Dr Gleave on Selecting Patients for Perioperative Therapy in High-Risk Prostate Cancer

“The problem with surgery alone in patients with high-risk prostate cancer is that positive margin rates are high [and] recurrence rates are high.”

Martin Gleave, MD, FRCSC, FACS, a distinguished professor in the Department of Urologic Sciences at the University of British Columbia, discussed patient selection and the rationale for combining systemic therapy with surgery in high-risk localized prostate cancer.

Gleave described surgery and radiation as standard treatment options for these patients, explaining that radiation was generally combined with androgen deprivation therapy (ADT), with an androgen receptor pathway inhibitor also considered according to risk. For patients undergoing surgery, he highlighted the possibility of subsequent salvage treatment if recurrence emerged.

He described early identification of recurrence, staging with prostate-specific membrane antigen PET imaging, and treatment with salvage approaches that could include hormonal therapy and radiation. Gleave compared this integration of surgery and subsequent treatment with approaches used in breast, lung, colorectal, and other cancers.

However, Gleave emphasized that surgery alone remains associated with substantial recurrence risk and positive surgical margin rates in high-risk disease. He outlined the rationale for introducing an active systemic treatment to induce tumor regression, improve resectability, and potentially increase the likelihood of cure when combined with surgery.

Patient selection is central to this strategy, he explained. Drawing on lessons from trials conducted over several decades, Gleave described the challenge of identifying a population in which additional treatment could demonstrate benefit.

Patients at the lower end of the high-risk spectrum could have sufficiently low failure rates after surgery that detecting an improvement became difficult, he noted. Conversely, he cautioned that selecting patients with excessively advanced or aggressive disease could mean operating on individuals who were not appropriate surgical candidates.

Therefore, Gleave emphasized patients with high-volume, high-grade disease that remained potentially resectable and curable. His discussion distinguished this group from both patients with less aggressive disease and those whose disease characteristics made surgery unsuitable.

Within that selected population, Gleave highlighted combining surgery with an active systemic regimen, including ADT and apalutamide (Erleada). He described the potential to induce regression, lower the risk of positive margins, address subclinical metastases, and reduce or delay subsequent metastatic progression.

Gleave framed these goals around identifying patients with recurrence risk who nevertheless retained an opportunity for curative surgery.