Effect of sex on treatment outcomes in rectal cancer patients after neoadjuvant radiotherapy or chemoradiation: A combined analysis of Polish-1 and Polish-2 studies.

Abstract

656 Background: Two independent studies have previously reported the equivalence of short-course radiotherapy (SCRT) and chemoradiation (CRT) in stage II/III rectal cancer patients (Bujko 2006 – Polish-1, Ngan 2012). Recently, in tumors with resection margin at risk (cT4 and fixed cT3), SCRT and chemotherapy when compared with CRT was associated with similar R0 resection rates, but improved overall survival (OS; Polish-2 study; Bujko 2016). The differences in pelvis anatomy and access to surgical field provide the rational for analysis of patients’ sex on treatment outcomes in locally advanced rectal cancers. Methods: We performed individual patients data analysis of Polish-1 (n = 312) and Polish-2 (n = 515) cohorts. The male-to-female ratio was similar in both studies (Polish-1: 65.1%; Polish-2: 65.8%). No major differences in treatment allocation, toxicities, complience to study procedures between males and females were observed. Results: In the combined cohort the prognostic effect of sex on survival was observed (74.5% female and 66.9% of male patients alive at the cut-off time; HR 0.72; p = 0.018). No differences in post-operative mortality were observed with 3-4% of patients dying in 6 months from randomization in each analyzed stratum. When analyzing the treatment outcomes by sex, male patients benefited more from SCRT than CRT. This effect was observed in more advanced tumors from Polish-2 (HR 0.65; 95% CI 0.45-0.95; p = 0.026), while it did not reached the significance in Polish-1 (HR 0.67; 95% CI 0.34-1.33). Conclusions: This individual patients data analysis indicates that female patients with locally advanced rectal has better prognosis than males. This observation is valid either for SCRT or CRT. In the future, rectal cancer studies should be stratified for sex in order to minimize the risk of bias. Although it should be confirmed by other studies, it is very likely that efficancy of SCRT is higher in male patients. Clinical trial information: NCT00833131.