Text

Introduction: Local treatment (LT) to the prostate demonstrated better cancer-control outcomes in combination with androgen deprivation therapy (ADT) monotherapy for 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.

Method: Relying on the multicentric international ARON-3 database, de novo low-volume mHSPC patients undergoing ARPI treatment were selected. Stratification was made according to LT vs. no LT with primary endpoint of time-on-treatment (ToT) and overall survival (OS).

Results: Of 454 de novo low-volume mHSPC patients, LT was administered in addition to ARPI in 18%. In the 6-month landmark cohort, ToT was longer in patients who received additional LT, although the association did not reach statistical significance (HR 0.54, 95% CI 0.27–1.10, p=0.088). The RMST at 36 months reported a difference of 2.76 months (95% CI 0.32–6.58, p = 0.031) in the LT group compared 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 months reported a difference of 4.67 months (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 in ToT and OS.

Conclusion: The current study suggests that adding LT to ARPIs in patients with de novo low-volume mHSPC patients may be associated with 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 disease.