3300 - Local Radiotherapy and ADT Monotherapy for Low-Volume mHSPC: Real-World Outcomes in the Era of PSMA PET-CT Staging

Purpose/Objective(s):

The survival benefit of primary tumor radiotherapy (RT) in low-volume metastatic hormone-sensitive prostate cancer (mHSPC) was established in randomized phase III trials, in which upfront docetaxel and/or androgen receptor pathway inhibitors (ARPI) were frequently utilized. Furthermore, these landmark trials predated the routine use of PSMA PET-CT staging. In clinical practice, many patients defer intensified systemic therapy due to advanced age, comorbidities, or financial constraints. We hypothesize that with more accurately defined volume status by PSMA PET-CT, patients with truly low metastatic burden can achieve durable disease and survival from local radiotherapy with androgen deprivation therapy (ADT) alone.

Materials/Methods: We retrospectively reviewed patients with newly diagnosed low volume mHSPC (CHAARTED criteria) that was PSMA PET-CT staged and treated in one institution from January 2019 to April 2025. All patients received high dose RT to the prostate and ADT monotherapy until biochemical progression (defined as PSA rise of =2ng/mL from nadir), or radiographic progression. RT to bony metastases was permitted. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan Meier method. Univariate and multivariate Cox regression models were utilized to identify prognostic factors for PFS.

Results:

Fifty patients were identified. The most common fractionation was 55 Gy in 20 fractions (n=45, 90%), followed by 72 Gy in 36 fractions (n=4) and 57.5 Gy in 23 fractions (n=1). Nine patients (18%) received concurrent RT to bony metastases. At a median follow-up duration of 27 months, median PFS and OS were not reached. The 2-year PFS and OS were 82% and 96% respectively. On univariate analysis, both high prostate specific antigen (PSA) nadir and high PSA value at 6 months post-RT were significant adverse prognosticators for PFS (p<0.001). On multivariate analysis, a PSA =1ng/mL at 6 months post-RT was a favorable independent prognostic factor (HR 0.1; 95% CI 0.1-0.96, p=0.047). The 2-year PFS of patients with PSA =1ng/mL and > 1ng/mL at 6 months post-RT were 97% and 40% respectively.

Conclusion:

In patients staged with PSMA PET-CT, local RT combined with ADT monotherapy demonstrates favorable PFS and OS for low-volume mHSPC. A PSA threshold of =1.0 ng/mL at 6 months post-RT appears to be a robust prognostic indicator, potentially identifying patients who may safely forego or require intensification of systemic therapy. Longer follow-up is warranted to confirm the durability of these outcomes and the impact on OS.