Lutetium-177 prostate-specific membrane antigen-617 (177Lu-PSMA-617) improves survival in metastatic castration-resistant prostate cancer, but more optimal tools are needed for therapeutic response assessment and early detection of resistance. We evaluated a quantitative imaging workflow using prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography to measure lesional changes following 177Lu-PSMA-617 therapy. Pre- and post-treatment gallium-68-labeled PSMA-11 PET scans from the trial were analyzed using a novel traffic light workflow (TLW), assessing lesion-specific changes in tumor volume and maximum standardized uptake value in men treated with up to six cycles of 177Lu-PSMA-617 and a radiation sensitizer (NOX66). Lesions were categorized as reducing (30% volume decrease), stable (50% of TTV increasing/new lesions). TLW response classifications were compared with Response Evaluation Criteria in PSMA PET (RECIP) 1.0 and correlated with overall survival (OS). Among 37 men who underwent pre- and post-treatment PET imaging, 68% (25/37) completed six cycles, 32% (12/37) received 25 cycles, and 70% (26/37) had a >50% prostate-specific antigen (PSA) decline. The median PSA progression-free survival (PSA-PFS) was 8.6 months; median OS was 22.0 months. At post-treatment imaging, 54% (20/37) showed progression. TLW classified 24% as responders, 41% as low-volume progressors, and 35% as high-volume progressors. Responders had longer OS than low-volume progressors (median 17.7 vs. 12.0 months) or high-volume progressors (median 7.5 months, p=0.005). RECIP 1.0 classified 24% as partial response, 51% stable disease, and 24% as progressive disease. In summary, TLW shows potential to delineate complex response patterns. Following validation in larger cohorts, TLW will inform therapeutic decision-making.
Pathmanandavel et al. (Tue,) studied this question.