What is the next step in management for a 50‑year‑old man with a history of male breast cancer surgery, elevated prostate‑specific antigen, normal digital rectal examination, and a 1‑cm PI‑RADS 4 lesion near the prostate apex?

Proceed with MRI-Targeted Prostate Biopsy

Given the PI-RADS 4 lesion near the apex with elevated PSA, the next step is to perform a targeted prostate biopsy of the suspicious lesion, ideally using MRI-TRUS fusion guidance, combined with systematic sampling (minimum 10-12 cores). 1

Rationale for Targeted Biopsy

• PI-RADS 4 lesions carry high probability of clinically significant prostate cancer and warrant tissue diagnosis before any treatment decisions. 1
• The normal DRE does not exclude cancer, as high-grade prostate cancer can occur with normal DRE findings, particularly in apical lesions that are difficult to palpate. 1
• A single elevated PSA should be verified, but in the context of a PI-RADS 4 lesion on MRI, proceeding to biopsy is appropriate without waiting for repeat PSA. 1

Biopsy Technique Specifications

• Perform MRI-TRUS fusion biopsy or MRI-guided biopsy to specifically target the 1-cm apical lesion, as this approach detects the majority of tumors capable of causing patient harm. 1
• Obtain minimum 10-12 systematic cores in addition to targeted cores from the PI-RADS 4 lesion, as systematic sampling may detect additional disease not visible on MRI. 1
• Administer antibiotic prophylaxis and local anesthesia for the procedure. 1

Special Considerations for This Patient

History of Male Breast Cancer

• This patient's history of male breast cancer raises concern for hereditary cancer syndromes (BRCA1/BRCA2 mutations), which are associated with more aggressive prostate cancer phenotypes and worse outcomes.
• Consider genetic counseling and testing for hereditary cancer mutations, as this may influence treatment intensity and surveillance strategies if cancer is confirmed.
• Men with BRCA mutations and prostate cancer may benefit from more aggressive treatment approaches compared to sporadic cases.

Apical Location Challenges

• Apical lesions are notoriously difficult to sample with standard TRUS biopsy and are more easily missed, making MRI-targeted approach particularly important in this case. 1
• The apex is a common site for clinically significant cancer that can be understaged on systematic biopsy alone.

Pathology Reporting Requirements

The biopsy report must specify: 1

• Histological type of any cancer detected
• Gleason score (most dominant pattern and highest grade pattern)
• Percentage of Gleason grades 4 or 5
• Proportion of involved cores as percentage of total cores
• Extent of involvement in each core
• Presence of extraprostatic extension
• Perineural invasion status

If Biopsy is Negative

• A negative biopsy does not definitively exclude cancer, particularly with a PI-RADS 4 lesion. 2
• If initial biopsy is negative but PSA remains elevated or continues rising, repeat biopsy should be strongly considered, potentially with saturation technique (>20 cores). 1
• Continue PSA monitoring at 3-6 month intervals if biopsy is negative. 1

Common Pitfalls to Avoid

• Do not delay biopsy waiting for repeat PSA confirmation when a PI-RADS 4 lesion is already identified on imaging. 1
• Do not rely on systematic biopsy alone without targeting the MRI-visible lesion, as this may miss the clinically significant cancer. 1
• Do not assume the cancer is low-risk based on PSA level alone; apical lesions and patients with hereditary predisposition can have aggressive disease despite modest PSA elevation.
• Do not perform imaging for staging (bone scan, CT) until cancer is confirmed on biopsy, unless PSA is markedly elevated (>20 ng/mL) or symptoms suggest metastatic disease. 2