Local Radiotherapy and Androgen Deprivation Therapy (ADT) Monotherapy for Low-Volume Metastatic Hormone-Sensitive Prostate Cancer: Real-World Outcomes in the Era of PSMA PET-CT Staging

BackgroundRandomized trials established the survival benefit of primary tumor radiotherapy (RT) in low-volume metastatic hormone-sensitive prostate cancer (mHSPC), typically alongside upfront docetaxel or androgen receptor pathway inhibitors (ARPI).However, in real-world practice, systemic intensification is frequently omitted due to age, comorbidities, or cost.In parallel, diagnostic imaging has shifted from conventional CT and bone scan to PSMA PET-CT.We hypothesized that patients with low metastatic burden accurately staged via highly sensitive PSMA PET-CT can achieve durable survival with prostate RT and androgen deprivation therapy (ADT) alone. MethodsWe retrospectively reviewed patients with newly diagnosed, PSMA PET-CT-staged, low-volume mHSPC treated at a single center between January 2019 and April 2025.All received high-dose prostate RT and continuous ADT monotherapy.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. ResultsFifty patients were identified.The most common radiotherapy fractionation was 55 Gy in 20 fractions (n=45, 90%).At a median follow-up duration of 31 months, median PFS and OS were not reached.The two-year OS and PFS were 96% and 82%, respectively.On univariate analysis, favorable prognostic factors included non-T4 stage, low PSA at six months post-RT, PSA <0.2 ng/mL at six months post-RT, and low absolute PSA nadir.PSA <0.2 ng/mL at six months post-RT remained as a significant prognostic factor in multivariate analysis.The two-year PFS for patients achieving a PSA <0.2 ng/mL at six months was higher than those with PSA ≥ 0.2 ng/mL (96% vs. 61%, HR 0.07, 95% CI 0.01-0.57,p=0.013). ConclusionWhile upfront systemic treatment intensification remains the current standard of care for mHSPC, for patients with low-volume disease staged by PSMA PET-CT who cannot receive or tolerate upfront systemic intensification, preliminary data show pairing prostate RT with ADT monotherapy still achieves favorable PFS and OS, and is an explorable alternative that should be validated by prospective studies.A six-month post-RT PSA threshold of <0.2 ng/mL is a significant prognostic factor for PFS and could be explored for its utility in identifying candidates for continued de-escalated therapy versus those requiring timely systemic re-intensification.