What is the next step for a 73-year-old man with elevated Prostate-Specific Antigen (PSA) levels of 14.3 and a previous negative prostate biopsy when PSA was 12?

Management of Elevated PSA in a 73-Year-Old Man with Previous Negative Biopsy

A multiparametric MRI followed by targeted biopsy plus systematic sampling is the recommended next step for this 73-year-old man with rising PSA from 12 to 14.3 ng/mL despite a previous negative biopsy. 1

Evaluation of Rising PSA After Negative Biopsy

Initial Assessment

• The patient's PSA has increased from 12 to 14.3 ng/mL, representing a significant rise that warrants further investigation
• PSA velocity (rate of rise) is often more important than absolute value in predicting aggressive disease 1
• Rising PSA despite previous negative biopsy raises concern for:
  • Sampling error in the initial biopsy
  • Disease progression since previous biopsy
  • Potentially higher-grade disease that was missed

Diagnostic Approach

1. Confirm PSA elevation

   • Repeat PSA testing to confirm elevation before proceeding with invasive testing 1
   • Note that short-term decreases in PSA may occur even in men with prostate cancer, including high-grade cancer, so decreases should not deter further evaluation 2

2. Multiparametric MRI

   • Multiparametric MRI before biopsy improves targeting of suspicious areas 1
   • Particularly valuable in patients with prior negative biopsy and persistently elevated PSA
   • Can help identify anterior tumors that may have been missed on initial biopsy 3

3. Combined biopsy approach

   • MRI-targeted biopsy plus systematic sampling is optimal 1
   • Extended biopsy schemes have been proven to identify more cancer at initial biopsy compared to standard sextant biopsies, decreasing false negative rates from 20% to 5% 4
   • Consider saturation biopsy (>20 locations) given the persistently elevated PSA and previous negative biopsy 4

Risk Factors and Considerations

Age Considerations

• At 73 years old, the patient is in an age group where prostate cancer mortality is significant, with 2 in 10 prostate cancer deaths occurring in men over 74 years 1
• However, many men with prostate cancer at this age die of other causes, so assessment of comorbidities is important 1

PSA Interpretation

• PSA levels between 4.0-10.0 ng/mL have a positive predictive value of 25-35% for prostate cancer 4
• PSA >10 ng/mL has a positive predictive value of 43-65% for prostate cancer 4
• Risk calculators and nomograms can improve efficiency in selecting men for biopsy 4

Potential Causes of PSA Elevation

Consider non-malignant causes of PSA elevation:

• Benign prostatic hyperplasia (BPH)
• Prostatitis
• Urethral or prostatic trauma 1

Clinical Pitfalls to Avoid

1. Avoiding repeat biopsy due to previous negative result

   • A single negative biopsy does not rule out significant prostate cancer, especially with rising PSA
   • Up to 20-30% of significant cancers may be missed on initial biopsy

2. Relying solely on PSA value

   • The decision to proceed to prostate biopsy should be based on multiple factors, not just PSA level 4
   • Consider free and total PSA, PSA velocity, PSA density, family history, ethnicity, prior biopsy history, and comorbidities 4

3. Missing anterior tumors

   • Men with elevated PSA but otherwise low-risk features are at greater risk of having anterior tumors that are undersampled at standard biopsy 3
   • This reinforces the need for MRI guidance and targeted sampling

4. Ignoring PSA trends

   • The rate of PSA rise is often more important than the absolute value in predicting aggressive disease 1
   • This patient's PSA increase from 12 to 14.3 ng/mL represents a concerning trend

By following this approach, you maximize the chances of detecting clinically significant prostate cancer while minimizing unnecessary procedures in this 73-year-old man with rising PSA despite a previous negative biopsy.