Association of PSMA pexpression with progression-free survival in low–intermediate-grade, organ-confined prostate cancer treated with radical prostatectomy

AIM: To investigate the prognostic value of immunohistochemical (IHC) PSMA expression and preoperative Ga-68 PSMA PET/CT metrics for predicting progression-free survival (PFS) after radical prostatectomy (RP) in patients with low–intermediate-grade, organ-confined prostate cancer (ISUP 1–2; pT2). MATERIALS AND METHODS: In this retrospective cohort, 76 consecutive patients who underwent RP between 01 May 2007 and 30 November 2023 and had final pathology of ISUP 1–2 and pT2 without positive surgical margins, extracapsular extension, lymphovascular or perineural invasion were included. In 46 patients with preoperative ^68Ga-PSMA-11 PET/CT, intraprostatic lesion SUVmax and PSMA tumour volume (PSMA-TV) were measured on whole-body standard images acquired at approximately 60 minutes and on delayed pelvic images acquired at 120–180 minutes. Absolute (ΔSUVmax) and percentage (Δ%SUVmax) changes between standard and delayed SUVmax were calculated. In RP specimens, PSMA IHC was performed on sections from the index tumour; staining intensity was scored as 0/1+/2+/3+ and the H-score (range 0–300) was calculated as 1×%1+ + 2×%2+ + 3×%3+. The primary endpoint was PFS, defined as the time from RP to biochemical recurrence (PSA ≥0.2 ng/mL confirmed by at least two consecutive measurements). Statistical analyses were performed using IBM SPSS Statistics. Continuous variables were summarized as mean±SD or median (min–max), categorical variables as n (%). PFS was estimated using Kaplan–Meier analysis and compared between groups with the log-rank test. Associations between PSMA-PET metrics and IHC variables were assessed using Spearman correlation. The discriminative ability of intraprostatic SUVmax for biochemical recurrence was evaluated by ROC analysis and optimal cut-off values were derived using the Youden index. Independent predictors of biochemical recurrence were identified by multivariable logistic regression. A two-sided p<0.05 was considered statistically significant. RESULTS: The mean age of the cohort was 65.5±7.3 years; the median follow-up was 33.9 months. Biochemical recurrence occurred in 13/76 patients (17.1%). The median preoperative PSA was 6.95 (1.46–39.45) ng/mL and median PSA density was 0.13 (0.04–0.41) ng/mL/cc. On biopsy, ISUP 1 and ISUP 2 rates were 39.4% and 59.2%, respectively; final RP ISUP distribution was 25% ISUP 1 and 75% ISUP 2. PSMA IHC staining intensity was 0, 1+, 2+ and 3+ in 28.9%, 17.1%, 32.9% and 21.1% of tumours, respectively; the median H-score was 30 (0–300). In the PSMA-PET subset (n=46), mean intraprostatic SUVmax was 9.44±6.11 on standard images and 11.41±7.04 on delayed images; median PSMA-TV was 2.93 (0.7–9.6) mL. In univariable analyses, PSMA staining intensity 3+ (vs ≤2), H-score >180, standard and delayed SUVmax, Δ%SUVmax, age and higher preoperative PSA were all significantly associated with shorter PFS. Correlations between H-score/IHC intensity and SUVmax/PSMA-TV were weak and not statistically significant. For standard-phase SUVmax, the optimal ROC-derived cut-off for predicting biochemical recurrence was 9.58, yielding a sensitivity of 83.3% and specificity of 67.6% (Youden J≈0.51). For delayed-phase SUVmax, the optimal cut-off was 13.14, again with a sensitivity of 83.3% but higher specificity of 75.7% (Youden J≈0.59), indicating better discrimination. PSMA-TV showed only borderline association with PFS (p≈0.09), and ΔSUVmax was not significant, whereas Δ%SUVmax was significantly associated with PFS. In the multivariable model including PSMA staining intensity 3+, H-score >180, PSMA-TV and SUVmax measures, only delayed intraprostatic SUVmax remained an independent and statistically significant predictor of PFS (OR≈1.8 per unit increase; p≈0.026). CONCLUSION: In low–intermediate-grade, organ-confined prostate cancer, delayed-phase intraprostatic SUVmax on preoperative ^68Ga-PSMA PET/CT emerges as an independent predictor of PFS after RP. High-intensity (3+) PSMA IHC staining and elevated H-score (>180) are associated with adverse outcome but did not retain independent significance in multivariable analysis. These findings suggest that PSMA-based imaging and tissue biomarkers reflect complementary aspects of tumour biology and that PSMA-PET parameters—particularly delayed SUVmax—may aid risk re-stratification and clinical decision-making in borderline cases between active surveillance and definitive treatment. Larger, prospective, multicentre studies are needed to validate these results and to define clinically applicable cut-offs. KEYWORDS: Prostate cancer; PSMA; PSMA PET/CT; immunohistochemistry; progression-free survival; biochemical recurrence.