Background: The perioperative period in cancer surgery is characterized by transient metabolic and inflammatory perturbations that may influence early postoperative biochemical dynamics. Surgical stress induces insulin resistance, hyperglycemia, cytokine activation, and metabolic shifts that interact with tumor cell signaling pathways. Intravenous lidocaine has been associated with anti-inflammatory and systemic stabilizing effects beyond analgesia. We investigated whether perioperative lidocaine administration during robotic-assisted radical prostatectomy (RARP) is associated with early postoperative prostate-specific antigen (PSA) dynamics within the context of perioperative metabolic–inflammatory modulation. Methods: In this single-center retrospective cohort study, 180 patients undergoing RARP for localized or locally advanced prostate cancer were stratified according to perioperative intravenous lidocaine exposure. The primary endpoint was undetectable PSA (<0.1 ng/mL) at 6–12 weeks postoperatively. Secondary endpoints included PSA detectability at 3 and 6 months and time to first detectable PSA. Multivariable logistic and Cox regression models were adjusted for established oncologic risk factors. Perioperative glycemic variation, intraoperative lactate dynamics, and postoperative IL-6 levels were analyzed as indicators of stress-induced metabolic activation. Results: Lidocaine exposure was independently associated with higher odds of undetectable PSA at 6–12 weeks (OR 2.10, 95% CI 1.15–3.85) and at subsequent time points. In Cox analysis, lidocaine was associated with a reduced hazard of PSA detectability (HR 0.58, 95% CI 0.37–0.92). Patients receiving lidocaine demonstrated significantly attenuated perioperative hyperglycemia, lower lactate elevation, and reduced IL-6 response. Conclusions: Perioperative intravenous lidocaine administration during RARP was associated with more favorable early PSA dynamics and attenuation of perioperative metabolic–inflammatory activation. Given the retrospective and non-randomized design of the study, these findings should be interpreted as associative and hypothesis-generating, and warrant confirmation in prospective controlled investigations.