Serum prostate-specific antigen trends and prostate cancer detection on follow-up in men with a prior negative biopsy: A cohort study

Introduction: Elevated serum prostate-specific antigen (PSA) is the most common trigger for a prostate biopsy. However, the range of normal PSA is poorly defined in many populations. Men with "elevated" PSA may not harbor cancer, and it is unclear if such men with a prior negative prostate biopsy should be biopsied again. We conducted a cohort study to assess the PSA trends and cancer detection rates in such men. Methods: In an Institutional Review Board-approved ambispective study, men who underwent prostate biopsy between January 2016 and December 2021 for PSA > 4 ng/mL were identified. Among them, those whose biopsy was negative for malignancy were contacted either telephonically or reviewed in person, and the most recent PSA and histopathology of any repeat prostate biopsy were determined. These were evaluated to assess the PSA trend, re-biopsy rate, and cancer detection rate. Results: During the study period, prostate biopsies were performed in a total of 1260 men; out of which 444 were negative for malignancy and 241 patients fulfilled the inclusion criteria. Their median prebiopsy PSA was 9.81 ng/mL (interquartile range [IQR]: 7.14-15.6), and the median follow-up PSA was 5.08 (IQR: 3.18-8.4). At a median follow-up of 53 months (range: 6-77 months), PSA had decreased in 177 (73.4%) patients, was static in 48 (19.9%) patients, and increased in only 16 (6.6%) patients. Repeat biopsy was performed on 20 patients; of whom seven had cancer (35%) with an overall positivity rate of 2.9% among the 241 patients. Although the positivity rate was higher in men with increased PSA, it was not statistically different from those with lower or similar PSA. No factors could be identified to predict a positive repeat biopsy. Conclusions: PSA, the sole trigger for a prostate biopsy, declined in nearly three-quarters of men with a negative first biopsy, and <3% of men were detected to have cancer on a repeat biopsy. This information could help appropriately counsel patients and allay anxiety after a negative biopsy.