Serum PSA levels fluctuations in patients with non-muscle-invasive bladder cancer (NMIBC) undergoing BCG therapy: a prospective study.

BACKGROUND: Intravesical bacillus Calmette–Guérin (BCG) therapy is the standard adjuvant treatment for intermediate-high risk non–muscle-invasive bladder cancer (NMIBC). Transient elevations in prostate-specific antigen (PSA) following BCG instillation can prompt unnecessary prostate biopsies and increase patient anxiety. This study investigated temporal changes in total PSA levels (TPSA) and Free-to-Total PSA ratio (f/tPSA) in NMIBC patients receiving intravesical BCG therapy. METHODS: We prospectively enrolled 25 male patients with NMIBC and baseline TPSA < 4 ng/mL. Serum TPSA and free PSA were measured at three time points: prior to BCG initiation as baseline, immediately after the induction course, and three months post-treatment. Patients with prior prostate cancer, inflammatory prostate conditions, or use of medications affecting PSA were excluded. Data were analyzed using Friedman test to compare the three time points, followed by post-hoc pairwise comparisons using Wilcoxon signed-rank tests (SPSS v27). RESULTS: Twenty patients completed the study (mean age 64.0 ± 8.4 years), Sixteen patients (80%) exhibited a significant elevation of TPSA immediately following induction therapy. In 14 of these patients (> 80%), PSA levels spontaneously returned to near-baseline values within three months. Mean TPSA rose from 1.17 ± 1.24 ng/mL at baseline to 2.02 ± 1.48 ng/mL following intravesical BCG therapy course, the declined to 1.27 ± 1.24 ng/mL at three months post-treatment. The mean f/tPSA exhibited a steadier trend, declining from 0.30 ± 0.16 at baseline to 0.26 ± 0.12 ng/mL post-treatment, and a slight increasing to 0.28 ± 0.16 ng/mL at three months. Statistical analysis confirmed that the post-treatment elevations in TPSA and was significant (p < 0.001). No patient developed clinical or histopathological evidence of prostate cancer during follow-up. CONCLUSION: Transient PSA elevation is a common but reversible phenomenon after intravesical BCG instillation, reflecting local inflammatory and immune responses rather than malignant transformation. In the absence of additional clinical findings, a strategy of “watchful waiting” with repeat PSA testing at three months may prevent unnecessary prostate biopsies, reduce patient anxiety, and optimize healthcare resource utilization.