stage iiia endometrial cancer represents a wide range of tumor involvement , including the uterine serosa , adnexa , parametria , and peritoneal space , based on the staging system of the international federation of gynecology and obstetrics ( figo ) in 1988 [ 1 - 3 ] .
in addition , the heterogeneity of histology , such as papillary serous or clear cell carcinoma , makes it difficult to compare outcomes between studies .
this variability has led to a wide range of 5-year overall survival ( os ) rates for stage iiia endometrial cancer , varying from 39% to 76% [ 3 - 6 ] . the optimal adjuvant management for patients with advanced endometrial cancer has yet to be defined , particularly for iiia patients as incidence is low , representing only 2.6% of patients with endometrial cancer .
radiotherapy ( rt ) has traditionally been employed in advanced endometrial carcinoma to improve locoregional control .
several studies have evaluated the role of combined modality adjuvant therapy compared with a single modality in advanced endometrial cancer and have suggested that combined chemoradiotherapy ( ctrt ) can provide additional benefits compared with computed tomography ( ct ) or rt alone [ 10 - 13 ] .
in contrast , a randomized study failed to show an improvement in disease - free survival ( dfs ) and os in patients treated with combined ctrt compared with adjuvant rt alone for high - risk endometrial cancer .
thus , the effects of different adjuvant therapies for stage iiia endometrial cancer remain controversial .
in addition , these previous studies involved a small portion of iiia populations , patient s stage was determined based on the 1988 figo stage , and both endometriod and non - endometrioid adenocarcinoma were included .
the current study included a group of patients with stage iiia endometrioid adenocarcinoma with favorable histology only , using the revised 2009 figo stage to overcome the aforementioned variabilities .
the revised figo iiia , which was published in 2009 , excluded positive peritoneal cytology alone and denoted parametrial involvement separately as stage iiib .
several studies have attempted to analyze risk factors for poor outcomes ; however , few studies have evaluated the role of particular adjuvant therapies according to risk group for revised 2009 figo stage iiia diseases . here
, we evaluated survival outcomes according to risk factors and sought to determine the benefit of combined modality treatment after surgery in the high - risk subset of stage iiia patients .
all patients with stage iiia endometrial cancer treated with surgery , followed by adjuvant rt or combined ctrt , in korea between january 1990 and december 2011 were evaluated .
nineteen patients with non - endometrioid type adenocarcinoma , such as papillary serous , clear cell , adenosquamous , or carcinosarcoma were excluded .
in addition , five patients with only positive peritoneal cytology , and those who underwent adjuvant ct alone ( n=3 ) or inadequate rt ( n=2 ) were also excluded .
the remaining 93 stage iiia patients who underwent surgery followed by adjuvant rt alone or combined ctrt were analyzed retrospectively .
after approval by the korean radiation oncology group ( krog 13 - 17 ) , the medical and rt records of the patients were reviewed retrospectively .
all patients underwent hysterectomy and bilateral salpingo - oophorectomy with pelvic and/or aortic lymphadenectomy , followed by postoperative rt or combined ctrt .
pelvic lymph node dissection was performed in 77 patients ( 82.8% ) and paraaortic lymph node ( paln ) dissection or sampling was performed in 31 patients ( 33.3% ) .
all patients underwent external pelvic rt , delivered to the tumor bed and regional lymphatics with 10-mv photons using the four - field box technique . the total dose to the pelvis ranged from 45 gy to 54 gy in 1.8 gy daily fractions , 5 days per week .
twenty - one patients ( 21.6% ) underwent additional vaginal brachytherapy using fletcher - suit after - loading applicators .
two to six fractions of 3 - 5 gy were delivered to the vaginal surface or 5 mm from the vaginal surface .
two patients ( 2.2% ) were treated with an extended - field rt encompassing a volume of paln , usually located at the t12-l1 interface .
another two patients received total abdominal rt of 30 gy in 1.5 gy fractions followed by a boost to the pelvis with the doses of 19.8 gy or 24 gy in 1.8 gy fractions .
thirty patients were treated with concurrent ctrt ( 83.3% ) , four patients with ct followed by rt ( 11.1% ) , and two patients with rt followed by ct ( 5.6% ) . patients receiving adjuvant ct were treated with cisplatin - based ct ( n=19 , 52.8% ) , carboplatin plus paclitaxel ( n=8 , 22.2% ) , paclitaxel alone ( n=6 , 16.7% ) , or other drugs ( n=3 , 8.3% ) .
adjuvant ct was delivered with a median of six cycles ( range , 1 to 9 cycles ) , although two patients received only one cycle , and another two patients only received two cycles .
five patients did not complete the full course of ct because of g3 hematologic toxicity ( n=2 ) , patient refusal ( n=1 ) , or no available data on toxicity ( n=2 ) .
in adjuvant rt alone , the average treatment period was 42.9 days ( range , 36 to 60 days ) and 46.9 days ( range , 35 to 117 days ) for the ctrt group .
no significant difference in the rt period was observed between the two treatment groups ( p=0.057 ) .
locoregional recurrence was defined as a recurrence in the pelvis , vagina , or paraaortic lymphatic region .
failure was defined as biopsy - proven recurrence or progression of disease on serial imaging studies .
time to recurrence and death was calculated from the date of surgery until failure or death from any cause .
survival curves were calculated using the kaplan - meier method , and comparison of the curves was performed using a log - rank test .
the chi - square test , fisher exact test , and independent samples t test were used for comparison of characteristics between the two groups .
21 ( ibm co. , armonk , ny ) , and p - values less than 0.05 were considered statistically significant .
all patients underwent hysterectomy and bilateral salpingo - oophorectomy with pelvic and/or aortic lymphadenectomy , followed by postoperative rt or combined ctrt .
pelvic lymph node dissection was performed in 77 patients ( 82.8% ) and paraaortic lymph node ( paln ) dissection or sampling was performed in 31 patients ( 33.3% ) .
all patients underwent external pelvic rt , delivered to the tumor bed and regional lymphatics with 10-mv photons using the four - field box technique . the total dose to the pelvis ranged from 45 gy to 54 gy in 1.8 gy daily fractions , 5 days per week .
twenty - one patients ( 21.6% ) underwent additional vaginal brachytherapy using fletcher - suit after - loading applicators .
two to six fractions of 3 - 5 gy were delivered to the vaginal surface or 5 mm from the vaginal surface .
two patients ( 2.2% ) were treated with an extended - field rt encompassing a volume of paln , usually located at the t12-l1 interface .
another two patients received total abdominal rt of 30 gy in 1.5 gy fractions followed by a boost to the pelvis with the doses of 19.8 gy or 24 gy in 1.8 gy fractions .
thirty patients were treated with concurrent ctrt ( 83.3% ) , four patients with ct followed by rt ( 11.1% ) , and two patients with rt followed by ct ( 5.6% ) . patients receiving adjuvant ct were treated with cisplatin - based ct ( n=19 , 52.8% ) , carboplatin plus paclitaxel ( n=8 , 22.2% ) , paclitaxel alone ( n=6 , 16.7% ) , or other drugs ( n=3 , 8.3% ) .
adjuvant ct was delivered with a median of six cycles ( range , 1 to 9 cycles ) , although two patients received only one cycle , and another two patients only received two cycles .
five patients did not complete the full course of ct because of g3 hematologic toxicity ( n=2 ) , patient refusal ( n=1 ) , or no available data on toxicity ( n=2 ) .
in adjuvant rt alone , the average treatment period was 42.9 days ( range , 36 to 60 days ) and 46.9 days ( range , 35 to 117 days ) for the ctrt group .
no significant difference in the rt period was observed between the two treatment groups ( p=0.057 ) .
locoregional recurrence was defined as a recurrence in the pelvis , vagina , or paraaortic lymphatic region .
failure was defined as biopsy - proven recurrence or progression of disease on serial imaging studies .
time to recurrence and death was calculated from the date of surgery until failure or death from any cause .
survival curves were calculated using the kaplan - meier method , and comparison of the curves was performed using a log - rank test . the chi - square test , fisher exact test , and independent samples t test were used for comparison of characteristics between the two groups .
21 ( ibm co. , armonk , ny ) , and p - values less than 0.05 were considered statistically significant .
the tumor and treatment characteristics of all 93 patients , 57 ( 61.3% ) who received postoperative rt alone and 36 ( 38.7% ) who received ctrt , are shown in table 1 .
the median age of patients in the ctrt group was older than that in the rt alone group . a larger portion of patients in the ctrt group showed involvement of serosa ( 27.8% vs. 19.3% , p=0.361 ) and lymphovascular space ( 30.6% vs. 15.8% , p=0.214 )
. a higher proportion of patients in the ctrt group underwent paraaortic lymphadenectomy compared to the rt alone group ( 52.8% vs. 21.1% , p=0.002 ) .
the extent of irradiation field of adjuvant rt and vaginal brachytherapy did not differ significantly in the two groups .
the median follow - up period was 62 months ( range , 3 to 188 months ) .
eight patients ( 14.0% ) in the rt alone group and 11 patients ( 30.6% ) in the ctrt group relapsed during the follow - up period ( p=0.054 ) ( table 2 ) .
the majority of recurrences were distant metastases including abdominal recurrence , 75% ( 6/8 ) in the rt alone group and 81.8% ( 9/11 ) in the ctrt group .
in the rt alone group , one patient developed combined local and distant metastases with pelvic lymph node and liver metastasis . the 5-year os and dfs were 93.7% and 79.0% , respectively .
univariate analyses showed statistically significant difference in dfs with regard to age ( p < 0.001 ) , tumor grade ( p=0.029 ) , and lymphovascular involvement ( p=0.041 ) ( table 3 ) .
no significant difference in os ( 91.9% vs. 96.3% , p=0.262 ) or dfs ( 82.4% vs. 74.1% , p=0.130 ) was observed between the rt alone group and the combined ctrt group .
five - year dfs was lower in patients with serosal involvement than in those without , but there was no statistical significance ( 81.5% vs. 67.2% , p=0.180 ) .
of the 93 patients , 57 ( 61.3% ) had solitary adnexal or serosal involvement .
patients with serosal involvement had a worse 7-year dfs ( 66.7% ) compared to those with solitary adnexal involvement ( 90.5% ) , but this difference did not reach statistical significance ( p=0.629 ) .
the above mentioned variables ( age  60 years , tumor grade 2/3 , and lymphovascular space involvement ) for prognosis in dfs were defined as risk factors . of 77 patients with available data for risk factors , 25 patients ( 32.5% ) had no risk factors , 30 ( 38.9% ) had one , 16 ( 20.8% ) had two , and six ( 7.8% ) had three . a significant correlation
the 5-year dfs was 91.7% in patients with no risk factors , 84.8% in patients with one , 55.0% in patients with two , and 33.3% in patients with three ( p=0.001 ) .
the 5-year os according to the number of risk factors was 95.0% in patients with no risk factors , 92.0% in patients with one , 93.8% in patients with two , and 80.0% in patients with three ( p=0.542 ) .
the patients were subgrouped according to low - risk ( patients with no or one risk factor ) and high - risk ( patients with two or three risk factors ) groups .
the proportion of high - risk patients in the combined ctrt group was more than twice that of the rt alone group ( 41.9% vs. 19.6% , p=0.033 ) .
thirty - seven patients ( 80.4% ) in rt alone were classified as low risk and nine ( 19.6% ) as high risk . in ctrt ,
18 patients ( 58.1% ) were classified as low risk , while 13 patients ( 41.9% ) as high risk .
a significant reduction in 5-year dfs was observed in the high - risk group ( 49.0% vs. 88.0% , p < 0.001 ) compared with the low - risk group ( fig .
five - year os was not significantly lower in the high - risk group ( 90.7% ) versus the low - risk group ( 93.5% ) ( p=0.618 ) . for rt alone ,
5-year dfs and os were lower in the high - risk group than in the low - risk group ( 66.7% vs. 84.6% , p=0.133 and 77.8% vs. 93.5% , p=0.149 , respectively ) , but the differences did not reach statistical significance ( fig .
the low - risk group showed an improved 5-year dfs ( 94.4% vs. 38.5% , p=0.001 ) compared with the high - risk group , but there was no significant difference in os ( 93.3% vs. 100% , p=0.465 ) . to examine the role of adjuvant multi - modality therapy
( 84.6% vs. 94.4% , p=0.852 ) was observed between the rt alone group and the combined ctrt group in the low - risk group . in the high - risk group ,
combined ctrt showed a trend for improved 5-year os ( 100% vs. 77.8% , p=0.086 ) compared with rt alone , but the difference did not reach statistical significance .
combined ctrt did not affect 5-year dfs ( 38.5% vs. 66.7% , p=0.274 ) compared with rt alone for the high - risk group .
in multivariate analysis including age , grade , lympohovascular involvement , number of risk factors , and type of adjuvant modality , more than one risk factor was the only predictor of worse dfs ( hazard ratio [ hr ] , 5.45 ; 95% confidence interval [ ci ] , 2.12 to 13.98 ; p < 0.001 ) .
in multivariate analysis for os , only old age was predictive of os ( hr , 5.8 ; 95% ci , 1.15 to 29.61 ; p=0.034 ) .
in multivariate analysis , combined ctrt did not show a statistical difference compared to rt alone in dfs or os ( table 4 ) .
twelve patients ( 33.3% ) in the ctrt group experienced grade 3 - 4 acute toxicity .
grade 3 - 4 acute hematologic toxicities were observed in 11 patients in the ctrt group and a grade 3 acute intestinal obstruction was found in one patient . in the rt alone group ,
one patient ( 1.8% ) treated with extended - field rt had grade 4 acute hematologic toxicity .
no patients in the ctrt group had grade 3 - 4 late toxicity and one patient in the rt alone group treated with whole abdominal irradiation had a grade 3 late leg edema .
the tumor and treatment characteristics of all 93 patients , 57 ( 61.3% ) who received postoperative rt alone and 36 ( 38.7% ) who received ctrt , are shown in table 1 .
the median age of patients in the ctrt group was older than that in the rt alone group . a larger portion of patients in the ctrt group showed involvement of serosa ( 27.8% vs. 19.3% , p=0.361 ) and lymphovascular space ( 30.6% vs. 15.8% , p=0.214 )
. a higher proportion of patients in the ctrt group underwent paraaortic lymphadenectomy compared to the rt alone group ( 52.8% vs. 21.1% , p=0.002 ) .
the extent of irradiation field of adjuvant rt and vaginal brachytherapy did not differ significantly in the two groups .
the median follow - up period was 62 months ( range , 3 to 188 months ) .
eight patients ( 14.0% ) in the rt alone group and 11 patients ( 30.6% ) in the ctrt group relapsed during the follow - up period ( p=0.054 ) ( table 2 ) .
the majority of recurrences were distant metastases including abdominal recurrence , 75% ( 6/8 ) in the rt alone group and 81.8% ( 9/11 ) in the ctrt group .
in the rt alone group , one patient developed combined local and distant metastases with pelvic lymph node and liver metastasis .
univariate analyses showed statistically significant difference in dfs with regard to age ( p < 0.001 ) , tumor grade ( p=0.029 ) , and lymphovascular involvement ( p=0.041 ) ( table 3 ) . no significant difference in os ( 91.9% vs. 96.3% , p=0.262 ) or dfs ( 82.4% vs. 74.1% , p=0.130 ) was observed between the rt alone group and the combined ctrt group .
five - year dfs was lower in patients with serosal involvement than in those without , but there was no statistical significance ( 81.5% vs. 67.2% , p=0.180 ) .
of the 93 patients , 57 ( 61.3% ) had solitary adnexal or serosal involvement .
patients with serosal involvement had a worse 7-year dfs ( 66.7% ) compared to those with solitary adnexal involvement ( 90.5% ) , but this difference did not reach statistical significance ( p=0.629 ) . the above mentioned variables ( age  60 years , tumor grade 2/3 , and lymphovascular space involvement ) for prognosis in dfs were defined as risk factors . of 77 patients with available data for risk factors , 25 patients ( 32.5% )
had no risk factors , 30 ( 38.9% ) had one , 16 ( 20.8% ) had two , and six ( 7.8% ) had three .
the 5-year dfs was 91.7% in patients with no risk factors , 84.8% in patients with one , 55.0% in patients with two , and 33.3% in patients with three ( p=0.001 ) .
the 5-year os according to the number of risk factors was 95.0% in patients with no risk factors , 92.0% in patients with one , 93.8% in patients with two , and 80.0% in patients with three ( p=0.542 ) .
the patients were subgrouped according to low - risk ( patients with no or one risk factor ) and high - risk ( patients with two or three risk factors ) groups .
the proportion of high - risk patients in the combined ctrt group was more than twice that of the rt alone group ( 41.9% vs. 19.6% , p=0.033 ) .
thirty - seven patients ( 80.4% ) in rt alone were classified as low risk and nine ( 19.6% ) as high risk . in ctrt ,
18 patients ( 58.1% ) were classified as low risk , while 13 patients ( 41.9% ) as high risk . a significant reduction in 5-year dfs
was observed in the high - risk group ( 49.0% vs. 88.0% , p < 0.001 ) compared with the low - risk group ( fig .
five - year os was not significantly lower in the high - risk group ( 90.7% ) versus the low - risk group ( 93.5% ) ( p=0.618 ) . for rt alone ,
5-year dfs and os were lower in the high - risk group than in the low - risk group ( 66.7% vs. 84.6% , p=0.133 and 77.8% vs. 93.5% , p=0.149 , respectively ) , but the differences did not reach statistical significance ( fig .
the low - risk group showed an improved 5-year dfs ( 94.4% vs. 38.5% , p=0.001 ) compared with the high - risk group , but there was no significant difference in os ( 93.3% vs. 100% , p=0.465 ) .
to examine the role of adjuvant multi - modality therapy , the risk groups were analyzed according to treatment modalities .
no significant difference in 5-year os ( 93.5% vs. 93.3% , p=0.785 ) or dfs ( 84.6% vs. 94.4% , p=0.852 ) was observed between the rt alone group and the combined ctrt group in the low - risk group . in the high - risk group ,
combined ctrt showed a trend for improved 5-year os ( 100% vs. 77.8% , p=0.086 ) compared with rt alone , but the difference did not reach statistical significance .
combined ctrt did not affect 5-year dfs ( 38.5% vs. 66.7% , p=0.274 ) compared with rt alone for the high - risk group . in multivariate analysis including age , grade , lympohovascular involvement , number of risk factors , and type of adjuvant modality ,
more than one risk factor was the only predictor of worse dfs ( hazard ratio [ hr ] , 5.45 ; 95% confidence interval [ ci ] , 2.12 to 13.98 ; p < 0.001 ) .
in multivariate analysis for os , only old age was predictive of os ( hr , 5.8 ; 95% ci , 1.15 to 29.61 ; p=0.034 ) . in multivariate analysis ,
combined ctrt did not show a statistical difference compared to rt alone in dfs or os ( table 4 ) .
twelve patients ( 33.3% ) in the ctrt group experienced grade 3 - 4 acute toxicity .
grade 3 - 4 acute hematologic toxicities were observed in 11 patients in the ctrt group and a grade 3 acute intestinal obstruction was found in one patient . in the rt alone group ,
one patient ( 1.8% ) treated with extended - field rt had grade 4 acute hematologic toxicity .
no patients in the ctrt group had grade 3 - 4 late toxicity and one patient in the rt alone group treated with whole abdominal irradiation had a grade 3 late leg edema .
the current study showed the impact of a number of risk factors for stage iiia endometrioid adenocarcinoma .
patients with more than one risk factor ( high - risk group ) had a worse prognosis . indeed , more than one risk factor was the only strong negative prognostic factor in multivariate analysis .
patients in the high - risk group were 4 to 5 times more likely to develop a distant metastasis compared to those in the low - risk group ( 40.9% vs. 9.1% , p < 0.001 ) , therefore , the addition of more intense systemic therapy to those in the high - risk group may improve the outcome .
the current study showed that combined ctrt showed a trend with an improved 5-year os ( 100% vs. 77.8% , p=0.086 ) compared with rt alone , although ctrt did not affect 5-year dfs compared with rt alone for the high - risk group .
several studies have suggested that combined ctrt can provide additional benefits compared with ct or rt alone [ 10 - 13 ] . the retrospective study in stage iii and iv endometrial cancer by alvarez secord et al .  
reported that adjuvant ct alone was associated with poor 3-year os ( 33% ) and progression - free survival ( 19% ) compared to either rt alone ( 70% and 59% ) or combined therapy ( 79% and 62% ) . in a multicenter retrospective study conducted with 78 patients with stage iii endometrial cancer treated with adjuvant ct and/or rt ,
the 3-year relapse - free survival rates were 86.5% for the combined ctrt group , 65.8% for the ct alone , and 44.1% for rt alone , suggesting that combined ctrt modality may induce an advantage in relapse - free survival compared to rt or ct alone .
the first trial was run by the italian oncology group with 153 patients ( iib - iiic , 65% stage iii ) , and the second by the nordic society of gynaecological oncology / european organisation for the research and treatment of cancer , which included patients with mainly high - risk early stage disease ( only 1.6% stage iii ) . in the italian trial ,
however , in joint pooled analysis in these two randomized trials , sequential addition of ct to rt improved at least progression - free survival ( 78% vs. 69% , p=0.009 ) , and trended a benefit of overall survival ( 82% vs. 75% , p=0.07 ) compared with rt alone .
an important question is whether or not it is reasonable to recommend adjuvant rt alone without chemotherapy in low - risk patients .
prior study has suggested that a subgroup of women with stage iiia who have endometrioid tumor , no lymphovascular space involvement , and positive peritoneal cytologic finding only show an excellent prognosis .
.   found that among 24 patients with peritoneal cytology only , non - serous histology , and grade 1 - 2 disease , no recurrence was found in 12 patients receiving adjuvant treatment , while one patient showed recurrence without adjuvant treatment .
our study included patients according to the 2009 figo staging system and excluded those with peritoneal cytology only . for 25 patients with no risk factors , 17 patients ( 68% )
were treated with adjuvant rt alone and eight patients ( 32% ) with adjuvant combined ctrt , resulting in excellent 5-year dfs ( 91.7% ) and os ( 95.0% ) , respectively . no difference in dfs and os
thus , a subset of stage iiia patients with no risk factors might be treated with adjuvant rt alone .
several studies have reported that patients with extrauterine spread limited to the adnexa showed favorable 5-year dfs rates , ranging from 71% to 89.6% .
a retrospective study of 15 patients with solitary serosal invasion had a poor 5-year dfs ( 41.5% ) due to the high incidence of distance metastases . a multicenter retrospective comparative analysis in netherlands published the outcomes for 67 patients with stage iiia endometrial carcinoma , evaluating differences in outcome between serosa and adnexal involvement .
those with involvement of the serosa alone had a worse 7-year distant metastasis - free survival ( 58.7% ) compared to adnexal involvement alone ( 72.7% ) , but this difference was not significant ( p=0.399 ) .
authors concluded that either adnexal or serosal involvement showed a comparable disease - specific survival and only presence of lymphovascular invasion was significant in multivariate analysis ( hr , 3.6 ; p=0.038 ) .
the current study was composed of a relatively large homogeneous subgroup of surgically staged iiia patients with only adnexal or serosal involvement .
of the 93 patients in our study , 57 ( 61.3% ) had solitary adnexal or serosal involvement .
consistent with previous studies , patients with serosal involvement had a worse 7-year dfs ( 66.7% ) compared to those with solitary adnexal involvement ( 90.5% ) ( p=0.629 ) . in this multicenter analysis , we failed to demonstrate additional benefit of combined adjuvant ctrt compared with adjuvant rt alone for stage iiia endometrial cancer .
while these findings might suggest a comparable survival outcome between combined ctrt and rt alone groups , our study is limited by the difference of high - risk features between the groups .
although there was no statistically significant difference in median age , grade , and lymphovascular involvement between the rt alone group and the combined ctrt group , the ctrt groups did show a trend with an older age , higher grade , and more involvement of lymphovascular space than the rt alone group .
in addition , a subset of patients with more than one risk factor , the high - risk group , in the combined ctrt group was more than twice that of the rt alone group ( 41.9% vs. 19.6% , p=0.033 ) . these factors might lead to comparable survival outcomes between the rt alone group and the combined ctrt group .
another limitation of this study is the retrospective design with heterogeneity of the ct agent , sequence of combined ctrt and surgical technique with paraaortic lymphadectomy .
this variability leads to difficulty in determining the additional benefit of ctrt in stage iiia endometrioid adenocarcinoma .
for gynecologic oncology group 258 ( gog258 ) , the current phase iii randomized trial for adjuvant modality , the ctrt followed by carboplatin+paclitaxel is being compared to combination of carboplatin and paclitaxel in stage iii and iva patients .
multi - center randomized trials are required to further evaluate the role of adjuvant combined modality , according to risk groups , particularly in stage iiia endometrial adenocarcinoma which is an uncommon entity .
in conclusion , the current study showed a favorable outcome in a subset of low - risk patients compared to the high - risk group in stage iiia endometrioid adenocarcinoma treated with adjuvant rt alone or adjuvant combined ctrt .
we found that patients classified as high risk (  2 risk factors ) showed a significant reduction in 5-year dfs compared with the low - risk group ( 49.0% vs. 88.0% , p < 0.001 ) with an increase in the development of distant metastasis ( 40.9% vs. 9.1% , p < 0.001 ) .
we identified a subset of stage iiia patients without risk factors who might be reasonable candidates for adjuvant rt alone .
 purposewe evaluated the role of adjuvant therapy in stage iiia endometrioid adenocarcinoma patients who underwent surgery followed by radiotherapy ( rt ) alone or chemoradiotherapy ( ctrt ) according to risk group.materials and methodsa multicenter retrospective study was conducted including patients with surgical stage iiia endometrial cancertreated by radical surgery and adjuvant rt or ctrt . 
 disease - free survival ( dfs ) and overall survival ( os ) were analyzed.resultsninety-three patients with stage iiia disease were identified . 
 nineteen patients ( 20.4% ) experienced recurrence , mostly distant metastasis ( 17.2% ) . 
 combined ctrt did not affect dfs ( 74.1% vs. 82.4% , p=0.130 ) or os 
 ( 96.3% vs. 91.9% , p=0.262 ) in stage iiia disease compared with rt alone . 
 patients with age  60 years , grade g2/3 , and lymphovascular space involvement had a significantly worse dfs and those variables were defined as risk factors . 
 the high - risk group showed a significant reduction in 5-year dfs (  2 risk factors ) ( 49.0% vs. 88.0% , p < 0.001 ) compared with the low - risk group ( < 2 ) . 
 multivariate analysis confirmed that more than one risk factor was the only predictor of worse dfs ( hazard ratio , 5.45 ; 95% confidence interval , 2.12 to 13.98 ; p < 0.001 ) . of patients with no risk factors , 
 a subset treated with rt alone showed an excellent 5-year dfs and os ( 93.8% and 100% , respectively).conclusionwe identified a low - risk subset of stage iiia endometrioid adenocarcinoma patients who might be reasonable candidates for adjuvant rt alone . 
 further randomized studies are needed to determine which subset might benefit from combined ctrt . 
Introduction
Materials and Methods
1. Treatment
2. Statistical analysis
Results
1. Patient characteristics and pattern of failure
2. DFS and OS
3. Multivariate analysis
4. Treatment related toxicities
Discussion
Conclusion