Which patients with negative PSMA-PET imaging can safely avoid biopsy for prostate cancer? a novel step towards PSMA-based biopsy-free strategy.

Purpose This study aimed to identify if a subset of men can safely avoid or delay prostate biopsy based on negative results of prostate-specific membrane antigen positron emission tomography (PSMA-PET).Materials And Methods Among 341 consecutive cases in a prospective biopsy cohort (NCT05073653), 111 treatment-naïve men with negative PSMA-PET (PRIMARY-score 1/2) were included. All participants underwent PSMA-PET and histopathological examinations. Clinically significant prostate cancer (csPCa) was defined as Grade Group ≥ 2. Multivariate logistic regression was employed to identify predictors of non-csPCa. Receiver operating characteristic (ROC) analysis was performed to detect non-csPCa on prostate pathology. PSMA-postive patients were additionally reviewed to assess the imaging and pathological outcomes.Results Younger age was identified as an independent predictor (P = 0.006) for the absence of csPCa. ROC analysis of csPCa revealed the largest areas under the curve of 0.77 (0.67-0.87) and 0.78 (0.68-0.88) for individual age in the entire PSMA-negative cohort and the MRI subset, respectively (both P < 0.001). The negative predictive value (NPV) of PSMA-PET for csPCa detection improved with a decreasing age, from 88% in all, to 98% in men aged under 65 yrs (98% vs. 88%, P = 0.021), and to 100% in men aged under 60 yrs (100% vs. 88%, P = 0.040). The NPV of PSMA-PET improved from 88 to 94% when combined with negative MRI, and to 100% in men with negative MRI and aged under 65 yrs. The prevalence was 57% for csPCa and 65% for PCa of any grade.Conclusion We preliminarily propose that omission or postponement of prostate biopsy should be considered for men under the age of 65 yrs with negative PSMA-PET scored as PRIMARY 1 or 2. Conversely, prostate biopsy might be considered in biopsy-naïve men aged 65 yrs or older with strong clinical suspicion of PCa, despite negative PSMA-PET. Further prospective and external evaluation is needed to prove the robustness of this novel strategy.