine ( greater than 20 mg/m2 versus 20 mg/m2 or less ) . At least one dose-limiting toxicity ( DLT ) was experienced by 5 ( 23 % ) of 22 patients . The FACT-G values were lower for those patients who experienced DLT ( difference of -13.1 , P = 0.07 ) . The physical well-being scores for patients who experienced DLT were lower after treatment ( difference of -5.2 , P = 0.03 ) compared with those without DLT . CONCLUSIONS Concurrent RT and gemcitabine failed to statistically influence patient-reported QOL , although patients who received higher doses reported lower FACT-BL scores . The results of this study suggest that concurrent gemcitabine with conformal RT is a tolerable treatment regimen for bladder preservation , as demonstrated by the excellent treatment compliance and similar FACT measurements PURPOSE We combined chemotherapy and surgery to improve local control and survival of patients with unresectable bladder cancer . MATERIAL S AND METHODS A total of 41 patients with unresectable bladder cancer ( T4bNX/N + M0 ) received methotrexate , vinblastine , doxorubicin and cisplatin ( M-VAC ) chemotherapy followed by radical cystectomy when possible . End points were response to M-VAC , local control and survival . RESULTS Minimum followup was 4 years ( range 4 to 7 ) . Of the 41 patients 14 ( 34 % ) achieved a complete ( T0 ) and 27 ( 66 % ) achieved an incomplete ( T+ ) clinical response to M-VAC , including 29 who underwent exploration and 24 who underwent cystectomy . Definitive surgery was not done in 17 patients due to lack of response to M-VAC with local or systemic tumor progression , or refusal . Nine patients ( 22 % ) are alive , including all but 1 after cystectomy for T0 disease , and 2 had T+ tumor confined to the bladder for longer than 5 years . None of the patients with no response or tumor progression on M-VAC survived . Resection of extravesical disease after M-VAC in 16 patients did not prolong survival or improve local tumor control . Six patients required laparotomy for palliation of tumor related complications . CONCLUSIONS Our results suggest that patients who present with unresectable bladder cancer may benefit from M-VAC and definitive surgery , especially when disease is T0 and P0 status . Surgery may salvage select cases of advanced pelvic tumor down staged by chemotherapy to tumors pathologically confined to the bladder . Alternative treatment strategies are needed for the majority of patients with locally advanced bladder cancer PURPOSE The present study aims to evaluate the feasibility , toxicity , and efficacy of concurrent chemotherapy with cisplatinum and docetaxel , and external radical radiotherapy for transitional cell carcinoma of urinary bladder . MATERIAL S AND METHODS 42 patients ( 34 men , 8 females ) with invasive bladder carcinoma ( clinical stages T1 - 4 ) were treated after transurethral biopsy with chemotherapy and concomitant external radiotherapy . Chemotherapy consisting of cisplatin infusion ( 30 mg/m2 ) and Docetaxel ( 40 mg/m2 ) was given twice a week simultaneously with-irradiation during the whole treatment period ( 6 - 8 weeks ) as follows : Cisplatin ( D1,D8,D15,D22 , D25,D36,D43,D50 ) and Docetaxel ( D4 , D11 , D18 , D25 , D32 , D39 , D46 , D53 ) . An external irradiation scheme 1.8 to 2.0 Gy per fraction , 5 days a week was used up to 68 - 74 Gy ( 6MeV photons ) total tumor dose . RESULTS All but S patients completed the planned chemoradiation protocol . The complete response rate ( CR-rate ) assessed at 3 months after completion of combined treatment was 100 % , 63.6 % , 46.15 % and 95 % for clinical stage ( c ) cT1 ( 9/9 ) , cT2 ( 7/11 ) , cT3 ( 6/13 ) and cT4 ( 1/4 ) cases respectively . None of 9 patients with T1 tumors had any local failure at 36.1 months mean follow-up time . In total , 9 of 37 patients ( 24.32 % ) relapsed locally and /or distantly and were followed for 25.04 months ( mean time ) , 50 % of the relapses occurred at a mean time of 7.25 months . The mortality rate was 10.81 % ( 4/37 ) . All these patients died with a mean time of 11 months . 32 cases remain alive 19 - 46 months after treatment ; 27 of those are with no evidence of disease with a mean follow-up time of 32.24 months . In total , there was a 78.50 % ( 30/37 ) and a 75.67 % , ( 28/37 ) rate of overall survival and pelvic control respectively at 25.04 months mean follow-up time . Chemotherapy was discontinued in 2 cases due to acute gastrointestinal toxicity and in 3 more , due to patient compliance . There was 1 toxic death 2 months after treatment completion due to ureteral obstruction and impaired renal function . The acute toxicity was estimated as moderate to severe and caused the interruption of treatment for 5 to 10 days in 8 of 37 patients ( 21.62 % ) . Myelotoxicity appeared in 22/37 patients but febrile grade III and IV neutropenia was observed in 3 patients ( 8.10 % ) and thrombocytopenia ( Grade I-III ) in 8 ( 21.62 % ) . Concerning late effects a sigmoid stricture , a transient small bowel obstruction , 4 patients with contracted bladder and 1 case with renal failure were found . Grade I to III hypersensitivity reactions appeared in 8/37 patients ( 21.62 % ) while stomatitis ( grade I-II ) and grade II skin toxicity appeared in 3 and 4 patients respectively . These and other symptoms ( Grade I to II peripheral edema , transient myalgias and arthralgias in 7/37 cases ) , paresthesias or numbness ( 3/37 ) and peripheral motor dysfunction ( 1/37 ) were responsible for early reduction of docetaxel dose from 40 mg/m2 to 20 mg/m2 . CONCLUSION This preliminary analysis suggest that the radiosensitizing effect of cisplatin and docetaxel to megavoltage irradiation yielded a high CR-rate in transitional cell bladder carcinoma patients with medium to severe early and late side effects . The value of such a combined treatment as far as the tumor eradication is concerned requires further evaluation , because of the small number of patients , the short follow-up , and the absence of other studies using docetaxel as a radiosensitizer in urothelial cell cancer OBJECTIVES Primarily to evaluate the toxicity and , secondarily , the tumor response and patient survival associated with a three-phase combined modality treatment plan for patients with invasive transitional cell carcinoma ( TCC ) of the bladder ( T2-T4,NX-N2 , MO ) who are medically unsuitable for or who refuse cystectomy . METHODS Eligible patients initially underwent extensive transurethral resection ( TUR ) of the primary tumor with the attempt to resect disease totally . Subsequently , they received systemic combination chemotherapy consisting of two cycles of methotrexate , cisplatin , and vinblastine ( MCV ) , followed by cystoscopic re-evaluation of the bladder tumor . Patients then received 6480 cGy radiotherapy to the bladder with concurrent systemic cisplatin .  Toxicity , primary tumor response , and overall survival were evaluated . RESULTS Of 34 eligible patients , 27 patients completed the treatment series . Twenty-two received 80 % to 100 % of the prescribed doses of MCV and only 2 patients experienced grade 4 hematologic toxicities . The most common toxicities were gastrointestinal ( 23 ) , hematologic ( 21 ) , and renal ( 8) . The complete response ( CR ) rate after all treatment phases was 56 % ( 19 of 34 ) , 10 patients achieving a complete tumor resection of visible tumor at the initial TUR of the bladder ( TURB ) ; 3 , a CR after MCV ; and 6 , after radiotherapy and concomitant cisplatin . The median overall survival was 21 months with 6 of 34 ( 18 % ) alive at 57 months ( range , 36 to 75 ) . Complete resection of tumor by TURB was associated with prolonged overall survival . The bladder was the initial site of recurrence in 85 % of patients who had achieved a CR status . CONCLUSIONS This older age patient group tolerated this combined modality therapy with acceptable toxicities , but the overall survival rate was not improved compared with those reported with radiotherapy alone PURPOSE We describe a protocol design ed to evaluate the use of twice daily radiation used together with cisplatin and 5 fluorouracil ( 5-FU ) in the treatment of operable transitional cell carcinoma of the bladder with potential bladder preservation . MATERIAL S AND METHODS A total of 18 consecutive patients with T2-T4a bladder tumors underwent as complete a transurethral resection  as possible , which was visibly complete in 14 cases . They then received twice daily radiation and infusion cisplatin and 5-FU during an induction phase . No therapy was given for 3 weeks , following which patients were reevaluated cystoscopically . Cases of clinical complete response by biopsy and cytology were consoli date d with further chemotherapy/radiation using the same chemotherapeutic agents and radiation schedule . Patients who had incomplete responses were advised to undergo an immediate radical cystectomy . Of the 18 patients 15 subsequently received 3 cycles of adjuvant chemotherapy , consisting of methotrexate , cisplatin and vinblastine . Median followup for the entire group is 32 months . RESULTS Of the 18 patients 14 had no detectable tumor after induction therapy . Of the 4 patients with persistent tumor 2 underwent radical cystectomy and 2 refused cystectomy , 1 of whom was treated with partial cystectomy and the other with consolidation chemotherapy/radiation . The actuarial overall survival at 3 years was 83 % . The chance of a patient being alive at 3 years with a native bladder was 78 % . No patient required cystectomy for hematuria or bladder shrinkage . Three patients in whom superficial tumors developed were treated successfully with bacillus Calmette-Guerin .  Small bowel obstruction in 1 case was corrected surgically . CONCLUSIONS This pilot study demonstrates a high rate of response to this combined chemotherapy/radiation regimen in conjunction with a visibly complete transurethral resection . Reevaluation after a short induction phase allows for the early selection of patients with persistent disease for radical cystectomy OBJECTIVE To assess in a phase II trial the effectiveness and toxicity of combined chemotherapy and radiation with selective bladder preservation by response in the treatment of muscle-invasive bladder carcinoma . PATIENTS AND METHODS Fifty-six eligible patients with T2 - 4 M0 transitional cell bladder cancer suitable for radical surgery and multi-agent chemotherapy  received two courses of methotrexate , cisplatin and vinblastine , followed by 40 Gy of pelvic radiotherapy in 1.8 Gy fractions with concomitant cisplatin . Tumour response was evaluated by cystoscopy and biopsy . Those responding completely were given a 24 Gy bladder boost plus cisplatin ; patients with residual tumour were assigned to immediate cystectomy . RESULTS After induction therapy , 28 patients ( 50 % ) responded completely ; 22 operable patients with residual tumour underwent immediate cystectomy , while 34 patients were consoli date d with cisplatin and radiation .  Bladder relapses developed in 16 patients ; seven had successful endovesical therapy for superficial disease and salvage cystectomy was possible in four of nine cases with invasive recurrence . Distant metastases occurred in 22 cases ( 39 % ) . After a median follow-up of 46 months , the 5-year actuarial disease-specific survival was 59 % , disease-free survival 54 % and local control without cystectomy ( bladder preservation ) 41 % . There were no treatment-related deaths ; grade 3 late complications occurred in two patients . CONCLUSION This combined chemotherapy-radiotherapy regimen with selective organ preservation should be considered as an option for muscle-invasive bladder carcinoma . The initial results suggest the possibility of retaining a functioning bladder in many patients , without compromising survival , compared with elective cystectomy approaches . A longer follow-up and quality -of-life assessment remain essential for a better definition of selection criteria and long-term results of this combined modality PURPOSE To determine the relationship between tumour and patient characteristics and local control and survival for patients with T2 and T3 bladder cancer treated with radical external beam radiotherapy  and to evaluate the predictive value of cystoscopic response evaluation during radiation on final outcome . MATERIAL S AND METHODS Records from 379 patients with non-metastasized T2 or T3 transitional cell carcinoma of the bladder were review ed . All patient received external beam radiotherapy at The Netherl and s Cancer Institute during the period from 1977 to 1990 . The total dose varied from 50 to 75 Gy with a mean of 60.5 Gy and a median of 60.4 Gy . The median follow-up was 22 months for all patients and 82 months for the 30 patients still alive at last follow-up . A stepwise procedure using proportional hazard regression was used to identify prognostic factors with respect to local recurrence and survival . RESULTS One hundred thirty-six patients experienced a local recurrence and 120 of these occurred before regional or distance metastases . The actuarial results at 5 years were 40.3 % local control ( SE 4.0 % ) , 24.9 % disease-free rate ( SE 3.0 % ) and 22.2 % overall survival ( SE 2.2 % ) . In the univariate analysis age , performance status , result of intravenous pyelography ( IVP ) and T-stage were found to be related to overall survival and multifocality was related to local control . Multivariate analysis revealed that only age and T-stage were related to survival and only multifocality was related to local control . In patients with solitary tumours who were identified as having the most favourable outcome . local control was 50 % at 5 years . Local control in 89 patients who had a cystoscopic evaluation during treatment was identical regardless of whether a complete , partial or no response was observed . Furthermore , local control was identical in patients selected on the basis of a favourable response and in unselected patients . CONCLUSIONS Although we identified some significant prognostic factors , their predictive value is not strong enough to allow accurate estimation of treatment effect and disease outcome . Cystoscopic response evaluation during treatment was found not to provide reliable information to direct further treatment . Prospect i ve studies to identify ways to select patients for bladder conservation using definitive radiotherapy are urgently needed BACKGROUND We assessed effectiveness , safety , and tolerability of paclitaxel or fluorouracil when added to radiation plus cisplatin followed by adjuvant chemotherapy in a programme of selected bladder preservation for patients with muscle invasive bladder cancer . METHODS In our r and omised phase 2 trial , we enrolled patients with T2 - 4a transitional cell carcinoma of the bladder at 24 medical centres in the USA . We r and omly allocated patients to receive paclitaxel plus cisplatin ( paclitaxel group ) or fluorouracil plus cisplatin ( fluorouracil group ) with twice-daily radiation in r and om block sizes per site on the basis of clinical T-stage ( T2 vs T3 - 4 ) . Patients and physicians were aware of treatment assignment . All patients had transurethral resection of bladder tumour and twice-daily radiotherapy to 40·3 Gy , along with allocated chemotherapy  , followed by cystoscopic and biopsy assessment of response . Patients who had a tumour response with downstaging to T0 , Tcis , or Ta received consolidation chemoradiotherapy to 64·3 Gy , with the same chemotherapy regimen as in the induction phase . Patients received adjuvant cisplatin-gemcitabine-paclitaxel after the end of chemoradiotherapy . If , after induction , persistent disease was grade d as T1 or worse , we recommended patients undergo cystectomy and adjuvant chemotherapy . We assessed the primary endpoints of rates of treatment completion and toxic effects in all r and omly allocated patients . This study is registered with Clinical Trials.gov , number NCT00055601 . FINDINGS Between Dec 13 , 2002 , and Jan 11 , 2008 , we enrolled 97 patients , of whom 93 were eligible for analysis . Median follow-up was 5·0 years ( IQR 5·0 - 6·2 ) . Of 46 patients in the paclitaxel group , 45 ( 98 % ) completed induction ( 16 [ 35 % ] with grade 3 - 4 toxicity ) , 39 ( 85 % ) completed induction and consolidation ( 11 [ 24 % ] with grade 3 - 4 toxicity due to consolidation ) , and 31 ( 67 % ) completed the entire protocol with adjuvant chemotherapy . 34 ( 85 % ) of 40 assessable patients in the paclitaxel group had grade 3 - 4 toxicity during adjuvant chemotherapy . Of 47 patients in the fluorouracil group , 45 ( 96 % ) completed induction ( nine [ 19 % ] with grade 3 - 4 toxicity ) , 39 ( 83 % ) completed induction and consolidation ( 12 [ 26 % ] had grade 3 - 4 toxicity due to consolidation ) , and 25 ( 53 % ) completed the entire protocol with adjuvant chemotherapy . 31 ( 76 % ) of 41 assessable patients in the fluorouracil group had grade 3 - 4 toxicity during adjuvant chemotherapy . Five ( 11 % ) patients treated with the paclitaxel regimen and three ( 6 % ) patients treated with the fluorouracil regimen developed late grade 3 - 4 radiotherapy toxicities . 11 ( 24 % ) patients treated with the paclitaxel regimen and 16 ( 34 % ) patients treated with the fluorouracil regimen developed late grade 3 - 4 toxicities unrelated to radiotherapy . One patient ( in the fluorouracil group ) died during follow-up . Six ( 13 % ) patients in the paclitaxel group and in three ( 6 % ) patients in the fluorouracil group discontinued due to treatment-related toxicity . INTERPRETATION In the absence of phase 3 data , our findings could inform selection of a bladder-sparing trimodality chemotherapy regimen for patients with muscle invasive bladder cancer . FUNDING US National Cancer Institute PURPOSE To evaluate bladder preservation and functional quality after concurrent chemoradiotherapy for muscle-invasive cancer in 53 patients included in a Phase II trial . PATIENT AND METHODS Pelvic irradiation delivered 45 Gy , followed by an 18-Gy boost . Concurrent chemotherapy with cisplatin and 5-fluorouracil by continuous infusion was performed at Weeks 1 , 4 , and 7 during radiotherapy .  Patients initially suitable for surgery were evaluated with macroscopically complete transurethral resection after 45 Gy , followed by radical cystectomy in case of incomplete response . The European Organization for Research and Treatment of Cancer quality of life question naire QLQ-C30 , specific items on bladder function , and the Late Effects in Normal Tissues-Subjective , Objective , Management , and Analytic ( LENT-SOMA ) symptoms scale were used to evaluate quality of life before treatment and 6 , 12 , 24 , and 36 months after treatment . RESULTS Median age was 68 years for 51 evaluable patients . Thirty-two percent of patients had T2a tumors , 46 % T2b , 16 % T3 , and 6 % T4 . A visibly complete transurethral resection was possible in 66 % . Median follow-up was 8 years . Bladder was preserved in 67 % ( 95 % confidence interval , 52 - 79 % ) of patients . Overall survival was 36 % ( 95 % confidence interval , 23 - 49 % ) at 8 years for all patients , and 45 % ( 28 - 61 % ) for the 36 patients suitable for surgery . Satisfactory bladder function , according to LENT-SOMA , was reported for 100 % of patients with preserved bladder and locally controlled disease 6 - 36 months after the beginning of treatment . Satisfactory bladder function was reported for 35 % of patients before treatment and for 43 % , 57 % , and 29 % , respectively , at 6 , 18 , and 36 months . CONCLUSIONS Concurrent chemoradiation therapy allowed bladder preservation with tumor control for 67 % patients at 8 years . Quality of life and quality of bladder function were satisfactory for 67 % of patients PURPOSE A prospect i ve r and omized trial was conducted to determine whether the addition of concurrent cisplatin to preoperative or definitive radiation therapy in patients with muscle-invasive bladder cancer improved local control or survival .  PATIENTS AND METHODS Ninety-nine eligible patients with T2 to T4b transitional cell bladder cancer participated , 64 % with cT3b or cT4 . Patients and their physicians selected either definitive radiotherapy or precystectomy radiotherapy ; patients were then r and omly allocated to receive intravenous cisplatin 100 mg/m2 at 2-week intervals for three cycles concurrent with pelvic radiation , or to receive radiation without chemotherapy . Patients were stratified by clinical tumor stage and by radiation plan . The median follow-up duration is 6.5 years . RESULTS The occurrence of distant metastases was the same in both study arms . However , 25 of 48 control patients have had a first recurrence in the pelvis , compared with 15 of 51 cisplatin-treated patients ( P = .036 ) . The pelvic relapse rate in the two groups was significantly reduced by concurrent cisplatin ( P = .038 , log-rank test ) and this effect was preserved in a stepwise Cox regression model of prognostic factors ( hazards ratio , 0.50 ; 90 % confidence interval [ CI ] , 0.29 to 0.86 ; P = .036 ) . The hazard reduction was similar for both radiation plans . Pretreatment leukocytosis and high clinical stage were independent adverse factors in a Cox model of overall survival , but the effect of cisplatin was not significant . CONCLUSION Concurrent cisplatin may improve pelvic control of locally advanced bladder cancer with preoperative or definitive radiation , but has not been shown to improve overall survival . The use of concurrent cisplatin had no detectable effect on distant metastases PURPOSE To investigate the tolerance and efficacy of a modified concurrent chemoradiation ( CCRT ) protocol for patients with invasive bladder cancer " unfit " for radical cystectomy . METHODS AND MATERIAL S Twenty-three muscle-invasive bladder cancer patients who were unfit for or unwilling to receive radical cystectomy were enrolled in this study . All patients had transitional cell carcinoma of bladder , and distribution of stage was 14 ( 61 % ) , 1 ( 4 % ) , and 8 ( 35 % ) for T3a , T3b , and T4 , respectively . This study included a relatively old-age population , with the median age being 75 and 70 % of patients over 70 years old . Patients were treated with maximal transurethral resection of the bladder tumor followed by curative CCRT . The chemotherapy ( C/T ) regimen was comprised of cisplatin , 50 mg/m(2 ) intravenously ( i.v . ) on Day 1 ; 5-fluorouracil ( 5-FU ) , 500 mg/m(2)/day by continuous i.v . infusion on Days 1 - 3 ; and leucovorin , 50 mg/day by continuous i.v . infusion on Days 1 - 3 . Chemotherapy course was repeated at 21-day intervals . The radiation dose was 44 - 45 Gy to whole pelvis and 60 - 61.2 Gy to bladder , with a daily fraction of 1.8 - 2 Gy . The completeness of the CCRT protocol was defined as patients receiving at least 55 Gy of radiotherapy to the whole bladder and at least three courses C/T. RESULTS Seventy-four percent of patients ( 17/23 ) completed the CCRT protocol . Radiation Therapy Oncology Group ( RTOG ) Grade 3 acute toxicities were observed in 4 patients , which included leucopenia , vomiting , genitourinary ( GU ) tract infection , and diarrhea . No treatment-related deaths occurred during the CCRT period . RTOG Grade 3 or more late complications were observed in 3 patients ; one of them died of radiation cystitis superimposed with GU infection . Of the 18 patients whose response to CCRT was evaluated , a complete tumor response was documented in 16 patients ( 89 % ) . With a median follow-up of 3 years , the 3-year overall survival ( OS ) and disease-free survival ( DFS ) for all patients was 69 % and 65 % respectively . Meanwhile , the 3-year overall and DFS rates for patients who completed CCRT vs. those who did not complete CCRT were 82 % vs. 33 % and 75 % vs. 33 % , respectively ( p = 0.18 for OS and p = 0.04 for DFS ) . CONCLUSIONS Concurrent cisplatin , 5-FU , leucovorin , and radiotherapy for treatment of invasive bladder cancer is a feasible and promising treatment even for relatively old patients . Our results are comparable to those in recent studies by using combined modality treatment or neoadjuvant chemotherapy plus radical cystectomy . Consequently , this novel protocol warrants a prospect i ve clinical trial and may be a safe , effective alternative to radical cystectomy OBJECTIVE To evaluate the 5-year results of the following trimodal therapy for treatment of some selected cases of muscle invasive bladder cancer . MATERIAL S AND METHODS In this prospect i ve study , we included 104 patients with transitional cell carcinoma ( TCC ) ( T2 and T3a , N0 , M0 ) who were amenable to complete transurethral resection . All patients received adjuvant chemo-radiotherapy ( CRT ) in the form of gemcitabine and cisplatin and conventional radiotherapy after the maximum resection of their tumors . Two weeks later , all cases had radiologic and cystoscopic evaluation . The patients who showed no evidence of the bladder tumors [ complete response ( CR ) ] went on to complete the CRT , while those with recurrent invasive tumors did not receive any more CRT and were assigned to have salvage cystectomy . Thereafter , all patients were subjected to a regular follow-up . RESULTS This trimodal therapy was well tolerated in most of cases with no severe acute toxicities . Complete response was achieved in 78.8 % of cases after the initial CRT , and tumor grade was found to be the most significant risk factor to predict this response ( P = 0.004 ) . With a median follow-up of 71 months for patients with initial CR , 16.2 % of cases showed muscle invasive recurrences , and multifocality was the only significant risk factor for their development ( P = 0.003 ) . Meanwhile , superficial recurrences were detected in 8.1 % of cases with initial CR and were successfully treated with transurethral resection and intravesical bacillus Calmette-Guerin ( BCG ) . On the other h and , we reported distant metastasis in 24.3 % of patients with initial CR , and tumor grade , stage and multifocality were the most significant risk factors for this complication ( P = 0.002 , 0.031 , 0.006 ) . No cases of contracted bladder or late gastrointestinal complications were demonstrated in this series . The 5-year overall survival rate for patients with initial CR was 67.6 % , and for all the patients in this study it was 59.4 % . CONCLUSIONS This trimodal therapy can be considered as a treatment option for patients with localized muscle invasive TCC . The best c and i date s for such therapy are those with solitary T2 , low grade tumors that are amenable to complete transurethral resection Purpose Organ preservation has been investigated in patients ( p ) with infiltrating transitional cell carcinoma ( TCC ) of the bladder over the past decade as an alternative to radical cystectomy .  This is a trimodal schedule study , including transurethral resection of bladder tumor ( TURB ) , neoadjuvant chemotherapy and concomitant radiochemotherapy ( RTC ) . Patients and methods From April 1996 until August 2005 , 29 evaluable patients ( p ) with T2-T3NXM0 bladder cancer were enrolled . After a transurethral resection of bladder tumor ( TURB ) , we administered 2 cycles of induction chemotherapy with CMV ( 15 p ) or Gemcitabine-Cisplatin ( 14 p ) followed by radiotherapy 45 Gy 1.8 Gy/fraction and two cycles of concomitant cisplatin 70 mg/m2 . 2–3 weeks later , a cystoscopy with tumor-site biopsy was performed . If complete histological response , p were treated with consolidation radiotherapy until 64.8 Gy . For p with residual or recurrent tumor , cystectomy was performed . Results We included 28 men and 1 women ( median age 63 , range 39–72 years ) with PS ( ECOG ) 0–1 . The stage was : 21 p T2 ; 6 p T3a ; and 2 p T3b . Toxicity was higher in CMV compared with Gem-Cis : grade 3/4 neutropenia 4/15 ( 26 % ) vs 1/14 ( 7 % ) ; febrile neutropenia 3/15 ( 20 % ) vs 1/14 ( 7 % ) ; grade 3/4 trombocytopenia 2/15 ( 13 % ) vs 1/14 ( 7 % ) . Toxicities with concomitant RCT were low-moderate : urocystitis ( 26 % ) and enteritis ( 18 % ) . Response : microscopically complete TURB was obtained in 20 p ( 69 % ) , but not in 9 p ( 31 % ) ( 7 microscopic , and 2 macroscopic residual tumor ) . We found a complete histologic response after induction RCT in 25 p ( 86 % ) . After a median follow-up of 69.4 months ( m ) ( range : 8–97.7 ) , there were 8 deaths , with a overall survival of 72 % . Furthermore 14 of 29 p ( 48 % ) were alive with intact bladder , and median survival time with intact bladder was 63.6 m ( 50.1–77.2 ) ; were predictive of best outcome T2 stage vs T3 ( p<0.0001 ) , and complete histologic resection in initial TURB vs residual tumor ( p=0.0004 ) . Conclusions Combined treatment provide high response rates and can be offered as an alternative option to radical cystectomy in selected patients with TCC . Patients with T2 stage and complete histologic resection in initial TURB had the best outcome BACKGROUND Despite aggressive local therapy , patients with locally advanced bladder cancer are at significant risk for metastases . We evaluated the ability of neoadjuvant chemotherapy to improve the outcome in patients with locally advanced bladder cancer who were treated with radical cystectomy .  METHODS Patients were enrolled if they had muscle-invasive bladder cancer ( stage T2 to T4a ) and were to be treated with radical cystectomy .  They were stratified according to age ( less than 65 years vs. 65 years or older ) and stage ( superficial muscle invasion vs. more extensive disease ) and were r and omly assigned to radical cystectomy alone or three cycles of methotrexate , vinblastine , doxorubicin , and cisplatin followed by radical cystectomy . RESULTS We enrolled 317 patients over an 11-year period , 10 of whom were found to be ineligible ; thus , 154 were assigned to receive surgery alone and 153 to receive combination therapy . According to an intention-to-treat analysis , the median survival among patients assigned to surgery alone was 46 months , as compared with 77 months among patients assigned to combination therapy ( P=0.06 by a two-sided stratified log-rank test ) . In both groups , improved survival was associated with the absence of residual cancer in the cystectomy specimen . Significantly more patients in the combination-therapy group had no residual disease than patients in the cystectomy group ( 38 percent vs. 15 percent , P<0.001 ) . CONCLUSIONS As compared with radical cystectomy alone , the use of neoadjuvant methotrexate , vinblastine , doxorubicin , and cisplatin followed by radical cystectomy increases the likelihood of eliminating residual cancer in the cystectomy specimen and is associated with improved survival among patients with locally advanced bladder cancer PURPOSE This phase II study was design ed to evaluate effectiveness and toxicity of a combined chemoradiotherapy program with selective bladder preservation in the management of patients with invasive bladder cancer . PATIENTS AND METHODS Ninety-one eligible patients with invasive bladder cancer stages T2M0 to T4AM0 suitable for radical cystectomy received two courses of methotrexate , cisplatin , and vinblastine ( MCV regimen ) followed by radiotherapy with 39.6 Gy and concurrent cisplatin . After complete urologic evaluation , operable patients who achieved complete response were selected for bladder preservation and treated with consolidation cisplatin-radiotherapy . RESULTS Of 91 eligible patients , 85 underwent complete urologic evaluation and 68 ( 75 % ; 95 % confidence interval [ CI ] , 59 % to 84 % ) had documented complete responses . Fourteen operable patients with residual tumor underwent immediate cystectomy . Of 70 patients treated with consolidation cisplatin-radiotherapy , 36 subsequently developed bladder recurrences , 23 of which were invasive . Patients with invasive recurrence ( n = 16 ) , extensive noninvasive recurrence ( n = 6 ) , or severe treatment complications ( n = 1 ) underwent salvage cystectomy . Thus , a total of 37 of 91 patients ( 40 % ) required cystectomy . The 4-year cumulative risk of invasive local failure ( which includes induction failures ) was 43 % ( 95 % CI , 33 % to 53 % ) . The 4-year actuarial risk of distant metastasis was 22 % ( 95 % CI , 13 % to 31 % ) . The 4-year actuarial survival rate of the entire group was 62 % ( 95 % CI , 52 % to 72 % ) . The 4-year actuarial rate of survival with bladder intact was 44 % ( 95 % CI , 34 % to 54 % ) . CONCLUSION Initial results of this combined chemoradiotherapy program show that bladder preservation can be achieved in the majority of patients , and that overall survival is similar to that reported with aggressive surgical approaches . Long-term survival and quality -of-life assessment s require longer follow-up study PURPOSE The aim of this prospect i ve , phase II trial was to determine the response of muscle-invasive bladder cancer ( MIBC ) to concurrent chemoradiotherapy of weekly gemcitabine with 4 weeks of radiotherapy ( RT ; GemX ) . PATIENTS AND METHODS Fifty patients with transitional cell carcinoma , stage T2 - 3 , N0 , M0 after transurethral resection and magnetic resonance imaging , were recruited .  Gemcitabine was given intravenously at 100 mg/m(2 ) on days 1 , 8 , 15 , and 22 of a 28-day RT schedule that delivered 52.5 Gy in 20 fractions . Chemotherapy was stopped for Radiation Therapy Oncology Group ( RTOG ) grade 3 bladder or bowel toxicity . The primary end points were tumor response , toxicity , and survival . RESULTS All patients completed RT ; 46 tolerated all four cycles of gemcitabine . Two patients stopped after two cycles , and two stopped after three cycles , because of bowel toxicity .  Forty-seven patients had a post-treatment cystoscopy ; 44 ( 88 % ) achieved a complete endoscopic response . At a median follow-up of 36 months ( range , 15 to 62 months ) , 36 patients were alive , and 32 of these had a functional and intact bladder . Fourteen patients died ; seven died as a result of metastatic MIBC , five died as a result of intercurrent disease , and two died as a result of treatment-associated deaths . Four patients underwent cystectomy ; three because of recurrent disease and one because of toxicity . One patient required a bowel resection for late toxicity . By using Kaplan-Meier analyses , 3-year cancer-specific survival was 82 % , and overall survival was 75 % . CONCLUSION Concurrent gemcitabine-based chemoradiotherapy ( ie , GemX ) produces a high response rate in MIBC and has durable local control and acceptable toxicity , which allows patients to preserve their own bladder . This treatment modality warrants additional investigation in a phase III setting BACKGROUND Radiotherapy is an alternative to cystectomy in patients with muscle-invasive bladder cancer . In other disease sites , synchronous chemoradiotherapy has been associated with increased local control and improved survival , as compared with radiotherapy alone . METHODS In this multicenter , phase 3 trial , we r and omly assigned 360 patients with muscle-invasive bladder cancer to undergo radiotherapy with or without synchronous chemotherapy .  The regimen consisted of fluorouracil ( 500 mg per square meter of body-surface area per day ) during fractions 1 to 5 and 16 to 20 of radiotherapy and mitomycin C ( 12 mg per square meter ) on day 1 . Patients were also r and omly assigned to undergo either whole-bladder radiotherapy or modified-volume radiotherapy ( in which the volume of bladder receiving full-dose radiotherapy was reduced ) in a partial 2-by-2 factorial design ( results not reported here ) . The primary end point was survival free of locoregional disease . Secondary end points included overall survival and toxic effects . RESULTS At 2 years , rates of locoregional disease-free survival were 67 % ( 95 % confidence interval [ CI ] , 59 to 74 ) in the chemoradiotherapy group and 54 % ( 95 % CI , 46 to 62 ) in the radiotherapy group . With a median follow-up of 69.9 months , the hazard ratio in the chemoradiotherapy group was 0.68 ( 95 % CI , 0.48 to 0.96 ; P=0.03 ) . Five-year rates of overall survival were 48 % ( 95 % CI , 40 to 55 ) in the chemoradiotherapy group and 35 % ( 95 % CI , 28 to 43 ) in the radiotherapy group ( hazard ratio , 0.82 ; 95 % CI , 0.63 to 1.09 ; P=0.16 ) . Grade 3 or 4 adverse events were slightly more common in the chemoradiotherapy group than in the radiotherapy group during treatment ( 36.0 % vs. 27.5 % , P=0.07 ) but not during follow-up ( 8.3 % vs. 15.7 % , P=0.07 ) . CONCLUSIONS Synchronous chemotherapy with fluorouracil and mitomycin C combined with radiotherapy significantly improved locoregional control of bladder cancer , as compared with radiotherapy alone , with no significant increase in adverse events . ( Funded by Cancer Research U.K. ; BC2001 Current Controlled Trials number , IS RCT N68324339 . ) PURPOSE Whole-pelvis ( WP ) concurrent chemoradiation ( CCRT ) is the st and ard bladder preserving option for patients with invasive bladder cancer . The st and ard practice is to treat elective pelvic lymph nodes , so our aim was to evaluate whether bladder-only ( BO ) CCRT leads to results similar to those obtained by st and ard WP-CCRT . METHODS AND MATERIAL S Patient eligibility included histopathologically proven muscle-invasive bladder cancer , lymph nodes negative ( T2-T4 , N- ) by radiology , and maximal transurethral resection of bladder tumor with normal hematologic , renal , and liver functions . Between March 2005 and May 2006 , 230 patients were accrued . Patients were r and omly assigned to WP-CCRT ( 120 patients ) and BO-CCRT ( 110 patients ) . Data regarding the toxicity profile , compliance , initial complete response rates at 3 months , and occurrence of locoregional or distant failure were recorded . RESULTS With a median follow-up time of 5 years ( range , 3 - 6 ) , WP-CCRT was associated with a 5-year disease-free survival of 47.1 % compared with 46.9 % in patients treated with BO-CCRT ( p = 0.5 ) . The bladder preservation rates were 58.9 % and 57.1 % in WP-CCRT and BO-CCRT , respectively ( p = 0.8 ) , and the 5-year overall survival rates were 52.9 % for WP-CCRT and 51 % for BO-CCRT ( p = 0.8 ) . CONCLUSION BO-CCRT showed similar rates of bladder preservation , disease-free survival , and overall survival rates as those of WP-CCRT . Smaller field sizes including bladder with 2-cm margins can be used as bladder preservation protocol for patients with muscle-invasive lymph node-negative bladder cancer to minimize the side effects of CCRT Purpose To test whether reducing radiation dose to uninvolved bladder while maintaining dose to the tumor would reduce side effects without impairing local control in the treatment of muscle-invasive bladder cancer . Methods and Material s In this phase III multicenter trial , 219 patients were r and omized to st and ard whole-bladder radiation therapy ( sRT ) or reduced high-dose volume radiation therapy ( RHDVRT )  that aim ed to deliver full radiation dose to the tumor and 80 % of maximum dose to the uninvolved bladder . Participants were also r and omly assigned to receive radiation therapy alone or radiation therapy plus chemotherapy in a partial 2 × 2 factorial design . The primary endpoints for the radiation therapy volume comparison were late toxicity and time to locoregional recurrence ( with a noninferiority margin of 10 % at 2 years ) . Results Overall incidence of late toxicity was less than predicted , with a cumulative 2-year Radiation Therapy Oncology Group grade 3/4 toxicity rate of 13 % ( 95 % confidence interval 8 % , 20 % ) and no statistically significant differences between groups . The difference in 2-year locoregional recurrence free rate ( RHDVRT − sRT ) was 6.4 % ( 95 % confidence interval −7.3 % , 16.8 % ) under an intention to treat analysis and 2.6 % ( −12.8 % , 14.6 % ) in the “ per- protocol ” population . Conclusions In this study RHDVRT did not result in a statistically significant reduction in late side effects compared with sRT , and noninferiority of locoregional control could not be concluded formally . However , overall low rates of clinical ly significant toxicity combined with low rates of invasive bladder cancer relapse confirm that (chemo)radiation therapy is a valid option for the treatment of muscle-invasive bladder cancer © 2 0 1 0 T H E A U T H O R S J O U R N A L C O M P I L A T I O N © 2 0 1 0 B J U I N T E R N A T I O N A L 7 5 3 prostate cancer . N Engl J Med 2010 ; 362 : 1192–202 2 Jemal A , Siegel R , Ward E et al . Cancer Statistics 2008 . CA Cancer J Clin 2008 ; 58 : 71–96 3 Thompson IM , Tangen CM , Goodman PJ , Lucia MS , Klein EA . Chemoprevention of prostate cancer . J Urol 2009 ; 182 : 499–508 4 Lippman SM , Klein EA , Goodman PJ et al . Effect of selenium and vitamin E on risk of prostate cancer and other cancers : the Selenium and Vitamin E Cancer Prevention Trial ( SELECT ) . JAMA 2009 ; 301 : 39–51 5 Stranges S , Marshall JR , Natarajan R et al . Effects of long-term selenium supplementation on the incidence of type2 diabetes : a r and omized trial . Ann Intern Med 2007 ; 147 : 217–23 6 Thompson IM , Goodman PJ , Tangen CM et al . The influence of finasteride on the development of prostate cancer . N Engl J Med 2003 ; 349 : 215–24 7 Thompson IM , Chi C , Ankerst DP et al . Effect of finasteride on the sensitivity of PSA for detecting prostate cancer . J Natl Cancer Inst 2006 ; 98 : 1128–33 8 Redman MW , Tangen CM , Goodman PJ , Lucia MS , Coltman CA , Thompson IM . Finasteride does not increase the risk of high- grade prostate cancer : a bias-adjusted modeling approach . Cancer Prev Res ( Phila Pa ) 2008 ; 1 : 174– 81 9 Pinsky P , Parnes H , Ford L. Estimating rates of true high- grade disease in the Prostate Cancer Prevention Trial . Cancer Prev Res ( Phila Pa ) 2008 ; 1 : 182–6 10 Walsh PC . Chemoprevention of prostate cancer . N Engl J Med 2010 ; 362 : 1237– 8 11 Thompson IM , Tangen CM , Goodman PJ et al . Finasteride improves the sensitivity of digital rectal examination for prostate cancer detection . J Urol 2007 ; 177 : 1749– 52 12 And riole GL , Bostwick D , Brawley O et al . The utility of PSA for detection of prostate cancer in men treated with dutasteride : results from the REduction by DUtasteride of prostate Cancer Events ( REDUCE ) study . J Men ’s Health 2009 ; 6 : 269 13 Kirby RS , Eeles RA , Kote-Jarai Z , Guy M , Easton D , Fitzpatrick JM . Screening for prostate cancer : the way ahead . BJU Int 2010 ; 105 : OBJECTIVES To evaluate the safety , tolerance , protocol completion rate , tumor response rate , and patient survival of chemoradiotherapy for patients with muscle-invasive operable bladder cancer . METHODS After transurethral resection of the tumor in patients with Stage T2-T4a bladder cancer , twice-daily radiotherapy with paclitaxel and cisplatin chemotherapy induction ( TCI ) was administered . If repeat biopsy showed less than Stage T1 disease , consolidation with TCI was given . If repeat biopsy showed greater than Stage T1 disease , cystectomy was recommended . Adjuvant gemcitabine and cisplatin were given to all patients . RESULTS A total of 80 patients met protocol eligibility .  TCI result ed in 26 % developing grade 3 - 4 acute toxicity , mainly gastrointestinal ( 25 % ) . During consolidation TCI , grade 3 - 4 acute toxicity , all transient , was reported in 8 % . Four cycles of adjuvant chemotherapy were completed per protocol or with minor deviations in 70 % of the patients . Adjuvant treatment was associated with grade 3 toxicity in 46 % and grade 4 in 26 % . One patient had a fatal hemorrhagic stroke . Late bladder radiation toxicity was evaluated in 53 patients with > or = 2 years of follow-up . Of these 53 patients , 3 experienced self-limited , late grade 3 bladder toxicity . The postinduction complete response rate was 81 % ( 65/80 ) , 36 of the 80 patients died ( 22 of bladder cancer ) . At a median follow-up of 49.4 months , the actuarial 5-year overall and disease-specific survival rate was 56 % and 71 % , respectively . CONCLUSIONS These favorable tumor response rates with possible increased bladder preservation rates suggest that this treatment regimen deserves further study OBJECTIVE To report long-term outcomes of selective organ preservation for muscle-invasive bladder cancer ( MIBC ) using 2 bladder-sparing trimodality approaches . MATERIAL S AND METHODS From 1990 to 2010 , 80 patients with T2-T4 bladder cancer were prospect ively enrolled in 2 successive bladder-sparing protocol s. Forty-one patients were treated with neoadjuvant methotrexate , cisplatin , and vinblastine ( MCV ) chemotherapy followed by radiotherapy ( 60 Gy ) in complete responders ( protocol 1 [ P1 ] ) and 39 patients were treated with weekly cisplatin concurrent with radiotherapy ( 64.8 Gy ) ( protocol 2 [ P2 ] ) . RESULTS The median follow-up was 72 months ( range , 9 - 204 months ) . Five and 10-year cumulative overall survival for all series were 73 % and 60 % and the corresponding numbers for cancer-specific survival were 82 % and 80 % , respectively . Of all surviving patients , 83 % maintained their own bladder . Although there were no significant differences in overall survival ( P = .820 ) , cancer-specific survival ( P = .688 ) and distant metastasis ( P = .417 ) between protocol s , complete response rates ( P = .003 ) , and disease-free survival ( P = .031 ) were significantly higher in P2 treatment . CONCLUSION Trimodality therapy with bladder preservation represents a real alternative to radical cystectomy ( RC ) in selected patients .  Overall survival and cancer-specific survival rates are encouraging with more than 80 % of survivors retaining functional bladders OBJECTIVES Radical cystectomy ( RC ) is the st and ard treatment for muscle-invasive urothelial carcinoma of the bladder . Trimodality bladder-preserving therapy ( BPT ) is an alternative to RC , but r and omized comparisons of RC versus BPT have proven infeasible . To compare RC versus BPT , we undertook an observational cohort study using registry and administrative cl aims data from the Surveillance , Epidemiology and End Results -Medicare data base . METHODS We identified patients age 65 years or older diagnosed between 1995 and 2005 who received RC ( n = 1426 ) or BPT ( n = 417 ) . We examined confounding and stage misclassification in the comparison of RC and BPT by using multivariable adjustment , propensity score-based adjustment , instrumental variable ( IV ) analysis , and simulations . RESULTS Patients who received BPT were older and more likely to have comorbid disease . After propensity score adjustment , BPT was associated with an increased hazard of death from any cause ( hazard ratio [ HR ] 1.26 ; 95 % confidence interval [ CI ] 1.05 - 1.53 ) and from bladder cancer ( HR 1.31 ; 95 % CI 0.97 - 1.77 ) . Using the local area cystectomy rate as an instrument , IV analysis demonstrated no differences in survival between BPT and RC ( death from any cause HR 1.06 ; 95 % CI 0.78 - 1.31 ; death from bladder cancer HR 0.94 ; 95 % CI 0.55 - 1.18 ) . Simulation studies for stage misclassification yielded results consistent with the IV analysis . CONCLUSIONS Survival estimates in an observational cohort of patients who underwent  RC  versus  BPT  differ by analytic method . Multivariable and propensity score adjustment revealed greater mortality associated with BPT relative to RC , while IV analysis and simulation studies suggest that the two treatments are associated with similar survival outcomes PURPOSE Phase II clinical studies suggest that hypoxic modification with carbogen and nicotinamide ( CON ) may increase the efficacy of radiotherapy ( RT ) . PATIENTS AND METHODS Three hundred thirty-three patients with locally advanced bladder carcinoma were r and omly assigned to RT alone versus RT with CON . A schedule of either 55 Gy in 20 fractions in 4 weeks or 64 Gy in 32 fractions in 6.5 weeks was used . The primary end point was cystoscopic control at 6 months ( CC(6 m ) ) and secondary end points were overall survival ( OS ) , local relapse-free survival ( RFS ) , urinary and rectal morbidity . RESULTS CC(6 m ) was 81 % for RT + CON and 76 % for RT alone ( P = .3 ) ; however , just more than half of patients underwent cystoscopy at that time . Three-year estimates of OS were 59 % and 46 % ( P = .04 ) and 3-year estimates of RFS were 54 % and 43 % ( P = .06 ) for RT + CON versus RT alone . Risk of death was 14 % lower with RT + CON ( P = .04 ) . In multivariate comparison , RT + CON significantly reduced the risk of relapse ( P = .05 ) and death ( P = .03 ) . There was no evidence that differences in late urinary or GI morbidity between treatment groups or between fractionation schedules were significant . CONCLUSION RT + CON produced a small nonsignificant improvement in CC(6 m ) . Differences in OS , risk of death , and local relapse were significantly in favor of RT + CON .  Late morbidity was similar in both trial arms . Results indicate a benefit of adding CON to radical RT BACKGROUND The optimal treatment strategy for muscle-invasive bladder cancer ( BCa ) remains controversial . OBJECTIVE Better define the long-term outcomes of radical cystectomy ( RC ) alone for BCa and determine the impact of pathologic downstaging after transurethral resection in a large and homogeneous single-center series . DESIGN , SETTING , AND PARTICIPANTS A cohort of 1100 patients undergoing RC with pelvic lymph node dissection ( PLND ) without neoadjuvant therapy for urothelial carcinoma of the bladder between January 1 , 1986 , and December 2009 was evaluated . Patients with other than metastases to the pelvic lymph nodes were excluded . Median age was 65 yr .  Clinical course , pathologic characteristics , and long-term outcomes were evaluated . Follow-up was obtained until December 2009 with a median of 38 mo and a completeness of 96.5 % . INTERVENTION RC with PLND ; urinary diversion with ileal neobladder whenever possible . MEASUREMENTS Primary end points were disease-specific survival ( DSS ) , recurrence-free survival ( RFS ) , and overall survival ( OS ) according to the tumor stage of the RC specimen versus the maximum tumor stage . The log-rank test was used to compare subgroups . RESULTS AND LIMITATIONS The 30-d ( 90-d ) mortality rate was 3.2 % ( 5.2 % ) . The 10-yr OS , DSS , and RFS rates were 44.3 % , 66.8 % , and 65.5 % , respectively . Based on the tumor stage of the RC specimen , the 10-yr DSS rate was pT0/a/is/1 pN0 : 90.5 % , pT2a/b pN0 : 66.8 % , pT3a/b pN0 : 59.7 % , pT4a/b pN0 : 36.6 % , and pTall pN+ : 16.7 % . Downstaging by transurethral resection of the prostate was observed in 382 patients . Patients with maximum tumor stage pT2a/b pN0 had distinctly better 10-yr DSS rates than those with pT2a/b pN0 in the RC specimen : pT2a pN0 : 92.2 % versus 73.8 % ; pT2b : 75.0 % versus 62.0 % . A total of 49 % female and 80 % male patients received an ileal neobladder . CONCLUSIONS This contemporary and homogeneous single-center series found acceptable OS , DFS , and RFS for patients undergoing RC . Pathologic downstaging had a significant impact on survival BACKGROUND Many phase 2 bladder-sparing programmes using transurethral resection of the bladder ( TURB ) plus chemotherapy or radio-chemotherapy have been undertaken , but some controversies remain . OBJECTIVE To determine the efficacy of complete TURB plus three cycles of cisplatin-based chemotherapy in selected patients with muscle-invasive bladder cancer ( MIBC ) . DESIGN , SETTING , AND PARTICIPANTS A phase 2 nonr and omized trial was design ed that included patients with MIBC who underwent complete TURB with positive biopsies of the tumour bed . Patients with negative biopsies of the tumour bed , with macroscopically residual tumour , with hydronephrosis , or with distant metastasis were excluded from this trial . Patients included in this trial were offered three cycles of systemic chemotherapy or radical cystectomy ( RC ) . Clinical response ( cR ) was denoted by either no tumour or the presence of Ta1-Tis bladder tumour at 3-mo evaluation ; clinical non-response ( cNR ) was denoted by cases of muscle-invasive tumour or distant metastasis . Of 146 patients who entered this trial , 75 choose the bladder-sparing programme and 71 chose RC . MEASUREMENTS At 5 yr and 10 yr , the cancer-specific survival ( CSS ) rate was 64.5 % and 59.8 % , respectively , with no significant difference compared to the RC arm ( p=0.544 ) . The progression-free survival with bladder preserved was 52.6 % and 34.5 % , respectively . In multivariate analysis , cR was the only predictive factor for survival ( p=0.001 ) and bladder preservation ( p=0.000 ) . RESULTS AND LIMITATIONS This was not a r and omized trial , and patients were included over 16 yr . However , no modifications were made to the therapy schedule except from chemotherapy schemes considered st and ard at the time . CONCLUSIONS Patients with microscopic residual cancer after complete TURB seem to be good c and i date s for the bladder-sparing programme using three cycles of systemic chemotherapy , with CSS comparable to RC
CONTEXT Aims of bladder preservation in muscle-invasive bladder cancer ( MIBC ) are to offer a quality -of-life advantage and avoid potential morbidity or mortality of radical cystectomy ( RC ) without compromising oncologic outcomes .
Because of the lack of a completed r and omised controlled trial , oncologic equivalence of bladder preservation modality treatments compared with RC remains unknown .
OBJECTIVE This systematic review sought to assess the modern bladder-preservation treatment modalities , focusing on trimodal therapy ( TMT ) in MIBC .
EVIDENCE SYNTHESIS Optimal bladder-preservation treatment includes a safe transurethral resection of the bladder tumour as complete as possible followed by radiation therapy ( RT ) with concurrent radiosensitising chemotherapy .