Revolutionary BPH Treatments Advance While Research Gaps Leave Potential Therapies Unexplored

 

Aquablation leads new wave of function-preserving procedures, but market forces stall investigation of older, unpatentable compounds like DMSO

For the IPCSG Newsletter

Men diagnosed with benign prostatic hyperplasia now have access to advanced treatments that effectively relieve urinary symptoms while preserving sexual function—a dramatic shift from traditional surgeries. Yet this success story highlights a troubling gap: potentially useful but unpatentable treatments remain largely unstudied, while men who undergo radical prostatectomy for prostate cancer face persistent nocturia requiring different therapeutic strategies.

Aquablation: Five-Year Data Confirms Durability

The WATER III trial, presented at the European Association of Urology Congress 2025, found that among men with large prostates (80-180 mL), retrograde ejaculation occurred in only 15% of Aquablation patients versus 77% with laser enucleation, while urinary incontinence rates were halved at 9% versus 20%. Among sexually active participants, 85% maintained antegrade ejaculation with Aquablation.

The WATER II trial's final 5-year results demonstrated 96.3% of patients remained free from secondary BPH procedures at five years, with symptom scores decreasing from 22.6 at baseline to 6.8 at five years.

Aquablation uses ultrasound-guided, robotic-assisted, heat-free waterjet technology to create personalized treatment plans. Traditional TURP has a 5-7% risk of bladder neck scarring, while Aquablation reduces this risk to less than 0.5%.

Over 33,000 Aquablation procedures were performed in 2024, surpassing holmium laser enucleation, though the procedure currently has limited U.S. insurance coverage as it is billed under a Category III T-Code.

Expanding Minimally Invasive Arsenal

The iTind procedure received new Category I CPT codes and Medicare reimbursement effective January 1, 2025. The device reshapes the prostatic urethra over 5-7 days without cutting or burning tissue and can be performed under local anesthesia. Clinical studies demonstrate durability out to 6.6 years.

Prostate artery embolization uses tiny beads to block blood flow to the prostate with virtually no risk of incontinence or impotence. Butterfly Medical's prostatic retraction device has demonstrated sustained improvements up to five years and is currently in pivotal U.S. clinical trials.

DMSO: A Cautionary Tale of Market Failure

Some BPH patients have explored dimethyl sulfoxide (DMSO) based on anecdotal reports, but this highlights systemic problems in pharmaceutical research. DMSO is FDA-approved only for treating interstitial cystitis through intravesical instillation. In medical settings, intravesical DMSO has treated chronic prostatitis with documented symptomatic relief, but oral use for BPH is entirely off-label and unsupported by research.

Why DMSO Remains Unstudied:

Discovered in 1866, DMSO cost about 35 cents a pint and could not be monetized like brand-name drugs. Because the drug is generic and cannot be patented, drug companies have shown little interest in researching its potency. The average cost of obtaining FDA approval for a new drug was estimated at $2.6 billion in 2014, and most brand-name manufacturers have a 12-to-16-year window of market exclusivity.

Without patent protection, any company investing in DMSO trials would immediately face generic competition, eliminating financial incentive.

Academic Research Gap:

Dr. Stanley Jacob (1924-2015), head of the organ transplant team at Oregon Health Sciences University, spent much of his career researching DMSO and advocating for its approval. There are more than 1,200 publications on DMSO, but it fell out of favor in the 1960s after the FDA became rigid following thalidomide, and only a 50% DMSO solution for interstitial cystitis was approved in 1978—which remains the only approved human indication.

As of 2008, only three studies were listed in ClinicalTrials.gov investigating DMSO for therapeutic use. While NIH institutes have established resources for investigator-initiated clinical trials, and these studies attempt to answer questions clinicians face in practice, DMSO hasn't received this attention.

Dr. Jacob's death in 2015 essentially ended the main academic advocacy, and no major institution has continued systematic investigation.

Safety Concerns Remain:

DMSO might harm kidneys and liver, and kidney function tests are recommended every 6 months for patients with kidney conditions. DMSO sold without prescription can range from 10% to 90% concentration, with some products containing industrial-grade impurities.

Post-Prostatectomy Nocturia: Different Problem, Different Solutions

Men who undergo radical prostatectomy face distinct challenges. Most patients experience persistent or increased nocturia even when other voiding symptoms improve. More than one-third experience exacerbated nocturia, increasing from an average of 1.0 to 3.0 episodes nightly.

Post-surgical nocturia results from changes in bladder storage function after prostate removal and potential nerve damage affecting bladder control, not obstruction.

Evidence-Based Treatments:

First-line approaches include avoiding excessive fluid intake before bedtime and addressing behavioral patterns. Behavioral treatment of insomnia involving sleep schedule regulation can improve nocturia without medication side effects.

Desmopressin may reduce nocturnal voids by 43% when used alone. However, desmopressin-induced hyponatremia increases with age and can be serious, making it particularly problematic for patients 65 years and older. Patients require serum sodium assessment before starting desmopressin and regular monitoring.

Anticholinergics and beta-3 agonists can relax bladder spasms. For persistent cases, intravesical botulinum toxin improved median nocturia scores from 3.0 to 1.0 at three months in one case series. Nerve stimulation options include percutaneous tibial nerve stimulation and sacral neuromodulation.

Why DMSO Is Not Appropriate Post-Prostatectomy:

There is no scientific rationale for using DMSO to treat post-prostatectomy nocturia. Anecdotal claims about DMSO "relaxing the bladder" in BPH involve an intact, enlarged prostate—fundamentally different from the post-surgical state where nocturia results from surgical alterations and nerve damage, not bladder spasm or inflammation.

Market Failures in Medical Research

The DMSO story illustrates fundamental challenges in pharmaceutical development. DMSO broke every rule: It was old, cheap, off-patent and threatened entire drug classes, so it was shelved not for safety concerns but because it could not be controlled.

This creates situations where:

• Economically viable drugs lack scientific evidence due to insufficient research funding
• Scientifically promising compounds lack commercial development due to insufficient profit potential
• Academic researchers face career disincentives to study controversial, unpatentable compounds
• Even positive academic findings have no clear FDA approval pathway without commercial partners

Investigator-initiated clinical trials aim to address scientific questions with insufficient commercial implications, unlike industry-sponsored trials focused on marketing approval. Yet these studies face myriad challenges including finances, regulatory submissions, and lack of expertise.

The Path Forward

Current BPH treatment follows a tiered system beginning with conservative management, followed by medical therapy, with minimally invasive procedures bridging the gap between medications and traditional surgery. Each treatment has distinct characteristics influencing suitability based on prostate anatomy, symptoms, comorbidities, and personal goals.

A 2024 review concluded that if Aquablation outcomes are replicated globally, the technique could become a new benchmark in robotic BPH treatment.

For men considering BPH treatment, advances offer hope that effective symptom management no longer requires accepting sexual dysfunction or incontinence. However, patients should pursue evidence-based treatments with established safety profiles rather than experimenting with unproven alternatives.

For prostate cancer survivors experiencing persistent nocturia, different evidence-based approaches address the specific post-surgical causes of nighttime urination.

The broader lesson: our current pharmaceutical research system, driven by patent economics, may leave potentially useful treatments unexplored—a market failure requiring alternative funding models through government agencies, academic institutions, or philanthropic foundations to address questions that lack commercial viability but matter to patients.

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Key Sources

Aquablation Studies:

1. Bhojani, N., et al. "Aquablation Therapy in Large Prostates: Final WATER II 5-Year Results." Journal of Urology, 2023. https://www.auajournals.org/doi/10.1097/JU.0000000000003483
2. PROCEPT BioRobotics. "WATER III Trial Results." March 2025. https://ir.procept-biorobotics.com/news-releases/news-release-details/water-iii-randomized-controlled-trial-results-announced-european
3. Berjaoui, Z., et al. "WATER versus WATER II 5-year update." BJUI Compass, September 2024. https://bjui-journals.onlinelibrary.wiley.com/doi/10.1002/bco2.430

iTind and Other Treatments: 4. Olympus Corporation. "CMS Publishes Final Category I CPT Codes for iTind™." November 2024. https://www.olympusamerica.com/press-release/2024-11-07/cms-publishes-final-category-i-cpt-codes-and-reimbursement-rates-itindtm 5. Olympus Medical. "iTind BPH Treatment." https://www.olympus-europa.com/medical/en/Products-and-Solutions/Products/Product/iTind.html

DMSO Research: 6. Stewart, B.H. "Dimethyl sulfoxide in treatment of inflammatory genitourinary disorders." PubMed, 1978. https://pubmed.ncbi.nlm.nih.gov/636125/ 7. Capriotti, K., et al. "Dimethyl Sulfoxide: History, Chemistry, and Clinical Utility in Dermatology." PMC, 2012. https://pmc.ncbi.nlm.nih.gov/articles/PMC3460663/ 8. McGill University. "DMSO Is Not a Cure-All." November 2023. https://www.mcgill.ca/oss/article/medical-critical-thinking-history/dmso-not-cure-all-fdas-panic-over-it-birthed-myth 9. Wikipedia. "Stanley Jacob." https://en.wikipedia.org/wiki/Stanley_Jacob

Post-Prostatectomy Nocturia: 10. Kim, S.J., et al. "Changes in Nocturia After Radical Prostatectomy." PMC, 2015. https://pmc.ncbi.nlm.nih.gov/articles/PMC4709436/ 11. Soliman, Y., et al. "Oral desmopressin in nocturia with BPH." PMC, 2018. https://pmc.ncbi.nlm.nih.gov/articles/PMC6277262/ 12. Takano, K., et al. "OnabotulinumtoxinA for nocturia after radical prostatectomy." African Journal of Urology, February 2025. https://afju.springeropen.com/articles/10.1186/s12301-025-00492-z

Clinical Trial Infrastructure: 13. NIAID. "Investigator-Initiated Clinical Trial Resources." https://www.niaid.nih.gov/grants-contracts/investigator-initiated-clinical-trial-resources 14. Gogtay, N.J., et al. "Investigator-initiated studies: Challenges and solutions." PMC, 2018. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6176691/

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Note: This article is for informational purposes only. Men considering BPH treatment or experiencing post-prostatectomy symptoms should consult with their urologist to determine appropriate evidence-based treatment options.