Nobody wants a prostate biopsy, but we’re stuck with it. Literally. Multiple times. And for the vast majority of men (more than 2 million in Europe and North America alone), those hollow, ultra-sharp biopsy needles go right through the rectum to reach the prostate. Unfortunately, the rectum is just chock full of bacteria, and this, in turn, means a couple of things: the risk of infection and sometimes sepsis, and the need for antibiotics, some of them quite powerful.
Because infection can be such a serious complication, urologists have gone to great lengths to try to minimize it – particularly for men with a chronic illness such as diabetes. These men at higher risk often need a longer course of antibiotics, or different antibiotics. Some options to reduce the risk of infection are to use more than one antibiotic for extra coverage, or to try to tailor the antibiotic to the specific bacteria found in a man’s rectum.
Before a transrectal prostate biopsy, “many urologists routinely swab a man’s rectum to see what bacteria he has, and then give antibiotics based on those bacteria,” says UPMC-Western Maryland urologist Michael Gorin, M.D. “But despite our best intentions, sometimes these antibiotics fail to prevent an infection. Additionally, antibiotics can cause complications on their own.”
If only there were alternative. Wait! There is! It’s a different way to reach the prostate: through the perineum, the area between the scrotum and rectum; this is called transperineal prostate biopsy. Now, don’t get too excited: Neither kind of prostate biopsy is ever going to be fun. However, the perineal approach has some important advantages. One big one: a near-zero risk of infection! “With the transperineal approach,” says Gorin, the risk of infection is so low that many performing this procedure don’t give any antibiotics at all! This is because instead of passing through the rectum, the needles go through the skin, which can be thoroughly cleansed before the procedure.” Gorin helped pioneer the transperineal approach while on the faculty at Johns Hopkins, and is one of the authors of an article that is shaking up the world of prostate biopsy: “TRexit 2020: why the time to abandon transrectal prostate biopsy starts now.”
The paper’s first author, and a leading proponent of the transperineal approach, is Australian urologist Jeremy Grummet, M.B.B.S., Associate Professor of Urology at Monash University in Melbourne. Grummet made a formidable argument in favor of transperineal biopsy at the American Urological Association’s annual meeting in 2017, in a presentation that featured, memorably, a slide of an angry poop emoji with these talking points: “TRUS biopsy is dirty,” and “We use antibiotics instead of basic hygiene.”
That image was followed by a picture of a headline from Bloomberg News, about fears of an “Antibiotic Apocalypse” being stoked by antibiotic-laden chickens. What’s happening in big agriculture, Grummet says, “is a very close analogy to what we do in hospitals. There’s an extraordinary lack of hygiene, replaced by the use of antibiotics. It works in the short term, but it also produces an immense amount of antibiotic resistance.” The antibiotics often used with transrectal biopsies are fluoroquinolones; however, “fluoroquinolone-resistant organisms, also known as ‘Superbugs,’ have been identified in 10 to 30 percent of patients undergoing rectal swab cultures before biopsies,” Grummet notes, “and the incidence of hospitalization due to severe infections after prostate biopsy is increasing.” A 2015 study of 455 patients in a VA hospital in Boston found that 2.4 percent of the men developed sepsis after prostate biopsy, and 90 percent had fluoroquinolone-resistant bacteria. In addition, side effects of fluoroquinolones can be serious or potentially disabling, including gastrointestinal distress, depression, disorientation, tendonitis and tendon rupture, pain in the muscles and extremities, and gait disturbances.
Lack of hygiene? But… but… don’t men do an enema before biopsy? That cleans it, right? Sadly, not really. An enema flushes out poop, but it does not eradicate rectal bacteria. It can’t. “You can imagine, sticking a needle into a rectum, which is purpose-built for feces, absolutely crawling with bacteria. It’s a dirty procedure; you take a clean needle, and put it through a contaminated area: that’s what a transrectal biopsy does every time. You’re playing roulette with your needles; you have no idea if you’re inoculating bacteria with rectal flora into the prostate. We try to overcome that with antibiotics.”
Going through the rectum, Grummet continues, goes against the basic surgical principle of sterile technique. “Why do we wear gloves, why do we wash our hands? Yet we completely turn a blind eye to that whole principle when we do a transrectal biopsy.”
What if, he says, “we could eradicate prostate biopsy sepsis? And what if we could do it without using big-gun antibiotics on a global scale? We can and we have.” In a multi-center study of transperineal biopsy in Australia, Grummet and colleagues showed that of 245 consecutive men who received transperineal biopsy, there were zero readmissions for infection. “Our series has since grown to 1,194 consecutive cases at five centers across Melbourne, with no complications and zero hospital admissions for infection.”
The actual perineal approach, itself, is not new, notes PCF-funded investigator Edward Schaeffer, M.D., Ph.D., Chair of Urology at Northwestern University’s Feinberg School of Medicine. “Transperineal biopsies have been around for several decades, and offer an opportunity to sample all regions of the prostate very efficiently” (more on this below). However, there was a good reason why they weren’t popular: “The limitations of transperineal biopsies in the past were that they required general anesthesia, as they are quite painful. Newer techniques in regional prostate blocks have enabled the use of in-office, awake, transperineal approaches.”
This may prove to be the big selling point for many urologists, says Grummet. “TRUS biopsy has been, certainly in Australia, a well-reimbursed procedure. You can do it in five minutes in your office. Because transperineal biopsy traditionally required a general anesthetic, it took longer and used hospital resources and personnel. It has been less convenient.”
Although Gorin routinely does transperineal biopsy in the outpatient setting, it’s a little different in Australia. In his home state of Victoria (over 5 million people), transperineal biopsy is more commonly performed than transrectal biopsy,” says Grummet. “In our practice, no one gets a transrectal biopsy; the transperineal procedure is common across Australia.” However, he adds, it is still done mainly in the hospital, under general anesthesia. “Only a few of us over here have shifted to local anesthetic. I have done only a handful with local anesthetic, and then COVID-19 hit,” and outpatient procedures were severely limited. Now that the country is opening up, he plans to do more transperineal biopsies with the local anesthetic and nerve block. “With the general anesthetic, transperineal biopsy is essentially perfect. But with the local nerve block, even if the pain relief is not perfect – if there’s some minor discomfort – if the overall greater good is to avoid infection, that is by far a bigger win than some mild discomfort. But if it’s too painful, we shouldn’t be doing it.”
Going in sideways: But wait! There’s more! Gorin and Grummet explain that not only is the transperineal prostate biopsy cleaner, there’s reason to believe this approach is more accurate, better able to sample the prostate’s anterior region – an area that Schaeffer and colleagues have shown to harbor more aggressive tumors, particularly in African American men.
Besides the risk of infection, there’s another big drawback to the transrectal approach: it’s hard to cover the entire prostate. Basically, as Schaeffer explains, if you think of a prostate as a house, the transrectal biopsy comes in from the basement. It’s pretty good at reaching the main floor, but not that great at reaching the attic. It’s a South to North approach. The transperineal approach goes from West to East, and instead of a house, let’s think of a car: The needle comes in from the headlights to the tail lights, but it can go lower, from the front tires to the back tires, or higher, from the front windshield to the rear windshield.
Is there a downside to the transperineal approach? Although there is not any published evidence, Grummet says, “there seems to be increased scarring of the apex of the prostate in patients who have had transperineal biopsy. That would make sense, because instead of moving the needle along the back of the prostate, which is what you do in TRUS [trans-rectal ultrasound-guided] biopsy, the needle in a transperineal biopsy is coming in at the apex. I certainly haven’t seen any evidence that it actually affects the outcome of surgery.” Another potential downside, as with transrectal biopsy, is of urinary retention, particularly in men with a large prostate who have more needle cores taken. “The more cores you take, the more swelling there is. Our published rate of retention is 2.5 percent; that is entirely reasonable. Urinary retention is not life-threatening like sepsis is; you put a catheter in, and you take it out the next day.” Another risk, as with the transrectal approach, is a “temporary, mild reduction of erectile function,” from inadvertently grazing the nerves involved in erection, “but this risk occurs in transrectal biopsy too.”
How can I get a transperineal biopsy? Unless you live in Australia, or you happen to live near one of the few places in the U.S. where they are being performed, you probably can’t. Yet. But that is expected to change fairly soon, as more urologists are performing this procedure.
