What is the appropriate next step in managing a 67-year-old man with a newly detected prostate-specific antigen of 4.37 ng/mL and no prior baseline?

Management of Elevated PSA in a 67-Year-Old Man

Confirm the PSA elevation with a repeat test in 2-3 weeks using the same laboratory and assay, then proceed to digital rectal examination and risk stratification to determine if prostate biopsy is indicated. 1

Initial Confirmation Step

• Repeat the PSA test before any further workup because PSA assays have inherent laboratory variability of 20-25%, and this alone could account for fluctuations in values 1, 2
• Use the same laboratory and assay method for the repeat test, as PSA assays are not interchangeable between testing facilities 1, 2
• Wait at least 2-3 weeks and ensure the patient avoids ejaculation, prostatic manipulation, and has no urinary tract infection before retesting 1

Risk Assessment After Confirmation

A PSA of 4.37 ng/mL in a 67-year-old man places him above the traditional threshold of 4.0 ng/mL, but this requires careful interpretation:

• The cancer detection rate for PSA in the 4-10 ng/mL range is approximately 25-30%, meaning most men with this PSA level do not have prostate cancer 1, 3
• However, at PSA levels greater than 4.0 ng/mL, approximately 1 in 3 men will have prostate cancer if biopsied 1
• The median PSA for men in their 60s is approximately 1.2 ng/mL, making 4.37 ng/mL significantly elevated and noteworthy 1

Essential Clinical Evaluation

Perform a digital rectal examination (DRE) as this is an independent indication for biopsy if abnormal, regardless of PSA level 1

Rule Out Reversible Causes

• Exclude prostatitis, as infection can cause dramatic PSA elevations that confound interpretation 1, 4, 5
• If clinical signs of prostatitis are present (pelvic pain, dysuria, fever), treat with antibiotics and anti-inflammatory agents for 4 weeks, then recheck PSA 4-6 weeks after symptom resolution 4, 5
• In men with prostatitis and elevated PSA, treatment normalizes PSA below 4.0 ng/mL in approximately 46% of cases, eliminating the need for biopsy 5
• Do not empirically treat with antibiotics in asymptomatic men—this has little value for improving test performance 1

Consider Additional PSA Testing

If the repeat PSA remains elevated above 4.0 ng/mL:

• Obtain percent free PSA to improve specificity, as men with prostate cancer have a lower proportion of free PSA compared to those with benign prostatic hyperplasia 1, 6
• A free/total PSA ratio below 25% increases cancer likelihood, while a ratio above 25% suggests benign disease 6
• Calculate PSA density if prostate volume is available from imaging (PSA divided by prostate volume), using a cutoff of 0.15 ng/mL/cc to predict clinically significant cancer 1

Decision to Proceed with Biopsy

If the confirmed PSA remains above 4.0 ng/mL and other reversible causes are excluded, proceed to multiparametric MRI before biopsy 1

MRI-Guided Approach

• Multiparametric MRI improves diagnostic yield and helps guide targeted biopsies 1
• If MRI shows suspicious lesions (PI-RADS 4-5), perform targeted biopsy plus systematic sampling with a minimum of 10-12 cores under antibiotic prophylaxis 1
• If MRI shows no suspicious lesions but PSA remains elevated with other risk factors (abnormal DRE, low free PSA percentage, elevated PSA density), systematic biopsy is still indicated 1

Biopsy Technique

• Transrectal ultrasound-guided prostate biopsy with a minimum of 10-12 cores should be performed under antibiotic cover and local anesthesia 1
• Patients should be informed about biopsy risks, including a 4% risk of febrile infections, hematuria (22.6%), hematospermia (50.4%), and pain (26% report moderate to severe pain) 1, 4

Important Caveats and Pitfalls

• Benign prostatic hyperplasia (BPH) is the most common cause of false-positive PSA results, with approximately 25% of men with BPH having PSA greater than 4.0 ng/mL 4
• PSA is more highly expressed gram-for-gram in hyperplastic prostate tissue than in prostate cancer tissue 4
• If the patient is taking 5α-reductase inhibitors (finasteride, dutasteride), these medications reduce PSA by approximately 50% within 6-12 months, though this effect is highly variable 4, 2
• Recent ejaculation, physical activity, or subclinical prostatic inflammation can transiently elevate PSA 1, 2
• At age 67, if the patient is in good health with minimal comorbidities, he remains a candidate for definitive treatment with curative intent if cancer is detected, so age alone should not preclude thorough evaluation 1
• Men with limited life expectancy (<10 years) should not undergo biopsy, as they will not benefit from cancer detection and will only experience harm from biopsy and potential overtreatment 1