Oncological outcomes after tailored PSMA-PET-guided treatment in biochemical relapse after prostatectomy (PSICHE Trial-NCT 05022914)

Background: Next-generation imaging (NGI) (68 Ga-prostate-specific membrane antigen (PSMA)-PET) represents a cornerstone in biochemical recurrent prostate cancer management. PSICHE is a multicentric prospective study, aimed to assess oncological outcomes of a predefined tailored imaging-guided treatment. Methods: Patients with biochemical recurrence (BCR) after surgery (prostate-specific antigen [PSA] > 0.2 ≤ 1 ng/mL) underwent staging with PSMA-PET. A predefined treatment algorithm was proposed to all patients: prostate bed salvage radiotherapy (SRT) in case of negative or positive PET within the prostate bed, stereotactic body radiotherapy (SBRT) if pelvic nodal recurrences or oligometastatic disease were detected, and androgen deprivation therapy (ADT) was proposed in widespread polymetastatic disease. Chi-square test was used to evaluate the relationship between baseline features and the rate of positive PSMA-PET/CT. Results: One hundred and fifty-nine patients were enrolled. One hundred and seven patients had a PSMA negative/positive in the prostate bed; pelvic nodal disease or oligometastatic metastatic disease was detected in 39 and 10 patients, respectively. Three patients had a polymetastatic disease. Seventeen patients underwent observation because of prior postoperative radiotherapy (RT)/treatment refusal. Eighty-eight patients were treated with SRT, and SBRT was performed in 49 patients with pelvic or extrapelvic oligometastatic disease. Stratifying patients according to EAU criteria (low risk: PSA doubling time > 12 months and Gleason score < 8; high risk: PSA doubling time ≤ 12 months or Gleason score ≥ 8) after a median follow-up of 19 months in the overall population, median BRFS and MFS were not significantly different between the two risk subgroups (p = 0.58 and p = 0.21, respectively). Median metastasis-free and ADT-free survival were not reached. Conclusions: A PSMA-targeted treatment strategy led to promising results, avoiding unnecessary toxicity from ADT or standard SRT administered in unselected patients. Analysis after longer follow-up is needed to clarify survival outcomes.