What are the implications of an elevated Prostate-Specific Antigen (PSA) level?

From the Guidelines

If you have an elevated PSA level, you should consult with your healthcare provider for proper evaluation, as the level of PSA correlates with the risk of prostate cancer, with approximately 30% to 35% of men with serum PSA between 4 to 10 ng/mL likely to have cancer, and a total PSA level >10 ng/mL conferring a greater than 67% likelihood of prostate cancer 1. When evaluating an elevated PSA level, it's essential to consider that it doesn't necessarily mean you have prostate cancer, as it can also be caused by benign conditions like prostate inflammation (prostatitis), benign prostatic hyperplasia (BPH), or recent ejaculation.

Key Considerations

• Your doctor will likely recommend additional testing, which may include a digital rectal exam, repeat PSA testing, or specialized tests like free PSA percentage, PSA density, or PSA velocity, to further define the probability of high-grade cancer, with biomarkers such as percent free PSA, 4Kscore, or phi potentially informative in patients who have never undergone biopsy or after a negative biopsy 1.
• If concerns persist, a prostate biopsy may be necessary for definitive diagnosis, with the decision to proceed to prostate biopsy based primarily on PSA and DRE results, but also taking into account multiple factors, including free and total PSA, patient age, PSA velocity, PSA density, family history, ethnicity, prior biopsy history, and comorbidities 1.
• The most common method of prostate biopsy is transrectal, ultrasound-guided prostate biopsy, which is usually performed as an outpatient procedure with local anesthesia, and extended biopsy schemes have been proven to identify more cancer at initial biopsy compared to sextant biopsies, decreasing the false negative rate from 20% to 5% 1.

Pre-Biopsy Precautions

• While waiting for your appointment, avoid activities that might artificially raise PSA levels, such as ejaculation or vigorous exercise involving the prostate area for 48 hours before any follow-up PSA test.
• Also, inform your doctor about any medications you're taking, particularly finasteride or dutasteride, which can affect PSA levels.

Importance of Medical Interpretation

• Remember that PSA is just a screening tool, and elevated levels require proper medical interpretation rather than self-diagnosis or treatment, with individualized risk assessment based on a variety of risk factors, including PSA level, DRE results, and other factors, to characterize the risk of prostate cancer and "significant" prostate cancer in an individual patient 1.

From the Research

Elevated PSA and Diagnostic Approaches

• Elevated PSA levels can indicate prostate cancer, and various diagnostic approaches are used to detect and diagnose the disease 2, 3, 4, 5, 6.
• Multiparametric MRI (mpMRI) has emerged as a valuable tool in prostate cancer diagnosis, helping to identify clinically significant cancers and reduce overdiagnosis 3, 5, 6.
• The use of PSA density (PSAD) as an adjunctive predictor of clinically significant prostate cancer detection has been evaluated, with studies suggesting that PSAD can help stratify patients and potentially avoid systematic biopsies in favor of MRI-targeted biopsy alone 2.

Biopsy Techniques and Imaging Modalities

• Different biopsy techniques, including MRI-transrectal ultrasound (TRUS) fusion prostate biopsy, have been developed to improve cancer detection rates 5.
• Advanced ultrasound modalities, such as transrectal prostate elastography and contrast-enhanced US, have also been explored as complementary tools to mpMRI 4.
• The combination of mpMRI and advanced ultrasound techniques can provide more accurate diagnoses and help identify the location of prostate cancer, which is essential for focal therapy 4.

Patient Selection and Future Directions

• Patient selection for prostate biopsy is complex and influenced by emerging use of prebiopsy imaging, with guidelines recommending biopsy for patients with elevated PSA, abnormal digital rectal examination, or lesions identified on mpMRI 5.
• Future efforts should focus on detailing the role of prebiopsy imaging as a triage tool for prostate biopsy and establishing consensus on the preferred modality of fusion biopsy 5.
• The evolution of novel biomarkers and artificial intelligence is expected to further improve screening and diagnostic practices for prostate cancer 6.