Melanie Cole, MS (Host): Welcome to Better Edge, a Northwestern Medicine podcast for physicians. I'm Melanie Cole. And joining me today is Dr. Edward Schaeffer. He's the Chair of the Department of Urology and the Harold Binstein Professor of Urology at Northwestern Medicine, and he's here today to highlight transperineal versus transrectal MRI for targeted and systemic prostate biopsy.

Dr. Schaeffer, thank you so much for joining us today. Can you start by providing us a little bit of an overview of the PREVENT randomized trial and your role as the co-primary investigator and site lead at Northwestern?

Dr Edward Schaeffer: Yeah. Thank you very much for asking. Prostate cancer is the most common cancer diagnosed in men and the diagnosis is made through a prostate biopsy. Traditionally, this biopsy was done with a transrectal approach, that is a needle traverses through the wall of the rectum sampling tissue within the prostate. This is a very effective way at identifying prostate cancers, but does carry some risk because there can be deposition and seeding of the prostate with bacteria or that are present in the rectum. Recently, there's been an evolution in types of prostate biopsies that can be performed, and there has been an interest in performing biopsies with a percutaneous transperineal approach. The benefit of this type of prostate biopsy is that it does not enter or involve the rectum at all, and therefore is considered to be a clean procedure. So, the purpose of the PREVENT trial was to determine if, with a transperineal prostate biopsy ,you could more safely sample prostate tissue and accurately diagnose men with prostate cancer.

Melanie Cole, MS: It's a fascinating study. So, it was funded by the National Cancer Institute. What inspired the design of the trial, doctor?

Dr Edward Schaeffer: Well, there's been a significant rise in the amount of multi drug resistant bacteria in healthcare, and all of our listeners know that, and we are not immune to that within urology. There's a huge increase in the amount of fluoroquinolone-resistant bacteria seen in individuals presenting with urinary tract infection and other systemic infections. Many and much of this resistant bacteria resides within our enteric tract within the gut. And so, one of the issues and concerns we have as urologists is when performing transrectal prostate biopsy, if you seed and introduce multidrug-resistant bacteria into the prostate, this could result in a serious infection. So, the impetus behind the study was really, can we perform a percutaneous clean biopsy, sampling the prostate in a fashion that is safer from an infection perspective than a transrectal approach?

Melanie Cole, MS: This study was conducted at 10 sites throughout the U.S. Can you provide a little bit of an overview of the study methods and results? What did you find out?

Dr Edward Schaeffer: The purpose was to determine if a transperineal prostate biopsy could be performed safely in men who had indications for a biopsy to begin with. That is, they had an elevation in their PSA blood test, had an MRI that was performed that demonstrated a suspicious lesion. If they met that criteria at these different sites, including Northwestern, Johns Hopkins, Memorial Sloan Kettering, Cornell, et cetera, they would then be randomized to receive either a traditional transrectal biopsy or this more newly developed and evolved transperineal approach. So, it was a one-to-one randomization. We included 658 men in the randomization. And the primary outcome of the study was infections after the biopsy. Individuals who had a transperineal biopsy had the biopsy with local skin prep only and no antibiotics. Individuals who had a transrectal biopsy, they were given directed prophylaxis and then subsequently had their transrectal biopsy approach.

The main outcome measure was infection. We also looked at other complications, including urinary retention, bleeding, pain, and the detection of clinically significant prostate cancer. The study found that there were zero infections in individuals undergoing a transperineal biopsy, even withholding antibiotics. This was compared to a 1.4% infection rate for individuals who underwent a transrectal prostate biopsy. So, the difference between 0% and 1.4% in this study was not statistically significantly different, but we as investigators and authors believe that although not statistically significant, the difference between 0% infections and 1.4% infections between the two arms of study is clinically significant, particularly because those who received the transperineal biopsy approach required no antibiotics for their procedure.

Additionally, we found that individuals had no difference in rates of urinary retention or bleeding after the biopsy, independent of the approach. We found that the detection of clinically significant meaningful cancers did not differ between both arms of the study. And therefore, we were able to meet our primary endpoint where we evaluated whether or not there was differences in infection, and we can ensure that the transperineal approach did not compromise cancer detection in these individuals.

Melanie Cole, MS: Dr. Schaeffer, based on the study findings, as we think about the implications for the use of transperineal biopsy without antibiotic prophylaxis in terms of infectious complications, speak about how the consideration of those factors and antibiotic stewardship, how it's guiding clinical decision-making. I'd like you to speak about that and tell other providers, as they're thinking about this, how it informs clinical decision-making regarding this biopsy approach.

Dr Edward Schaeffer: I think the transperineal prostate biopsy approach will emerge as the new standard of care. And in fact, I think our 10-center trial, the PREVENT trial, will really act as the foundation that really establishes it as a new standard of care. The other nice component of the work is that when done properly, we demonstrate that a transrectal prostate biopsy can be done safely. We believe that with time, all investigators, all urologists throughout the U.S. and the world will recognize that TP prostate biopsy or transperineal prostate biopsy is a better biopsy. But by utilizing the protocol that we deployed in this trial, we can also reassure individuals who are currently performing transrectal prostate biopsies that you too can do it safely based on the protocol design we had.

Melanie Cole, MS: Based on that, Dr. Schaeffer, I have a couple of questions for you. First, what about training and expertise? Can you speak a little bit about the learning curve for the transperineal biopsy? And I know we're discussing antibiotic prophylaxis, but how does that choice between the TP and transrectal impact patient comfort and acceptance? Can you tell us those two points?

Dr Edward Schaeffer: Fundamentally, transperineal and transrectal prostate biopsies are similar in that you use an ultrasound probe to visualize the prostate and then place needles directly into suspicious areas within the prostate. There are some mechanistic differences between the two biopsy approaches, and I do believe that there's a learning curve for really safely and effectively developing and deploying transperineal biopsy within a practice. In my mind, that's somewhere between 10 and 15 proctored prostate biopsies. We presently run intermittently through the year at Northwestern courses in how to perform transperineal prostate biopsy. This is an effective way to get started. And then after one gets started, I think having a proctor be present and help guide you through 10 to 15 biopsies is very helpful and enables you to perform a safe and effective biopsy for the patient.

Now, the other considerations when thinking about what type of prostate biopsy is best for your practice has to do with antimicrobial stewardship. Antimicrobial resistance, or AMR, is really the silent pandemic that is really widespread not only in the U.S., but throughout the world. During COVID-19, for example, there was much increased utilization of deployment of antibiotics for a variety of symptoms.

Individual patients were afraid to go to their doctor with real due cause, and often physicians would just prescribe medications without thorough examinations and without a thorough assessment. That's resulted in a marked increase in the amount of multidrug-resistant bacteria that exists within our communities. And so, one of the nice things about the transperineal prostate biopsy is it is a biopsy technique that incorporates all the best practices in terms of antimicrobial stewardship. We don't deploy any antibiotics for the biopsy and therefore, as citizens of the world, we're not increasing rates of drug-resistant bacteria because we're not exposing the bacteria to any drugs. So, it's a nice benefit and I think over time it will improve the state of drug resistance within the bacteria in the U.S. and the world.

One of the other secondary endpoints of the trial was to evaluate pain. in individuals undergoing TP or TR prostate biopsy. And we conducted a 10 point survey to discriminate pain immediately after the biopsy and then within seven days of the biopsy to our patients. We did note on a 1 to 10 scale that people who had a transrectal prostate biopsy on average characterized the biopsy as having a 3 out of 10 discomfort level. Conversely, people who had a transperineal prostate biopsy report their pain is a 3.6 out of 10. This is a statistically significant difference in pain between the two biopsy approaches. However, when evaluating this one through 10 pain scale, that change in pain between the two is not considered to be clinically significant. The good news is that the pain is completely resolved within several days. And by the seven day post-biopsy survey, pain scores were back to baseline, which was zero or one for all individuals.

Melanie Cole, MS: Dr. Schaeffer, do you have any final thoughts you'd like to share with other providers looking forward to areas of research or technological advancements that you're most excited about? Do you have anything you'd like to share?

Dr Edward Schaeffer: I think the trial is a practice-changing trial. And that based on the results of this study, transperineal prostate biopsy without antimicrobial prophylaxis will really become the standard of care for how we perform prostate biopsies in the U.S. and the world. I'd like to thank all the patients and investigators of the study that helped make it happen.

Melanie Cole, MS: Well, thank you so much, Dr. Schaeffer, for joining us today and sharing your incredible expertise and this fascinating study with us today. To refer your patient or for more information, please visit our website at breakthroughsforphysicians.mm.org/urology to get connected with one of our providers. That concludes this episode of Better Edge, a Northwestern Medicine Podcast for physicians. I'm Melanie Cole. Thanks so much for joining us today.