Evaluating the impact of single vs. combination therapy on survival outcomes in mHSPC patients stratified by BMI.

187 Background: Metastatic hormone sensitive prostate cancer (mHSPC) is a heterogenous disease with a variety of treatment options. De novo mHSPC can be treated with androgen deprivation therapy (ADT) monotherapy or combinations including docetaxel or androgen receptor pathway inhibitors. Body mass index (BMI) is known to be associated with survival, but there is little data to show the effectiveness of treatment intensity (single or combination therapy) based on BMI. Methods: Patients treated for mHSPC within the Veterans Health Affairs from 2017-2023 were included. BMI was assessed using height and weight at diagnosis and treatment intensity was determined by treatments within 4 months of start of ADT. Additional baseline characteristics for each group included age, prostate specific antigen (PSA), and Charlson Comorbidity Index (CCI). Survival was estimated using the Kaplan-Meier method and Cox proportion hazard modeling was used to account for known covariates. Results: There were 4184 veterans identified with 33.5% BMI <25, 35% BMI 25-30, and 31.5% with BMI >30. The BMI 25-30 group had longer survival compared to BMI of <25 (37.3 vs. 30.7 months, HR 0.78 95% CI 0.71-0.86) and the BMI >30 had longer survival compared to BMI 25-30 (42.5 vs. 37.3 months, HR 0.87 95% CI 0.79-0.96). In patients with BMI of <25 combination therapy was associated with longer survival (HR 0.73 (0.63-0.83)) and in patients with BMI of 25-30, combination therapy was also associated with longer survival 0.76 (0.67-0.88). However, in patients with BMI >30, there was no difference in overall survival based on combination or monotherapy (HR 0.97 (0.83-1.13)). In a multivariable model including age, PSA, CCI, and treatment intensity, BMI >30 and BMI 25-30 was associated with decreased risk of death compared to BMI <25, aHR 0.80 (95% CI 0.72-0.89) and aHR 0.89 (95% CI 0.81-0.98) respectively. Conclusions: In patients with mHSPC, higher BMI is associated with longer survival compared to lower BMI. In all patients, combination therapy was associated with longer survival, however, there was no difference in survival with combination therapy compared to monotherapy in patients with BMI >30. Future studies could investigate the reason why combination therapy is only associated with benefit in patients with BMI <30. BMI (kg/m 2 ) <25 n=1403 25-30 n=1465 >30 n=1316 P value (ANOVA) Age (mean years) 76.2 74.4 71.8 p<0.001 PSA (median ng/mL) 177 91.6 61.25 p<0.001 Overall Survival (median months) 30.7 37.3 42.5 p<0.001 ADT monotherapy 26.9 (n=736) 33.1 (n=683) 42.5 (n=582) Combination therapy 36.3 (n=667) 41.5 (n=782) 42.6 (n=734) HR (95% CI) 0.73 (0.63-0.83) 0.76 (0.67-0.88) 0.97 (0.83-1.13)