Can I have prostate cancer with a normal Prostate-Specific Antigen (PSA) test?

Can Prostate Cancer Occur with a Normal PSA Test?

Yes, prostate cancer can occur even with a normal PSA test result, as approximately 1 in 7 men (about 15%) with PSA levels below 4.0 ng/mL will have prostate cancer. 1

Understanding PSA Test Limitations

• PSA tests can produce "false-negative" results, meaning they can be normal even when prostate cancer is present 1
• The higher a man's PSA level is (even within the "normal" range), the more likely he is to have prostate cancer 1
• PSA is not cancer-specific but prostate-specific, meaning other conditions like benign prostatic hyperplasia (BPH) and prostatitis can also cause PSA elevation 1
• PSA screening has limited specificity for prostate cancer detection, leading to both overdiagnosis and missed cases 2

Factors Affecting PSA Results

• PSA levels can fluctuate naturally, with short-term decreases occurring even in men with prostate cancer 3
• 43% of men with confirmed prostate cancer showed a PSA decrease below their baseline level in repeat testing 3
• Medications like 5α-reductase inhibitors (finasteride, dutasteride) reduce serum PSA by approximately 50%, which can mask elevated levels 4
• For men taking 5α-reductase inhibitors, PSA values should be doubled for comparison with normal ranges to maintain the utility of PSA for cancer detection 4

Risk Stratification Beyond PSA

• Factors to consider beyond PSA include:
  • Patient age and prostate volume 1
  • Family history of prostate cancer 1
  • African descent (higher risk population) 1
  • Changes in PSA over time (PSA velocity) - men with steady rises in PSA are more likely to have cancer 1
  • Rapid PSA rises may indicate more life-threatening cancer 1

Alternative and Supplementary Testing

• The proportion of free PSA to total PSA can improve cancer detection specificity - a smaller free fraction is associated with higher cancer risk 5
• Additional biomarkers that can supplement PSA include:
  • Prostate Health Index (PHI) 2
  • 4K score 2
  • PCA3 (particularly useful for men with previously negative biopsies) 2
• Digital rectal examination (DRE) should be performed alongside PSA testing to improve detection rates 6

Clinical Implications

• Prostate biopsy remains the definitive test for diagnosing prostate cancer, not the PSA test 1
• Biopsies aren't perfect either and can sometimes miss cancer when present 1
• Some doctors recommend a second set of biopsies if the first set is negative but PSA levels continue to rise 1
• The decision to proceed to biopsy should not be influenced by short-term decreases in PSA, as these can occur even in men with high-grade cancer 3

Shared Decision Making

• Given the limitations of PSA testing, shared decision making is essential when considering prostate cancer screening 1
• Men should be informed about both potential benefits (early detection) and harms (false positives, unnecessary biopsies, overtreatment) of PSA screening 1
• The small potential benefit of prostate cancer screening corresponds to preventing, at most, 1 death from prostate cancer per 1000 men screened after 11 years of follow-up 1

Remember that while a normal PSA test reduces the likelihood of having prostate cancer, it cannot completely rule out the disease. If you have risk factors or symptoms concerning for prostate cancer, further evaluation may be warranted despite a normal PSA result.