Translating Guideline Updates to Clinical Practice: What's New and Why It Matters

The National Comprehensive Cancer Network Practice Guidelines for prostate cancer reflect a rapidly evolving treatment landscape shaped by recent FDA approvals and emerging clinical data. Oliver Sartor, MD, director of the Transformational Prostate Cancer Research Center at East Jefferson General Hospital in Metairie, Louisiana, highlights 2 headline updates with significant implications for clinical practice.

First, the guidelines now incorporate radiopharmaceuticals—specifically lutetium-177 PSMA-617—for taxane-naive metastatic castration-resistant prostate cancer (mCRPC), building on the VISION trial, and more recently, the PSMAfore trial. This marks a meaningful advancement in the therapeutic sequence for patients who have not yet received a taxane.

Sartor also notes a pivotal expansion in precision medicine: PARP inhibitors are now incorporated into the hormone-sensitive metastatic space for patients with BRCA1 or BRCA2 mutations. This is a significant shift from prior guidelines, which limited PARP inhibitor use to the castration-resistant setting.

Sartor also contextualizes the evolution of mCRPC management within the broader disease continuum. With androgen receptor pathway inhibitors (ARPIs)—including abiraterone, enzalutamide, apalutamide, and darolutamide—now widely established in the frontline hormone-sensitive space, the castration-resistant treatment landscape has been fundamentally reshaped. He notes the addition of darolutamide (based on the ARANOTE trial) as an exceptionally well-tolerated option with minimal drug interactions. The way patients are treated early in their disease course now has direct downstream implications for how clinicians will sequence therapies in the castration-resistant phase.