Role of Local Treatment to the Prostate in Patients With de Novo Low-volume Metastatic Hormone-sensitive Prostate Cancer Receiving Androgen Receptor Pathway Inhibitors

Background and objective: Local treatment (LT) to the prostate demonstrated better cancer-control outcomes in combination with androgen deprivation therapy (ADT) monotherapy for patients with low-volume metastatic hormone sensitive prostate cancer (mHSPC). However, the association of LT with outcomes in patients receiving ADT plus androgen receptor pathway inhibitors (ARPI) across different mHSPC subtypes is under debate. Methods: Relying on the multicentric international ARON-3 database, patients with de novo low-volume mHSPC undergoing ARPI treatment were selected. Stratification was made according to LT vs. no LT with the primary endpoint of time on treatment (ToT) and overall survival (OS). Key findings and limitations: Of 454 patients with de novo low-volume mHSPC, LT was administered in addition to ARPI in 18%. In the 6-mo landmark cohort, ToT was longer in patients who received additional LT, although the association did not reach statistical significance (hazard ratio [HR]: 0.54, 95% confidence interval [CI]: 0.27–1.10, p = 0.088). The restricted mean survival time (RMST) at 36 mo reported a difference of 2.76 mo (95% CI: 0.32–6.58, p = 0.031) in the LT group compared with the no-LT group. OS was significantly longer in patients receiving ARPI and LT compared with ARPI alone (HR: 0.09, 95% CI: 0.01–0.64, p = 0.016). The RMST at 36 mo reported a difference of 4.67 mo (95% CI: 3.18-6.17, p < 0.001) in favor of the LT group. In the ridge regression, LT remained the only statistically significant predictor of ToT and OS. Conclusions and clinical implications: The current study suggests that adding LT to ARPIs in patients with de novo low-volume mHSPC may be associated with improved ToT and OS. The addition of LT to ARPI as the backbone of therapy may be considered in patients presenting with de novo low-volume mHSPC.