What to make of a PCA3 score of ≥ 100

Some studies (e.g., this one by Roobol et al.) have previously indicated that not all men with very high prostate cancer antigen 3 (PCA3) scores are necessarily found to have prostate cancer on biopsy or re-biopsy. The implications of this are still unclear, but it definitely raises major questions about the utility of the PCA3 test.

The authors had originally identified 90 men with a PCA3 score ≥ 100, all of whom underwent biopsy. In this group of men

  • 28/90 (31.1 percent) were found to have prostate cancers on initial biopsy.
  • 62/90 (68.9 percent) remained at risk for a diagnosis of prostate cancer.
  • All the 62 men at continued risk were offered repeat testing.
  • 6 cases of prostate cancer were identified in 20 men at re-biopsy.

A new study by Schröder et al. addresses the 56 men who had a PCA3 score ≥ 100 and had had one or more negative biopsies. All of these men were given the opportunity to undergo further testing.

  • 28/56 men (50 percent) agreed in principle to participate in further testing, but …
  • Only 7 men actually agreed to undergo MRI studies and MRI-guided re-biopsies if indicated.
  • Suspicious lesions were identified in 2/7 patients based on the MRI data.
  • Of these 2 patients, 1 was found to have low-risk prostate cancer (clinical stage T1c, Gleason 3 + 3 = 6) on MRI-guided biopsy.

This means that

  • After a total of three possible rounds of testing and 2.8 years of follow-up (through linkage to the Dutch national cancer registry) for all men with negative biopsies
    • 35 cases of prostate cancer were detected in a total of 90 men with PCA3 scores ≥ 100.
    • The positive predictive value of a PCA3 score ≥ 100 was 38.9 percent.

Schröder et al.conclude that, “despite extended diagnostic efforts in many men with initial PCA3 scores ≥ 100” their finding of no sign of prostate cancer  in 55/90 such patients “is unexpected and might be clinically relevant.”

The “New” Prostate Cancer InfoLink is similarly concerned by this result, which makes one wonder just how appropriate the cut-point of 32 is for a PCA3 result that (supposedly) is meant to indicate meaningful risk for clinically significant prostate cancer in a man with at least one prior negative biopsy.

6 Responses

  1. I had two negative biopsies, a very low PCA3 score and ended up with a Gleason 10 subsequent to surgery. What does this say for PCA3?

  2. Reverse problem. … Comparable conclusion. … The PCA3 test is distinctly less than perfect when it comes to its application in the diagnosis of prostate cancer.

  3. The PCA3 score is the ratio of PCA3 RNA to PSA RNA. The hypothetical basis is that when the tumor volume of prostate cancer is higher, PCA3 will rise faster than PSA, leading to higher scores. Some believe that prostate size must be taken into account as well, because the odds of finding the cancer on TRUS biopsy is lower when the tumor volume is low relative to the volume of the prostate. They have come up with a derived number to indicate this — PCA3 density — which is the PCA3 score divided by the prostate volume. In a couple of studies, PCA3 density increased the specificity of the test:

    — Siegrist TC, et al. PCA3 permutation increases the prostate biopsy yield.
    — Ruffion A, et al. Additional value of PCA3 density to predict initial prostate biopsy outcome.

  4. Allen:

    I don’t think PCA3 density is going to explain the problem that Schroder et al. have identified (or the reverse problem mentioned by Larry Friedrichs).

  5. Gleason 10 was small, I believe — 0.5 cm near apex at margin. I did not have an enlarged prostate.

  6. Larry,

    Your situation aligns with the authors I cited who believe that PCA3 is not a good test when the relative tumor volume is low. They argue that it doesn’t tell you if you have the disease so much as it indicates whether it will be detectable on a biopsy. In your case, it predicted it wouldn’t be detectable, and it was right. Not a great test, huh? Just one clue in the armamentarium.

    The 4Kscore, released in the US yesterday, and phi may turn out to be much better indicators, but I doubt we will ever have a single biochemical test that simultaneously gives us 90+% sensitivity and specificity. Perhaps there will be a set of tests that gets close.

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