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Beyond PSA: newer prostate cancer tests

When PSA is borderline or rising, a second blood or urine test can help sort out whether a biopsy is likely to find significant cancer. None of them replaces your urologist's judgment, but they can help you avoid a biopsy you don't need, or move ahead with one you do.

When these tests are used

Most are designed for men with a PSA in the "gray zone," roughly 2 to 10 ng/mL, and a normal or only mildly abnormal rectal exam, who are deciding whether to have a first or repeat biopsy. They are also sometimes used alongside an MRI, especially a PI-RADS 3 result.

On mypsalevel, these results are shown next to your estimate and read against their own published cutoffs. They don't change the PBCG or PLUM numbers, because those models weren't built with them.

Blood tests

TestWhat it measuresHow results are read
Free PSA (%)The share of PSA floating unbound in the blood. Cancer tends to produce more bound PSA, so a lower percentage is more concerning.Above 25% is reassuring; below 10% is concerning. Most useful with PSA 4 to 10 (Catalona et al., JAMA 1998).
PHI
Prostate Health Index
Beckman Coulter
Combines total PSA, free PSA and a PSA precursor called [-2]proPSA into one score. FDA-approved for men 50 and older with PSA 4 to 10.Higher scores mean higher risk. Below 27 is low; 55 or more carries about a 50% chance of cancer on biopsy.
4Kscore
4kscore.com
Four kallikrein proteins (total, free and intact PSA plus hK2), combined with age, exam and biopsy history.Reported directly as a percent chance of Grade Group 2+ cancer. Below 5%: reassuring 5 to 20%: indeterminate 20% and above: concerning
IsoPSA
Cleveland Diagnostics
Changes in the structure of PSA molecules that are associated with cancer, rather than the amount of PSA. FDA-approved in 2025.An index of 6.0 or below suggests lower risk of high-grade cancer.
Stockholm3Several proteins and more than 100 genetic markers, combined with clinical information. Developed and validated in large Swedish screening trials.Reported as a risk of significant cancer, with a cutoff (often 11% or 15%) used to recommend MRI or biopsy. Availability in the US is still limited.

Urine tests

TestWhat it measuresHow results are read
ExoDx Prostate
EPI, now Exo mdx
mdxhealth
RNA from three genes carried in tiny particles (exosomes) in the urine. No rectal exam needed before the sample.Above 15.6 is associated with a higher likelihood of high-grade cancer. Indicated for men 50 and older with PSA 2 to 10 before a first biopsy.
MyProstateScore
MPS / MPS2
Michigan Medicine
Cancer-related genes (originally PCA3 and the TMPRSS2:ERG gene fusion; the newer MPS2 uses 18 genes) in urine collected after a rectal exam.Reported as a risk of significant cancer.
SelectMDx
mdxhealth
Two genes (HOXC6 and DLX1) in urine collected after a rectal exam, combined with clinical factors.Reported as a risk score for significant cancer.
PCA3A single prostate cancer gene in urine after a rectal exam. FDA-approved to help decide on a repeat biopsy.A score below 25 is associated with a lower chance that a repeat biopsy will find cancer.

Which test, if any?

  • No single test is best for everyone. Studies differ in who was tested, and few compare these tests head to head.
  • They work best for a specific decision, such as whether to biopsy after a borderline PSA, or after a PI-RADS 3 MRI.
  • Insurance coverage varies. Some are covered by Medicare and many private plans; others may be out of pocket. Ask before the sample is drawn.
  • Bring the result to your urologist, who can combine it with your PSA, PSA density, MRI and history.

Tests that are different

Inherited (germline) genetic testing looks for gene changes you were born with, such as BRCA2, that raise lifetime risk. It helps decide when to start PSA testing and what threshold to use, and can matter for your relatives. See higher-risk men.

Tumor genomic tests such as Decipher, Oncotype DX Genomic Prostate Score and Prolaris are run on biopsy tissue after cancer is found, to judge how aggressive it is. They are not used to decide whether to biopsy.

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