Breaking: Transperineal biopsies find more prostate cancer, but also cause patients more pain and embarrassment

Become an AS CaveMan? See below.

(Editor’s note: Please take a minute to respond to this survey on your experience with transperineal vs. transrectal biopsies: https://forms.gle/T5pRqU5ravLVQ8xk7 This is today’s topic, and I’ll run a follow-up.)

By Howard Wolinsky

The debate over transperineal vs. transrectal biopsies rages on, as there have been four major randomized trials published in the past year.

The latest round took place in a “game-changer” session at the European Association of Urology Annual Congress in Madrid March 23.

(Slide: Dr. Declan Murphy.)

This was the largest study of its kind to date with 1,126 patients and was presented by a British group led by Dr. Richard Bryant, an academic urologist at the Nuffield Department of Surgical Sciences at University of Oxford, who I snagged for an interview.

Most recent research has aimed at teasing out which biopsy approach—through the sterile perineum between the anus and testicles (transperineal) vs. through the germy rectum (transrectal)—is safer.

2,000 men/year die?

The stakes are high for us. Norwegian researchers have reported that 2,000 American men per year die from sepsis, the life-threatening condition that occurs when the body's immune system overreacts to an infection leading to widespread inflammation and organ damage.

EAU took this to heart (see sidebar) and in 2021 declared TP the preferred biopsy.

But American urologists from Missouri and elsewhere in the Land of Brave were skeptical. And the American Urological Association has emphasized the need for randomized trials, the highest-level of evidence, before taking a new stand. Fair enough.

In AUA-land, TP and TR were given equal preference in its 2023 guidelines.

Here comes TRANSLATE

Bryant looks at the biopsies from what may be the best angle: Which biopsy finds the most cancers. That was the goal in what is called the TRANSLATE trial.

He told The Active Surveillor in an interview: “I've always said that a man doesn't have a biopsy to avoid an infection, right? A man has a biopsy to either find, or hopefully not find in his case, clinically significant prostate cancer that needs treatment.

“So when my colleague and co-lead Alastair Lamb and I set up this trial in the UK about four years ago, we set out to evaluate the transperineal biopsy approach in the clinic, in the outpatient setting, against transrectal biopsy (TR).

“And for the primary outcome, we decided that the most important thing to look at is the detection rate of what we call “clinically significant” prostate cancer. Because as I just said a few moments ago, that is why the man is having the biopsy in the first place, right?”

The TRANSLATE researchers found more cancers—the goal—with the “local anesthesia transperineal” (LATP) group than with transrectal biopsy ultrasound (TRUS) group.

The key take-home, Bryant said, was in patients randomized to receive the LATP biopsy as compared to the TRUS, “We see an uplift a 5.7% uplift in the detection rates” of clinically significant prostate cancer, defined as Grade Group 2 or higher.

He said: “This is the first trial that I'm aware of that shows that finding.”

He stressed that TRANSLATE found: “Transperineal biopsy was superior for detection of grade group 2 and higher prostate cancer.”

Dr. Jim Hu, a researcher at Weill Cornell said TRANSLATE probably found more cancers because LATP “inherently samples more of the [prostate’s] peripheral zone vs. TRUS.” He said LATP’s “trajectory of samples from posterior to anterior captures the transition zone [the region of the prostate gland that surrounds the urethra] in smaller prostates.”

Hu led the PREVENT randomized trial in 2024 that found patients undergoing LATP zero cases of infection versus four (1.4%) in the TRUS group, showing a trend—though not persuading critics. Results from another study is coming within a yeae.

Finding prostate cancers may be #1, but there are other issues. I constantly hear complaints from U.S. patients about pain experienced in LATPs with localized anesthesia.

LATPs were designed to be performed in a urology office. But there has been a trend in the U.S. of men opting to go under general anesthesia in the operating theater for these biopsies.

Typically, these men say: “It was the best nap I’ve ever had.” But general amnesthesia can carry risks of its own to ask your urologist.

But TRANSLATE didn’t cover general anesthesia OR procedures, and the UK’s National Health Service would probably never pay for general anesthesia for everyone for these biopsies—too expensive, though Medicare patients get this coverage in the U.S. (Don’t tell Elon Musk and his cost-cutting raiders at DOGE.)
A major point of contention is infection-related events, especially sepsis.

TRANSLATE indirectly measured sepsis by counting the number of patients in the groups who were hospitalized within 35 days of their biopsies.

“We had fewer infection-related events for those who had the LATP transperineal biopsy. That's an important finding,” Bryant said.

Dr. Badar Mian, a urologist and researcher at Albany Medical College, argued that no cases of sepsis were reported in TRANSLATE.

Bryant said a much bigger trial would be required to reach statistical significance for infection-related complications of prostate biopsy.

At 35 days after biopsy, two patients randomized to receive transperineal biopsy had been admitted to hospital with infection-related problems. There were nine such patients in the transrectal group.

“Small numbers, but higher for the transrectal group,” Bryant said.

He said a “bonus” in the data was that it showed 88% of patients who underwent the transperineal procedure safely did so without needing antibiotic cover. This is important in trying to prevent development of antibiotic resistance. (See below.)

Bryant said: In the TRANSLATE protocol, we stated that the men having the transperineal biopsy ought to have it without antibiotic cover. Now, we did have some protocol deviations, but close to 90 percent of patients had the transperineal biopsy without needing antibiotics at all.

TRANSLATE also found patients generally experienced more pain and embarrassment from LATPs than with TRUS biopsies.

The research, appearing in the current issue of Lancet Oncology, found subjects receiving LATP more commonly reported the biopsy to be “immediately painful and embarrassing (36%) compared with TRUS (27%), and serious adverse events occurred in 2% of the TP group vs, 4% in the TR group.

Serious adverse events (defined as any adverse events that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, or consists of a congenital anomaly or birth defect) were recorded if reported. Serious adverse events occurred in 14 (2%) of 562 participants in the LATP group and 25 (4%) of 564 in the group.

None of these numbers was statistically significant. But Bryant said the numbers, even if insignificant could help guide urologists and patients.

Rersearchers didn’t probe the embarrassment factor. But it may relate to brief exposure of genitals during a transperineal procedure.

Dr. Richard Szabo, a urologist and researcher at University of California, Irvine, said: “As for embarrassment, it is true that the genitals are temporarily exposed at the start of putting a patient in the dorsal lithotomy position [here the patient lies on their back with their legs flexed and abducted-spread apart], but then they are quickly covered up during the procedure.”

ichard Szabo, MD, a prostate biopsy researcher at University of California, Irvine, said the TRANSLATE trial was not powered to specifically investigate post-biopsy infection (a secondary outcome of the study). He noted that reduction in post-biopsy sepsis has been an additional major advantage of transperineal over transrectal prostate biopsy.

Szabo added that in the TRANSLATE trial, the number of post-biopsy hospitalizations due to post-biopsy infections in the first 35 days after transrectal biopsies were 4 1/2 times the number seen with the transperineal approach.

Lots of data. What’s next?

Mian, the urologist at Albany Medical College, where TP and TR biopsies are performed at the same rate, led the 2024 PRoBE-PC, a randomized trial that found patients undergoing TR and TP experience the same rate of infectious or noninfectious complications. “Both biopsy approaches remain clinically viable and safe,” he said.

Mian, who co-authored an editorial to the Oxford study, told The Active Surveillor: “Prior to the randomized clinical studies, alarm had been raised about the large differences in complications and cancer detection between the two procedures. But the 3 large and 1 small randomized studies paint a different picture. The differences in complications and cancer detection turned to be small or none.

“The fractional differences in these outcomes, which are also not consistent across the studies, prevent us from favoring one procedure over the other. It’s time to shift our focus from picking a winner to instead focus whether prostate biopsy procedures are safe and effective. Patients should be reassured that both procedures can be performed safely and with a high degree of accuracy.”

Mian et al’s editorial notes: “Some experts have invoked antibiotic stewardship as the rationale to promote LATP and abandon TRUS. Importantly, none of the RCTs studied the effects of antibiotic prophylaxis on participants.”

They added re antibiotic stewardship: “This important topic requires further dedicated research. In the interim, far more impactful opportunities exist to advance antibiotic stewardship in urology and other medical specialties.”

Howverm Jeremy Grummet, MBBS, MS, FRACS, Director of Urology, Alfred Health, Melbourne, Australia, and Clinical Associate Professor, Monash University, said this position dismisses “the major advantage of not requiring any antibiotics in TPB (transperineal biopsies] and ignoring our crucial role as clinicians in antibiotic stewardship.”

[If you’re having a transperineal procedure, you ought to ask your urologist about this issue. I understand that many American patients who undergo TP in ORs still get antibiotics.]

Grummet, a leader in TRexit—a movement by urologists to end use of TRUS biopsies, said, “Transperineal biopsy is the standard of care across Australia. As a result, post-biopsy sepsis has happily disappeared from our practice.”

He argued, “As we head towards a post-antibiotic era, [continued use of TRUS] is a dereliction of duty to both our own patients, and to public health more generally.

“I do worry that now we have seen in TRANSLATE significantly higher rates of cancer detection with LATP and lower rates of sepsis (although not powered for significance) without any prophylaxis, that ongoing resistance to transperineal biopsies[TPB] may be related more to convenience and/or reimbursement for the surgeon. If this is the case, then simply reimbursing TPB appropriately as a superior form of biopsy could make all the difference. It certainly did in Australia.”

Grummet’s bottom line? “I would simply put that to our patients - which would you prefer?”

End of the road for TRUS biopsies? Not so fast, Dr. Declan Murphy

By Howard Wolinsky

Dr. Declan Murphy, discussant at the EAU plenary, and Director of Genitourinary Oncology, at the Peter MacCallum Cancer Centre, Melbourne, Australia has been a leader in TRexit, a movement to abandon transrectal biopsies.

But he took a moderate position at the plenary. (Watch an in-depth interview on the study with the authors at Murphy’s GU Cast.)

(Slide: Dr. Declan Murphy)

“Is this the end of the road for TRUS biopsy? I don't think it is,” he said.

He concluded that LATP and TRUS biopsy both have merit. He gave TRANSLATE a leg up on the other studies in advocating the transperineal approach for cancer detection—lead author Dr. Richard Bryant’s goal.

Will this research impact AUA guidelines scheduled to be reviewed in 2026? Hard to say though AUA guideline writers like availability of randomized trials in their process,

“The reality of antibiotic stewardship may become even more important in future years. We may be told you cannot use antibiotics for this TRUS biopsy, because you can do the same procedure without antibiotics and have a better cancer detection rate,” Murphy said.

Guideline writers for the European Association of Urology emphasized antibiotic resistance in giving an edge to LATP biopsies in 2021.

Murphy believes urologists needed to emphasize antibiotic stewardship by reducing antibiotic use. Antibiotic resistance is a phenomenon where bacteria become resistant to the effects of antibiotics, making it difficult or impossible to treat bacterial infection. The Centers for Disease Control estimates that 35,000 Americans per year die from antibiotic resistance.

(Slide: Dr. Declan Murphy)

Murphy said, “Cancer detection trumps infection, and what we've seen here from [Bryant et al.] is that cancer detection rate is inferior in the best-powered trial we have to date. And we know that to make prostate biopsy safe transrectally, we must use antibiotics.”

Meanwhile, he said antibiotics resistance “is not going to go away. In fact, it is going to become a bigger and a bigger issue for society in the coming decades. … if we just stop putting the needle through the rectum, we wouldn't have to use antibiotics. And I believe that will become a more and more important issue for us urologists, especially now, a trial is showing you have a better detection rate with no antibiotics.”

He said urologists need to reduce immediate discomfort in these patients. They also need to make procedures shorter to provide relief to patients and offer better cost effectiveness.

Bryant told me that a LATP biopsy takes on average about 12 minutes vs. 8 minutes for TRUS biopsy. You know how it goes: time is money.

Murphy concluded: “All of you in the audience who do TRUS biopsies next week should consider, why am I not doing this LATP biopsy? Because that's what these trials have shown is feasible in all urology practices.”

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How I got involved in the transrectal mess: No more men should die from prostate biopsies

By Howard Wolinsky

In April 2021, I began beating the drums for safer biopsies and moving away from transrectal--what critics call “transfecal”—biopsies that push germs from the rectum into the prostate.

In Medium, the online platform where I used to blog, I published an article entitled “Death by biopsy,” covering how a Norwegian man, Roar Gulbrandsen, a stone mason from Oslo, died unexpectedly from sepsis in 2019.

His daughter Agnes, a beauty shop entrepreneur, was suspicious. It just seemed too much of a coincidence that Roar had had a transrectal prostate biopsy and days later died from an embolism to the brain.

She started raising questions and was dismissed by doctors as “a dumb blonde,” who told her to stick to hair cutting.

Roar’s neurosurgeon demeaned Agnes. Roar’s family doctor refused to give Agnes Roar’s records. Sleuthing takes dedication and often weathering a BS storm. Agnes hung tough.

But her dad’s urologist, Dr. Truls Bjerklund Johansen, a prominent researcher at the Oslo University Hospital, listened and started researching what happened and then explored the bigger picture.

Johansen ultimately revealed what most likely occurred: a silent sepsis, caused by a transrectal prostate biopsy, threw off a septic arterial embolism to the brain that killed Roar,

Urologists generally don’t encounter these situations and don’t make the connection: They’re thinking horses (prostate), not Zebras (brain embolism).

Agnes and Johansen launched a ampaign to change hearts and minds of patients and physicians in Norway and, eventually, around Europe.

Agnes got coverage in the the national press in Oslo to alert men to the dangers posed by biopsies. Overnight men stopped undergoing transrectal biopsies and urologists who wanted to serve patients were forced to switch to transperineal biopses.

(Agness and her dad Roar Guibrandsen.)

Johansen did an epidemiologic study revealing risks from transrectal biopsies.In 2019, he reported that 2,000 American men per year likely died from sepsis from prostate biopsies.

He was dismissed when he made his case to urologists at an AUA meeting. They didn’t believe him.

As someone who underwent six transrectal biopsies early on in my Active Surveillance experiece, I was stunned and angry at what I heard. It seemed unacceptable and avoidable that men were dying from prostate biopsies.

I never got sick from a biopsy, but, on the other hand, a urologist NEVER told I was at risk from a biopsy, either. I mostly took antibiotics, even with an IV, and went about my business. But in some cases I went into this test with bareback—no antibiotics.

[Note: I did get early-stage sepsis following a kidney stone operation. Fever, Headache. My doctor had headed out for vacation after the surgery. He and his residents checked in on me daily.]

And no one was talking about the deadly risks of antibiotic resistance on my prostate watch.

I talked two urologists who are friends of mine. I asked them their sepsis and infection rates. They brushed me off. Both said they were fine, but one said he hadn’t looked recently but was certain his numbers were fine. Rampant arrogance.

European urologists began to listen to Johansen. But here’s the argument that grabbed them: Transperineal procedures dramatically could reduce antibotic resistance.

EAU in 2021 adopted a policy favoring TP over TR.

Debates started to break out where urologists gather, such as at AUA. I hosted a urologist debate at an AnCan meeting. I presented the case in Salon. (To read more: go to https://ancan.org/transperineal-prostate-biopsies/) I wrote a comparison of EAU vs. AUA policies in Medscape.

Now we have the large randomized trial, TRANSLATE, (see above), that found more cancers can be detected with TP.

Let’s see whether this moves the needle at AUA.

In 2023, I served as patient reviewer, repping AnCan on an AUA review panel that touched on several topics, including TP vs. TR. I warned the AUA that their patients’ houses were on fire with TR. and the urologists were waiting to call the fire brigade out once the fire had sputtered out on its own.

Maybe 2026 will bring us new direction from AUA?

Meanwhile, feel free to sign my petition to phase out transrectal biopsies:

https://www.change.org/p/time-to-phase-out-the-transrectal-biopsies-for-prostate-cancer

Join the AS CaveMen? Going small again.

Thrainn Thorvaldsson is the developer of the first support groups only for men on Active Surveillance.

He started small with meetings of men with low-risk prostate cancer in his native Iceland. They shared their stories and provided each other support.

Then, he contacted a few of us in the U.S., which led to creation of Active Surveillance Patients International and other AS support groups, such as from AnCan.

ASPI is now getting over 500 registrants for its monthly meetings. It’s impossible to build personal contacts there.

Now, Thrainn, with a little help from The Active Surveillor, is going small again.

We have met quarterly in a group of about 10—from U.S., Canada, Iceland, Ireland, Russia—for the past two years. We shared and updated our stories.

Thrainn is expanding the idea and creating other small groups of 8-12 men.

If you’re interested, contact Thrainn directly: tthorvaldsson@aspatients.org. We’re holding organizing meetings soon and may create groups based on whether they are Gleason 6 or 3+4, age, geography. Looking for group leaders.

We’ll find our way—with your help.

For more on the group, go to: https://howardwolinsky.substack.com/publish/post/159982824