Currently, prostate cancer (PCa) is the second most common cause of cancer death, and radical prostatectomy (RP) remains the primary treatment for localized PCa. Although there is no consensus on an optimal strategy, the determination of total serum prostate-specific antigen (tPSA) is the cornerstone for the detection of postoperative biochemical recurrence (BCR). The aim of this study was to evaluate the prognostic utility of serial tPSA levels together with other clinicopathological factors and to assess the impact of a commentary algorithm implemented in our laboratory information system.A descriptive and retrospective study of patients with clinically localized PCa who underwent RP. BCR-free survival was calculated over time (Kaplan-Meier analysis), and the ability of different clinicopathological factors to predict BCR was studied (univariate and multivariate analyses) with Cox models.A total of 203 patients underwent RP, of whom 51 presented with BCR during follow-up. In the multivariate model, doubling of tPSA, the Gleason score, tumour stage and tPSA nadir were detected as independent predictors of BCR.A patient with undetectable tPSA after 1959 days of RP is unlikely to develop BCR, regardless of preoperative or pathologic risk factors. Furthermore, doubling of tPSA in the first 2 years of follow-up was the main prognostic factor for BCR in patients undergoing RP. Other prognostic factors included a tPSA nadir detectable after surgery, a Gleason score ≥ 7 and a tumour stage T ≥ 2c.