Matthew Allaway: We're going to give a nice current overview of transperineal versus transrectal prostate biopsy. I do have one disclosure. I'm the CEO of Corbin Clinical Resources. If you were practicing urology in the 1970s, you probably remember that the biopsy was done transperineal, and in fact, you probably remember some of these little gizmos that we used to use back in those days. The most popular was the Vim-Silverman needle. This was a pretty big trocar, about seven or eight gauge, pierced through the perineum. Then with a thimble-protected index finger in the rectum, you would help guide that trocar, and often you did obtain prostate tissue, but often you obtained other tissue specimens of pelvic floor muscle or your finger. Ouch.

Then, everything started to change in the 1980s with the development of the transrectal ultrasound, and for the past 35 years, the transrectal ultrasound-guided prostate biopsy has become the gold standard for the diagnosis of prostate cancer. However, there's been a recent interest in revisiting the transperineal approach for two very important reasons. Have we actually gone back to the perineum?

So what are these two situations that we face with transrectal ultrasound-guided prostate biopsy? Well, the first one, most importantly is infectious complications, mainly due to the emergence of quinoline-resistant gram-negative bacteria, and the second important issue is the missed cancer, which can occur in up to 30% of cases after a TRUS biopsy. Let's take a closer look at the infectious complications. Globe's Group in 2011 published a very important manuscript in the White Journal which really brought front and center the complications of the TRUS biopsy. What they did was they tracked the code 55700 and they tracked through Medicare database 30-day admissions. The rate of admission was 6.9% and a vast majority of these patients were hospitalized due to infectious or sepsis complications. Across the pond, a prospective multinational, multicenter prostate study examined the same type of incidents and found the sepsis rate to be 5%.

In 2014, the AUA Improvement Summit convened in Washington D.C. to discuss these complications after needle biopsy, and they gave us two important recommendations. The first I call the smart bomb approach. This is basically where you do a rectal swab and you culture for the presence of these nasty little quinoline-resistant bacteria. Second suggestion was augmented or the shotgun approach, where you basically layer additional antibiotics just to cover all the bases.

Well, how did these two approaches fair? Well, last year we had two important manuscripts that were published. The first was published with Richard Szabo's group and Kaiser Permanente. 15,000 biopsies were analyzed and they have strict data on who had a rectal swab and who had the augmented approach. No statistical difference. In fact, on secondary analysis, there was a slight preference to the augmented arm. And internationally, they looked at the same question randomizing to rectal swab versus augmented. Again, found no significant difference with a sepsis rate of 2% in both groups.

Jeremy Grummet from Melbourne, Australia, who's been very passionate about transperineal, looked to answer the question with every peer-reviewed manuscript on transperineal biopsy. He pulled over 6,000 patients and found the sepsis rate to be 0.07%. And this manuscript just hit the press a couple of weeks ago from China, the randomized transrectal to transperineal, and they found a hospitalization rate of 0% in transperineal and hospitalization rate of 7.4% in the transrectal group, with a vast majority of those hospitalizations again due to infection and sepsis.

Let's take a closer look at this missed cancer or cancer detection rates. I feel that one of the most important manuscripts in the last few years on diagnosis is the PROMIS trial. The PROMIS trial was exceptionally important because they took 576 men, they all got MRIs by an experienced radiologist, they all received a transperineal biopsy saturation method, and they all had a 12 core TRUS biopsy. They've just published, it's in press now, their sub-analysis of the transrectal transperineal group. I feel this is a great reference point of comparing the two approaches as far as cancer detection is concerned.

Here are the results. If we look at just cancer detection of all types, all grades, 20% more pickup rate in the transperineal group versus transrectal. If we just look at clinically significant cancer, we also see a 20 point advantage in the transperineal arm. In fact, if you look at the patients in the transrectal biopsy group that had grade group one, 95 of the 135 patients that had grade group one were reclassified with the transperineal biopsy 70% of the time. In fact, 11% of the patients were reclassified as grade group three or higher.

So if the PROMIS trial transperineal does show some advantage from a cancer detection standpoint, then why aren't we doing it? Well, for one thing, who has the time to spend an hour doing a transperineal template-guided prostate biopsy? Number two, brachytherapy, grid step or stabilizer can be a little rambunctious and a little challenging to deal with at times. And finally, and most importantly, it can't be performed in the office. The resources and the learning curve are also a bit of a challenge. And let's not forget the data from the Picture Study, which is essentially an analysis of all those men, the 576 men in the PROMIS trial. When they looked at complications, they were pretty staggering. Retention rate, 24%. Perineal pain and hematoma, 40% and importantly, a reduction in their erectile function score by 23%.

But there's been a movement afoot to take the transperineal approach to what we call the freehand approach. The freehand transperineal biopsy can be performed essentially two methods. One is the simple angiocath method where one hand's on the ultrasound probe, the other hand's on the biopsy gun which you then re-insert through either a cheap hypodermic needle or some other type of coaxial needle.

What does the data look like for those cohorts? The first trial was from the group out of Toronto, Les Spevack's group was struggling with a sepsis rate of 4%. We trained them on this methodology and they took 1200 patients consecutively and most importantly, it was only local anesthesia. They had a modest cancer detection rate of 49% and most importantly, no sepsis. DiBianco, Similar cohort of patients, over 375 patients who had again the coaxial needle approach. What was important in this study to highlight was the mean procedural time of 7.9 minutes, respectable cancer detection rate and importantly, no sepsis.

Second option for the freehand approach is a device-driven approach. This is the precision point system, which utilizes two punctures in the perineum to deliver a full sampling of the prostate. There are two trials that we can discuss with this approach. The first is from Rick Popert's group from Guy's Hospital in London. These were 176 men that were all screened with MRI. Important findings and this was the fact that their cancer detection was 79% overall. Most importantly was in the MR negative patients, 61% of those patients had cancer. Now, these were men that were selected based on PSA density of 15% or higher, family history, et cetera, and 60% of those patients, of those cancers I should say, did have clinically significant disease and no sepsis.

The second trial is from UConn. It's 1,000 patients who underwent their first biopsy transperineal device-driven, and they looked at the experience of going from a coaxial needle into a device-driven approach from a shotgun approach, right and left to a strategic 10 sector mapping. And most importantly, with the 10 sector device-driven approach, the cancer detection rate was comparable to the cancer detection rate seen in the PROMIS trial for the transperineal cohort at 70% with a slightly higher clinically significant rate of 51%. Statistical significance was seen in the device-driven versus the coaxial needle approach, which you can see below. And most importantly, no sepsis.

So are we truly as urologists at a fork in the road? Is revisiting the perineum the direction we want to go? This is a difficult question. Can we wait for residents to be trained on new methods or do we have to train ourselves, and we have to work together to find better ways to mitigate some of these concerns? That's the question we have for all of you. Thank you.