How should I interpret elevated PSA levels in a patient, and what follow-up investigations are recommended?

Interpretation of elevated PSA levels: An elevated prostate-specific antigen (PSA) level may indicate the presence of prostate cancer but is not diagnostic on its own, as PSA can be raised due to other factors. The risk of prostate cancer is higher if additional risk factors are present, such as high-grade prostatic intra-epithelial neoplasia (HGPIN), atypical small acinar proliferation (ASAP) on biopsy, or an abnormal digital rectal examination (DRE) ¹.

Recommended follow-up investigations:

• For patients with raised PSA and no prior biopsy, a multiparametric MRI (mpMRI) is recommended to assess the likelihood of significant prostate cancer. The MRI Likert score guides further management ¹.
• If the MRI Likert score is 1 or 2 (low suspicion), repeat PSA testing at 3 to 6 months is advised. Prostate biopsy should be considered if there is a strong suspicion of cancer, such as PSA density >0.15 ng/ml/ml, PSA velocity >0.75 ng/ml/year, or a strong family history, taking into account life expectancy and comorbidities ¹.
• If the MRI Likert score is 3 or higher, discuss the case in a multidisciplinary team (MDT) meeting and consider repeating the prostate biopsy due to the possibility of significant disease ¹.
• For patients with a negative biopsy but persistent elevated PSA and MRI Likert score ≥3, MDT discussion and possible repeat biopsy are recommended ¹.
• PSA kinetics (density and velocity) should be monitored throughout follow-up to guide decisions on further investigations or referral ¹.
• Prostate biopsy is not routinely recommended if MRI and biopsy are negative unless clinical suspicion remains high ¹.

Summary: Elevated PSA requires assessment with mpMRI and risk stratification using PSA density, velocity, and clinical factors. Follow-up includes repeat PSA testing, MDT review, and selective biopsy based on MRI findings and risk factors ¹.