Most relevant studies investigating the adjuvant treatment for endometrial carcinosarcoma
| Author, year | Design | Setting | N | Treatment | Results | Conclusion |
| Radiotherapy (RT) | ||||||
| Gerszten et al, 199838 | Monocentric, retrospective study | Stage I–IV ECS | 60 | RT vs observation | RR 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 study | Stage I–III ECS | 50 | RT vs observation | 5 year OS, disease-specific survival, local control, and distant control were: 52.9, 57.5, 83.4, and 70.8%, respectively | Adjuvant RT improves local control and disease specific survival in the treatment of ECS |
| Callister et al, 200440 | Monocentric, retrospective study | Stage I–III ECS | 300 | RT vs observation | Pelvic 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 RCT | Stage I–IV ECS | 206 | Arm 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 patients | No 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 RCT | Stage I–II uterine sarcomas | 224 (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 study | Stage I–II ECS | 1819 | RT vs observation | Adjuvant 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 women | Adjuvant RT improves survival for select patients with early-stage ECS |
| Patel et al, 201544 | Multicenter, retrospective study | Stage I–II ECS | 1581 | EBRT vs BRT | RT, 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 study | Stage I–IV ECS | 2342 | RT vs observation | Better OS and CSS in the RT group: 42 vs 22 (p<0.0001) and 57 vs 28 months (p<0.0001), respectively | We observed greater survival rate in the RT group |
| Cha et al, 201646 | Multicenter, retrospective study | Stage I–IV ECS | 97 | Adjuvant pelvic RT vs observation | Locoregional 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 study | Stage I–IV ECS | 2357 | EBRT vs BRT vs EBRT+BRT vs observation | Survival 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 study | Stage I–III ECS | 1069 | Adjuvant EBRT and/or BRT | RT 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 study | Stage I–IV ECS | 3706 | RT vs observation | The 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 study | Stage I–IV ECS | 38 | CRT (sandwich approach: cisplatin/epirubicin → EBRT/BRT → cisplatin/epirubicin) vs observation | PFS (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 study | Stage I–IV ECS | 49 | CHT±RT vs RT alone | 3-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 study | Stage III–IV ECS | 44 | Adjuvant treatment (CRT or CHT alone) vs observation | OS: 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 study | Stage I–II ECS | 111 | Observation (40%), RT (20%), CHT (25%), CRT (14%) | CHT (±RT) significantly improved the PFS (HR=0.28; p=0.003) compared with CHT-free approaches | In 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 study | Stage I–IV ECS | 27 | Sandwich approach: 3 cycles ifosfamide±cisplatin → EBRT (45 Gy) + BRT (5 Gy)→ 3 more cycles ifosfamide±cisplatin | 2 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 study | Stage I–IV ECS | 322 | CHT and/or RT or observation | The 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 CRT | RT seems to be the most important constituent of the adjuvant therapy |
| Dickson et al, 201556 | Multicenter, retrospective study | Stage I–III ECS | 303 (195 stage I/II, 108 stage III) | Observation vs CHT vs CRT | Stage 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 study | Stage I–IV ECS | 10 609 | CHT and/or RT or observation | Women 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 study | Stage I–IV ECS | 66 | CRT or CHT or RT | In 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 study | Stage I–II ECS | 118 | Observation (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 study | Stage I–II ECS | 4906 | Observation (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 not | CRT was associated with significantly improved 5-year OS compared with no further therapy, RT alone, or CT alone |
| Seagle et al, 201761 | Multicenter, retrospective study | Stage I ECS | 5614 | CHT and/or RT or observation | Multiagent 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 study | Stage I ECS | 443 | CRT vs RT vs CHT | CHT, 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 study | ECS | 1140 | CRT vs RT vs CHT | CRT 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 study | Stage I–III ECS | 155 | CHT and/or RT or observation | Patients 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 study | Stage I–IV ECS | 3538 | CRT (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 study | Stage IA EC, unfavorable histotype | 5711 (2,701 ECS) | BRT vs observation | BRT 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 study | Stage I–IV ECS | 2357 | EBRT vs BRT vs EBRT+BRT vs observation | Survival 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 study | Stage I–II ECS | 140 | CHT and/or RT or observation | CRT 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; 0.86 | No statistically significant differences in terms of survival rates for adjuvant treatment, including CRT, compared with observation. |
| McEachron et al, 202068 | Multicenter, retrospective study | Stage I–IV ECS | 148 | CRT vs CHT alone | Median 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 study | Stage IIIC ECS | 1241 (139 ECS) | CRT vs RT vs CHT | CRT 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 study | Stage I–IV ECS | 66 | CHT and/or RT or observation | DSM 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.