PSMA PET for the Assessment of Metastatic Hormone-Sensitive Prostate Cancer Volume of Disease

Conventional imaging of low-volume disease (LVD) versus high-volume disease (HVD) is associated with survival in metastatic hormone-sensitive prostate cancer (mHSPC) according to the CHAARTED trial (Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer) and the STAMPEDE trial (Systemic Therapy for Advanced or Metastatic Prostate Cancer: Evaluation of Drug Efficacy). We propose a compatible quantitative PSMA PET framework for disease volume assessment in mHSPC. Methods: Three PET centers screened their PSMA PET database for mHSPC patients. CT versus PSMA PET stage, lesion number, and classification of LVD versus HVD were determined by 1 masked reader; PSMA-positive tumor volume was quantified semiautomatically. Results: In total, 85 CT-based CHAARTED LVD and 20 CT-based CHAARTED HVD patients were included. A PSMA tumor volume of about 40 cm³ was the optimal cutoff between CT-based CHAARTED LVD (nonunifocal) and HVD (non-M1c) (area under the curve, 0.86). Stratification into PET LVD (unifocal or oligometastatic/disseminated, ~40 cm³) and PET HVD (oligometastatic/disseminated $ ~40 cm³ or M1c) had 13% misalignment with the CHAARTED criteria. Conclusion: PSMA PET criteria with volume quantification deliver comparable LVD/HVD discrimination with additional subgroups for unifocal, oligometastatic, and disseminated disease, critical for guidance of targeted or multimodal therapy.