Sex and Menopausal Status Do Not Independently Predict Survival in Colorectal Liver Metastases

Background Estrogen has been suggested to influence the development and progression of colorectal cancer, but its role in colorectal liver metastases (CRLM) remains unclear. We sought to explore the prognostic effects of estrogen in CRLM using sex and menopausal status as clinical proxies for endogenous estrogen exposure. Methods Patients diagnosed with metastatic colorectal cancer to the liver between 2004 and 2017 were queried from the National Cancer Database. We performed three analyses to study the effect of estrogen on the overall survival (OS). First, we compared female patients <50 to age-matched males. Second, we compared female patients ≥50 to those <50. Finally, we compared female patients aged <45, 45-55, and >55. The totality of these analyses aimed to isolate sex at a fixed age, and to address age as a confounder. Results Among 29,818 patients with CRLM, there was no difference in survival between pre-menopausal females and similar aged males ( P = .850). Females <50 had a longer median survival (23.7 months) compared with females ≥50 (9.9 months, P < .001). When comparing pre- (<45), peri- (45-55), and post-menopausal (>55) females, we saw post-menopausal females experiencing shorter median survival (9.8 months) compared to pre-menopausal (24.4 months, P < .001) and peri-menopausal females (23.8 months, P < .001). However, there was no difference between pre- and peri-menopausal females ( P = .763). Discussion Sex and menopausal status demonstrated no consistent survival difference among patients with CRLM. These results suggest that neither should be used as an independent prognostic indicator of survival benefit in CRLM.