Rethinking Risk: Active Surveillance and Biomarker-Driven Care

Oliver Sartor, MD, director of the Transformational Prostate Cancer Research Center at East Jefferson General Hospital in Metairie, Louisiana, addresses 2 related shifts in recent National Comprehensive Cancer Network guidelines for prostate cancer: the elimination of the "very-low-risk" prostate cancer category and the expanded role of molecular testing across the disease continuum.

Sartor explains that the consolidation of very-low-risk patients into the broader low-risk (Gleason 6) category reflects an evolving clinical acceptance of active surveillance for this group as a whole. He emphasizes that surveillance decisions are inherently nuanced, driven by patient age and comorbidity burden. What is appropriate for a 45-year-old with no significant comorbidities may not be the right approach for a 75-year-old with declining functional status—and the guidelines now better capture this reality by moving away from overly granular risk stratification at the low end of the spectrum.

On the topic of molecular testing and PARP inhibitors, Sartor underscores the significant evolution that clinicians must now incorporate genetic testing for homologous recombination repair (HRR) defects—particularly BRCA1 and BRCA2 mutations—at the time of metastatic hormone-sensitive disease diagnosis, not just in the castration-resistant setting. The AMPLITUDE trial demonstrated the benefit of niraparib in hormone-sensitive patients with these mutations, making earlier testing not just preferable but necessary for appropriate treatment selection.

This represents a meaningful expansion of precision oncology earlier in the prostate cancer treatment pathway, with direct implications for how oncologists approach newly diagnosed metastatic disease. The shift underscores a broader theme in the 2026 guidelines: genetic characterization of a patient's tumor should begin at the outset of advanced disease management, not as an afterthought when earlier lines of therapy have been exhausted.