How to manage a patient with elevated Prostate-Specific Antigen (PSA) levels while on finasteride (5-alpha-reductase inhibitor)?

From the Guidelines

Managing a patient with elevated PSA levels while on finasteride requires careful interpretation and follow-up, with a prompt urological evaluation for rising PSA levels, as this may indicate prostate cancer despite therapy. When evaluating PSA in patients taking finasteride, it is essential to consider the effects of 5-alpha-reductase inhibitors on PSA levels, as they typically reduce PSA by approximately 50% 1. However, the most recent and highest quality study suggests that doubling the measured PSA value may not be a reliable method for cancer detection due to tremendous variability in the effect of 5-ARIs on PSA levels 1.

For patients with rising PSA while on finasteride, consider obtaining a free PSA percentage and PSA velocity (rate of change over time), as rapid increases (>0.75 ng/mL/year) warrant particular concern. Patients should undergo digital rectal examination to assess for prostate nodules or asymmetry. For concerning findings or continued PSA elevation, prostate biopsy may be necessary. Finasteride should generally be continued during this evaluation process to maintain consistent PSA interpretation. The adjusted interpretation is necessary because finasteride inhibits the conversion of testosterone to dihydrotestosterone, reducing prostate size and PSA production in benign tissue, but has less effect on PSA produced by malignant cells.

Key considerations in managing these patients include:

• Failure to achieve a significant PSA decrease while taking 5-ARIs can indicate a heightened risk for prostate cancer that warrants regular testing 1
• The effects of 5-ARIs on PSA before 12 months are variable, and a consistently uniform scale multiplier is currently unavailable due to inter- and intraindividual variability of PSA levels 1
• PSA testing may have enhanced specificity for men receiving finasteride or dutasteride, but reflex ranges for PSA among patients on 5-ARIs have not been established 1

From the FDA Drug Label

1. 1 Effects on Prostate Specific Antigen (PSA) and the Use of PSA in Prostate Cancer Detection In clinical studies, finasteride tablets reduced serum PSA concentration by approximately 50% within six months of treatment. This decrease is predictable over the entire range of PSA values in patients with symptomatic BPH, although it may vary in individuals For interpretation of serial PSAs in men taking finasteride tablets, a new PSA baseline should be established at least six months after starting treatment and PSA monitored periodically thereafter Any confirmed increase from the lowest PSA value while on finasteride tablets may signal the presence of prostate cancer and should be evaluated, even if PSA levels are still within the normal range for men not taking a 5α-reductase inhibitor.

To manage a patient with elevated Prostate-Specific Antigen (PSA) levels while on finasteride,

• a new PSA baseline should be established at least six months after starting treatment
• PSA should be monitored periodically thereafter
• any confirmed increase from the lowest PSA value while on finasteride may signal the presence of prostate cancer and should be evaluated, even if PSA levels are still within the normal range for men not taking a 5α-reductase inhibitor
• to interpret an isolated PSA value in patients treated with finasteride for six months or more, PSA values should be doubled for comparison with normal ranges in untreated men 2

From the Research

Management of Elevated PSA on Finasteride

To manage a patient with elevated Prostate-Specific Antigen (PSA) levels while on finasteride, a 5-alpha-reductase inhibitor, consider the following:

• Finasteride decreases PSA levels by approximately 50% 3, 4, which should be taken into account when interpreting PSA results.
• The reduction in PSA levels due to finasteride does not necessarily confer any therapeutic benefit 3.
• In patients with benign prostatic hyperplasia (BPH), finasteride reduces prostate size and decreases serum PSA levels 3.
• To preserve the usefulness of PSA for prostate cancer detection in men treated with finasteride, multiplying PSA by 2 and using normal ranges for untreated men may be necessary 5.

Monitoring and Biopsy

• Regular monitoring of PSA levels is crucial, and any significant changes should be evaluated further.
• Biopsy may be recommended if PSA levels exceed a certain threshold, taking into account the effect of finasteride on PSA levels 5, 6.
• The decision to perform a biopsy should be based on individual patient factors, including PSA velocity and other clinical parameters.

Interpretation of PSA Results

• When interpreting PSA results in patients on finasteride, consider the baseline PSA level and the percentage change in PSA over time 4.
• A doubling of PSA from nadir or an increase in proPSA may be a more accurate predictor of prostate cancer in men on finasteride, especially when baseline PSA is less than 4 ng/mL 4, 6.
• The performance characteristics of PSA for detecting high-grade prostate cancer may be improved in men on finasteride, as the decrease in benign prostatic hyperplasia contribution to PSA makes changes in PSA more cancer-specific 6.