Michael Cookson, MD, discusses new strategies for treatment intensification in prostate cancer

In this video, which was recorded at the 2025 Society of Urologic Oncology Annual Meeting in Phoenix, Arizona, Michael S. Cookson, MD, MMHC, FACS, a professor and the Donald D. Albers Endowed Chair in Urology at the University of Oklahoma Health Sciences Center in Oklahoma City, highlighted several major advances in prostate cancer care, particularly around treatment intensification and the strategic movement of effective therapies into earlier disease states. One notable trend is the shift of therapies originally reserved for heavily pretreated, castration-resistant prostate cancer into earlier phases of disease, where responses tend to be stronger. Cookson emphasized the example of ¹⁷⁷Lu-PSMA-617 (Pluvicto), initially approved for patients who had failed both hormonal and chemotherapeutic therapies. Newer data from trials such as PSMAfore now support the use of ¹⁷⁷Lu-PSMA-617 before chemotherapy, offering patients the possibility of better outcomes with fewer cumulative toxicities—an especially important consideration for men who are often anemic or frail by the time they reach late-line therapies.

Combination therapy is another emerging area of progress. Advances in germline testing have enabled more precise treatment selection, particularly for patients with inherited genetic mutations. PARP inhibitors, once used only after failure of multiple treatments, are now being incorporated earlier for molecularly selected patients and combined with androgen-receptor pathway inhibitors. These combinations have shown improved responses, reflecting a growing integration of precision medicine into prostate cancer care, though Cookson noted this applies only to a subset of patients.

Earlier intervention in biochemical recurrence is also evolving. Cookson pointed to data from the EMBARK study, which first demonstrated that combining enzalutamide (Xtandi) with leuprolide could significantly delay metastasis compared with leuprolide alone—an endpoint valued for its speed and clinical relevance. With further maturation, the study now shows an overall survival benefit, reinforcing the value of early intensified therapy.

Looking ahead, Cookson anticipates more data on how best to tailor intensification in metastatic castration-sensitive disease, determining when 2-drug or 3-drug approaches are appropriate and when treatment de-escalation can preserve outcomes while minimizing overtreatment.