carcinosarcoma of the uterus accounts for 1 - 5% of all uterine malignancies , with an incidence of < 2/100,000 women per year . uterine carcinosarcomas ( uc ) are monoclonal tumors classified as malignant mixed mllerian tumors , malignant mesodermal mixed tumors , or metaplastic carcinomas . metastases occur from carcinomatous and sarcomatous elements derived from de - differentiation of the carcinomatous component . these tumors are highly aggressive and often present with extrauterine - spread at stages iii - iv . the overall outcome of these patients is poor , with a 5-year survival ranging from 33 - 39% , accounting for 15 % of deaths related to uterine cancer . surgery is the primary treatment for uc ; however , as a result of its rarity , surgical management has not been well - defined . in addition , the high rates of both local and distant recurrence after surgery suggest a need for effective adjuvant therapies , although the benefit of adjuvant chemotherapy ( ct ) or radiotherapy ( rt ) remains to be determined . in this study , we performed a retrospective review of the clinical characteristics , management , and outcomes of 66 patients with uc who were treated at three gynecological oncology departments in turkey . the databases of three gynecological oncology departments at izmir tepecik education and research hospital eskisehir osmangazi university school of medicine , and zonguldak bulent ecevit university school of medicine were reviewed in order to identify patients with pathologically diagnosed uc treated between january 1 , 1996 , and december 31 , 2012 . this study was conducted in accordance with the ethical standards of the declaration of helsinki and was approved by the local ethics committees of all institutions . the following clinical data were collected from patient medical , surgical , pathological , ct and rt reports : demographic characteristics , presenting symptoms , serum cancer antigen 125 ( ca-125 ) level , date and type of surgical procedure , presence or absence of residual tumor after surgery , number of excised and positive lymph nodes , presence or absence of ascites , pathological tumor characteristics ( grade and size ) , histologic type ( homologous or heterologous ) , adjuvant therapy if any , date of recurrence , treatment after recurrence , date of last medical examination , and date of death . international federation of gynecology and obstetrics ( figo ) 2009 staging for endometrial carcinoma was used for all patients . the analysis included patients who received either ct with or without rt or rt alone . patients were classified without staging if only peritoneal washings , and total abdominal hysterectomy ( tah ) with bilateral salpingo - oophorectomy ( bso ) , with or without infracolic omentectomy , were performed . partial staging was defined as peritoneal washings , infracolic omentectomy , and bilateral pelvic lymphadenectomy with a tah and bso . complete staging was defined as peritoneal washings , infracolic omentectomy , and bilateral pelvic and para - aortic lymphadenectomy with a tah and bso . optimal debulking was defined as a procedure leaving a maximum residual tumor < 1 cm in diameter . although postoperative management was not absolutely consistent , the preferred treatment differed at the three institutions , with one institution preferring ct alone , one preferring rt alone , and one preferring ct with rt . patients received ct with or without rt or rt alone based on stage , age , presence of nodal metastasis , performance status , and medical co - morbidities . external beam radiotherapy ( ebrt ) was administered to a median dose of 50.4 gy ( range , 45 to 54 gy ) at 1.8 - 2.0 gy per fraction , five days per week . vaginal vault brachytherapy ( vbt ) ( 2650 cgy , prescribed to 0.5-cm depth ) was delivered using a vaginal applicator with high - dose rate iridium-192 source . patients returned for a follow - up evaluation every three months for the first two years , every six months for the next three years , and annually thereafter . computed tomography or magnetic resonance imaging patients were categorized according to two groups : adjuvant ct with rt group ( sequential group ) and adjuvant rt or ct alone group ( alone group ) . staging groups were classified as early figo stage ( i - ii ) and advanced stage ( iii - iv ) . survival analysis was based on the kaplan - meier method , and the results were compared using a log - rank test . diseasefree survival ( dfs ) was defined as the time from the date of primary surgery to detection of recurrence or the latest observation . overall survival ( os ) was defined as the time from the date of primary surgery to death or the latest observation . the  test and student s t - test for unpaired data were used for statistical analysis . cox regression analysis was used to determine factors affecting survival , presented as hazard ratios ( hr ) . two patients did not receive adjuvant therapy , were lost to follow - up , and were not included in the analysis . forty - one of 66 patients ( 62.1% ) received ct with rt ( early stage 20/37 and advanced stage 21/29 ) . sixteen of 66 patients ( 24.2% ) received rt alone ( early stage 14/37 and advanced stage 3/29 ) . only nine patients ( 13.6% ) received ct alone ( early stage 3/37 and advanced stage 6/29 ) . postoperative ct alone consisted of cisplatin+doxorubicin ( 6/9 patients ) , paclitaxel+carboplatin ( 1/9 patients ) , and vincristine+doxorubicin+cyclophosphamide+mesna ( 2/9 patients ) for 4 - 6 cycles . in the sequential treatment group , ct consisted of cisplatin+doxorubicin ( 28/41 patients ) , cyclophosphamide+doxorubicin+cisplatin ( 4/41 patients ) , ifosfamide+doxorubicin+mesna ( 6/41 patients ) , cyclophosphamide+ doxorubicin ( 1/41 patients ) , ifosfamide+etopo - side+mesna ( 1/41 patients ) , and ifosfamide+paclitaxel+ mesna ( 1/41 ) for 4 - 6 cycles . details of adjuvant ct regimens are shown in table 3 . postoperative rt alone consisted of ebrt ( 5/16 patients ) and ebrt+vbt ( 11/16 patients ) . in the sequential treatment group , rt consisted of ebrt ( 28/41 patients ) and ebrt+vbt ( 13/41 patients ) . in early stage disease , the median dfs and os of patients in the sequential treatment group was 44 months ( range , 19 to 123 months ) and 55 months ( range , 19 to 123 months ) , respectively , and that of patients receiving rt or ct alone was 34.5 months ( range , 17 to 96 months ) and 36 months ( range , 17 to 96 months ) , respectively . results of kaplan- meier analysis showed no significant difference in dfs ( hr , 1.4 ; 95% confidence interval [ ci ] , 0.7 to 3.1 ; p=0.23 ) ( fig . 1a ) , however , significant difference in os was observed ( hr , 2.2 ; 95% ci , 0.9 to 5.3 ; p=0.03 ) ( fig . the median dfs and os of patients receiving sequential treatment was 25.0 months ( range , 13 to 47 months ) and 38 months ( range , 24 to 64 months ) , respectively , and that of patients receiving rt or ct alone was 23.5 months ( range , 13 to 27 months ) and 24.5 months ( range , 14 to 37 months ) , respectively . results of kaplan - meier analysis showed a significant difference in dfs ( hr , 3.1 ; 95% ci , 0.6 to 16.0 ; p=0.03 ) ( fig . 1c ) and os ( hr , 3.3 ; 95% ci , 0.7 to 15.0 ; p=0.01 ) ( fig . the recurrence rate was 88.9% in the no staging group , 50.0% in the partial staging group , and 24.3% in the complete staging group . recurrence occurred in 16 patients ( 72.7% ) originally diagnosed in advanced stages and six patients ( 27.3% ) originally diagnosed in early stages . recurrent disease was located in the pelvis in 11 patients , characterized by distant metastases ( lung , liver , or mediastinal lymph nodes ) in eight patients , and by peritoneal dissemination in three patients . the results of univariate and multivariate analyses of dfs are shown in table 4 . in univariate and multivariate analysis , surgical staging type ( none or partial ) , advanced figo stage , and suboptimal surgery ( residual tumor  1 cm ) were independent prognostic factors for dfs . the 5-year os rate was 59.1% and the median duration of survival was 37.5 months ( range , 14 to 123 months ) . the 5-year os was 11.1% in the no staging group , 50.0% in the partial staging group , and 75.7% in the complete staging group . the results of univariate analysis of survival rates showed significant association of myometrial invasion  1/2 , advanced figo stage , suboptimal surgery , surgical staging type ( none or partial ) , tumor size  2 cm , and heterologous histological subtype with poor os . in contrast , in multivariate analysis of os , only advanced figo stage and suboptimal surgery showed significant association with poor os . in the current study , we performed a retrospective analysis of data from 66 patients with carcinosarcoma of the uterus who were treated with surgery followed by adjuvant therapy at three gynecologic oncology centers in turkey . our aim was to describe the demographic and clinical characteristics of uc , to determine the optimal adjuvant therapy strategy according to the early or advanced stage of disease , and to identify variables affecting dfs and os in patients with this disease . uc is a rare clinical entity , representing < 5% of uterine cancer cases in most studies . among uterine cancer cases treated in our clinics , patients with prior pelvic rt and use of tamoxifen , reported as risk factors for uc , were not observed in our cohort . in the literature , the median age of patients with uc is 62 years , similar to that in our patient population . surgery is the cornerstone of treatment , although the extent of surgical procedure remains unclear . tah with bso is the most common procedure ; however , the additive benefit of retroperitoneal lymphadenectomy ( rld ) remains undetermined . a recently published article by vorgias and fotiou   and park et al .   recommended performance of rld in patients with uc . nemani et al .   reported a significant os benefit associated with rld , with a 5-year os of 49% , compared with 35% for patients who had not undergone rld . in our study , the 5-year os was 11.1% in the no staging group , 50.0% in the partial staging group , and 75.7% in the complete staging group . in addition , the recurrence rate was 88.9% in the no staging group , 50.0% in the partial staging group , and 24.3% in the complete staging group . there is an ongoing debate regarding the most suitable method for adjuvant treatment of uc . in a series of cases described by gonzalez bosquet et al . , surgery followed by sequential treatment yielded a significantly longer median dfs versus surgery , rt or ct alone . published a multicenter retrospective study comparing ct with or without radiation to rt alone in patients who underwent surgical staging for uc . the authors reported that sequential treatment after surgery decreased mortality , as compared to patients taking rt or ct alone . similarly , wong et al . , who reported a protocol of cisplatin and ifosfamide - based ct along with rt in 43 patients , noted improved survival in patients who received both ct and rt . however , these two studies did not provide separate analysis for early or advanced stages of disease . in our cohort of 66 patients , we showed that surgery followed by a sequential treatment yields a significantly longer median os versus ct alone or rt alone for early and advanced stage uc . the 5-year os rate for all stages of uc varies from 10 - 69% , while in our study we reported a rate of 59.1% . several studies have reported various prognostic factors that predict the outcome of uc , including age , stage , lymphovascular space involvement , tumor histology , elevated preoperative ca-125 , residual tumor after surgery , positive peritoneal cytology , tumor size , and myometrial invasion [ 16 - 19 ] . in our study , advanced figo stage , presence of a residual tumor  1 cm after surgery , and surgical staging type ( none or partial ) showed significant association with poor dfs in both univariate and multivariate analyses . in addition , myometrial invasion  1/2 , advanced figo stage , suboptimal surgery , surgical staging type ( none or partial ) , tumor size  2 cm , and heterologous tumor histology showed significant association with poor os in univariate analysis . potential limitations of this study include its retrospective nature , the absence of some data , small sample size , and lack of a standard chemotherapeutic regimen , since selection of the regimen depended on the discretion of the medical oncologists . despite these limitations , the similarity of demographic characteristics in the study population , availability of good follow - up data , and performance of surgeries in three institutions by the same surgical team increased the validity of results and mitigated weaknesses . in summary , the three important findings of our study are 1 ) sequential treatment after surgery decreased mortality in both early and advanced stage disease ; 2 ) performing complete rld reduces the risk of recurrence and improves os ; 3 ) advanced figo stage and suboptimal surgery were the only significant independent predictors of os . a multicenter randomized clinical trial including a large series of patients is needed in order to definitively determine optimal management of this rare disease .
purposethe purpose of this study is to evaluate the clinicopathological characteristics , treatment , and prognosis of uterine carcinosarcoma ( uc).materials and methodsa retrospective review of three cancer registry databases in turkey was conducted for identification of patients diagnosed with uc between january 1 , 1996 , and december 31 , 2012 . 
 we collected clinicopathological data in order to evaluate factors important in disease- free survival ( dfs ) and overall survival ( os).resultsa total of 66 patients with uc with a median age of 65.0 years were included in the analysis . 
 the median survival time of all patients was 37.5 months and the 5-year os rate was 59.1% . in early stage patients ( 
 i - ii ) who received adjuvant chemotherapy ( ct ) with radiation therapy ( rt ) , the median dfs and os was 44 months and 55 months , respectively , compared to 34.5 months and 36 months , respectively , in patients who received adjuvant rt or ct alone ( hazard ratio [ hr ] , 1.4 ; 95% confidence interval [ ci ] , 0.7 to 3.1 for dfs ; p=0.23 and hr , 2.2 ; 95% ci , 0.9 to 5.3 for os ; p=0.03 ) . 
 in advanced stage patients ( iii - iv ) , the median dfs and os of patients receiving adjuvant rt with ct was 25 months and 38 months , respectively , compared to 23.5 months and 24.5 months , respectively , in patients receiving adjuvant rt or ct alone ( hr , 3.1 ; 95% ci , 0.6 to 16.0 for dfs ; p=0.03 ) ; ( hr , 3.3 ; 95% ci , 0.7 to 15.0 for os ; p=0.01 ) . in multivariate analysis , advanced international federation of gynecology and obstetrics ( figo ) stage and 
 suboptimal surgery showed significant association with poor os.conclusionin patients with early or advanced stage uc , adjuvant ct with rt is associated with improved dfs and os , as compared to ct or rt alone .