Top studies move BPH treatment forward

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Landmark studies have led to FDA approvals of new treatments for BPH/lower urinary tract symptoms (LUTS), updates to the AUA’s clinical guidelines for surgical treatment of BPH-related symptoms, and amended AUA guidelines that reflect still newer research. But with so much new research data released in the past 2 years alone, which studies were most impactful?

Urology Times interviewed four leading urologists who are experts in BPH to get their take on the most important BPH studies of 2018 and 2019. Based on these conversations, the following studies stood out.

Aquablation vs. TURP

A 2018 study known as WATER was a double-blind, randomized, controlled trial comparing Aquablation versus transurethral resection of the prostate (TURP) (J Urol 2018; 199:1252-61).

“This is the first study that actually got Aquablation approved by the FDA,” said study co-author Alexis E. Te, MD, professor of urology at Weill Medical College of Cornell University and director of the urology program at the Iris Cantor Men’s Health Center, New York. “It is one of the studies that greatly influenced the AUA’s decision to amend the AUA guidelines for surgical treatment of BPH.”

Also see: How has your management of BPH patients changed?

In this study, 181 patients with moderate to severe LUTS related to BPH underwent TURP or Aquablation. After 6 months, the Aquablation patients demonstrated “noninferior symptom relief” and a lower risk of sexual dysfunction, with the biggest improvements in safety and efficacy shown in men with larger prostates (50 to 80 mL). The AUA guideline on surgical treatment of BPH was subsequently amended to state, “Aquablation may be offered to patients with LUTS attributed to BPH provided prostate volume >30/<80g; however, patients should be informed that long-term evidence of efficacy and retreatment rates remains limited.”

Also important: a similar study that analyzed 2 years of data comparing Aquablation and TURP (Adv Ther 2019; 36:1326-36) as well as studies reporting 1-year data comparing Aquablation and TURP (Urology 2019; 125:169-73 and Urology 2019; 129:1-7).

Has the data around Aquablation influenced practice patterns? “No, simply because of reimbursement,” said Steven A. Kaplan, MD, professor of urology at the Icahn School of Medicine at Mount Sinai, New York, and a member of the AUA’s BPH Guideline Panel. “Insurance companies aren’t paying for it yet. So, as much as we would like to try it, the financial issues are precluding that.”

Large review of prostatic urethral lift

A comprehensive database review examined the use of the prostatic urethral lift (PUL [UroLift]) for the treatment of LUTS in men with BPH (Cochrane Database Syst Rev 2019; 5:CD012832).

“There is such a variety of minimally invasive treatments now for symptoms of BPH,” said Helen L. Bernie, DO, director of sexual and reproductive medicine, IU Health, and assistant professor of urology, Indiana University, Indianapolis. “This study sought to determine: What are the long-term data [on PUL]? Have they been successful?”

In this study, researchers performed a comprehensive search of multiple databases, trials registries, literature and conference proceedings through Jan. 31, 2019, and performed subgroup analyses by age, prostate volume, and severity of baseline symptoms. They studied 297 patients who underwent PUL versus placebo surgery or TURP and reviewed short-term outcomes (through the first 12 months after treatment) and long-term outcomes (up to 24 months). Among the 91 patients who underwent PUL or TURP:

• PUL appears less effective in improving urologic symptoms than TURP, with similar quality of life, the authors concluded.

• Ejaculatory function likely is substantially better with PUL. The impact on erectile function appears similar between the two procedures.

• There is uncertainty around retreatment rates for UroLift, both in the short term and long term.

“It was very surprising because it’s not what people thought the results would show,” Dr. Bernie said. Given that the quality of life outcomes from the two procedures are similar, she said the primary benefit of UroLift over TURP is preservation of ejaculatory function.

While other studies have examined medical and surgical retreatment rates for UroLift, “In some of the reports, retreatment rates are revealed only in the discussion, not in the results,” said Kevin McVary, MD, professor of urology, Loyola University Medical Center, Chicago. “This report pulls the information right up front. I like it.”

In May 2019, the AUA guidelines on BPH surgical treatment were amended to state that “patients should be informed that the evidence of efficacy and retreatment rates [of PUL] are poorly defined.”

The authors of a study that measured the 12-month impact of UroLift on treatment of obstructive median lobes concluded: “Prostates, including those with middle lobe obstruction, can be treated with the PUL procedure safely and effectively” (Prostate Cancer Prostatic Dis 2019; 22:411-9). The study, known as MedLift, was reviewed by the BPH Guideline Panel but ultimately was not included in the amendments because it was not a randomized trial.

Next: Durability of RezumDurability of Rezum

An April 2019 study examined 4-year outcomes in 135 men ages 50 and older with an International Prostate Symptom Score ≥13, a maximum flow rate ≤15 mL/s, and prostate volume of 30 to 80 cc who were treated with Rezum System water vapor thermal therapy (Urology 2019; 126:171-9). Researchers also followed 53 men who requalified for crossover from control to active treatment over a period of 3 years.

Read: Waterjet ablation shows same efficacy in small, large prostates

This study, too, has changed the discussions urologists have with patients regarding surgical treatment of LUTS, Dr. Te said.

The results showed LUTS significantly improved within 3 months after surgery and remained “consistently durable,” with no disturbances in sexual function. The surgical retreatment rate was 4.4% over 4 years.

In 2019, the AUA amended guidelines on BPH surgical treatment around water vapor thermal therapy:

• “Water vapor thermal therapy may be offered to patients with LUTS attributed to BPH provided prostate volume <80 g; however, patients should be counseled regarding efficacy and retreatment rates.”

• “Water vapor thermal therapy may be offered to eligible patients who desire preservation of erectile and ejaculatory function.”

“The AUA guidelines do temper everyone’s expectations,” Dr. Te said. For example, while this procedure is minimally invasive and preserves sexual function, the population for this randomized, controlled study is small, he said.

PSA monitoring after HoLEP

A recent study, performed by researchers at Indiana University, sought to assess the value of PSA levels and PSA density (PSAD) in predicting prostate cancer risk following HoLEP (J Urol Sept. 5, 2019 [Epub ahead of print]). For men with large prostates, HoLEP provides a minimally invasive option for treatment, enabling patients to return home the day of the procedure. But one big question remained: “Now that we’ve removed the prostate in this way, how are we supposed to monitor PSA in these patients?” Dr. Bernie said.

The researchers pulled data from HoLEP surgeries performed at Indiana University from 1999 to 2018 and identified 1,147 patients with post-HoLEP PSA data. Among these patients, 55 post-HoLEP biopsies were recorded, with cancer identified in more than 90% of the patients. 

The results showed:

• Men with a PSA above 1.0 ng/mL at time of biopsy had a 94% probability of cancer detection and an 80% risk of clinically significant disease.

• Men with a PSAD above 0.1 ng/mL faced a 95% risk of cancer and an 88% risk of clinically significant cancer.

• A PSA greater than 5.8 ng/mL or PSAD greater than 0.17 ng/mL² was universally associated with biopsy-proven cancer.

Also see: New online men’s health sites divide opinion

“Typically, we think of PSA thresholds in men who have not undergone surgery as having a value of 4,” Dr. Bernie said. “These results show the thresholds for PSA should actually be lower in men who have undergone HoLEP.”

Next: Anticholinergic use and dementiaAnticholinergic use and dementia

A study published in JAMA Internal Medicine (2019; 179:1084-93) found that individuals ages 55 years and older face increased risk of dementia after using anticholinergics, particularly anticholinergic antidepressants, bladder antimuscarinics, antipsychotics, and antiepileptic drugs.

“Discussion around whether anticholinergics predispose men to dementia has been going back and forth for several years,” Dr. McVary said. “It’s been hard to get a handle on this because it takes large groups of patients to make this determination, and you can only infer it from administrative datasets, which isn’t the best science, but sometimes it’s the only science you have.”

Also of interest to urologists: a study that examined whether the use of 5-alpha-reductase inhibitors (dutasteride or finasteride) to treat LUTS is associated with increased risk of diabetes (BMJ 2019; 365:l1204).

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“I think what we’re learning as we’re gaining experience is that the long-term use of medication may create unexpected, untoward, long-term consequences,” Dr. Kaplan said. “We need prospective studies to get some of those answers.”

The diabetes study is “a signal,” Dr. Kaplan said, but he added: “I don’t think there’s enough data there yet to change how we do business.”

Starting points for discussion

The studies outlined here provide the groundwork for discussion with BPH patients around the benefits, advantages, and concerns related to treatment, whether surgery or medical therapy, Dr. Te said.

“There is a trend right now to find alternatives to medical therapy, but I still think medical therapy has its place in a majority of patients because it is efficacious for a good portion of the population,” Dr. Te said. “BPH is a progressive disease. Studies such as these provide the basis for discussion of risks and advantages of various treatments so patients can make informed decisions.”