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.

Keywords: Chemotherapy efficacy; Occult extrapelvic metastases; Stage IIIC endometrial cancer; Survival.

Fig. 1

Kaplan–Meier survival estimates for stage IIIC EC. A, Overall survival (P = .06). B, Cause-specific survival (P < .001). C, Disease-free survival (P = .03). EC denotes endometrial carcinoma; G1/2EC, grade 1 and 2 endometrioid EC; G3EC, grade 3 endometrioid and nonendometrioid EC.

Fig. 2

Kaplan–Meier estimates of hematologic, peritoneal, and lymphatic recurrences beyond the radiation field. A, Improved disease-free survival was observed with receipt of chemotherapy in stage IIIC, grade 1/2 endometrioid endometrial carcinoma (P = .02). B, Disease-free survival was unchanged after adjuvant chemotherapy in stage IIIC grade 3 endometrioid and type II endometrial carcinoma combined (P = .91).