Should a patient with a rising Prostate-Specific Antigen (PSA) level from 4.5 to 6.5 and a negative Magnetic Resonance Imaging (MRI) of the prostate undergo a prostate biopsy?

Prostate Biopsy Recommendation for Rising PSA with Negative MRI

A patient with a PSA increase from 4.5 to 6.5 ng/mL and a negative prostate MRI should still undergo a prostate biopsy due to the significant risk of harboring clinically significant prostate cancer despite negative imaging. 1

Risk Assessment for Prostate Cancer

• PSA levels between 4.0-10.0 ng/mL carry a 17-32% risk of biopsy-detectable prostate cancer, regardless of MRI findings 1, 2
• The PSA increase of 2.0 ng/mL represents a concerning velocity that exceeds the recommended threshold of 0.75 ng/mL/year 1
• Negative MRI does not completely exclude the possibility of clinically significant prostate cancer:
  • Even with negative MRI, there remains a 4-6% risk of clinically significant prostate cancer 3
  • This risk increases with higher PSA density values

Role of PSA Density in Decision-Making

• PSA density (PSAD) should be calculated by dividing PSA by prostate volume 1
• For patients with negative MRI:
  • If PSAD <0.10 ng/mL/cm³, the risk of clinically significant cancer drops to approximately 4% 3
  • If PSAD ≥0.10 ng/mL/cm³, biopsy is strongly recommended due to increased risk 3
• Without knowing the prostate volume in this case, we cannot calculate PSA density to potentially avoid biopsy

Biopsy Approach Recommendations

• Standard biopsy scheme should include at least 10-12 cores targeting the peripheral zone 1
• Despite negative MRI, a systematic biopsy approach is recommended given the elevated and rising PSA 2
• Consider additional sampling of the transition zone, especially in repeat biopsy scenarios 2

Important Considerations and Caveats

• Short-term PSA fluctuations can occur even in men with prostate cancer, so the decision to biopsy should not be delayed based on a single repeat PSA measurement 4
• Age-specific PSA reference ranges should be considered when interpreting PSA values 2, 1
• Temporary causes of PSA elevation (infection, instrumentation, ejaculation, trauma) should be ruled out before proceeding to biopsy 1
• Recent evidence shows that MRI-targeted biopsy alone may miss some clinically significant cancers that would be detected on systematic biopsy 5

Follow-up if Biopsy is Negative

• If initial biopsy is negative, continue PSA monitoring at 6-12 month intervals 1
• Consider more frequent monitoring if PSA velocity exceeds 0.75 ng/mL/year 1
• For persistently elevated or rising PSA with prior negative biopsy, consider:
  • Repeat multiparametric MRI
  • Saturation biopsy techniques
  • Additional biomarkers (percent free PSA, 4Kscore, phi, PCA3) 2

The decision to proceed with prostate biopsy should be made based on the elevated PSA level, concerning PSA velocity, and understanding that negative MRI findings do not completely exclude the possibility of clinically significant prostate cancer.