Prostate. 2026 Jun 18. doi: 10.1002/pros.70210. Online ahead of print.
ABSTRACT
BACKGROUND: PI-RADS 3 lesions represent a diagnostic “gray zone” in which biopsy decision-making is particularly challenging, with reported clinically significant prostate cancer (csPCa) detection rates ranging from 13% to 50%. This study evaluated the predictive value of the systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR)-alone and in combination with PSA density (PSAD) and PI-RADS score-for the detection of prostate cancer (PCa) and csPCa, with a specific focus on the PI-RADS 3 subgroup.
METHODS: In this two-center retrospective observational study, 982 patients who underwent prostate biopsy between 2020 and 2025 were included. csPCa was defined as ISUP Grade Group ≥ 2. Univariable and multivariable logistic regression analyzes were performed to identify independent predictors of PCa and csPCa. In the PI-RADS 3 subgroup (n = 251), two predictive models were compared using receiver operating characteristic analysis and the DeLong test: Model 1 (age, free/total PSA ratio, PSAD) and Model 2 (Model 1 + SII + NLR).
RESULTS: Of the 982 patients, 188 (19.1%) were diagnosed with PCa and 150 (15.3%) with csPCa. In the overall cohort, NLR ≥ 2.11 was independently associated with csPCa (OR, 15.924; 95% CI, 2.472-102.567; p = 0.004), whereas SII did not retain independent significance. PLR showed an inverse association with PCa, possibly reflecting tumor-related platelet dynamics. In the PI-RADS 3 subgroup, SII ≥ 661.37 (OR, 2.317; p = 0.039) remained an independent predictor of PCa alongside age, free/total PSA ratio, and PSAD ≥ 0.20 (OR, 6.111; p = 0.013), while NLR showed borderline significance. The addition of SII and NLR to the clinical model increased the AUC from 0.795 to 0.816 in the PI-RADS 3 subgroup, although this improvement did not reach statistical significance (p = 0.134).
CONCLUSIONS: Systemic inflammatory markers-particularly SII and NLR-provide complementary predictive information in the pre-biopsy risk stratification of prostate cancer. SII emerged as an independent predictor of PCa specifically within the PI-RADS 3 gray zone, while NLR independently predicted csPCa in the overall cohort. These routinely available, low-cost parameters may serve as practical adjuncts to PSA derivatives and mpMRI in the individualization of biopsy decisions, particularly for PI-RADS 3 patients.
PMID:42314010 | DOI:10.1002/pros.70210
