Outcomes of radical radiotherapy in de novo low-burden metastatic hormone-sensitive prostate cancer vs prostate radiotherapy alone.

Abstract

5097 Background: The current standard of care (SoC) for metastatic hormone-sensitive prostate cancer (mHSPC) is androgen deprivation + systemic therapy. Oligometastatic HSPC, however, represents a unique disease entity following the STAMPEDE trial, where de novo mHSPC patients with a CHAARTED-defined low disease burden (DN-mHSPC-LV) had a hazard ratio of death of 0.68 after prostate radiotherapy (PRT). Despite the SABR-COMET results of a survival benefit with stereotactic RT on metachronous oligometastatic sites of predominantly prostate patients, radical RT (RRT) in the DN-mHSPC-LV setting has not been studied. This study analysed the outcomes of such patients receiving RRT to all disease sites vs PRT alone. Methods: DN-mHSPC-LV patients receiving RRT to the prostate and all oligometastatic sites (Arm A) vs PRT alone (Arm B) in a Hong Kong tertiary hospital between 1 st January 2012 and 1 st January 2023 were reviewed. Outcomes of progression-free survival (PFS), overall survival (OS) and treatment-related toxicity (TrT) were analysed using the Kaplan-Meier and multivariable Cox-proportional hazards models. Results: 127 eligible patients (60 in Arm A & 67 in Arm B) were identified. The median numbers of oligometastatic sites of 1-3 and = > 4 were balanced between the two arms. The median Gleason score was 8 in both arms. Median T/N/M staging was mostly balanced but more patients in Arm B had N1 disease. Presenting PSA (ng/mL) was higher in Arm A (38.5) than Arm B (27.9). Arm A received up to 76Gy/38# to the prostate + a boost of up to 67.5Gy or stereotactic RT to the oligometastatic sites. Arm B received 55-60Gy/20# to the prostate alone. Patients were started on long-term androgen deprivation therapy. Median follow-up was 40.2 months and 30.3 months in Arms A and B, respectively. Median PFS was not reached (NR) in either of the treatment arms. On multivariate analysis, 5-year PFS was 86.1% vs 50.3% in Arms A and B, respectively ( P = 0.0173; HR 0.213; 95% CI 0.059-0.761). OS data were not yet mature and there was no difference in TrT between the arms. Conclusions: To our knowledge, this is the first study comparing radical RT against the SoC of prostate RT alone in DN-mHSPC-LV. Radical RT was well tolerated and is significantly cheaper than next-generation hormone agents in prostate cancer. 5-year PFS was significantly better with radical RT vs prostate RT alone. PFS is an established surrogate for OS in prostate cancer. This study therefore justifies prospective studies on RRT for DN-mHSPC-LV. More importantly, as prospective trials with an OS endpoint in prostate cancer will take close to a decade to mature, this study provides interim evidence to support radical treatment in this group of patients, in whom cure or long-term control may be achieved, where prospective trials are anticipated to take much longer to complete.