Predictive value of the ⁶⁸Ga-PSMA-11 PET/CT PRIMARY score for pathological upgrading in patients with ISUP Grade 1 prostate cancer and PSA < 20 ng/mL undergoing radical prostatectomy

Pathological upgrading is common in men with ISUP Grade Group (GG) 1 prostate cancer due to sampling limitations. ⁶⁸Ga-PSMA-11 PET/CT is promising for characterizing tumor biology. The 5-point PRIMARY score, which considers uptake, focality, and location, has limited data on predicting occult high-grade cancer in GG1 biopsy patients. This study assessed the score's accuracy in predicting upgrading in GG1 prostate cancer patients with PSA < 20 ng/mL undergoing radical prostatectomy.

This retrospective study included 71 patients with biopsy-proven GG1 prostate adenocarcinoma, PSA < 20 ng/mL, and ⁶⁸Ga-PSMA-11 PET/CT performed within 2 months before radical prostatectomy. PRIMARY scores [1-5] were assigned by two blinded nuclear medicine physicians; scores ≥ 4 were considered high-risk. Pathological upgrading was defined as ISUP GG ≥ 2 on prostatectomy specimens. Diagnostic performance was assessed using ROC analysis, and univariate and multivariate logistic regression models were constructed to determine independent predictors of upgrading.

Pathological upgrading occurred in 45/71 patients (63.4%). Upgrading rates increased markedly across PRIMARY score categories: 25% for scores ≤ 3, 81.3% for score 4, and 100% for score 5 (p < 0.001). A PRIMARY score ≥ 4 demonstrated excellent diagnostic performance (AUC = 0.979), with 97.8% sensitivity, 88.5% specificity, 93.6% PPV, 95.6% NPV, and 94.3% accuracy. SUVmax (AUC = 0.944) and PI-RADS ≥ 4 (AUC = 0.721) were also associated with upgrading; however, in multivariate analysis, only the PRIMARY score remained an independent predictor (OR: 19.9; 95% CI: 2.92-135.28; p = 0.002).

"The ⁶⁸Ga-PSMA-11 PET/CT PRIMARY score was strongly associated with pathological upgrading in this surgically treated cohort of biopsy-confirmed ISUP GG1 patients with PSA < 20 ng/mL undergoing radical prostatectomy. Incorporating PSMA-based intraprostatic pattern analysis could improve the accuracy of preoperative grading, potentially supporting consideration of surgical management rather than definitive radiotherapy when determining the optimal treatment strategy. Prospective multicenter validation is warranted before broader clinical implementation.