Another presentation at the ASCO annual meeting yesterday morning came from the PROMIS trial in the UK.
The PROMIS trial was a prospective, paired-cohort confirmatory study, designed to provide level 1b evidence of the value of multi-parametric MRI (mpMRI) scanning as a test to see whether some men at hypothetical risk for prostate cancer could avoid the need for prostate biopsy altogether.
Between May 2012 and December 2015, at a total of 11 clinical centers in the UK, men with an elevated PSA level of up to 15 ng/ml and no prior history of biopsy were given (a) a 1.5 T mpMRI (without the use of any endorectal coil); (b) a standard TRUS biopsy; and (c) a template prostate mapping biopsy (with 5-mm sampling of prostate tissue). The conduct and reporting of each test was performed by clinicians who were blinded to the results of each of the other two tests. Clinically significant cancer was defined as Gleason ≥ 4 + 3 = 7 and/or maximum cancer core length ≥ 6 mm.
The radiologists at the 11 clinical centers were all carefully trained and monitored as with regard to their ability to conduct and accurately “read” the mpMRI scans, which were read using the LIKERT scale as opposed to the now more commonly used PI-RADS scale.
The physicians carrying out the different procedures were all blinded as to the results of the other tests. In other words, the doctors who did the two different types of biopsy did not know the results of either the mpMRI scans or either of the biopsies until after all tests had been completed.
Ahmed et al. (see abstract 5000) reported the following results from this study:
- 576 men who met the study entry criteria underwent all three tests (and the two types of biopsy were done consecutively while the patients were fully anesthetized).
- 230/576 men (39.9 percent) had clinically significant prostate cancer detected using the template mapping biopsy (used as the reference standard).
- For mpMRI,
- Sensitivity was 93 percent.
- Specificity was 41 percent.
- The positive predictive value was 51 percent.
- The negative predictive value was 89 percent.
- For the standard 12-core TRUS-guided biopsy (with no use of the mpMRI scan data to take additional biopsy cores)
- Sensitivity was much lower than mpMRI, at 48 percent.
- Negative predictive value was also significantly lower, at 74 percent.
Having made it clear that, in their opinion, these data confirmed that the standard 12-core TRUS-guided biopsy was no longer an appropriate form of standard practice for the accurate diagnosis of clinically significant prostate cancer, Ahmed et al. presented two potential scenarios as strategic alternatives.
In the first scenario, the use of mpMRI as a triage test would, at least, avoid a primary biopsy in 27 percent of men, with just 2 percent of cases of clinically significant cancer being detected.
Alternatively, in the second scenario, if biopsies targeted to areas of the prostate suggested to be suspicious on the basis of finding from mpMRI data can come close to the sensitivity level of template mapping biopsies, then triage with mpMRI scanning would again avoid primary biopsy 27 percent of patients but would detect 3 percent more cases of clinically significant cancer than the standard TRUS-guided biopsy for all patients.
Ahmed et al. concluded that:
- The standard 12-core TRUS-guided biopsy performs poorly both in detecting and ruling-out clinically significant prostate cancer.
- In their data set, 1.5-T mpMRI as a triage test (with no use of an endorectal coil) was able to identify 158/576 patients (27.4 percent) who might safely avoid unnecessary biopsy, without impairing the detection of clinically significant cancer.
There was a good deal of discussion about the cost-effectiveness and “value” of the use of mpMRI related to this presentation, but no one (to your sitemaster’s ears) appeared to be suggesting that mpMRI should not be being used in one or other of the ways suggested by Ahmed and his colleagues. The greater concerns were around the ability of mpMRI to detect very small prostate cancer lesions; the cost-effectiveness in mpMRI (especially here in the USA, where it is expensive); access to the technology; and the skill and training needed among members of the radiology community in being able to accurately “read” such mpMRI scans of the prostate. These are certainly issues that would need to be addressed.
Filed under: Diagnosis, Risk | Tagged: accuracy, biopsy, Diagnosis, mpMRI, triage |
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I’m perplexed by their study. I remember Mark Emberton saying that the ideal candidate for focal therapy was intermediate risk, and patients presenting with Gleason 3+4 are certainly the largest proportion of intermediate risk patients. Why then would Ahmed recommend a method that is not very good at detecting the very kind of tumor that his group seeks to identify? I have safety concerns about triaging away men with GS 3+4 or with smaller (than 6 mm) high grade tumors.
Also, the way mpMRI targeting is most often used is “in addition to” rather than “instead of” biopsy. Several studies have shown increased accuracy in finding clinically significant tumors by combining them. Perhaps in their full analysis they will show the ROCs for the combined detection.
Allen:
This study was started several years ago and was designed to do one thing and one thing only … see whether the type of MRI available then in hospitals in the UK could help to eliminate unnecessary biopsies in men with low-risk disease. Things have evolved a great deal since then, and no one is suggesting that this is the “only” thing that could be done to eliminate the need for unnecessary biopsies, but in my view the study was highly successful in demonstrating what it set out to prove.
But it didn’t show that they could “eliminate unnecessary biopsies in men with low risk disease,” as you say. What it shows is that their mpMRI could distinguish favorable risk from unfavorable risk, which is quite a different thing. I might be content to NOT know if I had GS 3+3, but if I had GS 3+4, I’d certainly want to know about it. ISUP guidelines now call for pathologists to include the % of Gleason grade 4 in GS 3+4 — very important information to have in making decisions about treatment.
Allen:
Respectfully, you are missing the entire point of the study as it was designed. It was not a study that had anything to do with the patients’ actual diagnoses or subsequent decisions. It was a study designed to compare the ability of a specific type of mpMRI to two types of biopsy as a method to identify the presence of clinically significant prostate cancer. You may not agree with its intent or its design, but that doesn’t invalidate the findings.
Although I admire their intent, I definitely disagree with their design. I don’t think I am missing the point — They say the intent is to validate mpMRI as a “triage test to safely avoid a biopsy.” They did not accomplish this objective because of the cutoff they used (a design flaw). It remains important to identify GS 3+4. It is not “safe” to miss those tumors, as they aver.