The Interpretation of Serum Prostate Specific Antigen in Men Receiving 5α-Reductase Inhibitors: A Review and Clinical Recommendations

Purpose: We reviewed the effects of 5α-reductase inhibitors on prostate specific antigen and clarified the adjustments that should be made to compensate for these effects to ensure that the usefulness of prostate specific antigen for detecting prostate cancer is maintained. Materials and Methods: We reviewed articles published in the scientific literature with relevance to the effects of 5α-reductase inhibitors on the usefulness of prostate specific antigen for detecting prostate cancer. Results: A total serum prostate specific antigen of 4.0 ng/ml has traditionally been used as the threshold for triggering prostate biopsy. However, clinical trials of finasteride and dutasteride have shown that 5α-reductase inhibitors decrease serum prostate specific antigen in patients with and without prostate cancer. To compensate, the doubling rule has been applied in clinical trials and clinical practice. However, doubling serum prostate specific antigen may overestimate actual prostate specific antigen in some patients receiving 5α-reductase inhibitors for up to 6 to 9 months, accurately estimate prostate specific antigen from 1 to 3 years and underestimate it thereafter. An increase in prostate specific antigen of 0.3 ng/ml from nadir as a trigger for biopsy maintains 71% sensitivity for prostate cancer in men receiving dutasteride with 60% specificity, similar to the 4.0 ng/ml prostate specific antigen cutoff using placebo. Conclusions: We propose that a prostate specific antigen increase from nadir of 0.3 ng/ml or greater could represent an alternative to the doubling rule for monitoring prostate specific antigen in patients on 5α-reductase inhibitors. The prostate specific antigen increase from nadir appears to be a more accurate cancer indicator than a doubled value in some patients.