Purpose <p>Up to one-third of patients treated with primary radiotherapy (RT) for prostate cancer (PCa) experience biochemical failure (BCF). In selected cases, re-irradiation represents a salvage option. PSMA PET/CT is a valuable tool for detecting intraprostatic recurrence and guiding re-treatment planning. Although visual scoring systems such as the PRIMARY score (PS) have been proposed, none are currently validated for this setting. This pilot study investigates the role of a visual classification system in optimizing salvage re-irradiation strategies.</p> Methods <p>We retrospectively analysed patients with histologically confirmed PCa who underwent re-irradiation for intraprostatic recurrence, following PSMA PET/CT between 2021 and 2024. Only patients without extra-prostatic disease were included. Clinical, imaging, and treatment data were collected. Re-irradiation was delivered using image-guided volumetric modulated arc therapy. Outcomes included BCF and toxicity (CTCAE v5).</p> Results <p>Thirteen patients (median age: 76 years) were included. The International Society of Urological Pathology (ISUP) grade group at diagnosis was 1–2 in ten patients and ≥ 4 in three. Median PSA at diagnosis and at re-irradiation was 9.43 and 2.22 ng/mL, respectively. PSMA PET/CT showed uptake in all cases (focal: 8, diffuse: 4, mixed: 1); PS was ≥ 4 in eight patients. Re-irradiation was delivered after a mean interval of 8.1 years, with a median dose of 30&#xa0;Gy in 5 fractions. PET/CT guided target delineation in 11 cases. After 16 months of median follow-up, four patients had BCF, and two experienced mild toxicity (Grade 1).</p> Conclusion <p>These preliminary findings highlight the limitations of visual interpretation alone; further optimization by Nuclear Medicine and Radiation Oncology specialists is needed to enhance BCF and limit local toxicities.</p>