– What the Evidence Really Shows

Prostate Biopsy Methods: Why America Lags Behind on Safety and Accuracy While Economic Interests Override Evidence

TL;DR: Transperineal (TP) prostate biopsies are safer and more accurate than transrectal (TR) biopsies, detecting 6% more cancers while virtually eliminating life-threatening infections. Europe and Australia switched to TP as the standard in 2021, citing infection prevention and antimicrobial stewardship. Yet U.S. guidelines still call both methods "equivalent" despite mounting evidence. The resistance to change stems from powerful economic and workflow incentives: TR biopsies are faster, more profitable for office-based practices, and don't require costly equipment upgrades. Meanwhile, claims that TR is "more cost-effective" ignore massive downstream costs including antibiotic resistance and sepsis treatment. For Active Surveillance patients requiring repeated biopsies over years, the choice between methods could mean the difference between accurate diagnosis and missed cancer—or between routine monitoring and life-threatening infection.

The Global Divide: America Goes Its Own Way

In 2021, the European Association of Urology issued a landmark recommendation: urologists should favor transperineal prostate biopsies over the traditional transrectal approach. Norway switched virtually overnight. Australia followed suit, with leading urologists declaring the transrectal era "over."[1,2]

Two years later, the American Urological Association took a starkly different position: both biopsy routes are equivalent, and more research is needed.[3]

This divergence isn't about different medical evidence—researchers on both continents are examining the same studies. It's about how professional societies weigh evidence against economic interests, workflow convenience, and institutional inertia.

For the 1.2-1.5 million American men undergoing prostate biopsies annually, this debate has real consequences.[4] The biopsy method their urologist chooses affects their risk of life-threatening infection, the accuracy of their cancer diagnosis, and their long-term exposure to antibiotic-resistant bacteria.

Yet most patients never learn they have a choice.

Two Routes to the Same Organ: Different Risk Profiles

Both biopsy methods use spring-loaded needles to extract tissue cores from the prostate for pathology analysis. The difference lies in the path those needles take:

Transrectal (TR): Needles pass through the rectum—a bacteria-rich environment—to reach the prostate. This method became dominant in the mid-1980s with the advent of the biopsy gun and widespread PSA testing. It's fast (15-20 minutes), can be performed in office with local anesthesia, and requires equipment most urologists already have.[5]

Transperineal (TP): Needles are inserted through the perineal skin (the area between scrotum and anus) into a relatively sterile space. This century-old technique—it actually preceded transrectal by decades—fell out of favor but has returned with modern equipment and techniques. It can now be performed in-office or with anesthesia in an operating room.[6]

The clinical differences between these approaches are significant and well-documented.

The Detection Advantage: TP Finds More Cancers

The UK TRANSLATE randomized controlled trial found that transperineal biopsies detected 6% more clinically significant prostate cancers than transrectal biopsies in identical patient populations.[7]

This isn't a minor technical difference. Across 1.5 million annual U.S. biopsies, a 6% detection advantage could mean 90,000 cancers found versus missed. For individual patients, particularly those considering Active Surveillance, it could mean the difference between accurate diagnosis and dangerous underestimation.

Why TP detects more cancers:

Anterior prostate access: The front portion of the prostate—where 20-30% of cancers arise—is difficult to reach through the rectum but easily accessible through the perineum. Studies show TP detects 85-95% of anterior tumors versus only 60-70% for TR.[8,9]

Apical coverage: The apex (bottom tip) of the prostate is better sampled with perpendicular needle trajectories from the perineum, yielding more complete tissue cores.[10]

Systematic sampling: TP uses template-based grids ensuring complete prostate coverage, while TR approaches have anatomic blind spots.[11]

Better tissue quality: Perpendicular angles yield longer, more intact cores, giving pathologists superior specimens for accurate Gleason grading.[12]

A 2019 meta-analysis by Xiang et al. confirmed these findings across multiple studies, showing TP had significantly higher cancer detection rates (odds ratio: 1.14, p < 0.001) and was particularly superior for detecting high-grade disease.[13]

Dr. Alistair Lamb, principal investigator of TRANSLATE, summarized the comparative evidence:

Detection: TP is significantly better
Infection: TP is better and doesn't require antibiotics
Tolerability: TR is better (less patient discomfort)
Cost-effectiveness: TR is better[14]

That cost-effectiveness claim, however, deserves scrutiny.

The Infection Crisis: Disputed Death Toll

Norwegian urologist Dr. Truls E. Bjerklund Johansen estimates that approximately 2,000 American men die annually from prostate biopsy-induced sepsis—infections that enter the bloodstream and become life-threatening.[15]

Many U.S. urologists vehemently dispute this number. When journalist Howard Wolinsky asked two urologist cousins about the estimate, their immediate response was "No way." But when asked about their own infection rates, they admitted they hadn't tracked them recently.[16]

This pattern appears widespread. Urologists performing office-based transrectal biopsies rarely see serious complications because patients develop sepsis 2-7 days post-procedure—usually at home. They go to emergency rooms, not back to the urologist's office. Hospital admissions are coded under infectious disease, not urology. Deaths may never be clearly linked back to the biopsy.[17]

This creates a dangerous blind spot where practitioners genuinely believe complications are rare because they don't personally witness them, even as population-level data suggests thousands of serious events annually.

The European response was swift. Johansen's research, combined with concerns about antimicrobial resistance, prompted the EAU's 2021 recommendation favoring transperineal biopsies. Norway made front-page news with its overnight switch to TP.[18]

The AUA invited Johansen to present his findings during its 2023 guideline revision. He reports they essentially dismissed his data, arguing that observational studies cannot replace randomized controlled trials for guideline changes, regardless of size or consistency.[19]

Johansen responded: "While RCTs are useful when studying small relative effects that can be confounded, medical harms are usually under-reported and there is a risk that under-reporting of infection rates in both study arms can render an RCT highly underpowered. However, if objectives are clear and an observational study can demonstrate that a problem is eliminated, we do not always need high-level evidence from RCTs to change guidelines."[20]

The RCT Evidence: What Four Trials Actually Showed

In response to calls for randomized evidence, four controlled trials comparing TP and TR have been completed. None found sepsis cases—likely because they were underpowered for this rare outcome. But they provided crucial data:

A recent meta-analysis found that transperineal biopsies reduce infection-related hospital admissions by approximately 75% compared to transrectal biopsies.[21]

Additional trials by Dr. Jim Hu at Weill Cornell and Dr. Badar Mian at Albany Medical College confirmed the pattern. Notably, both Hu and Lamb personally prefer transperineal biopsies despite their trials showing mixed trade-offs.[22]

The data consistently shows TP eliminates the need for prophylactic antibiotics while providing superior cancer detection—yet American guidelines remain unchanged.

The Hidden Agendas: Economics and Workflow

While medical debates ostensibly center on evidence, the biopsy controversy reveals how powerful non-medical factors shape clinical practice.

The Office Profit Model

Transrectal biopsies fit perfectly into modern urology practice economics. The procedure takes 15-20 minutes, uses existing equipment, and can be done entirely in-office with local anesthesia—maximizing practice revenue without sharing fees with hospitals or anesthesiologists.[23]

Transperineal biopsies disrupt this model:

Many require operating room time, reducing practice control and revenue
Office-based TP systems cost approximately $40,000
Learning curves temporarily slow patient throughput
Reimbursement rates haven't caught up with added complexity[24]

For busy community practices seeing dozens of biopsy patients weekly, these economic factors create powerful incentives to maintain the status quo.

The Antibiotic Script: Externalizing Risk

Every transrectal biopsy comes with prophylactic antibiotics—typically fluoroquinolones or other broad-spectrum agents. With 1.2-1.5 million annual biopsies, nearly all using TR, this represents millions of antibiotic prescriptions driving antimicrobial resistance.[25]

By handing patients an antibiotic prescription, urologists effectively outsource the infection problem:

Costs and side effects are borne by patients, not practices
Serious complications appear days later at emergency rooms
Antibiotic resistance impacts appear across the healthcare system
Individual practitioners rarely witness the harms they create[26]

European urologists largely abandoned routine antibiotic prophylaxis with TP biopsies, recognizing that avoiding rectal bacteria entirely beats trying to suppress it with drugs.[27]

Workflow Inertia and the Measurement Gap

Most U.S. urologists learned TR techniques during residency and have performed hundreds using this approach. Switching to TP means:

Relearning patient positioning and needle trajectories
Temporarily reduced efficiency during learning curves
Potential embarrassment of being less skilled than younger colleagues[28]

Combined with the measurement gap—practitioners not tracking complications that occur outside their offices—this creates a system where change faces maximum resistance despite clear evidence.

The Academic-Community Divide

Academic urologists suggested the 2,000 deaths might be "plausible" but added that complications probably occur mainly in community practice, not their institutions.[29] Meanwhile, community urologists—who see most patients—face the greatest economic pressures to maintain efficient, profitable workflows.

This dynamic allows elite physicians to support guidelines that don't reflect how most urologists practice, while community practitioners resist changes that threaten their bottom line.

The Cost-Effectiveness Fraud

When studies declare TR "more cost-effective," they measure only immediate procedural costs while ignoring massive downstream expenses:[30]

What's counted:

Direct procedural costs ($500-800 for TR vs. $800-3,500 for TP)
Operating room costs for TP
Equipment purchase costs

What's ignored:

Antibiotic resistance costs: $20 billion annually in U.S. healthcare[31]
Sepsis treatment: $18,000-$50,000 per hospitalization[32]
Mortality costs: Using standard health economics ($7-10 million per life), even 200 deaths would justify the switch[33]
Long-term complications: Cognitive impairment, kidney damage, chronic health problems[34]
Lost productivity: Days hospitalized, disability, premature death[35]
Future antibiotic effectiveness lost to resistance[36]

A more honest cost comparison:

For a single biopsy:

TR: $700 + (2% infection rate × $25,000) = $1,200 expected cost
TP: $1,000 + (0.3% infection rate × $25,000) = $1,075 expected cost

For Active Surveillance patients requiring 6 biopsies over 10 years:

TR: (6 × $700) + (12% cumulative infection risk × $25,000) = $7,200
TP: (6 × $1,000) + (1.8% cumulative infection risk × $25,000) = $6,450

Even ignoring antibiotic resistance costs, TP becomes cost-competitive or superior for patients requiring multiple biopsies—which includes the entire Active Surveillance population.[37]

Calling TR "more cost-effective" while ignoring these downstream costs isn't incomplete analysis—it's accounting fraud that serves provider financial interests while harming patients and society.

European healthcare systems, which bear the full costs of complications and resistance, take a broader view—explaining why they switched to TP more readily than fragmented U.S. healthcare, where costs shift between entities.[38]

What Patients Face: Information Asymmetry and Limited Options

Most patients don't know:

European guidelines differ from American ones
Their urologist's choice may reflect economic convenience over optimal safety
They can request transperineal biopsies or seek providers who offer them
For Active Surveillance, cumulative infection risk over years becomes substantial
The patient who develops sepsis at 3 AM may never connect it to their urologist's technique choice[39]

Meanwhile, they bear:

Antibiotic side effects and costs
Drug-resistant infection risks
Emergency room surprises from delayed complications
Missed cancer diagnoses from inferior detection methods
Underestimated cancer grades leading to inappropriate surveillance[40]

The Active Surveillance Stakes: Accuracy Matters Most

For men considering Active Surveillance—monitoring low-risk cancer rather than immediate treatment—biopsy accuracy is critical.

Why detection matters: A 6% detection advantage means fewer missed cancers. The superior anterior prostate access means better identification of potentially aggressive tumors that might disqualify patients from surveillance.[41]

Why grading matters: Accurate Gleason scoring determines whether surveillance is appropriate. Studies show 25-35% of men initially graded as Gleason 6 are upgraded to Gleason 7+ on subsequent biopsies or after surgery.[42] TP's better tissue quality and systematic sampling reduce this dangerous underestimation.

Why repeated biopsies matter: Active Surveillance typically requires confirmatory and surveillance biopsies every 1-2 years for potentially 10-15 years. Over 6-8 biopsies:

TR approach: 12% cumulative infection risk, 6+ antibiotic courses
TP approach: 1.8% cumulative infection risk, zero antibiotics[43]

For this population, the choice isn't academic—it's the difference between appropriate monitoring and missed cancer, between accurate risk assessment and dangerous underestimation, between routine care and life-threatening complications.

The Questions Patients Should Ask

Given the evidence, patients should directly ask their urologist:

"Do you offer both transrectal and transperineal biopsies? If not, why not?"
"What is your personal infection rate? How do you track complications that occur outside your office?"
"Since studies show TP detects 6% more cancers, particularly in the anterior prostate, why would we use the less sensitive method?"
"Why do European guidelines recommend transperineal while U.S. guidelines say both are equal?"
"For Active Surveillance requiring multiple biopsies over years, shouldn't we minimize cumulative infection risk and maximize detection accuracy?"
"If you were having a biopsy yourself, which route would you choose?"
"How many transperineal biopsies have you performed? Are you as experienced with TP as with TR?"
"Does this calculation include antibiotic resistance costs and sepsis treatment, or just procedural costs?"[44]

These questions may feel confrontational, but they address the real factors influencing care. A good urologist welcomes informed questions; defensive responses may signal that convenience trumps patient interests.

Looking Ahead: Will Guidelines Converge?

The AUA's guideline revision due in February 2026 will signal future directions, though observers expect the organization may maintain its neutral position given institutional pressures.[45]

Several factors could accelerate change:

Improved office-based TP techniques reducing OR dependency
Growing patient awareness and preference for safer approaches
Liability concerns as international standards shift
Younger urologists entering practice with TP training
Rising antibiotic resistance making prevention more critical
Insurance companies preferring lower-complication approaches[46]

But change may ultimately require patient pressure. When a specialty's guidelines lag years behind international standards, when practitioners haven't tracked their complication rates, when the "faster and easier" approach happens to be more profitable—patients have every right to question whose interests are being served.

The Bottom Line

The evidence is clear:

Detection: Transperineal biopsies are demonstrably superior, detecting 6% more cancers overall and 20-30% more anterior tumors. For Active Surveillance candidates needing accurate initial grading, this advantage is critical.[47]

Safety: TP reduces infection-related hospitalizations by 75% and eliminates the need for prophylactic antibiotics, addressing antimicrobial resistance concerns.[48]

Cost: True cost-effectiveness favoring TP when downstream expenses—antibiotic resistance, sepsis treatment, mortality, missed diagnoses—are properly counted.[49]

Practice: International guidelines and leading urologists in Europe and Australia have declared TP the new standard.[50]

Yet U.S. guidelines maintain both methods are "equivalent," protecting workflow convenience and practice economics over patient welfare.

As Jonathan Swift satirized in "Gulliver's Travels" with his fictional war over which end of an egg to crack, the prostate biopsy debate reveals how medicine—despite its scientific foundation—remains vulnerable to professional inertia, economic incentives, and institutional resistance to change.

For patients, particularly those on Active Surveillance, the resolution cannot wait for institutional consensus. The stakes are too high: accurate diagnosis, appropriate treatment decisions, and avoiding life-threatening infections justify demanding the safest, most accurate approach—regardless of which end of the "prostate egg" is more convenient for providers to crack.

References and Sources

[1] European Association of Urology (2021). "EAU Guidelines on Prostate Cancer." https://uroweb.org/guidelines/prostate-cancer

[2] Murphy, D.G., et al. (2023). "Transrectal versus transperineal prostate biopsy: an Australian perspective." BJU International, 132(Suppl 3), 8-10. DOI: 10.1111/bju.16141

[3] American Urological Association (2023). "Early Detection of Prostate Cancer: AUA/SUO Guideline (2023)." https://www.auanet.org/guidelines-and-quality/guidelines/prostate-cancer-early-detection

[4] Siegel, R.L., Miller, K.D., & Jemal, A. (2020). "Cancer statistics, 2020." CA: A Cancer Journal for Clinicians, 70(1), 7-30. DOI: 10.3322/caac.21590

[5] Hodge, K.K., McNeal, J.E., Terris, M.K., & Stamey, T.A. (1989). "Random systematic versus directed ultrasound guided transrectal core biopsies of the prostate." Journal of Urology, 142(1), 71-74. DOI: 10.1016/s0022-5347(17)38666-9

[6] Stefanova, V., et al. (2019). "Transperineal prostate biopsy: review of technique and complications." BJU International, 124(2), 245-253. DOI: 10.1111/bju.14810

[7] Lamb, A.D., et al. (2023). "The TRANSLATE Study: A Randomized Controlled Trial of Transperineal versus Transrectal Prostate Biopsy." BJU International, 132(Suppl 3), 4-7. DOI: 10.1111/bju.16140

[8] Al-Ahmadie, H.A., et al. (2008). "Anterior-predominant prostatic tumors: zone of origin and pathologic outcomes at radical prostatectomy." American Journal of Surgical Pathology, 32(2), 229-235. DOI: 10.1097/PAS.0b013e31815a565e

[9] Hossack, T., et al. (2012). "Location and pathological characteristics of cancers in radical prostatectomy specimens identified by transperineal biopsy compared to transrectal biopsy." Journal of Urology, 188(3), 781-785. DOI: 10.1016/j.juro.2012.05.007

[10] Abdollah, F., et al. (2011). "Selecting the optimal candidate for adjuvant radiotherapy after radical prostatectomy for prostate cancer: a long-term survival analysis." European Urology, 63(6), 998-1008. DOI: 10.1016/j.eururo.2012.10.036

[11] Valerio, M., et al. (2014). "Detection of clinically significant prostate cancer using magnetic resonance imaging-ultrasound fusion targeted biopsy: a systematic review." European Urology, 68(1), 8-19. DOI: 10.1016/j.eururo.2014.10.026 https://www.europeanurology.com/article/S0302-2838(14)01089-2/fulltext

[12] Epstein, J.I., et al. (2016). "Contemporary Gleason grading of prostatic carcinoma: an update with discussion on practical issues to implement the 2014 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma." American Journal of Surgical Pathology, 41(4), e1-e7. DOI: 10.1097/PAS.0000000000000820

[13] Xiang, J., Yan, H., Li, J., Wang, X., Chen, H., & Zheng, X. (2019). "Transperineal versus transrectal prostate biopsy in the diagnosis of prostate cancer: a systematic review and meta-analysis." World Journal of Surgical Oncology, 17(1), 31. DOI: 10.1186/s12957-019-1573-0 https://wjso.biomedcentral.com/articles/10.1186/s12957-019-1573-0

[14] Wolinsky, H. (2024). "Part 3: Dr. Gulliver and the War of the Biopsies." The Active Surveillor, December 26, 2024. https://theactivesurveillor.substack.com

[15] Bjerklund Johansen, T.E., Batura, D., Cai, T., et al. (2021). "Hospital-acquired urinary tract infections in urology departments: pathogens, susceptibility and use of antibiotics." International Journal of Antimicrobial Agents, 58(3), 106360. DOI: 10.1016/j.ijantimicag.2021.106360

[16] Wolinsky, H. (2024). Op. cit.

[17] Loeb, S., Carter, H.B., Berndt, S.I., et al. (2011). "Complications after prostate biopsy: data from SEER-Medicare." Journal of Urology, 186(5), 1830-1834. DOI: 10.1016/j.juro.2011.06.057

[18] European Association of Urology (2021). Op. cit.

[19] Wolinsky, H. (2024). "Part I: Transperineal vs. transrectal Biopsy: What the new biopsy studies really mean for men on active surveillance." The Active Surveillor, December 2, 2024. https://theactivesurveillor.substack.com

[20] Johansen, T.E., et al. (2020). "Critical review of current definitions of urinary tract infections and proposal of an EAU/ESIU classification system." International Journal of Antimicrobial Agents, 56(2), 106046. DOI: 10.1016/j.ijantimicag.2020.106046

[21] Wolinsky, H. (2024). "Part 2: Biopsy Beat Goes On: Meta-analysis finds TP cuts infection-related admissions by three-quarters." The Active Surveillor, December 10, 2024.

[22] Wolinsky, H. (2024). "Part 3: Dr. Gulliver and the War of the Biopsies." Op. cit.

[23] Roberts, M.J., et al. (2020). "Transperineal biopsy of the prostate: Is this the future?" Urologic Clinics of North America, 47(4), 461-470. DOI: 10.1016/j.ucl.2020.07.007

[24] Economic analysis based on practice management data and equipment costs reported in urology trade publications and Howard Wolinsky's investigative reporting.

[25] Liss, M.A., et al. (2017). "Fluoroquinolone resistant rectal colonization predicts risk of infectious complications after transrectal prostate biopsy." Journal of Urology, 197(1), 197-204. DOI: 10.1016/j.juro.2016.08.001 https://www.jurology.com/article/S0022-5347(16)31147-8/fulltext

[26] Centers for Disease Control and Prevention (2019). "Antibiotic Resistance Threats in the United States, 2019." https://www.cdc.gov/drugresistance/pdf/threats-report/2019-ar-threats-report-508.pdf

[27] Grummet, J.P., et al. (2014). "Sepsis and 'superbugs': should we favour the transperineal over the transrectal approach for prostate biopsy?" BJU International, 114(3), 384-388. DOI: 10.1111/bju.12556

[28] Observation based on medical education literature and professional society discussions regarding adoption of new surgical techniques.

[29] Wolinsky reporting and analysis in The Active Surveillor series.

[30] Marra, G., et al. (2019). "Controversies in MRI targeted biopsy: alone or combined, cognitive versus software-based fusion, transrectal versus transperineal approach?" World Journal of Urology, 37(2), 277-287. DOI: 10.1007/s00345-018-2432-6

[31] Centers for Disease Control and Prevention (2019). Op. cit.

[32] Torio, C.M., & Moore, B.J. (2016). "National Inpatient Hospital Costs: The Most Expensive Conditions by Payer, 2013." Healthcare Cost and Utilization Project Statistical Brief #204. Agency for Healthcare Research and Quality. https://www.hcup-us.ahrq.gov/reports/statbriefs/sb204-Most-Expensive-Hospital-Conditions.pdf

[33] Viscusi, W.K. (2018). "Pricing Lives: Guideposts for a Safer Society." Princeton University Press.

[34] Prescott, H.C., & Angus, D.C. (2018). "Enhancing recovery from sepsis: a review." JAMA, 319(1), 62-75. DOI: 10.1001/jama.2017.17687

[35] Iwashyna, T.J., et al. (2010). "Long-term cognitive impairment and functional disability among survivors of severe sepsis." JAMA, 304(16), 1787-1794. DOI: 10.1001/jama.2010.1553

[36] World Health Organization (2021). "Antimicrobial Resistance: Global Report on Surveillance." https://www.who.int/publications/i/item/9789241564748

[37] Analysis based on cumulative probability calculations and published infection rates from multiple studies.

[38] Cylus, J., et al. (2016). "Health system efficiency: How to make measurement matter for policy and management." European Observatory on Health Systems and Policies. https://www.ncbi.nlm.nih.gov/books/NBK436886/

[39-40] Patient impact analysis based on medical literature, patient advocacy organization reports, and healthcare delivery research.

[41] Baco, E., et al. (2015). "Predictive value of magnetic resonance imaging-determined tumor contact length for extracapsular extension of prostate cancer." Journal of Urology, 193(2), 466-472. DOI: 10.1016/j.juro.2014.08.084

[42] Epstein, J.I., et al. (2012). "The 2014 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma." American Journal of Surgical Pathology, 40(2), 244-252. DOI: 10.1097/PAS.0000000000000530

[43] Cumulative risk calculations based on published infection rates.

[44] Recommended patient questions developed based on analysis of hidden agendas and economic incentives in biopsy practice.

[45] Anticipated guideline revision referenced in Wolinsky (2024).

[46] Factors driving potential practice change based on healthcare trends analysis and medical innovation adoption literature.

[47] Lamb, A.D., et al. (2023). Op. cit.; Xiang, J., et al. (2019). Op. cit.

[48] Wolinsky, H. (2024). "Part 2." Op. cit.

[49] Cost analysis synthesized from multiple economic and clinical sources.

[50] European Association of Urology (2021). Op. cit.; Murphy, D.G. (2023). Op. cit.

Additional Resources:

Active Surveillance Patients International (ASPI) https://aspatientsintl.org

Informed Prostate Cancer Support Group (IPCSG) https://prostatecancersupport.org

The Active Surveillor Newsletter by Howard Wolinsky https://theactivesurveillor.substack.com

Note: This article was prepared for educational purposes for prostate cancer patients and should not replace consultation with qualified urologists and oncologists. Individual treatment decisions should be made in consultation with healthcare providers familiar with your specific medical situation.

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The Great Prostate Biopsy Debate: Transperineal vs. Transrectal