What is the workup for a patient with a normal Prostate-Specific Antigen (PSA) level but an elevated percentage of free Prostate-Specific Antigen (PSA)?

From the Guidelines

In cases where the total Prostate-Specific Antigen (PSA) level is within normal limits but the percentage of free PSA (%fPSA) is elevated, a more detailed workup is warranted to rule out prostate cancer.

Workup Recommendations

• The patient should undergo a digital rectal examination (DRE) and a multiparametric prostate magnetic resonance imaging (mpMRI) to assess for any suspicious lesions 1.
• Consideration should be given to administering 5-alpha-reductase inhibitors, such as finasteride 5mg daily for 6 months, to reduce PSA levels and improve the specificity of PSA testing, although this should be done under close monitoring 1.
• If the %fPSA remains elevated, a prostate biopsy may be necessary to definitively rule out malignancy 1.

Rationale

The NCCN guidelines recommend using percent fPSA as an alternative in the management of patients with normal DREs and tPSA levels between 4 and 10 ng/mL if they have a contraindication to biopsy 1.

• Percent fPSA levels less than 10% are clearly associated with a high risk for having prostate cancer, and patients should be encouraged to undergo a biopsy if percent fPSA values fall below this level 1.
• A negative linear relationship exists between the likelihood of having prostate cancer and percent fPSA values between the levels of 10% and 25% 1.
• The risks associated with these values should be carefully discussed with the patient before electing to forego prostate biopsy 1.

Additional Considerations

• PSA velocity, or the rate of change of PSA over time, can also be useful in assessing the risk of prostate cancer 1.
• A PSA velocity of 0.75 ng/ml yearly or greater may indicate an increased risk of prostate cancer 1.
• Multiparametric MRI can help identify regions of cancer missed on prior biopsies and should be considered in selected cases after at least 1 negative biopsy 1.

From the Research

Workup for Patients with Normal PSA and Elevated Percentage of Free PSA

• The workup for a patient with a normal Prostate-Specific Antigen (PSA) level but an elevated percentage of free Prostate-Specific Antigen (PSA) involves further evaluation to determine the risk of prostate cancer 2, 3.
• Studies have shown that the percentage of free PSA (%fPSA) can be a useful adjunct to PSA screening in men with total PSA levels between 2.5-4.0 ng/mL and normal digital rectal examination (DRE) findings 2.
• A %fPSA cutoff of 15% or less has been suggested as a criterion for further evaluation, including biopsy, in men with PSA levels between 2.5-3.9 ng/mL and normal DRE findings 2.
• The use of %fPSA as a biopsy indication in men with normal DRE and PSA 2.5-4.0 ng/mL has been shown to increase cancer detection rates, with tumors in this subset of patients having similar pathological characteristics to those with higher PSA levels 2.
• Other studies have also evaluated the use of %fPSA in detecting prostate cancer in men with intermediate PSA levels (4-10 ng/mL) and normal DRE findings, with varying results 4, 5.
• A study published in 2002 found that the use of %fPSA in the PSA 2-4 ng/mL range did not substantially increase the number of biopsies needed to detect clinically significant prostate cancer compared to the 4-10 ng/mL range 6.

Diagnostic Criteria

• A %fPSA cutoff of 15% or less has been suggested as a criterion for further evaluation, including biopsy, in men with PSA levels between 2.5-3.9 ng/mL and normal DRE findings 2.
• Other studies have used different %fPSA cutoffs, such as 14% or 18-20%, to determine the risk of prostate cancer in men with normal PSA levels and elevated %fPSA 3, 6.
• The choice of %fPSA cutoff may depend on the individual patient's risk factors and medical history, as well as the specific clinical setting 4, 5.

Biopsy and Treatment

• Men with a %fPSA cutoff of 15% or less and PSA levels between 2.5-3.9 ng/mL may be considered for biopsy, regardless of DRE findings 2.
• The decision to perform a biopsy should be based on a comprehensive evaluation of the patient's risk factors, medical history, and laboratory results, including %fPSA and PSA levels 4, 3, 5, 6.
• Treatment options for prostate cancer detected through biopsy will depend on the individual patient's disease characteristics, medical history, and personal preferences, and may include active surveillance, surgery, radiation therapy, or other approaches 2, 3.