Precision Medicine: The Future of ARPI-PARP Combos and PSMA PET Imaging

At the 2025 American Society of Clinical Oncology Genitourinary Cancers Symposium, a roundtable of expert panelists convened to discuss the latest research and practice updates related to metastatic hormone-sensitive prostate cancer (mHSPC). Dr. Tanya Dorff of City of Hope Comprehensive Cancer Center was joined by Drs. Dan Childs, Andrew Hahn, Cora Sternberg, and Vadim Koshkin in the discussion.

In the fourth part of the roundtable, the panel zooms in on the evolving use of radium, enzalutamide, and other therapeutic agents in prostate cancer, touching on patient preference trials, clinical experiences in different regions, and the impact of combination therapies, including AR pathway inhibitors, PARP inhibitors, and PSMA-targeted treatments, while also debating the utility of PSMA PET scans for disease monitoring and the need for precision medicine in treatment selection.

View the next segment on From Vintage Imaging to Cutting-Edge Trials: The Future of Prostate Cancer Management.

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Dr. Dorff: There was another patient preference trial presented at ESMO last year that examined radium and docetaxel, and it favored radium. I find these patient preference studies particularly interesting as they help guide discussions with patients about different treatment options. Now that we have the PS3 data ending in radium, do we anticipate increased use of radium, or has its use remained consistent?

Dr. Sternberg: Possibly, after that presentation at ESMO. It is interesting because the first trial included only patients with pain and painful bone metastases. In this study, both arms received enzalutamide, which may lead to greater use of radium. I used it more frequently when I was in Italy. However, I am using it less here because we have lutetium and numerous ongoing trials at Cornell.

Dr. Koshkin: In that context, how would you position radium relative to lutetium?

Dr. Sternberg: The challenge is that, in the PEACE trial presented at ESMO, only 2% of patients had received abiraterone. The study compared enzalutamide alone versus enzalutamide with radium in patients who had only received ADT. This treatment approach may be more common in Europe, as it was primarily a European trial. However, even in the United States, 50% of patients receive ADT alone without a doublet, often because they are treated by urologists or in community settings where physicians manage various cancer types.

Dr. Hahn: To be honest, I have not used radium frequently, but that study certainly caught my attention. There has been significant discussion about increasing the use of AR pathway inhibitors in addition to ADT. However, even at a tertiary center like mine, there is still a subset of about 10% of patients for whom I prescribe ADT monotherapy, primarily due to concerns about frailty or the potential harm of additional therapy. I recall a point made to me that these patients might be the ideal candidates for first-line metastatic CRPC treatment with radium plus enzalutamide, particularly in cases of bone-predominant or bone-only disease. Radium is very well tolerated. While it is not a large patient group, I found that to be an intriguing perspective.

Dr. Dorff: If a patient is frail enough that you prefer ADT monotherapy, how do you view the combination studies involving AR pathway inhibitors and PARP inhibitors? Would you consider combination therapy once they develop castration-resistant disease and are still on ADT alone?

Dr. Hahn: If there were a clear reason to prescribe a PARP inhibitor—setting aside TALAPRO-2 for a moment—such as a BRCA1 or BRCA2 mutation, I would likely prioritize the PARP inhibitor rather than adding two agents. I believe the primary benefit in those cases would come from the PARP inhibitor itself.

Dr. Dorff: That is a challenging decision. Both drugs are highly effective, and while there is some thought that patients with HR alterations may not respond as robustly to standard treatments, skipping an AR pathway inhibitor still feels counterintuitive. It is beneficial to have combination therapy as an option, and we did not observe significantly increased toxicity when using combinations versus monotherapy.

Dr. Childs: We are discussing multiple topics here: ADT monotherapy versus ADT with an ARPI, as well as ARPI-PARP combinations in CRPC. I believe our ability to predict which patients will experience toxicity is quite limited. In the ARANOTE study, there were no higher discontinuation rates for darolutamide compared to placebo, which speaks to its excellent tolerability. In my practice, I have started giving patients the benefit of the doubt when deciding on ADT and ARPIs in the hormone-sensitive setting. More than anything else, disease progression impacts quality of life—even in elderly and frail patients—and ARPIs help prevent that.

Regarding ARPI-PARP combinations in CRPC, the situation remains complex. I prefer moving toward precision medicine, rather than away from it, by using these combinations in patients who stand to benefit the most. I am concerned about potential approvals for non-HRR patients. Instead of broadening the indications, we should investigate additional markers of PARP responsiveness within the non-HRR patient group.

Dr. Dorff: PSMA lutetium may soon enter a similar space as a pre-chemotherapy option. Will we start using PET scans, along with genomic data, to tailor treatment decisions? Are you using PET scans to monitor patients as they develop CRPC?

Dr. Sternberg: No. I recently published an article in ASCO News on this topic, and there is no current research supporting the use of PET scans to monitor patients. When I was asked to comment on the use of PET scans for following M1 patients, I reviewed the literature and found no supporting evidence.

Dr. Koshkin: Are you referring specifically to PSMA PET scans?

Dr. Sternberg: Yes, PSMA PET scans.

Dr. Hahn: I agree, Dr. Sternberg. Additionally, if a patient initially had a high PSA and responded well to treatment, a PSMA PET scan may not be the most reliable follow-up tool. When PSA levels drop to zero, the concern shifts to identifying potential disease progression that may not be PSMA-avid. In such cases, a CT scan provides a higher-resolution image and is more effective for detecting radiographic progression.

Patients often question why we do not use PET scans for follow-up, especially when their diagnosis was initially made using PSMA PET. It is understandably distressing for them, but I explain that while PET scans are valuable for initial staging, they may not be the best tool for monitoring treatment response.