NIH Launches New Study to Compare Prostate Surgery and Drugs

The Minimally Invasive Surgical Therapies (MIST) Consortium for Benign Prostatic Hyperplasia (BPH) has launched a new study to compare long-term benefits and risks of transurethral needle ablation (TUNA) and transurethral microwave thermotherapy (TUMT) to a regimen of the alpha-1 inhibitor alfuzosin and the 5-alpha reductase inhibitor finasteride. The National Institute of Diabetes and Digestive and Kidney Diseases at NIH, part of the Department of Health and Human Services, is investing more than $15 million in the study.

TUNA and TUMT use heat to destroy part of the enlarged prostate to improve urine flow and symptoms. Early studies suggest that these procedures reduce the occurrence of erection or bladder control side effects, which occur more often with the traditional surgery for BPH, known as transurethral resection of the prostate (TURP). TUNA and TUMT are said to be minimally invasive in part because they typically are done with local anesthesia and men go home the same day, whereas TURP requires general anesthesia and an overnight hospital stay. As for drug therapy, a recently published large randomized study showed that a regimen of finasteride (Proscar) and the alpha-1 inhibitor doxazosin (Cardura) prevents progression of BPH in a significant percentage of symptomatic men and it helps men at high risk avoid surgery.

“It’s easy to see why drug therapy, TUNA and TUMT have been embraced by many urologists and patients,” said Leroy M. Nyberg Jr., Ph.D., M.D., director of NIDDK’s urology trials. “Yet, we don’t know which treatment is more effective in the long run and, for the most part, who would be better served by the drug combination versus one of the minimally invasive therapies.”

By July 2006, researchers plan to have recruited and randomly assigned more than 700 men with moderate to severe symptoms and no prior prostate surgery to one of the three MIST therapies. The men, age 50 and over, will be followed closely for 3 to 5 years, until about July 2009, to see who develops urinary retention, urinary tract infection or unacceptable incontinence after treatment; who needs more treatment; and whose symptoms don’t improve by at least 30 percent after treatment.

Consortium members recruiting patients are Baylor College of Medicine in Houston; Columbia University in New York City; Mayo Clinic in Rochester, Minn.; Medical College of Wisconsin in Milwaukee; Northwestern University in Chicago; University of Colorado Health Sciences Center in Denver; and the University of Texas Southwestern Medical Center in Dallas. George Washington University Biostatistics Center in Rockville, MD, provides overall coordination for the study and data collection and analysis. For contact information visit www.mistbph.org.

BPH is increasingly common after age 50. Mild symptoms may wax and wane on their own, but Nyberg predicts that as more Baby Boomers cross into their 50s, physicians are likely to start seeing more men who are up frequently at night using the bathroom, a typical symptom of BPH along with embarrassing episodes of needing to go right away (urgency), daytime frequency, and occasional episodes of unavoidable wetting. Over time, the progressive symptoms associated with BPH can have a significant impact on quality of life for the individual as well as his close family members.

In 2000, BPH accounted for about 8 million office visits, 117,000 trips to emergency rooms, 105,000 hospital stays and 87,400 TURPs. BPH also cost patients and insurers about $1.1 billion, without considering nutritional supplements and 2.2 million prescriptions, according to NIDDK’s Urologic Diseases in America interim compendium, released this spring.

MIST will also compare TUNA to TUMT and seeks to identify men best suited for each of the three therapies. Changes in sexual function, ejaculation, bladder changes, PSA, prostate size and shape, and ratio of various prostate tissues; and pain before, during and after surgery, among other parameters, will be tracked in search of characteristics predicting likely outcome and effectiveness of therapies. “Having a protocol to fit the man to the therapy without having to try each treatment along the way should translate into lower costs and more-satisfied patients,” said John W. Kusek, Ph.D., a clinical trials expert at NIDDK.

MIST therapies are approved by FDA, but relative benefits, risks and cost have never been compared. Further, there have been few rigorously conducted randomized trials of the minimally invasive surgical approaches. “Previous studies of TUMT and TUNA haven’t looked at side-effects and symptom relief long-term but, after we’ve finished MIST, men and their doctors should be a lot smarter about the options,” said Kusek.

Other support for MIST comes from Diagnostic Ultrasound, Bothell, Washington; Urologix Inc. and Medtronic, both in Minneapolis; Merck & Co., Whitehouse Station, New Jersey; and Sanofi-Synthelabo Inc., New York.