Table 2

Most relevant studies investigating the adjuvant treatment for endometrial carcinosarcoma

Author, yearDesignSettingNTreatmentResultsConclusion
Radiotherapy (RT)
Gerszten et al, 199838 Monocentric, retrospective studyStage I–IV ECS60RT vs observationRR for local recurrence: 17.54 (p=0.0055)Adjuvant RT reduced the risk of distant failure and death in patients with disease confined to the uterus but did not impact distant recurrence or survival in stage III patients
Knocke et al, 199939 Monocentric, retrospective studyStage I–III ECS50RT vs observation5 year OS, disease-specific survival, local control, and distant control were: 52.9, 57.5, 83.4, and 70.8%, respectivelyAdjuvant RT improves local control and disease specific survival in the treatment of ECS
Callister et al, 200440 Monocentric, retrospective studyStage I–III ECS300RT vs observationPelvic recurrence rate: 28% vs 48% (p=0.0002)
OS: 36% vs 27% (p=0.10)
Distant metastasis rates: 57% vs 54% (p=0.96)
Adjuvant pelvic RT decreased the risk of pelvic recurrence and may delay the appearance of distant metastases after hysterectomy. However, the survival rates remain poor because of a high rate of distant recurrence
Wolfson et al, 2007 (GOG-150)41 Open-label, multicenter, phase III RCTStage I–IV ECS206Arm 1 (105): WAI
Arm 2 (101): CIM (3 cycles)
Recurrence rate was 21% lower (HR=0.789, 95% CI, 0.530 to 1.176; p=0.245) and death rate 29% lower (HR=0.712, 95% CI: 0.484 to 1.048, p=0.085) for CIM patientsNo statistically significant advantage in recurrence rate or survival for CIM over WAI. However, the observed differences favor the use of combination CHT in future trials
Reed et al, 2008
(EORTC 55874)42
Open-label, multicenter, phase III RCTStage I–II uterine sarcomas224 (92 ECS)Adjuvant pelvic RT (112 patients) vs observation (112 patients)Local relapse at 6.8 years (whole cohort): 4% (RT) vs 24% (Observation)No difference in either OS or PFS was demonstrated but there was an increased local control for ECS patients receiving radiation
Wright et al, 200843 Multicenter, retrospective studyStage I–II ECS1819RT vs observationAdjuvant RT reduced the risk of death by 21% in women with ECS (HR=0.79; 95% CI, 0.7 to 0.9). RT reduced mortality rates in patients with ECS who had not undergone LND but had only a marginal effect on survival in node-negative womenAdjuvant RT improves survival for select patients with early-stage ECS
Patel et al, 201544 Multicenter, retrospective studyStage I–II ECS1581EBRT vs BRTRT, including BRT alone vs EBRT+BRT, was not significantly associated with OS in both the univariate and multivariate analysis with p=0.153 and p=0.059, respectively.For patients with stages I–II ECS, adjuvant RT did not influence survival after hysterectomy
Manzerova et al, 201645 Multicenter, retrospective studyStage I–IV ECS2342RT vs observationBetter OS and CSS in the RT group: 42 vs 22 (p<0.0001) and 57 vs 28 months (p<0.0001), respectivelyWe observed greater survival rate in the RT group
Cha et al, 201646 Multicenter, retrospective studyStage I–IV ECS97Adjuvant pelvic RT vs observationLocoregional recurrence: 17.5% vs 28.5% (p=0.107).
RT significantly improved the 5-year LRRFS rate of patients who did not undergo PLND (52.7% vs 18.7%; p<0.001).
Adjuvant RT decreased the risk of locoregional recurrence after hysterectomy for ECS, particularly in patients without surgical nodal staging
Stokes et al, 201847 Multicenter, retrospective studyStage I–IV ECS2357EBRT vs BRT vs EBRT+BRT vs observationSurvival was significantly improved among patients receiving EBRT+BRT (HR=0.72, 95% CI, 0.58 to 0.89, p<0.01), but not among those receiving EBRT alone (HR=0.93, 95% CI, 0.79 to 1.10, p=0.41) or BRT alone (HR=0.84, 95% CI, 0.68 to 1.03, p=0.09)EBRT+BRT combination is associated with an overall survival advantage in ECS
Li et al, 201948 Multicenter, retrospective studyStage I–III ECS1069Adjuvant EBRT and/or BRTRT significantly reduced the risk of death and cancer-specific death (HR=0.47 and 0.53, respectively; both p<0.05)Adjuvant RT may provide a survival benefit for ECS
Nama et al, 202049 Multicenter, retrospective studyStage I–IV ECS3706RT vs observationThe use of RT in ECS patients was independently associated with decreased mortality (OR=0.1, 95% CI, 0.02 to 0.6, p<0.005)Primary radiotherapy or combination radiotherapy confers a survival advantage to ECS patients
Chemoradiation (CRT)
Manolitsas et al, 200150 Single-institution, prospective studyStage I–IV ECS38CRT (sandwich approach: cisplatin/epirubicin EBRT/BRT cisplatin/epirubicin) vs observationPFS (median FU: 55 months): 90% vs 47% (p=0.01)In this pilot study, patients with clinical stage I–II ECS who received adjuvant RT and CHT had an excellent survival rate
Makker et al, 200851 Monocentric, retrospective studyStage I–IV ECS49CHT±RT vs RT alone3-year PFS: CHT±RT 35% vs RT 9% for RT alone (HR=1.74, 95% CI, 0.79 to 3.85; p=0.164).
3-year OS: CHT±RT 66% vs RT 34% (HR=2.02, 95% CI, 0.77 to 5.33; p=0.146)
This study corroborates GOG-150 results and shows that paclitaxel–carboplatin appears to be an efficacious adjuvant CHT regimen for completely resected ECS
Tanner et al, 201152 Monocentric, retrospective studyStage III–IV ECS44Adjuvant treatment (CRT or CHT alone) vs observationOS: 30.1 vs 4.7 months (p<0.001)Combined adjuvant treatment was associated with better outcomes than observation
Cantrell et al, 201253 Multicenter, retrospective studyStage I–II ECS111Observation (40%), RT (20%), CHT (25%), CRT (14%)CHT (±RT) significantly improved the PFS (HR=0.28; p=0.003) compared with CHT-free approachesIn women with FIGO stage I–II ECS, adjuvant CHT is associated with improved PFS compared with RT or observation alone
Einstein et al, 201254 Single-institution, phase II prospective studyStage I–IV ECS27Sandwich approach: 3 cycles ifosfamide±cisplatin EBRT (45 Gy) + BRT (5 Gy) 3 more cycles ifosfamide±cisplatin2 year OS: 80.8% (stage I–II); 30.3% (stage III–IV)Ifosfamide ‘sandwiched’ with RT appears to be an efficacious regimen for surgically staged ECS patients with no residual disease, even at advanced stage. The addition of cisplatin to the regimen added toxicity without improving efficacy
Sorbe et al, 201355 Multicenter, retrospective studyStage I–IV ECS322CHT and/or RT or observationThe 5 year LRRFS rate was 63% for patients treated with surgery alone, 68% after addition of adjuvant CHT, 86% after adjuvant RT, and 95% after CRTRT seems to be the most important constituent of the adjuvant therapy
Dickson et al, 201556 Multicenter, retrospective studyStage I–III ECS303 (195 stage I/II, 108 stage III)Observation vs CHT vs CRTStage I/II: Observation was associated with a fourfold increased risk of death compared with CHT (HR=4.48; p=0.003). Patients receiving CRT had significantly improved PFS compared with those receiving CT alone (HR=0.43; p=0.04), but no difference in OS.
Stage III cohort: Observation was associated with worse OS and PFS compared with CHT (OS: HR=2.46, p=0.04; PFS: HR=2.39, p=0.03, respectively). A potential improvement in PFS was seen for those treated with CRT compared with CT alone; however, it was not statistically significant (HR=0.53; p=0.09)
Observation after surgery was associated with poor outcomes in ECS compared with CHT and RT alone. Multimodality therapy for stage I/II disease was associated with improved PFS compared with CHT alone
Rauh-Hain et al, 201557 Multicenter, retrospective studyStage I–IV ECS10 609CHT and/or RT or observationWomen who received CHT only had a median OS of 22 months (95% CI 19 to 23), RT-only group was 32 months (95% CI 30 to 38), in women who underwent CRT was 65 months (95% CI 56 to 77), and in patients who did not received any adjuvant treatment the median OS was 22 months (95% CI 20 to 22)Adjuvant CHT and CRT were associated with improved survival
Gungorduk et al, 201558 Multicenter, retrospective studyStage I–IV ECS66CRT or CHT or RTIn early-stage patients who received CRT, median DFS and OS were 44 months and 55 months, respectively, compared with 34.5 months and 36 months, respectively, in patients who received RT or CT alone (HR=1.4; 95% 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, the median DFS and OS of patients receiving CRT were 25 months and 38 months, respectively, compared with 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 patients with early or advanced stage ECS, adjuvant CHT with RT is associated with improved DFS and OS, as compared with CHT or RT alone
Guttmann et al, 201659 Multicenter, retrospective studyStage I–II ECS118Observation (31%) vs CHT (16%) vs RT (20%) vs CRT (32%)Adjuvant treatment was associated with improved OS (HR=0.74; 95% CI, 0.58 to 0.96; p=0.02), freedom from vaginal recurrence (HR=0.55; 95% CI, 0.37 to 0.82]; p=0.004), and freedom from any recurrence (HR=0.70; 95% CI, 0.54 to 0.92; p=0.01).In women with early-stage uterine ECS, our data suggest superior survival endpoints with combined RT and chemotherapy. The frequency of vaginal recurrence suggests a role for incorporating vaginal brachytherapy in the adjuvant management
Wong et al, 201760 Multicenter, retrospective studyStage I–II ECS4906Observation (36.2%), CHT (19.8%), RT 1060 (21.6%), CRT (22.4%)CRT (HR=0.50; 95% CI, 0.44 to 0.57; p<0.001) and CHT alone (HR=0.78; 95 CI, 0.69 to 0.88; p<0.001) were significantly associated with improved OS, whereas RT alone was notCRT was associated with significantly improved 5-year OS compared with no further therapy, RT alone, or CT alone
Seagle et al, 201761 Multicenter, retrospective studyStage I ECS5614CHT and/or RT or observationMultiagent CHT and VBT were associated with decreased hazard of death (HR=0.62, 95% CI, 0.54 to 0.73), p=1.1×10–9 and HR=0.83, 95% CI 0.70 to 0.97), p=0.02, respectively). Highest 5-year survival was observed after VBT and multiagent CHT (74.1% (68.3–80.3%), p<2.0×10-16)Adjuvant BRT and multiagent CHT is associated with increased survival
Matsuo et al, 201762 Multicenter, retrospective studyStage I ECS443CRT vs RT vs CHTCHT, but not RT, decreased the risk of local (HR=0.46; p=0.01) and distant recurrence (HR=0.41; p<0.001).
The CRT group had a lower 5-year cumulative local-recurrence rate vs CHT (HR=0.46; p=0.22)
Adjuvant CHT appears to be effective to control both local and distant recurrences in stage I ECS. Adding RT to CHT may be effective to control local recurrence when the tumor exhibits multiple risk factors
Versluis et al, 201863 Multicenter, retrospective studyECS1140CRT vs RT vs CHTCRT significantly improved the OS vs CHT (HR=2.49, 95% CI, 1.24 to 4.99; p=0.01) and RT (HR=2.53, 95% CI, 1.29 to 4.97; p=0.007)Adjuvant therapy improves survival when LND is omitted or when nodes are positive
Gunther et al, 201864 Monocentric, retrospective studyStage I–III ECS155CHT and/or RT or observationPatients treated with EBRT had a higher 5-year pelvic disease control rate (88.3%) than patients treated with VBT only (67.4%) or no radiation (71.2%; p=0.04).
In stage III patients, EBRT was associated with higher 5-year pelvic disease control (90.0% vs 55.5%, p=0.046), DSS (64.6% vs 46.4%, p=0.13), and OS (64.6% vs 34.0%, p=0.04)
EBRT improves locoregional control in all stages and may improve survival in stage III patients who are at the highest risk of pelvic relapse
Odei et al, 201865 Multicenter, retrospective studyStage I–IV ECS3538CRT (1751) vs CHT (1787)Median survival for the CHT and CRT groups was 24 months and 31.3 months, respectively. When compared with CHT alone, CRT was associated with a benefit in OS (HR=0.65; p<0.01).When compared with CHT alone, the use of CRT in ECS patients was associated with a significant OS benefit
Shinde et al, 201866 Multicenter, retrospective studyStage IA EC, unfavorable histotype5711 (2,701 ECS)BRT vs observationBRT was associated with increased survival (HR=0.75, 95% CI, 0.65 to 0.87, p=0.001).In stage IA EC of unfavorable histology, the use of BRT was associated with improved survival
Stokes et al, 201847 Multicenter, retrospective studyStage I–IV ECS2357EBRT vs BRT vs EBRT+BRT vs observationSurvival was significantly improved among patients receiving EBRT+BRT (HR=0.72, 95% CI, 0.58 to 0.89, p<0.01), but not among those receiving EBRT alone (HR=0.93, 95% CI, 0.79 to 1.10, p=0.41) or BRT alone (HR=0.84, 95% CI, 0.68 to 1.03, p=0.09)EBRT+BRT combination is associated with an overall survival advantage in ECS.
Kurnit et al, 201967 Monocentric, retrospective studyStage I–II ECS140CHT and/or RT or observationCRT vs observation: for OS, HR=1.01; 95% CI, 0.42 to 2.41; p=0.99; for PFS, HR=0.93; 95%, 0.41–2.09; 0.86No statistically significant differences in terms of survival rates for adjuvant treatment, including CRT, compared with observation.
McEachron et al, 202068 Multicenter, retrospective studyStage I–IV ECS148CRT vs CHT aloneMedian PFS: 15 vs 11 months; 2-year PFS: 22.5% vs 13.6% (p=0.006).
Median OS: 26 vs 20 months; 2-year OS: 50.0% vs 35.6% (p=0.018)
CRT was associated with improvement in both PFS and OS for all staged of ECS compared with CHT alone. Sandwich sequencing was associated with superior OS compared with the alternate sequences.
van Welden et al, 202069 Multicenter, retrospective studyStage IIIC ECS1241 (139 ECS)CRT vs RT vs CHTCRT significantly improved the OS vs CHT (HR=1.84, 95% CI, 1.34 to 2.52; p=0.01) and EBRT alone (HR=1.37, 95% CI, 1.05 to 1.79; p=0.007)In this population-based study, adjuvant EBRT+CT was associated with improved OS compared with CT or EBRT alone in FIGO stage IIIC carcinosarcoma.
Beckmann et al, 202170 Multicenter, retrospective studyStage I–IV ECS66CHT and/or RT or observationDSM was reduced among those who underwent adjuvant CHT (HR=0.39; 95% CI: 0.18 to 0.84) or multimodality treatment (HR=0.11; 95% CI: 0.06 to 0.30)These findings indicate better survival among those who received CHT and multimodal adjuvant therapy, with the latter applying to early and late-stage disease
  • BRT, brachytherapy; CHT, chemotherapy; CIM, cisplatin–ifosfamide and mesna; CRT, chemoradiation therapy; CSS, cancer-specific survival; DFS, disease-free survival; DSM, disease-specific mortality; DSS, disease-specific survival; EBRT, external beam radiotherapy; EC, endometrial cancer; ECS, endometrial carcinosarcoma; FIGO, International Federation of Gynecology and Obstetrics; FU, follow-up; HR, hazard ratio; LND, lymph node dissection; LRRFS, locoregional recurrence-free survival; N, number of participants; OS, overall survival; PFS, progression-free survival; PLND, pelvic lymph node dissection; RCT, randomized clinical trial; RR, relative risk; VBT, vaginal brachytherapy; WAI, whole abdominal irradiation.