A new article in this week’s New England Journal of Medicine has just reported the full results of the so-called PRECISION trial of MRI-targeted vs. standard biopsy techniques in the diagnosis of prostate cancer. The full text of this article by Kasivisvanathan et al. is available on line for anyone to read.
The PRECISION trial was designed as a multi-center, non-inferiority trial, in which men suspected to have prostate cancer but who had not yet had a biopsy were randomly assigned to either
- Be given an MRI scan and then have or not have a targeted biopsy (Group A), depending on the MRI findings or
- To not have an MRI but simply be given a standard, 10- to 12-core, TRUS-guided, systematic biopsy (Group B)
The men in Group A were only given an MRI-guided, targeted biopsy (with no standard biopsy cores) if the MRI was suggestive of prostate cancer. The men in Group A whose MRI results were not suggestive of prostate cancer (because they had a PI-RADS v2 score of ≤ 2) were not offered biopsy. The full trial protocol is also available on line.
The primary outcome of the study was was the proportion of men who received a diagnosis of clinically significant cancer, defined as the presence of at least one biopsy core indicating prostate cancer with a Gleason score of 3 + 4 = 7. Secondary outcomes included the proportion of men who received a diagnosis of clinically insignificant cancer.
Since, as we have said, the full details of this trial and its results are available on line, we are not going to get into all of those details. Interested readers can review those for themselves. Basically, what the trial showed was the following:
- 500 men were randomized into either Group A (n = 252) or Group B (n = 248).
- Among the men in Group A
- 71/252 men (28 percent) had MRI results that were not suggestive of prostate cancer, and they did not undergo biopsy.
- 181/252 men (72 percent) had MRI results that were suggestive of prostate cancer and went on to have a biopsy
- In Group A, 95/252 men were found to have clinically significant cancer (i.e., 37.7 percent of the men randomized to this group or 52.5 percent of the men who were given the targeted biopsy).
- In Group B, 64/248 men were found to have clinically significant prostate cancer.
- The difference between the positive biopsy rates for clinically significant prostate cancer was statistically significant.
- MRI, with or without targeted biopsy, was non-inferior to standard biopsy.
- Fewer men in Group A than in Group B received a diagnosis of clinically insignificant cancer (and this difference was also statistically significant).
- Health-related quality of life at 24 hours and at 30 days after the intervention did not differ significantly between the men in Group A and Group B.
The authors conclude that:
The use of risk assessment with MRI before biopsy and MRI-targeted biopsy was superior to standard TRUS-guided biopsy in men at clinical risk for prostate cancer who had not undergone biopsy previously.
However, even though this seems to be a highly significant result, the unanswered question remains:
- Does a targeted, MRI-guided biopsy alone diagnose clinically significant prostate cancer with similar accuracy and at least the same level of safety as a targeted, MRI-guided biopsy in combination with a standard, systematic 12-core biopsy?
We know that targeted, MRI-guided biopsies alone (and even transperineal mapping biopsies) can “miss” clinically significant prostate cancer, and we also know that 12-core, systematic biopsies commonly “miss” clinically significant prostate cancer. Your sitemaster has to say that he is disappointed by the fact that the PRECISION trial didn’t include the combination biopsy methodology so that we could have answered this question once and for all.
One also has to ask whether it would have further helped to resolve questions if the 71 men in Group A for whom an MRI-targeted biopsy was assumed to be unnecessary (based on the MRI data) weren’t at least asked if they would be willing to have standard, 12-core, systematic biopsy so as to see if any of those patients were diagnosed with clinically significant prostate cancer. This would also have provided valuable information.
It is as though we keep doing only a half of the trial that needs to be done as opposed to doing the entire trial!
As with the data from the PROMIS trial, previously reported, we have once again validated the idea that, among a set of men at apparent risk for prostate cancer, and who had had no prior biopsy, multiparametric MRIs that are carried out by and interpreted by skilled, experienced uroradiologists can be used to reduce the number of men who appear to need a prostate biopsy at all. However, what we have not successfully done is answer the basic question that needs to be answered (i.e., the question asked four paragraphs above).
Filed under: Diagnosis, Risk | Tagged: biopsy, MRI, outcome, standard, targeted |
THE "NEW" PROSTATE CANCER INFOLINK 
I fully agree with your comments. I spent hours poring over the data and was left with more questions than answers. You raised the most important question: in statistical terminology — what is the negative predictive value (NPV) of each procedure? That is, what percentage of the negatives were false negatives, where men who truly harbored significant disease were told they didn’t even need a biopsy? In single institution studies, the NPV of a single mpMRI ranges between 80 and 90%. Is that good enough to avoid a biopsy entirely?
50% of the mpMRI group had negative findings (with about half of those only assumed to be negative without a biopsy). 46% of the TRUS biopsy group had negative findings (with all of them confirmed by biopsy, of course). Those negative rates were not statistically different (p = 0.28).
Another question I have (and I have no firm answer) is: Do we want to nonetheless know if we harbor low-grade prostate cancer or insignificant higher grade prostate cancer? 22% of the TRUS-biopsied men had a Gleason score of 3 + 3. These are the men that active surveillance was designed for. Are these men better off not knowing and having less anxiety, or are they better off knowing and watching it closely on a well-designed active surveillance protocol? I was one of those men myself, and I don’t know the answer. We recall that about half the men on active surveillance with a Gleason score of 3 + 3, and who have multiple confirmatory and follow-up biopsies, are eventually found to have higher grade prostate cancer and need treatment.
Also, is it worth the cost to give every man with suspicious PSA an mpMRI? To qualify, the men in this study only had to have an elevated PSA, a positive DRE, or both. More rigorous diagnosis (using PSA density, phi or other biomarkers, and attempting to rule out BPH and prostatitis as culprits) before men are sent for mpMRI might shift the economics even favor of mpMRI. In Europe and Canada it may be easier to justify the cost than in the US. There is the problem too of whether there would be enough adequately trained radiologists.
Allen:
One thing I am quite sure about is that (at least at present) there aren’t sufficient adequately trained radiologists to make this practical in the US — even if we were to decide that it was the right thing to do.
Dear Sitemaster:
Thank you for posting this. A prominent radiologist posted it on Twitter several days ago. I was too busy then to download and read it, so your summary will come in handy.
I will send it to two prostate cancer organisations here. The Board of Social Something and Health rejected general periodic screening last month, I am almost sure wrongly. Philosophical shills fancying themselves “bioethicists” supplied the desired justification, with the lack of evidence for MRI testing a main reason. I’m almost ashamed to have been an academic philosopher. I have argued with one of them. Well, they do get the usual freebies: trips abroad for conventions and free meals in posh restaurants, so who am I to object?
I am interested in your opinion on saturation biopsies.
Diagnosed with Gleason 6, 18 months ago; PI-RADs 3; clinical stage T2.
Had a 3-T MRI 2 months ago and my urologist wants to carry out a saturation biopsy.
I want a targeted biopsy — if at all.
Dear Kieran:
There is an argument that saturation biopsy is the most effective and efficient way to assure that a urologist minimizes the risk of “missing” the presence of higher grade forms of prostate cancer in a patient initially diagnosed with low-risk disease (i.e., you). Some patients appreciate these points
There is an alternative argument that saturation biopsy is “overkill”. It has to be carried out under anesthesia (which comes with its own risks). And many patients don’t like the idea at all.
The one fact that nearly all physicians agree on is that a patient like you should have a confirmatory biopsy something like a year after their initial biopsy.
I’m in your camp. If I was wearing your shoes, I would want the confirmatory biopsy to comprise a standard, 12-core systematic biopsy in combination with an MRI/TRUS-guided biopsy of any portion of the prostate that clearly showed signs of risk on your PI-RADs 3 MRI scan. In my entirely personal opinion this provides a high chance of identification of any amount of cancer that might have a higher Gleason score than 3 + 3 = 6. But it ain’t perfect. Nothing is.
In the end, this is your body. Not the doctor’s. If he isn’t willing to biopsy you in a way you are willing to be biopsied, then I suggest you smile and politely ask him whether he can suggest another doctor who would be more willing to consider your point of view. BUT … you also need to give him the chance to explain to you why he believes that the saturation biopsy might be essential in your case.