Impact of adjuvant therapy on recurrence patterns in stage I uterine carcinosarcoma

Abstract

Background: To examine recurrence patterns in women with stage I uterine carcinosarcoma (UCS) stratified by adjuvant therapy pattern.

Methods: We examined 443 cases of stage I UCS derived from a retrospective cohort of 1192 UCS cases from 26 institutions. Adjuvant therapy patterns after primary hysterectomy-based surgery were correlated to recurrence patterns.

Results: The most common adjuvant therapy was chemotherapy alone (41.5%) followed by chemotherapy/radiotherapy (15.8%) and radiotherapy alone (8.4%). Distant-recurrence was the most common recurrence pattern (5-year cumulative rate, 28.1%) followed by local-recurrence (13.3%). On multivariate analysis, chemotherapy but not radiotherapy remained an independent prognostic factor for decreased risk of local-recurrence (5-year cumulative rates 8.7% versus 19.8%, adjusted-hazard ratio [HR] 0.46, 95% confidence interval [CI] 0.25-0.83, P=0.01) and distant-recurrence (21.2% versus 38.0%, adjusted-HR 0.41, 95%CI 0.27-0.62, P<0.001). The chemotherapy/radiotherapy group had a lower 5-year cumulative local-recurrence rate compared to the chemotherapy alone group but it did not reach statistical significance (5.1% versus 10.1%, adjusted-HR 0.46, 95%CI 0.13-1.58, P=0.22). Radiotherapy significantly decreased local-recurrence when tumors had high-grade carcinoma, sarcoma component dominance, and deep myometrial tumor invasion (all, P<0.05); and combining radiotherapy with chemotherapy was significantly associated with decreased local-recurrence compared to chemotherapy alone in the presence of multiple risk factors (5-year cumulative rates, 2.5% versus 21.8%, HR 0.12, 95%CI 0.02-0.90; P=0.013) but not in none/single factor (P=0.36).

Conclusion: Adjuvant chemotherapy appears to be effective to control both local- and distant-recurrences in stage I UCS; adding radiotherapy to chemotherapy may be effective to control local-recurrence when the tumor exhibits multiple risk factors.

Keywords: Chemotherapy; Radiotherapy; Recurrence; Stage I; Survival outcome; Uterine carcinosarcoma.

Fig. 1.

Study selection schema (N = 1192). *including 2 cases that sarcoma component was not determined. Abbreviations: UCS, uterine carcinosarcoma; hyst, hysterectomy; chemo, chemotherapy alone; and RT, radiotherapy alone.

Fig. 2.

Disease-free survival of uterine carcinosarcoma (n = 443). Log-rank test for P-values. Survival curves are shown for A) disease-free survival, B) overall survival, C) cumulative incidence for local recurrence in the pelvis with or without the vaginal cuff, D) cumulative incidence for distant recurrence in outside the pelvis, E) cumulative incidence for local recurrence among cases with 0–1 risk factor, and F) cumulative incidence for local recurrence among cases with 2–3 risk factors. Risk factors: high-grade carcinoma, > 50% myometrial tumor invasion, and sarcoma dominance. Abbreviations: chemo, chemotherapy; and RT, radiotherapy.