Tumor-specific outcome of metachronous uterine malignancy after pelvic irradiation for cervical cancer

Objective. To examine survival of women who develop metachronous uterine malignancy after definitive pelvic radiotherapy for cervical cancer. Methods. This retrospective observational study examined the Surveillance, Epidemiology, End Results Program between 1973 and 2013. Women with cervical cancer who received definitive radiotherapy without hysterectomy were examined for the diagnosis of metachronous uterine malignancy (n = 5277). Survival was compared between metachronous and non-metachronous uterine malignancies according to tumor factors. Results. The 10- and 20-year cumulative incidences of metachronous uterine malignancy were 0.6% and 1.2%, respectively. When compared to non-metachronous uterine malignancy, metachronous tumor were more likely to be non-endometrioid and advanced-stage (both, P < 0.001). As a whole cohort, metachronous uterine malignancy was significantly associated with decreased overall survival (OS) compared to non-metachronous tumors (hazard ratio [HR] 4.22, P < 0.001). OS was significantly worse in metachronous compared to non-metachronous malignancies, although the magnitude of statistical significance was greater for endometrioid tumors (I-IRs for endometrioid versus non-endometrioid: 6.17 versus 1.92). For grade 1-2 endometrial cancer, metachronous cases had significantly decreased OS compared to non-metachronous cases, a larger difference than that seen in higher grade tumors (HRs for grade 1-2 versus 3: 7.79 versus 2.15). Similarly, in early-stage endometrial cancer, metachronous cases had significantly decreased OS, with a greater HR compared to advanced-stage disease (HRs for stage I-II versus III-IV 5.29 versus 2.29). Conclusion. Radiotherapy-associated metachronous uterine malignancy after cervical cancer is rare but commonly presents with aggressive tumor characteristics. The impact on survival is considerably high when metachronous uterine malignancy is endometrioid, low-grade, and early-stage. (C) 2018 Elsevier Inc. All rights reserved.