Prognostic value of baseline PSMA PET/CT for survival in synchronous metastatic hormone-sensitive prostate cancer: towards redefining low- and high-volume disease.

BACKGROUND: Traditional metastatic burden classifications in metastatic hormone-sensitive prostate cancer (mHSPC) rely on conventional imaging using CHAARTED criteria. As PSMA PET/CT is increasingly used for staging, revised definitions of low-volume (LVD) and high-volume disease (HVD) are needed to guide treatment decisions. MATERIALS AND METHODS: This study included 204 patients with synchronous mHSPC staged with PSMA PET/CT between 2017 and 2023. As part of standard clinical practice, patients were prospectively classified as LVD or HVD by a multidisciplinary team (MDT) consensus. Retrospective analysis collected PSMA-total tumour volume (PSMA-TV), total lesion uptake (TL-PSMA), maximum distance between voxels (DmaxVox), SUVmax, SUVmean and metastatic status. Additionally, age, WHO performance status (WHO-PS), Gleason score and laboratory values were retrieved. Cox regression identified predictors of overall survival (OS). Model performance was assessed using Harrell's C-index with internal validation via bootstrapping. RESULTS: By MDT consensus, 75 patients (37%) had LVD and 129 patients (63%) had HVD, differing significantly in PSMA-TV (median: 60 vs. 483 mL) and OS (median: 69 vs. 41 months). PSMA-TV was a robust predictor of OS (HR = 1.39 per doubling, p < 0.001), independent of WHO-PS (HR = 1.69 per score increase, p < 0.001) and treatment. A model combining PSMA-TV and WHO-PS achieved a C-index of 0.71 (95% CI 0.66-0.77) after bootstrapping. In an exploratory post hoc analysis, the optimal threshold for PSMA-TV-based high-volume disease was PSMA-TV ≥ 150 mL or any visceral metastasis, which performed similarly to MDT-based classification (HR = 3.01 vs. HR = 2.68). CONCLUSION: While MDT-based stratification of mHSPC patients was adequate, incorporating PSMA-TV can further improve risk assessment. Instead of dichotomising, we propose using a model with PSMA-TV as a continuous variable to guide treatment decisions. Multicentre validation is needed before clinical implementation. KEY POINTS: Question As PSMA PET/CT replaces conventional imaging for staging metastatic hormone-sensitive prostate cancer, revised PSMA PET/CT-based metastatic burden classifications are needed to guide treatment decisions. Findings PSMA-total tumour volume (PSMA-TV) was a robust predictor of overall survival, and a model combining PSMA-TV with performance status achieved a C-index of 0.71 after bootstrapping. Clinical relevance Quantitative tumour burden assessment with PSMA PET/CT can improve prognostic stratification in metastatic hormone-sensitive prostate cancer, supporting more individualised treatment selection.