Impact of Nerve-Sparing Techniques on Prostate-Specific Antigen Persistence Following Robot-Assisted Radical Prostatectomy: A Multivariable Analysis of Clinical and Pathological Predictors

Background/Objectives: Prostate-specific antigen (PSA) persistence, defined as a postoperative PSA level ≥ 0.1 ng/mL measured within 4–8 weeks after radical prostatectomy (RP), predicts biochemical recurrence (BCR) and adverse oncological outcomes. The influence of nerve-sparing (NS) surgical techniques on PSA persistence remains debated, especially among patients with high-risk pathological features. This study aimed to evaluate the impact of NS techniques on PSA persistence following robot-assisted radical prostatectomy (RARP), considering tumor characteristics, surgical parameters, and patient-specific factors. Methods: A retrospective cohort analysis was performed on 779 patients who underwent RARP at a single institution between January 2002 and December 2015. The inclusion criteria consisted of histologically confirmed prostate cancer with available preoperative and postoperative data, including PSA measurements taken 4–8 weeks after surgery. PSA persistence served as the primary outcome. Statistical analyses included descriptive statistics, univariate and multivariable logistic regression models to identify predictors of PSA persistence, and Spearman’s correlation along with the Kruskal–Wallis H test to evaluate associations. Results: Of the 779 patients included, 55% underwent NS surgery (51% unilateral, 49% bilateral). The mean preoperative PSA was 11.85 ng/mL (SD: 7.63), while the mean postoperative PSA was 0.70 ng/mL (SD: 4.42). An elevated postoperative PSA was associated with a larger tumor size (r = 0.1285, p < 0.001), advanced pathological stages (χ2 = 45.10, p = 3.79 × 10−9), and higher Gleason scores (χ2 = 24.74, p = 1.57 × 10−4). NS surgery correlated with a lower postoperative PSA (mean: 0.20 ng/mL) compared to non-NS procedures (mean: 0.65 ng/mL), with slight differences between unilateral (mean: 0.30 ng/mL) and bilateral (mean: 0.35 ng/mL) NS approaches. Multivariable regression analysis identified advanced pathological stage (coefficient = 1.16, p = 0.04) as an independent predictor of PSA persistence, while NS techniques had no significant independent effect (coefficient = −0.01, p = 0.99). Conclusions: Nerve-sparing surgical techniques do not independently predict PSA persistence after RARP when adjusting for tumor-related factors and confounders. Advanced pathological stage, particularly stage pT3b, primarily determines PSA persistence. These findings highlight the necessity of personalized surgical planning informed by preoperative imaging and patient-centered decision making to optimize oncological and functional outcomes.