Managing PSMA-PET–Positive Oligometastatic Prostate Cancer

In a clinical landscape increasingly shaped by advanced imaging, the management of patients with rising prostate-specific antigen (PSA) levels and negative conventional imaging, but PSMA-PET–positive oligometastatic disease, has become a daily reality. Oliver Sartor, MD, who spoke at the 19th Annual New York GU Cancers Congress®, estimated that approximately 750,000 patients in the US currently fall into this category. To him, resolving the discrepancies between traditional and molecular imaging requires a nuanced, patient-centric approach that balances targeted intervention with systemic considerations.

Current management strategies often center on stereotactic body radiation therapy (SBRT) directed at all detectable lesions. However, Sartor emphasized that treatment escalation, such as the addition of hormonal therapy or enrollment in clinical trials, depends heavily on factors like PSA doubling time, lesion location, and patient preference. For instance, the phase 3 PSMA-DC trial (NCT05939414) is exploring the synergy of SBRT with lutetium-177 vipivotide tetraxetan (Pluvicto) for those with a PSA doubling time of 10 months or less. When nodal involvement is present, clinical teams may also expand radiation fields to encompass entire nodal groups. Ultimately, the transition from conventional to PSMA-PET–guided care necessitates a sophisticated strategy aiming for precise disease eradication while avoiding the unnecessary adverse effects of over-treatment.

Transcript:

The biochemical recurrent patient with PSMA-PET–positive disease is seen every day in the clinic. It's an extremely common scenario; [there are] probably 750,000 patients like this across the US. We manage oligometastatic disease by consideration of SBRT to all available lesions. Maybe we will consider the possibility of adding in hormonal therapy. Maybe we will consider the possibility of a protocol…and maybe we will consider the possibility of using some type of alternative to hormonal therapy. It depends on the patients, their circumstances, and the location of the lesions and the number of lesions.

There's a bit of complexity here. I mentioned the protocol called PSMA-DC. For those with oligometastatic disease for whom all the lesions can be radiated with SBRT, we have a randomization between SBRT alone and the SBRT plus/minus the lutetium-177. That is a protocol sponsored by Novartis, a phase 3 protocol. That's a nice protocol for these patients. But it does require PSA doubling time that is of a certain type. That can be important when PSA doubling time is 10 months or less.

Whether or not we add in hormonal therapy depends, in part, on patient preferences. Whether or not we add a little more radiation beyond SBRT is dependent on what nodal group might be involved. With nodal groups, we try to encompass the entire nodal group with a boost to PSMA-PET–positive lesions. There's a lot of complexity in making that decision. The bottom line is we see these patients every day and we try to [treat] them in a [patient-centric] fashion.

Reference

Sartor AO, Kiess AP, Feng FY, et al. PSMA-delay castration (DC): an open-label, multicenter, randomized phase 3 study of [177Lu]Lu-PSMA-617 versus observation in patients with metachronous PSMA-positive oligometastatic prostate cancer (OMPC). J Clin Oncol. 2025;43(suppl 16):TPS5127. doi:10.1200/JCO.2025.43.16_suppl.TPS5127