Utility of metastasis-directed radiotherapy with and without hormonal therapy in management of oligometastatic prostate cancer

JNCI Cancer Spectr. 2025 Nov 3;9(6):pkaf096. doi: 10.1093/jncics/pkaf096.

Abstract

Background: Metastasis-directed radiotherapy (MDT) is the mainstay in management of oligometastatic prostate cancer (PCa), and PSMA-PET is currently the most sensitive imaging modality for localizing PCa metastases. The efficacy of MDT guided by PSMA-PET imaging with and without androgen deprivation therapy (ADT) ± androgen-receptor pathway inhibitor (ARPI) has not yet been well characterized. We sought to evaluate the efficacy of PSMA PET-guided MDT.

Methods: This is a single-institutional retrospective study of patients diagnosed with metastatic PCa by PSMA-PET imaging who were treated with MDT. Survival analyses were performed using the Kaplan-Meier method with Cox proportional hazards testing for significance. Cumulative incidence analyses were performed with Gray's testing for significance.

Results: One hundred and ninety-four metastatic lesions from 101 patients identified by PSMA PET were irradiated with MDT. Forty-seven of the 79 (59%) patients with hormone-sensitive PCa (HSPC) received ADT ± ARPI along with MDT. Four of 194 lesions (2.1%) demonstrated radiographic progression after MDT, with a median follow-up of 22.4 months. Two-year cumulative incidence of progression from HSPC to CRPC was 11% in patients who received ADT ± ARPI and 35% in those who did not (P = .027). Median biochemical progression free survival of patients with CRPC, HSPC treated without ADT or ARPI, and HSPC treated with ADT ± ARPI was 5.4, 7.6, and 43.9 months, respectively (P < .0001). No Grade 3-5 adverse effects were observed.

Conclusions: MDT guided by PSMA-PET imaging is well-tolerated and delays biochemical progression in patients with CRPC and HSPC, with a greater effect observed in patients also receiving ADT ± ARPI.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Androgen Antagonists* / therapeutic use
  • Glutamate Carboxypeptidase II
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Positron-Emission Tomography / methods
  • Proportional Hazards Models
  • Prostate-Specific Antigen / blood
  • Prostatic Neoplasms* / diagnostic imaging
  • Prostatic Neoplasms* / drug therapy
  • Prostatic Neoplasms* / mortality
  • Prostatic Neoplasms* / pathology
  • Prostatic Neoplasms* / radiotherapy
  • Radiotherapy, Image-Guided* / methods
  • Retrospective Studies

Substances

  • Androgen Antagonists
  • Prostate-Specific Antigen
  • Glutamate Carboxypeptidase II