What are the implications and next steps for a patient with a Prostate-Specific Antigen (PSA) level of 5.5?

Management of PSA 5.5 ng/mL

A PSA of 5.5 ng/mL warrants immediate digital rectal examination (DRE) and repeat PSA testing, followed by prostate biopsy if the elevation is confirmed and DRE is abnormal, or if free/total PSA ratio is less than 15%. 1

Immediate Actions Required

Perform a digital rectal examination immediately to assess for nodules, asymmetry, or increased firmness—any abnormality mandates urgent urology referral regardless of the PSA level. 1 The combination of DRE findings with PSA provides critical risk stratification that PSA alone cannot offer. 1

Repeat the PSA test before proceeding to biopsy to account for laboratory variability (20-25%) and rule out transient elevations from benign causes. 1 Ensure the patient has avoided:

• Prostate manipulation within 3-6 weeks 1
• Urinary tract infection (active or recent) 1
• Ejaculation within 48-72 hours 1

Any of these factors can cause false elevations and should be addressed before repeat testing.

Risk Assessment

At a PSA of 5.5 ng/mL, approximately 30-35% of men will have prostate cancer on biopsy, meaning roughly 2 out of 3 men will not have cancer despite this elevation. 2 However, this level is clearly above the traditional 4.0 ng/mL threshold where most guidelines recommend consideration of biopsy. 2

Order a free/total PSA ratio on the confirmatory PSA test. 1 This is particularly valuable in the 4.0-10.0 ng/mL range where your patient falls:

• Free/total PSA ratio <15% indicates higher cancer risk and warrants biopsy 1
• A ratio >25% suggests lower cancer risk and may allow for closer surveillance rather than immediate biopsy 1

Consider age-specific context. For men aged 70-79 years, the upper limit of "normal" extends to 5.5-6.5 ng/mL depending on ethnicity, whereas for younger men (50-59 years), the upper limit is only 3.5-4.0 ng/mL. 2 A PSA of 5.5 ng/mL is more concerning in a 55-year-old than a 75-year-old.

Biopsy Decision Algorithm

Proceed directly to biopsy if:

• DRE reveals any abnormality (nodule, asymmetry, or firmness) 1
• Free/total PSA ratio <15% on confirmatory testing 1
• PSA velocity >0.4-0.75 ng/mL/year (depending on age and baseline PSA) 2, 1
• Patient is African-American or has first-degree family history of prostate cancer, as these factors increase risk independent of PSA level 2

Consider surveillance with repeat PSA in 3-6 months if:

• DRE is completely normal 1
• Free/total PSA ratio >25% 1
• Patient has significant comorbidities limiting life expectancy to <10 years 2
• Patient is taking 5α-reductase inhibitors (see critical caveat below) 2

Biopsy Technique

If biopsy is indicated, transrectal ultrasound-guided biopsy with 10-12 cores targeting the peripheral zone at apex, mid-gland, and base is the standard approach. 2, 1 Extended sampling schemes may be considered for repeat biopsies if initial biopsy is negative but PSA remains elevated. 2

Critical Caveats

If the patient is taking finasteride or dutasteride (5α-reductase inhibitors for benign prostatic hyperplasia), the PSA value must be doubled after 6-12 months of therapy to interpret it correctly. 2, 1 A measured PSA of 5.5 ng/mL in a patient on these medications represents an adjusted PSA of approximately 11.0 ng/mL, which significantly changes risk stratification. 2

Additionally, monitor for PSA increase from nadir in patients on 5α-reductase inhibitors—an increase of ≥0.3 ng/mL from nadir should trigger biopsy consideration even if the absolute PSA remains below traditional thresholds. 2, 1

Benign conditions commonly elevate PSA, including benign prostatic hyperplasia, prostatitis, and urinary retention. 2, 1 This is why approximately 65% of men with PSA >4.0 ng/mL do not have cancer on biopsy. 2

Shared Decision-Making

Discuss with the patient that:

• Prostate cancer is common (1 in 6 lifetime risk), but many prostate cancers grow slowly and may never cause symptoms or death. 2, 1
• Early detection allows curative treatment but also risks detecting clinically insignificant cancers that may lead to overtreatment with potential side effects including urinary incontinence and erectile dysfunction. 2, 1
• At PSA 5.5 ng/mL, if cancer is detected, approximately 70% will have organ-confined disease amenable to curative treatment with surgery or radiation. 1
• Men older than 75 years or those with serious medical problems limiting life expectancy have little to gain from PSA testing and aggressive workup. 2