External pelvic and vaginal irradiation versus vaginal irradiation alone as postoperative therapy in medium-risk endometrial carcinoma--a prospective randomized study. Efficacy of systematic pelvic lymphadenectomy in endometrial cancer (MRC ASTEC trial): a randomised study A phase III trial of surgery with or without adjunctive external pelvic radiation therapy in intermediate risk endometrial adenocarcinoma: a Gynecologic Oncology Group study. Systematic pelvic lymphadenectomy vs. no lymphadenectomy in early-stage endometrial carcinoma: randomized clinical trial. Postoperative External Irradiation and Prognostic Parameters in Stage I Endometrial Carcinoma: CLINICAL AND HISTOPATHOLOGIC STUDY OF 540 PATIENTS Intravaginal Brachytherapy in FIGO Stage I Low-Risk Endometrial Cancer: A Controlled Randomized Study Vaginal brachytherapy versus pelvic external beam radiotherapy for patients with endometrial cancer of high-intermediate risk (PORTEC-2): an open-label, non-inferiority, randomised trial Postoperative radiotherapy for Stage 1 endometrial carcinoma: long-term outcome of the randomized PORTEC trial with central pathology review.
PURPOSE To evaluate the value of adjuvant external beam pelvic radiotherapy as adjunct to vaginal brachytherapy ( VBT ) in medium-risk endometrial carcinoma , with regard to locoregional tumor control , recurrences , survival , and toxicity . METHODS AND MATERIAL S Consecutive series of 527 evaluable patients were included in this r and omized trial . Median follow-up for patients alive was 62 months . The primary study endpoints were locoregional recurrences and overall survival . Secondary endpoints were recurrence-free survival , recurrence-free interval , cancer-specific survival , and toxicity . RESULTS Five-year locoregional relapse rates were 1.5 % after external beam radiotherapy ( EBRT ) plus VBT and 5 % after vaginal irradiation alone ( p = 0.013 ) , and 5-year overall survival rates were 89 % and 90 % , respectively ( p = 0.548 ) . Endometrial cancer-related death rates were 3.8 % after EBRT plus VBT and 6.8 % after VBT ( p = 0.118 ) . Pelvic recurrences ( exclusively vaginal recurrence ) were reduced by 93 % by the addition of EBRT to VBT .  Deep myometrial infiltration was a significant prognostic factor in this medium-risk group of endometrioid carcinomas but not International Federation of Gynecology and Obstetrics grade or DNA ploidy . Combined radiotherapy was well tolerated , with serious ( Grade 3 ) late side effects of less than 2 % . However , there was a significant difference in favor of VBT alone . CONCLUSIONS Despite a significant locoregional control benefit with combined radiotherapy , no survival improvement was recorded , but increased late toxicity was noted in the intestine , bladder , and vagina . Combined RT should probably be reserved for high-risk cases with two or more high-risk factors . VBT alone should be the adjuvant treatment option for purely medium-risk cases BACKGROUND Hysterectomy and bilateral salpingo-oophorectomy ( BSO ) is the st and ard surgery for stage I endometrial cancer . Systematic pelvic lymphadenectomy has been used to establish whether there is extra-uterine disease and as a therapeutic procedure ; however , r and omised trials need to be done to assess therapeutic efficacy . The ASTEC surgical trial investigated whether pelvic lymphadenectomy could improve survival of women with endometrial cancer . METHODS From 85 centres in four countries , 1408 women with histologically proven endometrial carcinoma thought preoperatively to be confined to the corpus were r and omly allocated by a minimisation method to st and ard surgery ( hysterectomy and BSO , peritoneal washings , and palpation of para-aortic nodes ; n=704 ) or st and ard surgery plus lymphadenectomy ( n=704 ) . The primary outcome measure was overall survival . To control for postsurgical treatment , women with early-stage disease at intermediate or high risk of recurrence were r and omised ( independent of lymph-node status ) into the ASTEC radiotherapy trial . Analysis was by intention to treat . This study is registered , number IS RCT N 16571884 . FINDINGS After a median follow-up of 37 months ( IQR 24 - 58 ) , 191 women ( 88 st and ard surgery group , 103 lymphadenectomy group ) had died , with a hazard ratio ( HR ) of 1.16 ( 95 % CI 0.87 - 1.54 ; p=0.31 ) in favour of st and ard surgery and an absolute difference in 5-year overall survival of 1 % ( 95 % CI -4 to 6 ) . 251 women died or had recurrent disease ( 107 st and ard surgery group , 144 lymphadenectomy group ) , with an HR of 1.35 ( 1.06 - 1.73 ; p=0.017 ) in favour of st and ard surgery and an absolute difference in 5-year recurrence-free survival of 6 % ( 1 - 12 ) . With adjustment for baseline characteristics and pathology details , the HR for overall survival was 1.04 ( 0.74 - 1.45 ; p=0.83 ) and for recurrence-free survival was 1.25 ( 0.93 - 1.66 ; p=0.14 ) . INTERPRETATION Our results show no evidence of benefit in terms of overall or recurrence-free survival for pelvic lymphadenectomy in women with early endometrial cancer . Pelvic lymphadenectomy can not be recommended as routine procedure for therapeutic purpose s outside of clinical trials BACKGROUND Despite their low risk for recurrence , many women with endometrial adenocarcinoma receive postoperative radiation therapy ( RT ) . This study was developed to determine if adjunctive external beam irradiation lowers the risk of recurrence and death in women with endometrial cancer International Federation of Gynaecology and Obstetrics ( FIGO ) stages IB , IC , and II ( occult disease ) . METHODS Four hundred forty-eight consenting patients with " intermediate risk " endometrial adenocarcinoma were r and omized after surgery to either no additional therapy ( NAT ) or whole pelvic radiation therapy ( RT ) .  They were followed to determine toxicity , date and location of recurrence , and overall survival . A high intermediate risk ( HIR ) subgroup of patients was defined as those with ( 1 ) moderate to poorly differentiated tumor , presence of lymphovascular invasion , and outer third myometrial invasion ; ( 2 ) age 50 or greater with any two risk factors listed above ; or ( 3 ) age of at least 70 with any risk factor listed above . All other eligible participants were considered to be in a low intermediate risk ( LIR ) subgroup . RESULTS Three hundred ninety-two women met all eligibility requirements ( 202 NAT , 190 RT ) . Median follow-up was 69 months . In the entire study population , there were 44 recurrences and 66 deaths ( 32 disease or treatment-related deaths ) , and the estimated 2-year cumulative incidence of recurrence ( CIR ) was 12 % in the NAT arm and 3 % in the RT arm ( relative hazard ( RH ) : 0.42 ; P=0.007 ) . The treatment difference was particularly evident among the HIR subgroup ( 2-year CIR in NAT versus RT : 26 % versus 6 % ; RH=0.42 ) . Overall , radiation had a substantial impact on pelvic and vaginal recurrences ( 18 in NAT and 3 in RT ) . The estimated 4-year survival was 86 % in the NAT arm and 92 % for the RT arm , not significantly different ( RH : 0.86 ; P=0.557 ) . CONCLUSIONS Adjunctive RT in early stage intermediate risk endometrial carcinoma decreases the risk of recurrence , but should be limited to patients whose risk factors fit a high intermediate risk definition BACKGROUND Pelvic lymph nodes are the most common site of extrauterine tumor spread in early-stage endometrial cancer , but the clinical impact of lymphadenectomy has not been addressed in r and omized studies . We conducted a r and omized clinical trial to determine whether the addition of pelvic systematic lymphadenectomy to st and ard hysterectomy with bilateral salpingo-oophorectomy improves overall and disease-free survival . METHODS From October 1 , 1996 , through March 31 , 2006 , 514 eligible patients with preoperative International Federation of Gynecology and Obstetrics stage I endometrial carcinoma were r and omly assigned to undergo pelvic systematic lymphadenectomy ( n = 264 ) or no lymphadenectomy ( n = 250 ) . Patients ' clinical data , pathological tumor characteristics , and operative and early postoperative data were recorded at discharge from hospital . Late postoperative complications , adjuvant therapy , and follow-up data were collected 6 months after surgery . Survival was analyzed by use of the log-rank test and a Cox multivariable regression analysis . All statistical tests were two-sided . RESULTS The median number of lymph nodes removed was 30 ( interquartile range = 22 - 42 ) in the pelvic systematic lymphadenectomy arm and 0 ( interquartile range = 0 - 0 ) in the no-lymphadenectomy arm ( P < .001 ) . Both early and late postoperative complications occurred statistically significantly more frequently in patients who had received pelvic systematic lymphadenectomy ( 81 patients in the lymphadenectomy arm and 34 patients in the no-lymphadenectomy arm , P = .001 ) . Pelvic systematic lymphadenectomy improved surgical staging as statistically significantly more patients with lymph node metastases were found in the lymphadenectomy arm than in the no-lymphadenectomy arm ( 13.3 % vs 3.2 % , difference = 10.1 % , 95 % confidence interval [ CI ] = 5.3 % to 14.9 % , P < .001 ) . At a median follow-up of 49 months , 78 events ( ie , recurrence or death ) had been observed and 53 patients had died . The unadjusted risks for first event and death were similar between the two arms ( hazard ratio [ HR ] for first event = 1.10 , 95 % CI = 0.70 to 1.71 , P = .68 , and HR for death = 1.20 , 95 % CI = 0.70 to 2.07 , P = .50 ) . The 5-year disease-free and overall survival rates in an intention-to-treat analysis were similar between arms ( 81.0 % and 85.9 % in the lymphadenectomy arm and 81.7 % and 90.0 % in the no-lymphadenectomy arm , respectively ) . CONCLUSION Although systematic pelvic lymphadenectomy statistically significantly improved surgical staging , it did not improve disease-free or overall survival From 1968 to 1974 , 540 patients with stage I adenocarcinoma of the corpus uteri entered a prospect i ve clinical trial to evaluate the effect of postoperative external pelvic irradiation . After primary surgery all patients received intravaginal radium irradiation ; 6000 rads was delivered to the surface of the vaginal mucosa . At the time vaginal radium was given , r and omization was performed : Group A received no further treatment ( controls ) ; group B received additional high-voltage irradiation to the pelvic field with a dose of 4000 rads to the pelvic lymph nodes . During the follow-up period of 3 to 10 years a significant reduction in vaginal and pelvic recurrences was found in group B as compared with group A ( 1.9 versus 6.9 % , P<.01 ) . On the other h and , more patients in group B developed distant metastases than those in group A ( 9.9 versus 5.4 % ) . Thus , the 5-year survival rate was not improved by external irradiation . A more detailed analysis of the series led to the conclusion that only patients with poorly differentiated tumors ( grade 3 ) , which infiltrate more than half the myometrial thickness , might benefit from additional external radiotherapy . In almost 20 % of 151 consecutive patients , tumor cells were found in endothelial lined spaces . Significantly more deaths and recurrences were found among these patients compared to those without vessel invasion ( 26.7 versus 9.1 % , P<.01 ) . ( Obstet Gynecol 56:419 , 1980 The purpose of the study was to compare postoperative vaginal irradiation with surgery alone in low-risk International Federation of Gynecology and Obstetrics ( FIGO ) stage IA-IB endometrial carcinoma . The study was a prospect i ve , r and omized trial of 645 evaluable low-risk endometrial carcinoma patients from 6 European gynecologic cancer centers . All tumors were in FIGO stage IA-IB , of endometrioid histological type , and FIGO grade 1 - 2 .  High-dose-rate afterloading equipments ( iridium [ Ir ] 192 or cobalt [ co ] 60 ) were used at 5 centers , and low-dose-rate ( LDR ) afterloading equipment ( cesium [ Cs ] 137 ) at 1 center . Perspex vaginal applicators or ovoids were normally used , and the dose was specified at 5 mm from the surface of the applicator . Three to 6 fractions ( 3.0 - 8.0 Gy ) were given , and the overall treatment time was 4 to 15 days . A total of 319 patients were treated with surgery plus vaginal irradiation ( treatment group ) , and 326 patients with surgery alone ( control group ) . Twenty-six recurrences ( 4.0 % ) were recorded in the complete series . The locoregional recurrence rate was 2.6 % , whereas distant metastases occurred in 1.4 % . The rate of vaginal recurrences was 1.2 % in the treatment group versus 3.1 % in the control group . The difference was not statistically significant ( P = 0.114 ) . Side effects were few and mild ( grade 1 - 2 ) . Dysuria , frequency , and incontinence were slightly more common after vaginal irradiation ( 2.8 % vs 0.6 % , respectively ) . Late intestinal problems were few and similar in the 2 groups . The conclusions were that the impact of postoperative brachytherapy on even the locoregional recurrence rate seems to be limited in patients with low-risk endometrial carcinoma . The overall recurrence rate and survival were similar in the 2 groups BACKGROUND After surgery for intermediate-risk endometrial carcinoma , the vagina is the most frequent site of recurrence . This study established whether vaginal brachytherapy ( VBT ) is as effective as pelvic external beam radiotherapy ( EBRT ) in prevention of vaginal recurrence , with fewer adverse effects and improved quality of life . METHODS In this open-label , non-inferiority , r and omised trial undertaken in 19 Dutch radiation oncology centres , 427 patients with stage I or IIA endometrial carcinoma with features of high-intermediate risk were r and omly assigned by a computer-generated , biased coin minimisation procedure to pelvic EBRT ( 46 Gy in 23 fractions ; n=214 ) or VBT ( 21 Gy high-dose rate in three fractions , or 30 Gy low-dose rate ; n=213 ) . All investigators were masked to the assignment of treatment group . The primary endpoint was vaginal recurrence . The predefined non-inferiority margin was an absolute difference of 6 % in vaginal recurrence . Analysis was by intention to treat , with competing risk methods . The study is registered , number IS RCT N16228756 . FINDINGS At median follow-up of 45 months ( range 18 - 78 ) , three vaginal recurrences had been diagnosed after VBT and four after EBRT . Estimated 5-year rates of vaginal recurrence were 1.8 % ( 95 % CI 0.6 - 5.9 ) for VBT and 1.6 % ( 0.5 - 4.9 ) for EBRT ( hazard ratio [ HR ] 0.78 , 95 % CI 0.17 - 3.49 ; p=0.74 ) . 5-year rates of locoregional relapse ( vaginal or pelvic recurrence , or both ) were 5.1 % ( 2.8 - 9.6 ) for VBT and 2.1 % ( 0.8 - 5.8 ) for EBRT ( HR 2.08 , 0.71 - 6.09 ; p=0.17 ) . 1.5 % ( 0.5 - 4.5 ) versus 0.5 % ( 0.1 - 3.4 ) of patients presented with isolated pelvic recurrence ( HR 3.10 , 0.32 - 29.9 ; p=0.30 ) , and rates of distant metastases were similar ( 8.3 % [ 5.1 - 13.4 ] vs 5.7 % [ 3.3 - 9.9 ] ; HR 1.32 , 0.63 - 2.74 ; p=0.46 ) . We recorded no differences in overall ( 84.8 % [ 95 % CI 79.3 - 90.3 ] vs 79.6 % [ 71.2 - 88.0 ] ; HR 1.17 , 0.69 - 1.98 ; p=0.57 ) or disease-free survival ( 82.7 % [ 76.9 - 88.6 ] vs 78.1 % [ 69.7 - 86.5 ] ; HR 1.09 , 0.66 - 1.78 ; p=0.74 ) . Rates of acute grade 1 - 2 gastrointestinal toxicity were significantly lower in the VBT group than in the EBRT group at completion of radiotherapy ( 12.6 % [ 27/215 ] vs 53.8 % [ 112/208 ] ) . INTERPRETATION VBT is effective in ensuring vaginal control , with fewer gastrointestinal toxic effects than with EBRT . VBT should be the adjuvant treatment of choice for patients with endometrial carcinoma of high-intermediate risk . FUNDING Dutch Cancer Society PURPOSE In 2000 , the results of the multicenter Post Operative Radiation Therapy in Endometrial Carcinoma ( PORTEC ) trial were published . This trial included 714 Stage I endometrial carcinoma patients r and omly assigned to postoperative pelvic radiotherapy ( RT ) or no further treatment  , excluding those with Stage IC , Grade 3 , or Stage IB , Grade 1 lesions .  Radiotherapy significantly decreased the risk of locoregional recurrence ( 4 % vs. 14 % ) , without affecting overall survival . In this report the long-term outcome and results with central pathology review are presented . METHODS AND MATERIAL S The slides of 569 patients ( 80 % ) could be obtained for pathology review . Median follow-up for patients alive was 97 months . Analysis was done according to the intention-to-treat principle . The primary study endpoints were locoregional recurrence and death . RESULTS Ten-year locoregional relapse rates were 5 % ( RT ) and 14 % ( controls ; p < 0.0001 ) , and 10-year overall survival was 66 % and 73 % , respectively ( p = 0.09 ) . Endometrial cancer related death rates were 11 % ( RT ) and 9 % ( controls ; p = 0.47 ) . Pathology review showed a substantial shift from Grade 2 to Grade 1 , but no significant difference for Grade 3 . When cases diagnosed at review as Grade 1 with superficial myometrial invasion were excluded from the analysis , the results remained essentially the same , with 10-year locoregional recurrence rates of 5 % ( RT ) and 17 % ( controls ; p < 0.0001 ) . CONCLUSIONS In view of the significant locoregional control benefit , radiotherapy remains indicated in Stage I endometrial carcinoma patients with high-risk features for locoregional relapse
BACKGROUND The role of adjuvant radiotherapy in stage I endometrial cancer has changed in recent years .
This up date d Cochrane systematic review aim ed to reexamine the efficacy and toxicity of adjuvant radiotherapy vs no treatment in stage I endometrial cancer .