Transperineal prostate biopsy is a novel method used by urologists to detect prostate cancer, but is it going to surpass the use of transrectal biopsy?
At the recent 2021 Society of Urologic Oncology Annual Meeting, Badar M. Mian, MD, FACS, presented a talk on the “Clinical Trials of TP Biopsy,” discussing the ongoing research on this newer modality and how it measures up against the current standard of care. Mian is a professor of surgery and urology at Albany Med Urology in Albany, New York.
The biggest concern we have had in the last few years, maybe over the last decade, is the risk of infection, which seems to be increasing,in many parts of the world—the United States, Canada, and of course, Europe and Asia as well. Some of that has to do with the overuse or abuse of antibiotics resulting in antibiotic resistance, so that's the concern. Now, the transrectal procedure itself is quite easy. We've been doing this for 25 years. All graduating residents and urologists in practice are familiar with it. It's fairly quick. It's been validated in terms of how to take samples and where in the prostate to take samples from So, really the main concern is the risk of infection. The question is: Can we reduce it? The challenge, of course, is that the risk of infections, as reported, is not uniform. To make a final categorical judgment [that is] black and white, good or bad, is not something that we can do at the moment.
The [advantage of the] transperineal [biopsy] is that we can avoid or minimize exposure to rectal bacteria. Certainly, the transrectal biopsy results in exposure to more bacteria. Whether that always results in an infection, or to what extent. is unclear. The reports of post-biopsy infection rates are highly variable.
So, the thought is that if you can avoid introducing rectal bacteria into the tissue, we may be able to totally avoid or at least minimize the post-biopsy infections. That's the one advantage that's worth pursuing. There are some other proposed advantages, such as better cancer detection rates. Some colleagues feel they can sample the prostate better and may be able to get a higher yield of, let's say, clinically significant prostate cancers. That question is less of a concern. Based on recent studies, I think we may find that the cancer detection rates are similar. The real question, that has much bigger impact, is the potential decrease in infection rates that we are trying to realize with this transperineal approach. The transperineal prostate biopsy tends to be more painful so it often required the use of anesthesia. However, the idea of performing transperineal biopsy using local anesthesia alone has gained traction as more studies have demonstrated the feasibility of an office-based procedure.
We're doing both, and we're doing both procedures in the office, under local anesthesia without any additional analgesics. But we are doing this primarily as part of a randomized control trial.1 Patients who wish to not participate can have the prostate biopsy based on their urologist’s standard practice. Amongst the 12 of us in our practice, the physicians can perform the biopsy that they feel best for that patient, but our focus is randomizing patients to 1 or the other approach. We started transperineal biopsy in 2019 with the goal to conduct comparative effectiveness study.
What we see in the published literature, and also in informal discussions and presentations, is a resurgence of the transperineal approach and vociferous support despite the fact that there is wide variability in the infectious complications. One study may report infections in 5% to 10% of transrectal biopsies, which is alarming, while another study may report the rate to be less than 1%. Is it just an issue with patient selection? Is it the technique used by various centers and urologists? Our stance was that since its not exactly clear as to why there are big differences amongst the studies and amongst different centers, randomized controlled trials (RCT) should be performed to inform this discussion. The idea of RCT to compare these two biopsy approaches was not received well, initially, since many colleagues had already accepted the superiority of the transperineal approach.
As it turns out, since the start of our study in 2019 – which was first of its kind to include all of the desirable features including randomization —2 other large RCTs, with similar outcomes of interest, have been initiated. Our study, called ProBE-PC: Prostate Biopsy, Efficacy, and Complication, is going to recruit more than 600 patients for randomization to one or the other techniques to answer the question regarding infectious complications. Other desirable features of the trial that we wanted to study included feasibility of transperineal biopsy in the office, safety of biopsy without the use of prophylactic antibiotics, and using MRI fusion-targeted approach. The trial is ongoing and about to completed in the near future.
Earlier this year, another multicenter trial RCT was initiated, being led by Jim Hu [MD, MPH] from Cornell and Ed Schaeffer [MD, PhD] from Northwestern University.2 They are going to include over 1100 patients, to study the infectious complication rates and cancer detection rates. The third study is actually from the UK where transperineal biopsy has been pushed more vigorously.3 The UK study is led by Dr. Richard Bryant and Dr. Alastair Lamb from Oxford University. They will study the cancer detection and infectious complication rates in nearly 1100 patients.
These are the 3 studies evaluating infectious complications which I highlighted in my talk that will provide high-level scientific evidence. Right now, as we read the literature, there is a 10-fold difference in the magnitude of infectious complications after transrectal biopsy amongst various studies, ranging from 1% to > 10%. That's a huge gap, and we have to understand why the gap exists. The Level-1 evidence from these trials will allow us to make informed decision regarding the superiority of one biopsy technique over the other and to determine the magnitude of the difference.
It is ready to be performed. I think that we had—'we' meaning urology community—this concern that [this] procedure may be too painful, and that it could not be performed in the office. However, there is increasing evidence of the feasibility of transperineal biopsy using local anesthesia alone. In fact, even before the recent popularity of this procedure, some centers have been doing this for years. While transperineal biopsy appears quite feasible, and quite tolerable, it does seem to be somewhat more pain that we've noticed, but the concerns that we had seemed to have been unfounded. There appears to be a learning curve to delivering an effective local anesthesia nerve block.
Feasibility and tolerability aside, should transrectal biopsy be abandoned and replaced by transperineal approach? Not at this moment. It is not clear, due to lack of Level-1 evidence, whether transperineal biopsy is truly superior in terms of infections or cancer detection.
This question will be resolved through the randomized trials mentioned above.
I'm very excited that our trial has been recruiting patients quite well, and I'm very happy to see that there are 2 other multicenter trials that have started. There was a point when people thought an RCT [would] not be necessary because the answers [were] so clear cut. So, the research results coming over the next couple of years, will be really very helpful. In the end, we're looking at a very major paradigm shift, where you have thousands of urologists who are very familiar and comfortable with doing a procedure. But that procedure, transrectal biopsy, may be causing more infections. Before we can make such a major change where everybody is advised or forced to switch to a new procedure, we at least need to have strong, Level-1, evidence to support those claims and mandates.
1. Mian BM, Kaufman RP, Fisher HAG. Rationale and protocol for randomized study of transrectal and transperineal prostate biopsy efficacy and complications (ProBE-PC study). Prostate Cancer Prostatic Dis 24, 688–696 (2021). Doi:10.1038/s41391-021-00352-1
2. National Institutes of Health US National Library of Medicine ClinicalTrials.gov. Transperineal vs. transrectal MRI-targeted prostate biopsy. Updated October 28, 2021. Accessed December 21, 2021. https://clinicaltrials.gov/ct2/show/NCT04815876
3. Lamb A, Bryant R. A randomised controlled trial comparing TRANSrectal biopsy versus Local Anaethetic Transperineal biopsy in Evaluation (TRANSLATE) of men with potential clinically significant prostate cancer. Accessed
December 21, 2021. https://translate.octru.ox.ac.uk/