Recurrence rate of superficial basal cell carcinoma following successful treatment with imiquimod 5% cream: interim 2-year results from an ongoing 5-year follow-up study in Europe. Five-year follow-up of a randomized, prospective trial of topical methyl aminolevulinate photodynamic therapy vs surgery for nodular basal cell carcinoma. Intralesional interferon therapy for basal cell carcinoma. The effect of intralesional 5-fluorouracil therapeutic implant (MPI 5003) for treatment of basal cell carcinoma. Photodynamic therapy versus topical imiquimod versus topical fluorouracil for treatment of superficial basal-cell carcinoma: a single blind, non-inferiority, randomised controlled trial. Cryosurgery is more effective in the treatment of primary, non-superficial basal cell carcinomas when applied during and not prior to a five week imiquimod course: a randomized, prospective, open-label study. Photodynamic therapy with methyl aminolevulinate for primary nodular basal cell carcinoma: results of two randomized studies. Light fractionation significantly improves the response of superficial basal cell carcinoma to aminolaevulinic acid photodynamic therapy: five-year follow-up of a randomized, prospective trial. Topical methyl aminolaevulinate photodynamic therapy versus cryotherapy for superficial basal cell carcinoma: a 5 year randomized trial. Surgical excision versus Mohs' micrographic surgery for primary and recurrent basal-cell carcinoma of the face: a prospective randomised controlled trial with 5-years' follow-up. Basal cell carcinoma of the face: surgery or radiotherapy? Results of a randomized study. Sustained clearance of superficial basal cell carcinomas treated with imiquimod cream 5%: results of a prospective 5-year study. A randomized parallel study to assess the safety and efficacy of two different dosing regimens of 5% imiquimod in the treatment of superficial basal cell carcinoma Recurrence rate of superficial basal cell carcinoma following treatment with imiquimod 5% cream: conclusion of a 5-year long-term follow-up study in Europe. Photodynamic therapy vs. cryosurgery of basal cell carcinomas: results of a phase III clinical trial Nonsurgical treatment of basal cell carcinomas with intralesional 5-fluorouracil/epinephrine injectable gel. Imiquimod 5% cream for the treatment of superficial basal cell carcinoma: results from a randomized vehicle‐controlled phase III study in Europe A Pilot Study to Evaluate the Treatment of Basal Cell Carcinoma with 5‐Fluorouracil Using Phosphatidyl Choline as a Transepidermal Carrier Surgical Excision versus Curettage plus Cryosurgery in the Treatment of Basal Cell Carcinoma Imiquimod 5% cream for the treatment of superficial basal cell carcinoma: results from two phase III, randomized, vehicle-controlled studies. PEP005 (ingenol mebutate) gel for the topical treatment of superficial basal cell carcinoma: Results of a randomized phase IIa trial Comparison of imiquimod 5% cream versus radiotherapy as treatment for eyelid basal cell carcinoma Treatment of basal-cell carcinoma: comparison of radiotherapy and cryotherapy. The effect of an intralesional sustained-release formulation of interferon alfa-2b on basal cell carcinomas. Randomized Comparison of Mohs Micrographic Surgery and Surgical Excision for Small Nodular Basal Cell Carcinoma: Tissue‐Sparing Outcome Two‐year interim results from a 5‐year study evaluating clinical recurrence of superficial basal cell carcinoma after treatment with imiquimod 5% cream daily for 6 weeks Fractionated illumination significantly improves the response of superficial basal cell carcinoma to aminolevulinic acid photodynamic therapy. Inhibiting the hedgehog pathway in patients with the basal-cell nevus syndrome. A clinical study comparing methyl aminolevulinate photodynamic therapy and surgery in small superficial basal cell carcinoma (8-20 mm), with a 12-month follow-up.
Imiquimod is an immune response modifier that acts through Toll-like receptor 7 to induce innate and cell-mediated immune responses . This ongoing phase III , open-label study conducted in Europe is evaluating the long-term ( 5 year ) clinical efficacy and safety of imiquimod 5 % cream applied once daily 5 times per week ( 5 x/week ) for 6 weeks for the treatment of superficial basal cell carcinoma ( sBCC ) . A total of 182 subjects were enrolled . The initial sBCC clearance rate was 90 % ( 12-week post treatment ) , whereas the proportion of subjects who were clinical ly clear at 2 years ( current time point ) was estimated to be 79.4 % . Local skin/application site reactions were the most frequently reported safety findings . Initial efficacy rates of imiquimod applied 5 x/week for 6 weeks demonstrate its clinical utility as an alternative approach to the treatment of sBCC . The recurrence rate seen to date supports ongoing follow up of subjects treated with imiquimod OBJECTIVE To compare 5-year lesion recurrence rates in primary nodular basal cell carcinoma treated with topical methyl aminolevulinate photodynamic therapy ( PDT ) or simple excision surgery . DESIGN Prospect i ve , r and omized , multicenter study . SETTING University hospital dermatology departments . PATIENTS A total of 97 patients , 50 with 53 lesions treated with methyl aminolevulinate PDT and 47 with 52 lesions treated by excision surgery  , were included in the per protocol analysis . Of the lesions treated with methyl aminolevulinate PDT and surgery , 49 and 52 , respectively , showed complete clinical response at 3 months after treatment and were observed for long-term outcome evaluation . INTERVENTIONS Topical methyl aminolevulinate cream , 160 mg/g , applied for 3 hours before illumination ( 75 J/cm(2 ) of red light at 570 to 670 nm ) on 2 or 4 occasions ( 12 [ 23 % ] of 53 lesions ) ; or excision surgery . MAIN OUTCOME MEASURES Histologically confirmed lesion recurrence , sustained lesion complete response rate ( time-to-event analysis ) , and investigator assessment of cosmetic outcome , 5 years after the last treatment . RESULTS At 5 years , recurrence was documented in 7 ( 14 % ) of 49 lesions ( 95 % confidence interval [ CI ] , 6%-27 % ) treated with methyl aminolevulinate PDT vs 2 ( 4 % ) of 52 lesions ( 95 % CI , 1%-13 % ) treated with excision surgery ( P = .09 ) . Estimated sustained lesion complete response rates were 76 % ( 95 % CI , 59%-87 % ) and 96 % ( 95 % CI , 84%-99 % ) , respectively ( P = .01 ) . More patients treated with methyl aminolevulinate PDT than surgery had an excellent or good cosmetic outcome : 27 ( 87 % ) of 31 patients ( 95 % CI , 70%-96 % ) vs 19 ( 54 % ) of 35 patients ( 95 % CI , 37%-71 % ) ( P = .007 ) . CONCLUSIONS Long-term follow-up indicates superior efficacy of surgery to methyl aminolevulinate PDT in nodular basal cell carcinoma . However , methyl aminolevulinate PDT is also an effective treatment for this indication and exhibits a more favorable cosmetic outcome In a clinical trial of 172 patients at four medical centers , interferon alfa-2b ( 1.5 x 10(6 ) IU ) or a placebo was injected directly into biopsy-proved noduloulcerative or superficial basal cell carcinomas three times weekly for 3 weeks , for a cumulative dose of 13.5 million IU . Efficacy of treatment was determined at 16 to 20 weeks by examination of biopsy specimens that demonstrated cure of lesions in 86 % of interferon-treated patients and in only 29 % of placebo-treated patients . During the treatment course and follow-up , an initial inflammatory response was observed at the treatment sites , followed by diminished erythema , improvement in overall appearance , and a decrease in size of lesions . Side effects of treatment , mainly flu-like symptoms , were usually mild and transient and occurred more commonly in the interferon-treated group . Only three patients , all in the interferon-treated group , discontinued therapy because of side effects . One year after initiation of therapy , 81 % of interferon recipients and 20 % of those given the placebo remained tumor free . Noduloulcerative and superficial lesions were equally responsive to treatment with interferon . For some patients with noduloulcerative or superficial basal cell carcinomas , intralesional interferon alfa-2b may be an alternative , effective treatment BACKGROUND Basal cell carcinomas ( BCCs ) are usually treated with ablative procedures . A nonsurgical treatment alternative would be of value in selected patients . OBJECTIVE We evaluated the safety and efficacy of a new preparation for intralesional sustained-release chemotherapy with MPI 5003 , 5-Fluorouracil Therapeutic Implant , for treatment of BCCs . METHODS Two doses of intralesional MPI 5003 ( 0.25 and 0.5 ml ) were compared in a double-blind study of 20 patients with biopsy-proven BCC . One BCC per patient was treated weekly for up to 6 weeks and followed up monthly for 3 months until excisional biopsy for histologic examination . Before excision the cosmetic appearance of the test site was grade d. RESULTS Eighty percent of 10 BCCs treated with 0.5 ml of MPI 5003 had histologically confirmed cures as compared with 60 % of 10 tumors treated with the lower dose ( 0.25 ml ) . Cosmetic assessment s before excision were typically good to excellent . No systemic side effects occurred . CONCLUSION Results indicate the potential of MPI 5003 for targeted local chemotherapy for BCC BACKGROUND Superficial basal-cell carcinoma is most commonly treated with topical non-surgical treatments , such as photodynamic therapy or topical creams . Photodynamic therapy is considered the preferable treatment , although this has not been previously tested in a r and omised control trial . We assessed the effectiveness of photodynamic therapy compared with imiquimod or fluorouracil in patients with superficial basal-cell carcinoma . METHODS In this single blind , non-inferiority , r and omised controlled multicentre trial , we enrolled patients with a histologically proven superficial basal-cell carcinoma at seven hospitals in the Netherl and s. Patients were r and omly assigned to receive treatment with methylaminolevulinate photodynamic therapy ( MAL-PDT ; two sessions with an interval of 1 week ) , imiquimod cream ( once daily , five times a week for 6 weeks ) , or fluorouracil cream ( twice daily for 4 weeks ) . Follow-up was at 3 and 12 months post-treatment . Data were collected by one observer who was blinded to the assigned treatment . The primary outcome was the proportion of patients free of tumour at both 3 and 12 month follow up . A pre-specified non-inferiority margin of 10 % was used and modified intention-to-treat analyses were done . This trial is registered as an International St and ard R and omised controlled trial ( IS RCT N 79701845 ) . FINDINGS 601 patients were r and omised : 202 to receive MAL-PDT , 198 to receive imiquimod , and 201 to receive fluorouracil .  A year after treatment , 52 of 196 patients treated with MAL-PDT , 31 of 189 treated with imiquimod , and 39 of 198 treated with fluorouracil had tumour residue or recurrence . The proportion of patients tumour-free at both 3 and 12 month follow-up was 72.8 % ( 95 % CI 66.8 - 79.4 ) for MAL-PDT , 83.4 % ( 78.2 - 88.9 ) for imiquimod cream , and 80.1 % ( 74.7 - 85.9 ) for fluorouracil cream . The difference between  imiquimod and  MAL-PDT was 10.6 % ( 95 % CI 1.5 - 19.5 ; p=0.021 ) and 7.3 % ( -1.9 to 16.5 ; p=0.120 ) between fluorouracil and MAL-PDT , and between fluorouracil and imiquimod was -3.3 % ( -11.6 to 5.0 ; p=0.435 . For patients treated with MAL-PDT , moderate to severe pain and burning sensation were reported most often during the actual MAL-PDT session . For other local adverse reactions , local skin redness was most often reported as moderate or severe in all treatment groups . Patients treated with creams more often reported moderate to severe local swelling , erosion , crust formation , and itching of the skin than patients treated with MAL-PDT . In the MAL-PDT group no serious adverse events were reported . One patient treated with imiquimod and two patients treated with fluorouracil developed a local wound infection and needed additional treatment in the outpatient setting . INTERPRETATION Topical fluorouracil was non-inferior and imiquimod was superior to MAL-PDT for treatment of superficial basal-cell carcinoma . On the basis of these findings , imiquimod can be considered the preferred treatment , but all aspects affecting treatment choice should be weighted to select the best treatment for patients . FUNDING Grant of the Netherl and s Organization for Scientific Research ZONMW ( 08 - 82310 - 98 - 08626 ) Combinational cryosurgery during daily imiquimod application ( ' immunocryosurgery ' ) efficiently cures invading  basal cell carcinoma ( BCC ) . Since timing of the cryosurgery is considered crucial for effectiveness , our aim was to compare efficacy of two different timing schemes of the combination of cryosurgery and topical imiquimod : Cryosurgery ( a ) 2 weeks after ( Arm I ) vs ( b ) prior to the initiation of a 5 week daily imiquimod course ( Arm II ) . 16 patients with 21 BCC were recruited in this prospect i ve , r and omized , open-label trial . 14 patients with 17 BCC were evaluated ( Arm I : 7 patients /10 tumors vs Arm II : 7 patients /7 tumors ) during scheduled interim analysis at 6 month follow-up ( two patients dropped out , one non-compliant and one lost to follow up ) . The trial was revoked because study Arm I ( ' immunocryosurgery ' ) was significantly superior to Arm II ( adjuvant imiquimod ) in achieving tumor clearance ( 10/10 vs 3/7 tumors ; p=0.0147 ) and by overall treatment efficacy ( 9/10 vs 2/7 relapse-free tumors ; p=0.0345 ) . The same overall efficacy persisted after at least 18 months follow-up for those patients with tumor clearance after the trial treatment . The timing of cryosurgery during imiquimod application substantially determines the efficacy of this combinational approach in the treatment of BCC BACKGROUND Data suggest that photodynamic therapy using topical methyl aminolevulinate ( MAL PDT ) may be a noninvasive alternative to excisional surgery for nodular basal cell carcinoma ( BCC ) . In the studies described here , we investigated the histologic response , tolerability , and cosmetic outcome with MAL PDT for primary nodular BCC ( < or= 5 mm in depth ) . METHODS Two multicenter , r and omized , double-blind studies with similar design and procedures were conducted . After surface debridement and minor tumor debulking , MAL cream 160 mg/g  ( 66 patients with 75 lesions )  or placebo cream ( 65 patients with 75 lesions ) was applied for 3 h , followed by illumination with broad-spectrum red light ( 75 J/cm(2 ) , 570 - 670 nm ) . This was repeated 7 days later . Lesions with a partial response ( > or= 50 % reduction in greatest diameter ) at 3 months were re-treated ( 21 % ) . Treatment sites were excised at 3 months ( clinical nonresponders ) or 6 months ( clinical responders ) after the last treatment . RESULTS Histologically verified lesion complete response rates were higher with MAL PDT than with placebo [ 73 % ( 55/75 ) vs. 27 % ( 20/75 ) ] . Treatment was most effective for facial lesions ( 89 % complete response ) . Cosmetic outcome was good or excellent in 98 % of evaluable , completely responding lesions treated with MAL PDT . CONCLUSION Although longer follow-up studies are required , these promising data indicate the potential of topical MAL PDT as a noninvasive treatment alternative for nodular BCC Photodynamic therapy ( PDT ) using topical porphyrin-precursors is a promising treatment for  superficial basal cell carcinoma ( sBCC ) , but it needs further optimization . The aim of this study was to compare 5-year lesion ( complete ) response rates of sBCC treated with topical aminolaevulinic acid (ALA)-PDT using a single illumination vs. ALA-PDT using a 2-fold illumination scheme . A prospect i ve , r and omized study was performed , in which 91 patients with 299 lesions were treated with a 2-fold  illumination scheme  with 2 light fractions of 20 and 80 J/cm2 delivered 4 and 6 h after a single application of 20 % ALA , and 106 patients with 274 lesions were treated with a single illumination of 75 J/cm2 4 h after a single application of 20 % ALA . All lesions were treated at a fluence rate of 50 mW/cm2 . An interim time to event analysis of complete response ( CR ) rates at 12 months showed encouraging results , and therefore lesions were followed for 5 years post-therapy . A third group of 50 patients with 172 lesions treated with 2-fold illumination were included after the initial period and analysed separately . The CR rate was significantly greater following the 2-fold illumination than the single illumination ( p = 0.0002 , log-rank test ) . Five years after therapy the CR rate after 2-fold illumination was 88 % , whereas the CR rate after single illumination was 75 % . The CR rate in the third group of lesions , treated with 2-fold illumination was 97 % and 88 % at 12 months and 5 years after therapy , respectively . Long-term follow-up indicates superior efficacy in sBCC of ALA-PDT with 2-fold illumination compared with ALA-PDT with single illumination This multicentre , r and omized study compared photodynamic therapy using topical methyl aminolaevulinate ( MAL PDT ) , a non-invasive modality , with cryotherapy for treatment of  superficial basal cell carcinoma . Sixty patients with 114 lesions were treated with MAL cream ( 160 mg/g ) applied for 3 hours before illumination ( 570 - 670 nm , light dose 75 J/cm ) ( 1 session ) , and 58 with 105 lesions received cryotherapy ( 2 freeze-thaw cycles ) . Patients with an incomplete response at 3 months received 2 further MAL PDT sessions ( n = 20 ) or repeat cryotherapy ( n = 16 ) . 100 lesions treated with  MAL PDT and 93 lesions treated with cryotherapy were in complete response at 3 months after the last treatment and evaluable for recurrence over 5 years . There was no difference in 5-year recurrence rates with either treatment ( 20 % with cryotherapy vs. 22 % with MAL PDT , p = 0.86 ) . However , more patients had an excellent cosmetic outcome with MAL PDT ( 60 % vs. 16 % with cryotherapy , p = 0.00078 ) . These results provide support for the use of MAL PDT as a non-invasive , selective treatment alternative for primary superficial basal cell carcinoma BACKGROUND Basal-cell carcinoma ( BCC ) is the most common form of skin cancer and its incidence is still rising worldwide . Surgery is the most frequently used treatment for BCC , but large r and omised controlled trials with 5-year follow-up to compare treatment modalities are rare . We did a prospect i ve r and omised controlled trial to compare the effectiveness of surgical excision with Mohs ' micrographic surgery ( MMS ) for the treatment of primary and recurrent facial BCC . METHODS Between Oct 5 , 1999 , and Feb 27 , 2002 , 408 primary BCCs ( pBCCs ) and 204 recurrent BCCs ( rBCCs ) in patients from seven hospitals in the Netherl and s were r and omly assigned to surgical excision or MMS . R and omisation and allocation was done separately for both groups by a computer-generated allocation scheme . Tumours had a follow-up of 5 years . Analyses were done on an intention-to-treat basis . The primary outcome was recurrence of carcinoma , diagnosed clinical ly by visual inspection with histological confirmation . Secondary outcomes were determinants of failure and cost-effectiveness . This study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N65009900 . FINDINGS Of the 397 pBCCs that were treated , 127 pBCCs in 113 patients were lost to follow-up . Of the 11 recurrences that occurred in patients with pBCC , seven ( 4.1 % ) occurred in patients treated with surgical excision and four ( 2.5 % ) occurred in patients treated with MMS ( log-rank test chi(2 ) 0.718 , p=0.397 ) . Of the 202 rBCCs that were treated , 56 BCCs in 52 patients were lost to follow-up . Two BCCs ( 2.4 % ) in two patients treated with MMS  recurred , versus ten BCCs ( 12.1 % ) in ten patients treated with surgical excision ( log-rank test chi(2 ) 5.958 , p=0.015 ) . The difference in the number of recurrences between treatments was not significant for pBCC , but significantly favoured MMS in rBCC . In pBCC , Cox-regression analysis showed no significant effects from risk factors measured in the study . In rBCC , aggressive histological subtype was a significant risk factor for recurrence in the Cox-regression analysis . For pBCC , total treatment costs were euro1248 for MMS and euro990 for surgical excision , whereas for rBCC , treatment costs were euro1284 and euro1043 , respectively . Dividing the difference in costs between MMS and surgical excision by their difference in effectiveness leads to an incremental cost-effectiveness ratio of euro23 454 for pBCC and euro3171 for rBCC . INTERPRETATION MMS is preferred over surgical excision for the treatment of facial rBCC , on the basis of significantly fewer recurrences after MMS than after surgical excision . However , because there was no significant difference in recurrence of pBCC between treatment groups , treatment with surgical excision is probably sufficient in most cases of pBCC Basal cell carcinomas ( BCCs ) are very frequent cutaneous cancers , often located on the face . Cure rates with surgery and radiotherapy are high , but these treatments have never been compared prospect ively . A r and omized trial was initiated in 1982 to compare surgery and radiotherapy in the treatment of primary BCC of the face measuring less than 4 cm . The primary end point was the failure rate ( persistent or recurrent disease ) after 4 years of follow-up . The secondary end point was the cosmetic results assessed by the patient , the dermatologist and three persons not involved in the trial . In the course of the trial , 347 patients were treated . Of the 174 patients in the surgery group , 71 % had local anaesthesia and 91 % frozen section examination .  Of the 173 patients in the radiotherapy group , 55 % were treated with interstitial brachytherapy , 33 % with contactherapy and 12 % with conventional radiotherapy . The 4-year actuarial failure rate ( 95 % CI ) was 0.7 % ( 0.1 - 3.9 % ) in the surgery group compared with 7.5 % ( 4.2 - 13.1 % ) in the radiotherapy group ( log-rank P = 0.003 ) . The cosmetic results assessed by four of the five judges were significantly better after surgery than after radiotherapy . Eighty-seven per cent of the surgery-treated patients and 69 % of the radiation-treated patients considered the cosmetic result as good ( P < 0.01 ) . Thus , in the treatment of BCC of the face of less than 4 cm in diameter , surgery should be preferred to radiotherapy We conducted a prospect i ve , multicenter , phase 3 , open-label study to assess long-term sustained clearance of superficial basal cell carcinomas ( sBCCs ) treated with  imiquimod cream 5 % . A biopsy-confirmed tumor ( area > or = 0.5 cm2 and diameter < or = 2.0 cm ) was treated once daily 7 times per week for 6 weeks . Participants with initial clinical clearance at 12 weeks posttreatment were followed for 60 months . Tumor recurrence , serious adverse events ( AEs ) , local skin reactions ( LSRs ) , and skin quality assessment s ( SQAs ) were measured . The initial clearance  rate was 94.1 % ( 159/169 ) . Estimated sustained clearance ( proportion of participants who achieved initial clearance at the 12-week posttreatment visit and remained clinical ly clear at each time point during the long-term follow-up period ; N=157 ) was 85.4 % at 60 months ( life-table method : 95 % confidence interval [ CI ] , 79.3%-91.6 % ) . The overall estimate of treatment success was 80.4 % at 60 months ( N=169 ; 95 % CI , 74.4%-86.4 % ) . Of 20 recurrent tumors , 74 ( 70 % ) occurred within the first 24 months of follow-up . Local skin reactions and application site reactions , the AEs reported by the most participants , occurred predominantly during the treatment period and resolved posttreatment . Compared to baseline , investigator-assessed SQA scores for the target tumor site improved for skin surface abnormalities and hyperpigmentation , and worsened for hypopigmentation . For low-risk sBCCs , daily application of imiquimod for 6 weeks had high initial and 5-year sustained clearance rates Objectives : This study was design ed to compare the safety and efficacy of two cycled dosing regimens of imiquimod 5 % cream for treatment of superficial basal cell carcinoma ( sBCC ) . Methods : Patients ( n = 32 ) were r and omized to receive one of two treatment regimens : 8 weeks of treatment with once‐daily dosing for alternate weeks ( R1 ) and 5 weeks of once‐daily dosing with a 1‐week interval in the middle of the course ( R2 ) . Efficacy measures were tumour clearance at weeks 19 and 52 and measures of patients ' acceptability . Results : Data from 30 patients ( 13 females ) , 14 on R1 and 16 on R2 , were analysed . The results revealed an initial clearance rate of 64 % at week 19 for R1 and 81 % for R2 ( 95 % CI for difference : −14 % to 45 % , p = 0.21 ) . However , clearance rates at week 52 were significantly different : 43 % for R1 and 88 % for R2 ( 95 % CI for difference : 11 % to 68 % , p = 0.02 ) . There was no difference in acceptability of treatment as measured by composite median visual analogue scores at week 8 . Conclusion : Five weeks of 5 % imiquimod cream once daily with a 1‐week interval was more effective but as well tolerated as the 8‐week alternate week regimen for sBCC Imiquimod 5 % cream is an immune response modifier approved for the treatment of superficial basal cell carcinoma ( sBCC ) once daily , 5 x per week for 6 weeks . This report reveals the final results of a 5-year follow-up study to evaluate the recurrence rate of sBCCs  treated with imiquimod . As previously reported , 182 patients were enrolled in the study and 163 ( 89.6 % ) had no clinical evidence of their target sBCC at the 12-week post-treatment assessment ; these 163 were followed for up to 5 years . During the follow-up period , 18 clinical recurrences occurred at the target tumour site , 8 and 10 of which occurred during the first 6 and 12 months of follow-up , respectively . The 5-year Kaplan-Meier and life-table estimates for sustained clinical clearance of those patients initially cleared were 84.5 % and 86.9 % , respectively , and 90.3 % considering histology . The estimate of overall treatment success for all treated patients at the end of follow-up was 77.9 % ( 80.9 % considering histology ) . The data support clinical assessment of initial response as predictive of long-term outcome . Most of the recurrences occurred early , indicating that careful follow-up is important during the first year after treatment Background A previously reported r and omized clinical trial showed treatment of Bowen 's disease using photodynamic therapy ( PDT ) with topically applied δ‐aminolaevulinic acid ( ALA ) to be at least as effective as cryosurgery  and to be associated with fewer adverse effects BACKGROUND To develop a nonsurgical treatment alternative for basal cell carcinomas ( BCCs ) , we evaluated intralesional sustained-release chemotherapy with 5-fluorouracil/epinephrine injectable gel ( 5-FU/epi gel ) . OBJECTIVE To optimize the dose and treatment schedule , we compared the safety , tolerance , and efficacy of six treatment regimens of 5-FU/epi gel in patients with BCCs . METHODS Two doses and four treatment schedules of 5-FU/epi gel were compared in an open-label , r and omized study of 122 patients with biopsy-proven BCCs . One BCC per patient was treated for up to 4 to 6 weeks , then observed for 3 months at which time the tumor site was completely excised for histologic examination . RESULTS Overall , 91 % of evaluable treated tumors ( 106 of 116 ) in all regimens had histologically confirmed complete tumor resolution . No clinical ly significant treatment-related systemic adverse events occurred . The best response rate , tolerance , and patient compliance with assigned dose were in patients receiving 0.5 ml of 5-FU/epi gel three times a week for 2 weeks . The complete response rate based on histologic assessment in this group was 100 % . CONCLUSION Results demonstrate that treatment of BCC with 5-FU/epi gel is both safe and effective , may result in histologically confirmed complete response rates comparable to surgery , and provides a nonsurgical treatment alternative in selected patients Background Imiquimod is an immune response modifier that acts through toll‐like receptor 7 to induce cytokine production and a subsequent innate and adaptive cell‐mediated immune response . Clinical studies have demonstrated clinical and histological clearance of superficial basal cell carcinoma ( sBCC )  after treatment with imiquimod 5 % cream Background . In certain situations , successful topical therapy of basal cell carcinoma ( BCC ) without the inconvenience , risk , and expense of surgery would be of great value to patients . Placing 5‐fluorouracil ( FU ) in an appropriate carrier may solve these problems . Phosphatidyl choline ( PC ) penetrates effectively throughout the epidermis of shaved rabbits and may be able to carry small water‐soluble molecules such as nucleotides across lipid barriers when applied topically . Objective . We propose that employing PC as a vehicle will facilitate the penetration of 5‐FU and increase efficacy as compared to petrolatum‐based 5‐FU cream . Methods . This pilot study is a double‐blinded and r and omized therapeutic trial . Thirteen patients with 17 biopsy‐proven , moderate thickness BCCs were r and omized to receive either cream A ( 5 % 5‐FU in a PC vehicle ) or cream B ( Efudex ® : 5 % 5‐FU in a petrolatum base ) . Patients applied cream A or cream B twice a day for 4 weeks . The patients underwent an excisional biopsy of the treated BCC site at week 16 . Results . There was a 90 % cure rate ( 9/10 ) in those lesions treated with 5 % 5‐FU in PC cream and a 57 % cure rate ( 4/7 ) in those treated with 5 % 5‐FU in a petrolatum‐based cream . Conclusion . Although the study was unable to detect any statistically significant differences in outcome between the study groups , this small pilot study shows preliminary findings which may indicate an increase in the short‐term eradication of BCC using a PC‐based vehicle as compared to conventional petrolatum‐based formulations BACKGROUND Both cryosurgery , with and without prior curettage , and surgical excision ( SE ) are common therapeutic strategies for basal cell carcinoma ( BCC ) . OBJECTIVE The objective was to compare the efficacy between  curettage plus cryosurgery ( C&C ) and SE in nonaggressive BCC of the head and neck . MATERIAL S AND METHODS A r and omized controlled trial was carried out , in which tumors were assigned to either C&C  ( n=51 ) or  SE ( n=49 ) .  C&C was performed with a double freeze – thaw cycle after prior curettage of the tumor . SE was performed with a margin of 3 mm and with delayed histologic examination . RESULTS Recurrences occurred 9 times after C&C ( 17.6 % ) and 4 times after SE ( 8.2 % ) . The overall 5-year recurrence probability was 19.6 % for C&C and 8.4 % for SE ( p = .10 ) . A hazard ratio of 2.57 ( 95 % CI , 0.79–8.34 ) indicated a putative , but not statistically significant , advantage of SE . CONCLUSION These data reflect the outcome of the first r and omized controlled trial with long-term follow-up in the treatment of BCC , comparing C&C with SE . Although not statistically significantly different , the observed differences could still be of clinical relevance . Owing to the trend toward lower recurrence rates , better cosmetic results , and reduced wound healing time , we believe that SE should be preferred to C&C in the treatment of primary , nonaggressive BCC of the head and neck BACKGROUND Imiquimod is an immune response modifier that is a Toll-like receptor 7 agonist that induces interferon and other cytokines through the innate immune system and stimulates cell-mediated immunity through T cells . Imiquimod has been shown to be efficacious as a topical treatment for basal cell carcinoma ( BCC ) . OBJECTIVE We sought to evaluate the efficacy and safety of imiquimod 5 % cream compared with vehicle for treating superficial BCC ( sBCC ) . METHODS Two identical studies were conducted . Subjects with one sBCC were dosed with imiquimod or vehicle cream once daily 5 or 7x/week for 6 weeks in these 2 r and omized , double-blind , vehicle-controlled Phase III studies . The lesion site was clinical ly examined 12 weeks posttreatment and then excised for histological evaluation . RESULTS Data from both studies were pooled . Composite clearance rates ( combined clinical and histological assessment s ) for the 5 and 7x/week imiquimod groups were 75 % and 73 % , respectively . Histological clearance rates for the 5 and 7x/week imiquimod groups were 82 % and 79 % , respectively . Increasing severity of erythema , erosion , and scabbing/crusting was associated with higher clearance rates . CONCLUSION Imiquimod appears to be safe and effective for the treatment of sBCC when compared with vehicle cream . The difference in clearance rates between the two imiquimod dosing groups was not significant . The 5x/week regimen is recommended Objectives : To evaluate the safety of two applications of PEP005 ( ingenol mebutate ) gel in superficial basal cell carcinoma .  Efficacy was a secondary end‐point Background To compare the efficacy , cosmesis and tolerance of two non-surgical treatments — imiquimod ( IMQ ) 5 % cream and radiotherapy (RT)—to combat periocular nodular basal cell carcinoma ( BCC ) . Methods Twenty-seven patients with clinical and histopathological diagnosis of nodular BCC on the eyelid were included and r and omly selected : 15 patients were treated with IMQ 5 % cream once daily , 5 days/week for 6 weeks , and 12 patients were treated with RT . Results All tumours showed histopathological remission within 3 months of the treatment , and sustained clinical remission was documented in each patient after 24 months ' follow-up . Treatment tolerability was rated as moderate with IMQ and good with RT .  Functional results were better in patients treated with IMQ .  Loss of eyelashes was reported for most of the patients treated with RT . Conclusions IMQ and RT therapies are effective for treating eyelid nodular BCCs . Cosmesis and functional results were better with IMQ , while tolerability was higher with RT A prospect i ve r and omised trial to compare radiotherapy and cryotherapy in the treatment of basal-cell carcinomas was carried out in 93 patients . Two years after treatment , 4 % of tumours treated with radiotherapy and 39 % of those treated with cryotherapy had recurred . It is concluded that cryotherapy does not offer a satisfactory alternative to radiotherapy  in the treatment of basal-cell carcinomas Intralesional interferon alfa-2b has been proven effective in the treatment of basal cell carcinomas . Because nine injections over a 3-week period have been necessary to produce clinical ly significant cure rates , a sustained-release protamine zinc chelate interferon formulation has been developed . In this study , 65 basal cell carcinomas were treated in one of two dosing schedules with intralesional sustained release interferon alfa-2b ( 10 million IU per injection ) . Thirty-three patients received a single injection and 32 patients received one injection per week for 3 weeks . At study week 16 , 80 % of evaluable tumors treated with three injections and 52 % treated with one injection were cured histologically . Two patients discontinued injections because of side effects . A sustained-release protamine zinc preparation of interferon alfa-2b shows promise as a practical , effective , and cosmetically elegant treatment for basal cell carcinoma BACKGROUND Mohs micrographic surgery ( MMS ) is recognized globally as the criterion st and ard for high‐risk basal cell carcinoma ( BCC ) . The main advantage of MMS over conventional surgery is the chance of complete tumor removal , but it is also thought , based on experience , to be tissue sparing . OBJECTIVE To determine whether MMS leaves smaller surgical defects than st and ard surgery . METHODS AND MATERIAL S This was a r and omized trial involving 30 patients with a clinical diagnosis of BCC . Patients were r and omly assigned to MMS or st and ard surgery . In the st and ard surgery group the BCCs were excised with 4‐mm margins . In the MMS group , tumors were excised with 2‐mm margins and subsequent stages of MMS until the tumor was completely removed . An observer unaware of the treatment allocation calculated the defect size . The main outcome measure was defect size in mm2 . RESULTS The median area of the surgical defects in the MMS group was 116.6 mm2 , versus 187.7 mm2 in the st and ard surgery group ( 95 % confidence interval for difference=61‐126 , p<.001 ) . CONCLUSIONS This is the first r and omized trial demonstrating that MMS is a tissue‐sparing treatment . Trial registration : http://www . clinical trials.gov Identifier : NCT00571363 Imiquimod 5 % cream is approved in the USA , Europe and Australia to treat superficial basal cell carcinoma , using a regimen of once daily , 5 times per week for 6 weeks . Vehicle‐controlled , phase III clinical trials show that imiquimod is safe and effective for treating superficial basal cell carcinoma with dosing 5 or 7 times per week for 6 weeks . This phase III , open‐label study evaluates the long‐term ( 5 years ) clinical efficacy and safety of dosing once daily , for which this manuscript reports the 2‐year time point in the follow‐up period . For the 169 enrolled subjects , the tumour selected for treatment was assessed clinical ly to determine initial clearance at the 12‐week post‐treatment visit . If clinical ly clear of superficial basal cell carcinoma , subjects entered a 5‐year , long‐term follow‐up period . Subjects were evaluated for recurrence at the 3‐ , 6‐ , 12‐ and 24‐month follow‐up visits . The initial clearance rate at 12 weeks post treatment was 94.1 % . The proportion of subjects who were clinical ly clear at the 2‐year follow‐up visit was estimated to be 82.0 % . Imiquimod was tolerated when applied daily , with erythema reported for all subjects participating in the study . The recurrence rate observed suggests that once daily dosing and 5 × /week dosing yield similar clearance rates , but daily dosing increases local skin reactions Photodynamic therapy ( PDT ) of superficial basal cell carcinoma ( sBCC ) using topical 5-aminolevulinic acid ( ALA ) and a light fluence of 75 - 100 J cm(-2 ) yields unsatisfactory long-term results . In several animal models , illumination with two light fractions 2 hours apart was considerably more effective than single illumination . Response is further enhanced if the fluence of the first light fraction is reduced , although the cumulative fluence is maintained . We compared the response of sBCC to a single illumination and 2-fold illumination scheme in which two light fractions of 20 and 80 J cm(-2 ) are performed 4 and 6 hours after the application of a single dose of 20 % ALA . We r and omly assigned 154 patients with a total of 505 primary sBCC into two treatment groups . Two hundred and forty-three lesions were treated using a single illumination of 75 J cm(-2 ) at a fluence rate of 50 mW cm(-2 ) . Fractionated PDT , at the same fluence rate , was performed on 262 lesions . The complete response ( CR ) following a 2-fold illumination scheme is significantly greater than that following a single light fraction ( P=0.002 , log-rank test ) . Twelve months after therapy , CR rate to a 2-fold illumination is 97 % , whereas the CR to a single illumination is 89 % BACKGROUND Dysregulated hedgehog signaling is the pivotal molecular abnormality underlying basal-cell carcinomas . Vismodegib is a new orally administered hedgehog-pathway inhibitor that produces objective responses in locally advanced and metastatic basal-cell carcinomas . METHODS We tested the anti-basal-cell carcinoma efficacy of vismodegib in a r and omized , double-blind , placebo-controlled trial in patients with the basal-cell nevus syndrome at three clinical centers from September 2009 through January 2011 . The primary end point was reduction in the incidence of new basal-cell carcinomas that were eligible for surgical resection ( surgically eligible ) with vismodegib versus placebo after 3 months ; secondary end points included reduction in the size of existing basal-cell carcinomas . RESULTS In 41 patients followed for a mean of 8 months ( range , 1 to 15 ) after enrollment , the per-patient rate of new surgically eligible basal-cell carcinomas was lower with vismodegib than with placebo ( 2 vs. 29 cases per group per year , P<0.001 ) , as was the size ( percent change from baseline in the sum of the longest diameter ) of existing clinical ly significant basal-cell carcinomas ( -65 % vs. -11 % , P=0.003 ) . In some patients , all basal-cell carcinomas clinical ly regressed . No tumors progressed during treatment with vismodegib .  Patients receiving vismodegib  routinely had grade 1 or 2 adverse events of loss of taste , muscle cramps , hair loss , and weight loss . Overall , 54 % of patients ( 14 of 26 ) receiving vismodegib discontinued drug treatment owing to adverse events . At 1 month , vismodegib use had reduced the hedgehog target-gene expression by basal-cell carcinoma by 90 % ( P<0.001 ) and diminished tumor-cell proliferation , but apoptosis was not affected . No residual basal-cell carcinoma was detectable in 83 % of biopsy sample s taken from sites of clinical ly regressed basal-cell carcinomas . CONCLUSIONS Vismodegib reduces the basal-cell carcinoma tumor burden and blocks growth of new basal-cell carcinomas in patients with the basal-cell nevus syndrome . The adverse events associated with treatment led to discontinuation in over half of treated patients . ( Funded by Genentech and others ; Clinical Trials.gov number , NCT00957229 . ) OBJECTIVE To compare the efficacy and cosmetic outcome ( CO ) of photodynamic therapy with topical methyl aminolevulinate ( MAL-PDT ) with simple excision surgery for superficial basal cell carcinoma ( sBCC ) over a 1-year period . METHODS In this multicentre , r and omised , controlled , open study , patients were treated at baseline either with MAL-PDT ( two sessions , 7 days apart , repeated 3 months later if incomplete clinical response ) or surgery ( at baseline ) . Primary endpoints were clinical lesion response ( CR ) 3 months after last treatment and CO assessed by the investigator 12 months after last treatment . Secondary endpoints were CR at 12 months ( i.e. recurrence ) and CO assessed by the investigator at 3 and 6 months and by the patient at 3 , 6 and 12 months . RESULTS Overall , 196 patients were enrolled with 1.4 sBCC lesions on average per patient .  Mean lesion count reduction at 3 months was 92.2 % with MAL-PDT vs. 99.2 % with surgery [ per protocol ( PP ) population ] confirming the non-inferiority hypothesis ( 95 % confidence interval , -12.1 , -1.9 ) . A total of 92.2 % lesions showed CR at 3 months with MAL-PDT vs. 99.2 % with surgery ( PP population ) . At 12 months , 9.3 % lesions recurred with MAL-PDT and none with surgery . CO was statistically superior for MAL-PDT at all time points . At 12 months , 94.1 % lesions treated with MAL-PDT had an excellent or good CO according to the investigator compared with 59.8 % with surgery . This difference was confirmed with the patients ' assessment . The proportion of excellent CO markedly improved with time with MAL-PDT unlike surgery . CONCLUSIONS MAL-PDT offers a similarly high efficacy and a much better CO than simple excision surgery in the treatment of sBCC
Background Basal cell carcinoma ( BCC ) is the most common skin cancer .
Surgical excision remains the st and ard of treatment , but several alternative treatment modalities exist .
Objectives This review aims to provide a current analysis of evidence for the treatment of BCC ; specifically , which treatments have the lowest recurrence rates and the best cosmetic outcomes .