Efficacy of contemporary chemotherapy in stage IIIC endometrial cancer: A histologic dichotomy

Abstract

Background Treatment failures in stage IIIC endometrial carcinoma (EC) are predominantly due to occult extrapelvic metastases (EPM). The impact of chemotherapy on occult EPM was investigated according to grade (G), G1/2EC vs G3EC. Methods All surgical-stage IIIC EC cases from January 1, 1999, through December 31, 2008, from Mayo Clinic were included. Patient-, disease-, and treatment-specific risk factors were assessed for association with overall survival, cause-specific survival, and extrapelvic disease-free survival (DFS) using Cox proportional hazards regression. Results 109 cases met criteria, with 92 (84%) having systematic lymphadenectomy (>10 pelvic and >5 paraaortic lymph nodes resected). In patients with documented recurrence sites, occult EPM accounted for 88%. Among G1/2EC cases (n = 48), the sole independent predictor of extrapelvic DFS was grade 2 histology (hazard ratio [HR], 0.28; 95% CI, 0.08–0.91; P = .03) while receipt of adjuvant chemotherapy approached significance (HR 0.13; 95% CI, 0.02, 1.01; P = .0511). The 5-year extrapelvic DFS with and without adjuvant chemotherapy was 93% and 54%, respectively (log-rank, P = .02). Among G3EC (n = 61), the sole independent predictor of extrapelvic DFS was lymphovascular space involvement (HR, 2.63; 95% CI, 1.16–5.97; P = .02). Adjuvant chemotherapy did not affect occult EPM in G3EC; the 5-year extrapelvic DFS for G3EC with and without adjuvant chemotherapy was 43% and 42%, respectively (log-rank, P = .91). Conclusions Chemotherapy improves extrapelvic DFS for stage IIIC G1/2EC but not stage IIIC G3EC. Future efforts should focus on prospectively assessing the impact of chemotherapy on DFS in G3EC and developing innovative phase I and II trials of novel systemic therapies for advanced G3EC.

Chemotherapy Reduces Para-aortic Node Recurrences in Endometrial Cancer With Positive Pelvic and Unknown Para-aortic Nodes

“…28 In addition, a recent publication from the Mayo Clinic Endometrial Cancer Study Group suggested that chemotherapy improves survival in node-positive grades 1 and 2 endometrioid EC. 29 Another important aspect that the present study underlines is that patients with endometrioid EC had a high prevalence of PANR (5/36 [14%]), whereas no PANRs were detected among nonendometrioid EC (0/17 [0%]). Although our data are preliminary and needed to be confirmed in a large population, this feature is highly relevant.…”

Clinical Outcome of Patients With High-Risk Endometrial Carcinoma After Treatment With Chemotherapy Only

“…19 There are evolving data on the molecular subtypes of EC underlining the heterogeneity and overlapping profiles in types I and II EC. Copy-number-high tumors have been pointed out as a group with high prevalence of p53 mutation and poor prognosis in several data sets.…”

Staging for endometrial cancer: The controversy around lymphadenectomy – Can this be resolved?

“…Since approximately half of patients where stage III because of metastatic LN (FIGO 1988 Stage IIIC), these results constitute a strong argument for adequate systematic surgical staging (including LN assessment) and justify to deliver chemotherapy in patients with metastatic LN 20,93,95 . This study is pivotal since it showed for the first time that EC is a chemosensitive …”