<p>Recent technological and therapeutic advancements have enabled improvements in both the identification and treatment of patients with oligometastatic hormone-sensitive prostate cancer (omHSPC). Several studies were presented at the <strong>2025 ASTRO Annual Meeting</strong> that investigated the multimodal use of metastasis-directed therapy (MDT) for these patients.</p> <p><br></p> <p><em>Following these presentations, featured expert Amar U. Kishan, MD, was interviewed by </em>Conference Reporter<em> Editor-in-Chief Tom Iarocci, MD. Clinical perspectives from Dr Kishan on these findings are presented here.</em></p>

MDT, specifically stereotactic body radiation therapy (SBRT), has emerged as a tool for prolonging progression-free survival (PFS) in men with recurrent omHSPC based on data from phase 2 randomized trials comparing MDT with observation alone and MDT plus ADT vs MDT alone. Compelling randomized data have also come out from trials in metastatic castration-resistant prostate cancer showing PFS improvements when MDT is added to ARPI therapy.

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The use of prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) in prostate cancer has been an important development that has allowed for the optimal identification of patients for MDT based on its high sensitivity. In the phase 2 ORIOLE trial, patients with recurrent omHSPC who had concordance between PSMA PET/CT and conventional imaging—and, therefore, had all of their lesions treated—experienced PFS improvements, while those with discordance did not do as well. These data tell us that PSMA PET/CT is a useful tool for helping us select patients for MDT, while also suggesting that there may still be existing microscopic disease that we are not seeing.

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At ASTRO 2025, I presented findings from the LUNAR trial, an ongoing, phase 2, randomized trial in patients with recurrent omHSPC characterized by 1 to 5 lesions outside the prostate or prostate bed detected on PSMA PET/CT (abstract 3). In this trial, patients received either 2 cycles of neoadjuvant ¹⁷⁷Lu-PSMA PNT2002 followed by PSMA PET/CT–determined, dose-adapted SBRT or SBRT alone. Our hypothesis for this trial was that most patients with recurrent omHSPC have occult microscopic disease, and so, by adding a PSMA-targeting radioligand therapy (RLT), we could potentially eliminate microscopic disease by using RLT and then macroscopic disease by using SBRT. We chose 2 consecutive cycles of PSMA-targeting RLT to limit potential toxicity and to more clearly define the impact of RLT on microscopic disease before using SBRT. At a median follow-up of 20 months, we saw a significant PFS improvement in the experimental arm compared with the SBRT-only arm (18 months vs 7 months, respectively). To me, the results of the LUNAR study further support our hypothesis that RLT may be acting on microscopic disease.

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Alexander D. Sherry, MD, presented a key late-breaking abstract for the phase 2 EXTEND trial at ASTRO 2025 (abstract LBA 11). This trial leveraged the “basket” design to assess the effect of MDT on various histologies, including pancreatic, breast, kidney, and prostate cancers. Patients received standard of care (SOC) with or without MDT, which, in the prostate cancer cohort, included either intermittent or continuous ADT. Significant PFS improvements were observed in the aggregate population, while results varied in the individual cohorts. SOC plus MDT resulted in PFS improvements in patients with prostate cancer. There were also clear data showing that the addition of MDT to SOC improved T-cell activation. To me, this indicates that there may be a number of factors at play and that the benefit of MDT may also be correlated with this immune activation.

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Kara M. Ruicci, MD, PhD, presented data from the ongoing, phase 2, single-arm RADIANT basket trial in which patients with oligoprogressive prostate cancer who had progressed on systemic therapy were treated with SBRT (abstract 238). The primary end point was cumulative incidence of change in systemic therapy. At 1 year, 55.1% of individuals remained on the same systemic therapy, and local control was 84%. Overall, what we learn from RADIANT is that SBRT can be useful—even in heavily pretreated populations—by maintaining a patient on their current line of systemic therapy. However, thus far, this has only been observed in single-arm studies, and we would benefit from randomized trials that could provide more concrete insights.