What is the next step for a patient with low-risk prostate cancer on active surveillance with a prostate MRI showing a Prostate Imaging-Reporting and Data System (PI-RADS) 4 lesion?

Management of Low-Risk Prostate Cancer on Active Surveillance with PI-RADS 4 Lesion

A patient with low-risk prostate cancer on active surveillance who has a prostate MRI showing a PI-RADS 4 lesion should undergo MRI-targeted biopsy of the suspicious lesion to rule out clinically significant disease progression. 1

Rationale for MRI-Targeted Biopsy

PI-RADS 4 lesions have a high probability of harboring clinically significant prostate cancer, with studies showing:

• PI-RADS 4 lesions have approximately 67% likelihood of containing clinically significant prostate cancer (Gleason Score ≥3+4) 1
• Recent data shows that 84% of patients with PI-RADS 4-5 lesions and initial ISUP 1 (Gleason 3+3) biopsies were upgraded at radical prostatectomy 2
• PI-RADS 4 lesions are strong independent predictors of upgrading and adverse pathology even when initial biopsies showed only low-grade disease 2

Management Algorithm

1. Confirm MRI Quality

   • Ensure the MRI was performed according to PI-RADS v2 standards
   • Verify adequate image quality (using a dedicated scoring system like PI-QUAL) 1

2. Perform MRI-Targeted Biopsy

   • Target the PI-RADS 4 lesion specifically
   • Use either MRI-ultrasound fusion technique or in-bore MRI-guided biopsy 1
   • Consider additional systematic biopsies to sample the "penumbra" around the target 1

3. Based on Biopsy Results:

   • If upgraded to ISUP ≥2 (Gleason ≥3+4): Discontinue active surveillance and consider definitive treatment options
   • If remains ISUP 1 (Gleason 3+3): Continue active surveillance with more intensive monitoring

Important Considerations

• The PRECISE recommendations (Prostate Cancer Radiological Estimation of Change in Sequential Evaluation) should be used to report MRI findings in active surveillance patients 1
• PI-RADS 4 lesions should be saved as key images in the reporting system 1
• MRI and genomic biomarkers can provide independent and complementary information regarding the likelihood of upgrading on subsequent biopsy 1

Potential Pitfalls to Avoid

1. Do not rely solely on PSA changes without imaging and biopsy confirmation, as PSA fluctuations may not accurately reflect disease progression

2. Do not ignore the PI-RADS 4 lesion even if previous biopsies showed only low-grade disease - approximately 10-15% of clinically significant cancers can be missed by systematic biopsies alone 1

3. Do not automatically recommend radical treatment without histological confirmation of the PI-RADS 4 lesion, as false positives can occur

4. Avoid delaying the targeted biopsy, as PI-RADS 4 lesions represent a high likelihood of clinically significant disease that may affect mortality and morbidity if left untreated

Follow-up After Targeted Biopsy

If the targeted biopsy confirms clinically significant cancer (Gleason ≥3+4):

• Discuss definitive treatment options including radical prostatectomy or radiation therapy based on patient factors and preferences 3

If the targeted biopsy shows continued low-risk disease:

• Continue active surveillance with more frequent monitoring
• Consider repeat MRI in 12 months 1
• Consider genomic testing to further stratify risk 1

By following this approach, you can ensure appropriate management of patients with low-risk prostate cancer on active surveillance who develop PI-RADS 4 lesions on MRI, balancing the need to identify clinically significant disease progression while avoiding overtreatment.