Association of Weight Loss and BMI on PSA Levels and Overall Survival in Veterans With Metastatic Castrate-Resistant Prostate Cancer.

Background: There is a complex relationship between body weight and survival in prostate cancer. While increased BMI is associated with increased prostate cancer incidence and death, obesity is associated with improved survival in metastatic castrate-resistant prostate cancer (mCRPC). However, little is known about the effect of weight change before the treatment of mCRPC on survival. We assessed the association between BMI, weight loss before treatment, PSA levels, and overall survival in mCRPC.

Methods: Veterans treated with abiraterone or enzalutamide for de novo mCRPC from May 2011 to June 2017 were identified within the VHA. BMI and weight loss in the year before treatment were determined. Kruskal-Wallis, χ² tests, ANOVA, Kaplan-Meier, and Cox proportional hazard modeling tests were used to assess the association between BMI, weight loss, PSA at the start of treatment, and overall survival, with covariates including age, race, and Charlson Comorbidity Index.

Results: We identified 8857 veterans treated for mCRPC with weight loss values available and 8438 patients with BMI values available. There was shorter survival in veterans with weight loss > 10% of body weight (median = 9.8 months, n = 1332) compared with 5%-10% loss (median = 16.1 months, n = 1619) and stable weight (median = 25.1 months, n = 5906). Mean PSA levels increased (106.3, 160.0, 267.8) as BMI decreased (BMI > 30, BMI 25-30, BMI < 25), respectively. As weight loss increased (stable weight vs. weight loss 5%-10% vs. weight loss > 10%), mean PSA levels increased (112.2, 205.8, 405.9), respectively. Compared with a stable weight, both losing 5%-10% of weight (HR: 1.30, 95% CI: 1.22-1.38) and losing > 10% of weight (HR: 1.98, 95% CI: 1.85-2.12) are independently associated with increased mortality. Analyses in subgroups revealed BMI > 30 with stable weight to be the most favorable group in terms of survival, while BMI < 25 with > 10% weight loss had the highest mortality risk (HR: 2.63, 95% CI: 2.39-2.89).

Conclusion: Weight loss the year before treatment is associated with increased mortality and higher PSA levels in patients with mCRPC. The effect of weight loss is independent of BMI, where we found that lower BMI is associated with increased mortality and higher PSA levels in patients with mCRPC. This risk increases with the magnitude of weight loss, with lower BMI categories compounding the risk. Both weight loss and BMI should be incorporated into survival models to improve prognostication in mCRPC.