Expert Panel Addresses 5 Areas of Need in Metastatic Prostate Cancer

A multidisciplinary panel of experts developed consensus recommendations through the modified Delphi process for metastatic prostate cancer (mPC) management during the 2024 US Prostate Cancer Conference (USPCC 2024). The panel provided guidance in the following 5 areas of need: biochemical recurrence (BCR), metastatic castration-sensitive prostate cancer (mCSPC), PARP inhibitors, prostate-specific membrane antigen (PSMA) radioligand therapy, and metastatic castration-resistant prostate cancer (mCRPC).¹

“There are many shades of gray in clinical management, as we all know, and we have various guidelines that try to help the practicing clinician on how to approach prostate cancer management. However, all those guidelines are based on level 1 evidence, and the reality is that very few of our patients actually fit the exact scenario the guidelines are trying to address,” Alan H. Bryce, MD, chief clinical officer and professor of medical oncology and developmental therapeutics at City of Hope in Phoenix, Arizona, said in an interview with Targeted Therapies in Oncology.

Recommendation Rationale

Current available guidelines from the National Comprehensive Cancer Network, the American Urological Association, the American Society for Radiation Oncology, and the American Society of Clinical Oncology contain guidance based on high-level data, study authors noted.^1-5 “However,” the authors stated, “these guidelines do not address the many nuanced, practical clinical questions that are too narrow or novel to be supported by prospective trial data.” Thus, the consensus recommendations address clinical decision-making guidance for circumstances in which level 1 evidence is lacking.

The Consensus

An adapted version of the consensus recommendations is located on the next page of this article and organized by the 5 categories mentioned.¹

Consensus Methods

Investigators were chosen from different areas of PC care based on location and background, with the goal that at least 10% of them practiced in community settings: medical oncology (n = 21), urology (n = 7), nuclear medicine (n = 4), and radiation oncology (n = 2). During the USPCC 2024 meeting, 33 experts voted on 85 questions, with at least 75% agreement needed for each. These questions were reviewed and updated twice by all experts, who disclosed any conflicts of interest. The authors noted that no one was asked to step out because the large panel size and expertise made it unlikely anyone could unfairly influence results.

“In the Delphi process, questions were written for each of the [5] sections and submitted to the entire faculty. We went through a long process of all the faculty commenting on the questions to ensure we were asking clear questions that address specific problems. There were 2 revisions following the initial questions,” Bryce explained. The process took approximately 6 months and concluded with an in-person meeting where the investigators discussed areas of consensus and disagreement, followed by point-counterpoint debates.

Ongoing Challenges

“I think a main challenge in the field of prostate cancer right now is developing clear guidelines for different genotypes of [the disease],” Bryce explained. “There is tremendous diversity in how patients with prostate cancer progress, and a principal challenge over the next several years is to develop the different treatment paradigms for different genotypes of prostate cancer,” he added.

Next Steps

Noncastrating treatments are being evaluated as patients are hoping for approaches that do not require suppressing testosterone, Bryce said. Although significant progress is being made with bipolar antigen therapy, these treatments still fall short of being truly noncastrating. Radioligand therapy is a promising area of development, offering the potential to target not only PSMA but also other cell surface markers, and using various isotopes beyond lutetium. Current research is exploring the use of alpha emitters and other targets in combination with radioligand therapy.²⁰

“The USPCC is an annual meeting. The third meeting is already being planned, and questions are starting to be written. The 2025 meeting will focus on a different set of new data and unaddressed data. For example, we did not dive deep into biomarkers beyond homologous recombination repair, so there are categories that we will need to dive into as the field changes and data [change],” Bryce concluded.

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