Another new urine test for risk of prostate cancer

As we have mentioned previously, data on the use of a variety of methods of urine testing in assessment of risk for clinically significant prostate cancer (and therefore the need for a follow-up biopsy) continues to evolve.

A very recent paper by Tosoian et al. in the Journal of Urology, reports data from a prospective study of a urine-based test known as the MyProstateScore test from a company called LynxDX. This test was developed in association with the University of Michigan. Dr. Tosoian and two of his coauthors are shareholders in LynxDX. Additional; information is available in a media release from Michigan Medicine – The University of Michigan.

According to the data from the paper by Tosoian et al. and the associated media release, the MyProstateScore test

measures levels of cancer-specific genes in a patient’s urine. It is based on … research that discovered that half of all prostate tumors harbor a certain genetic anomaly in which the genes TMPRSS2 and ERG relocate on a chromosome and fuse together — creating an on-switch for prostate cancer development.

This test was used in a validation study including biopsies and post-digital rectal exam urine samples (prior to biopsy) and transrectal ultrasound (TRUS)-guided biopsies from 1,525 previously biopsy-naive men suspected of having prostate cancer on the basis of a PSA tests and other clinical findings and who were seen at either academic or community medical centers.

Among these 1,525 men

  • 977 were enrolled at academic medical centers (and had a median PSA level of 4.5 ng/ml).
  • 548 were enrolled at community medical centers (and had a median PSA level of 4.9 ng/ml).
  • 338 men (22.2 percent) were found to have a Grade Group of ≥ 2 on biopsy (equating to potentially clinically significant prostate cancer)

Using a MyProstateScore test threshold of 10 as a surrogate for Grade Group ≥ 2 on biopsy, the MyProstateScore test provided

  • 97 percent sensitivity and
  • A negative predictive value of 98 percent

Thus the MyProstateScore test could have been used to

  • Prevent 387/1,525 biopsies (33 percent)
  • Missed 10/338 Grade Group ≥ 2 cancers (3.0 percent)

Among 1,242 patients who met all relevant guideline-based criteria, a MyProstateScore of ≤ 10 provided

  • 96 percent sensitivity
  • A negative predictive value of 97 percent

and would have

  • Prevented 32 percent of biopsies
  • Missed 3.7 percent of Grade Group ≥2 cancers

The validation study included patients seen at academic health centers and in community health settings. Among these 1,525 patients, 338 — 22% — had cancers detected on biopsy that were group grade 2 or higher, meaning they were serious enough to warrant immediate treatment.

If the MyProstateScore test had been available to patients in the study, 387 biopsies that found no cancer or slow-growing cancer could have been avoided, the study found. Meanwhile, the test would have missed only 10 clinically significant cancers that would have warranted immediate treatment.

The authors conclude that:

In a large, clinically pertinent biopsy referral population, MyProstateScore ≤10 provided exceptional sensitivity and negative predictive value for ruling out grade group ≥2 cancer. This straightforward secondary testing approach would reduce the use of more costly and invasive procedures after screening with prostate specific antigen.

Two things are particularly worthy of note from this paper:

  • The urine samples for this test all had to be taken after a digital rectal examination or DRE, which is something that many men refuse and which can be done with varying levels of “vigorousness”.
  • It is not clear from the abstract of this paper or from the associated media release that all biopsy specimens were subject to central pathology review (i.e., seen by the same pathologist) — although we suspect that that was probably the case.

As we have said before, there is increasing clarity that urine tests are going to become key to the differentiation between men with

  • Probably no prostate cancer
  • Probably clinically insignificant prostate cancer, i.e., men with Grade Group 1 who don’t need a biopsy (but who may need to be monitored annually over time for at least a while)
  • Possibly clinically significant prostate cancer (i.e., Grade Group 2) who may need a biopsy but who may still be manageable on active surveillance
  • Probably clinically significant prostate cancer (i.e., Grade Group 3 to 5) who will need additional; tests and potentially early treatment with curative intent

However, what is not yet clear at all is whether we are going to need all of these tests as opposed (perhaps) to only one or two of them because these one or two tests have the highest level of discriminatory value when it comes to risk assessment and may be usable not only to assess risk but also to manage men effectively on active surveillance.

These tests are also going to call into question the value of MRI scans as methods for the accurate evaluation of clinical risk for prostate cancer. It is starting to seem as though the value of MRI scanning (and of other scans such as gallium-67 PSMA scans in early stage disease) may be limited to men who need a biopsy based on one of the new urine tests … but there will be a way to go before we can have any certainty about all of this, and (in the view of the sitemaster) it is going to be essential that the new urine tests will need to be validated against each other in head-to-head studies in order to be sure that only the most accurate of these tests can and should be in regular use.

There will be little value to a test with 90 percent accuracy in the identification of no prostate cancer, clinically insignificant prostate cancer, or clinically significant prostate cancer if another test can do these things with 99 percent accuracy. And then there is going to be the question of whether we need to go on doing PSA and similar blood-based tests when it is becoming clear that some of these urine tests are significantly more accurate for assessment of prostate cancer risk.

The diagnosis and work-up of prostate cancer is probably going to change significantly (again) over the next 5 to 10 years, and its management will probably also change for the same reasons.

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