It has been hoped (at least by some) that a possible use of the prostate cancer gene 3 or PCA3 test — approved in parts of Europe but still in clinical trials in the US – would be as a better tool than PSA tests and annual biopsies to monitor patients on expectant management (active surveillance).
Tosoian et al. set out to examine the relationship between PCA3 data and prostate biopsy results in men on the Johns Hopkins active surveillance program, and we should be clear up front that these patients all have to have very low-risk disease as specified by the so-called Epstein criteria:
- Their PSA density must be < 0.1.
- They must have a Gleason score of < 7.
- They can have only one or two biopsy cores that are positive for prostate cancer.
- No biopsy core can have > 50 percent of the core showing prostate cancer.
The researchers obtained urine specimens from 294 men with prostate cancer who had enrolled in the Hopkins expectant management initiative (and therefore met the above criteria). These patients were all followed with semiannual free and total PSA measurements, DREs, and an annual prostate biopsy. Disease progression was defined as the presence of any Gleason pattern 4 or 5, more than 2 positive biopsy cores, or more than 50 percent involvement of any core with cancer on a follow-up annual biopsy.
The results of the study showed the following:
- 38/294 patients (12.9 percent) met the criteria for disease progression based on their follow-on biopsies
- These 38 patients had a mean PCA3 score ( of 60.0) similar to the 256 patients without progression (50.8).
- Detailed statistical analysis suggested that PCA3 alone could not be used to identify men with progression on biopsy.
- After adjustment for age and date of diagnosis, PCA3 was not significantly associated with progression on biopsy.
It is apparent that – in men in this series – a single PCA3 score at the time of diagnosis could not be used to predict the patients most likely to be at risk for prostate cancer progression. However, what we still do not know is whether:
- Sequential PCA3 tests (every 6 months or every year) might be able to predict risk for progression in men on active surveillance.
- A single PCA3 might be able to predict risk for progression in men with an initial Gleason score of 3 + 4 = 7 who enroll in an active surveillance program and are subsequently upgraded to Gleaosn 4 + 3 = 7 or higher based on an annual biopsy.
In practical terms, the Johns Hopkins active surveillance program probably has the most restrictive criteria of any of the current active surveillance programs at a major medical center. While it would clearly have been helpful if a single PCA3 test at the time of diagnosis could have been used to predict which of these patients were most likely to progress over time, this was probably not going to be likely. We will still need more data to be able to assess the prognostic value (if any) of the PCA3 test in low-risk patients.