Retesting Strategies and PSMA PET Selection in Advanced Prostate Cancer

The panelists outline when to retest patients with prostate cancer, since tumors evolve under treatment and a first genomic test is only a snapshot. Triggers include acquired RB1, TP53, or androgen receptor alterations; possible neuroendocrine transformation; prior tests limited by low tumor shedding, such as circulating tumor DNA drawn after starting androgen deprivation therapy; clinical trial screening; and discordant progression, such as enlarging lymph nodes without a proportional prostate-specific antigen rise. The discussion then turns to prostate-specific membrane antigen (PSMA) PET for selecting patients for lutetium Lu 177 vipivotide tetraxetan in castration-resistant and hormone-sensitive disease. Because trial selection criteria were designed for visual inspection, clinicians relying on outside reports need standardized reporting of liver and lesion uptake, since greater avidity predicts greater benefit. The panelists review new consensus definitions of progression on PSMA PET, caution that a few new lesions amid overall response may represent flare, and anticipate artificial intelligence-assisted reads.