How should a patient with hypercalcemia and an elevated Prostate Specific Antigen (PSA) level on finasteride (dutasteride) be evaluated, considering the free PSA percentage?

From the Guidelines

A patient with hypercalcemia and elevated PSA on finasteride/dutasteride should undergo comprehensive evaluation, considering the free PSA percentage as a valuable diagnostic tool despite the use of 5α-reductase inhibitors, with a free PSA percentage below 25% suggesting higher risk for prostate cancer. The evaluation should start with confirmation of hypercalcemia through repeat testing and assessment of calcium-related parameters (PTH, vitamin D, phosphorus) 1. For the elevated PSA, the actual value should be interpreted with caution, as finasteride and dutasteride can lower PSA levels by approximately 50% 1. However, doubling the measured PSA value may not be reliable due to the variable effect of 5-ARIs on PSA levels 1.

The free PSA percentage remains a useful tool in assessing the risk of prostate cancer, with a percentage below 25% indicating a higher risk 1. The evaluation should include:

• Digital rectal examination
• Consideration of prostate imaging (MRI)
• Possible biopsy based on adjusted PSA values and clinical findings
• Bone scan or other skeletal imaging to assess for metastatic prostate cancer to bone, given the concern raised by hypercalcemia
• Serum protein electrophoresis to rule out multiple myeloma
• PTH-related protein measurement to assess for paraneoplastic hypercalcemia

This approach addresses both the potential for advanced prostate cancer and other causes of hypercalcemia, recognizing that the combination of these findings requires urgent and thorough investigation 1.

From the FDA Drug Label

1. 1 Effects on Prostate Specific Antigen (PSA) and the Use of PSA in Prostate Cancer Detection ... The ratio of free to total PSA (percent free PSA) remains constant even under the influence of finasteride tablets. If clinicians elect to use percent free PSA as an aid in the detection of prostate cancer in men undergoing finasteride therapy, no adjustment to its value appears necessary.

The free PSA percentage in a patient with elevated PSA on finasteride should be evaluated without any adjustment, as the ratio of free to total PSA remains constant under the influence of finasteride.

• The percent free PSA value does not need to be adjusted for comparison.
• 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 2.

From the Research

Evaluation of Free PSA Percentage in Patients with Elevated PSA on Finasteride

• The effect of finasteride on free and total serum prostate-specific antigen (PSA) levels has been studied in men with benign prostatic hyperplasia (BPH) 3.
• Finasteride therapy results in a marked lowering of serum PSA levels, with a 50% decrease in total PSA levels after 6 months of treatment 3.
• However, the mean percent free PSA (13 to 17% at baseline) was not altered significantly by finasteride or placebo 3.
• Another study found that finasteride decreased PSA levels by 48% after 12 months of treatment, but had no effect on the proliferation index of prostatic epithelial cells 4.
• The proportion of BPH patients with PSA levels of 2.0 ng/ml and 5.0 ng/ml after 12 months of finasteride treatment was comparable to the proportion with pretreatment PSA levels of 4.0 ng/ml and 10.0 ng/ml 5.

Implications for Prostate Cancer Diagnosis

• Finasteride has been shown to reduce the incidence of prostate cancer, but its effect on PSA levels can make it difficult to interpret PSA results 4.
• A study found that long-term treatment with finasteride reduces PSA serum concentration by about 50% without changing the free PSA ratio 6.
• The free PSA ratio can help increase PSA specificity and avoid unnecessary biopsies, even in finasteride-treated patients 6.
• However, the adjustment factor required to preserve median PSA may need to be adjusted over time in men who have been receiving finasteride for more than 1 year 7.

Considerations for Patients with Hypercalcemia and Elevated PSA

• Patients with hypercalcemia and elevated PSA on finasteride should be evaluated carefully, taking into account the effects of finasteride on PSA levels 3, 4, 5.
• The free PSA percentage may be useful in evaluating these patients, as it can help distinguish between BPH and prostate cancer 6.
• However, further studies are needed to fully understand the implications of finasteride on PSA levels and prostate cancer diagnosis in patients with hypercalcemia and elevated PSA 3, 4, 7.