What is the next step in diagnosis for a patient with elevated Prostate-Specific Antigen (PSA) level and multiparametric Magnetic Resonance Imaging (MRI) results?

Management of Rising PSA with Negative Biopsy and Abnormal MRI

The next step for this patient should be a systematic plus targeted biopsy of the right peripheral zone (option D). 1

Case Analysis

This 64-year-old man presents with:

• Rising PSA (5 ng/mL to 6.2 ng/mL over 6 months)
• Normal digital rectal examination
• Previous negative 12-core biopsy
• Large prostate (95 grams)
• Suspicious lesion on multiparametric MRI in the right peripheral zone

Evidence-Based Approach

Why Combined Systematic and Targeted Biopsy is Indicated

The NCCN guidelines and other authoritative sources strongly recommend a combined approach of systematic biopsy plus targeted biopsy of suspicious MRI lesions for men with prior negative biopsies and rising PSA. This approach maximizes cancer detection while minimizing missed clinically significant disease 1.

The American College of Radiology (ACR) Appropriateness Criteria specifically states that "MRI-targeted biopsy is particularly appropriate for patients with an elevated PSA after one or more negative TRUS-guided biopsies who have a high-value target at diagnostic multiparametric MRI" 2.

Benefits of Combined Approach

1. Higher detection rates: A combined approach of systematic and targeted biopsy detects more clinically significant cancers than either method alone 1

   • Targeted biopsies identify up to 91% of significant cancers
   • Standard biopsy alone identifies only about 54% of significant cancers

2. Reduced risk of missing significant cancer:

   • Performing only targeted biopsy may miss some clinically significant cancers
   • Performing only systematic biopsy may miss cancers in the MRI-visible lesion, especially in a large prostate (like this patient's 95g prostate) where sampling error is more likely 1

Why Right Peripheral Zone

The multiparametric MRI shows a suspicious lesion in the right peripheral zone. The images provided (T2 and DWI) indicate an area of concern in this region that requires targeted sampling.

Alternative Options Considered

1. PSA in three to six months (Option A): Inadequate approach given the rising PSA, large prostate, and suspicious MRI finding. Further delay could miss clinically significant cancer.

2. Decipher genomic test (Option B): Not indicated at this stage as tissue diagnosis has not been established.

3. Targeted biopsy only of right peripheral zone (Option C): Suboptimal as it may miss clinically significant cancer outside the MRI-visible lesion. The NCCN guidelines recommend combining systematic and targeted approaches 2, 1.

4. Systematic plus targeted biopsy of left peripheral zone (Option E): Incorrect target location as the MRI shows the suspicious lesion in the right peripheral zone.

Clinical Pearls

• In patients with large prostates (>80g), the risk of sampling error with standard systematic biopsy alone is higher, making MRI-targeted approaches particularly valuable 3

• MRI has demonstrated good performance at both detecting and ruling out clinically significant disease, with negative predictive values of up to 95% for high-grade disease 4

• The combination of rising PSA, prior negative biopsy, and a suspicious lesion on MRI represents a high-risk scenario that warrants thorough evaluation with both systematic and targeted sampling 1