Integration of prostate-specific membrane antigen-PET and multiparametric MRI for gross tumour volume definition in localised and locally advanced prostate cancer treated with image-guided radiotherapy

This review evaluates recent evidence on the utility of multiparametric MRI (mpMRI), prostate-specific membrane antigen (PSMA) PET, and their combined application for accurately delineating the intraprostatic gross tumour volume (GTV) in patients with primary localised and locally advanced prostate cancer. It further explores the impact of GTV-based dose escalation on treatment-related toxicity and clinical outcomes. Recent studies suggest that combining PSMA-PET with mpMRI enhances lesion coverage of clinically significant, histopathologically verified intraprostatic tumours and yields higher interobserver agreement. However, this improved sensitivity is offset by reduced specificity, and it remains uncertain whether expanding the GTV to include additional PSMA-PET-defined regions impacts long-term treatment-related toxicity or improves oncological outcomes. Multiple phase I/II trials using PSMA-PET and mpMRI have reported acceptable acute and late toxicity profiles. Nevertheless, extensive data on long-term toxicity and disease outcomes following PSMA-PET-guided interventions remain limited, warranting further investigation to assess its impact. The combination of mpMRI and PSMA-PET has been shown to improve coverage of dominant intraprostatic lesion and reduce interobserver variability. While GTVs derived from combined imaging modalities are typically larger than those based on mpMRI alone, hypofractionated focal boost treatments targeting PSMA-PET/mpMRI-defined GTVs have demonstrated acceptable acute toxicity profiles. More data are needed to determine the impact of PSMA-PET expanded GTVs on long-term clinical outcomes.