Objective
Metastatic castration-resistant prostate cancer (mCRPC) is a heterogeneous disease with varying survival outcomes. This study investigated whether baseline PSMA PET/CT parameters are associated with survival and treatment response.

Methods
Sixty mCRPC patients underwent [18F]PSMA-1007 PET/CT before treatment with androgen receptor-targeted agents (ARTAs) or chemotherapy. Intensity-based parameters, volumetric parameters, metastatic sites and DmaxVox (distance between the two outermost voxels) from baseline PSMA PET/CT were collected, as well as age, Gleason score and laboratory parameters. Cox regression analysis evaluated their prognostic value for overall survival (OS). Additionally, a preliminary lesion-level analysis was done (n = 241 lesions) with lesion location and twelve radiomic features selected from previous literature. Logistic regression evaluated their association with PSMA PET/CT-based lesion progression after 3–4 months of treatment.

Results
Total tumour volume (PSMA-TV) (HR = 1.41 per doubling [1.17–1.70]), total lesion uptake (TL-PSMA) (HR = 1.40 per doubling [1.16–1.69]) and DmaxVox (HR = 1.31 per 10 cm increase [1.07–1.62]) were prognostic for OS, each independent of baseline PSA level (HR = 0.82 per doubling [0.68–0.98]), haemoglobin level (HR = 0.68 per mmol/L increase [0.49–0.95]) and line of treatment. On lesion-level, location (prostate vs bone OR = 0.23 [0.06–0.83]) and SUVmean (OR = 1.72 per doubling [1.08–2.75]) were independent prognostic markers for lesion progression, morphological and texture-based radiomic features were not.

Conclusion
Baseline PSMA PET/CT scans have prognostic value in mCRPC patients and can potentially aid in treatment decision-making. DmaxVox can serve as a simpler alternative to PSMA-TV when automated segmentation software is not available. When combined with PSMA-TV, lower PSA levels indicated worse OS, which may be a marker of tumour dedifferentiation. Further research is needed to validate these models in larger patient cohorts.@en