BPH progression: Prevention is determined by risk

"Patients have increased risk of retention based on certain parameters: the higher the risk, the greater the benefit. Treatment is a very individual decision between the patient and doctor," said Dr. Roehrborn, professor and chairman of the department of urology, University of Texas Southwestern Medical Center, Dallas.

The committee said that most preventive interventions are based on continuous factors that can be better judged when converted to symptom categories such as mild, moderate, and severe. Physicians more commonly use dynamic variables, such as changes in the International Prostate Symptom Score, to make decisions about choices of treatment and treatment changes. Not much research is done regarding those dynamic changes and how they are utilized in physicians' decision making, Dr. Roehrborn said.

In longitudinal studies of the natural history of LUTS and BPH, selection bias was responsible for most of the placebo effect, introducing a unilateral regression to the mean, the committee said.

Predicting worsening symptoms

The committee's view was that evidence of BPH progression is contained in many studies with widely varying results.

"They come in all shades of gray," said Dr. Roehrborn.

Men with mild LUTS progress on a continuous scale from mild to severe between 6 and 48 months. Flow rate changes have been categorized by decades of life. Prostate growth at 7-year follow-up has a mean volume increase of 1.9%, the committee said. Outcomes based on 1,000 patient years averaged 1%, or one patient per year for retention, and a surgery rate of 4% to 8% per year.

Making the case that worsening symptoms can be predicted in older men, the committee said that extrapolating 20 years in a patient diagnosed with BPH would result in a prostate volume of 40 to 90 mL and a 60% risk of surgery. In addition, data from the Medical Therapy of Prostatic Symptoms (MTOPS) study show a dramatic worsening of baseline symptom values and flow rates as men age.

PSA values are the most significant predictor for acute urinary retention and need for surgery in men with BPH, according to the committee.

Drug therapy

Five-alpha-reductase inhibitors have been shown to decrease PSA levels by 50% up to 8 years, independent of baseline PSA or prostate volume, the committee said. The percentage of prostate volume decrease ranges from 15% to 30% over a 6- to 48-month period in various studies. The MTOPS evidence on alpha-blockers shows that despite the suggested apoptosis, there is no effect on volume or growth of the gland over time.

MTOPS data show combination therapy is more effective than single-arm therapy in prevention of symptom progression. Treatment with the 5-alpha-reductase inhibitor finasteride (Proscar) resulted in a 57% reduction in symptoms, compared with 81% for combination therapy using finasteride and the alpha-blocker doxazosin (Cardura).

The committee recommended more research on symptom progression and prevention of progression, including an improved understanding of the relationship between continuous variables (on which preventive interventions are based) and dynamic variables (on which treatment decisions are based).

For men at high risk for progression, the urologist's considerations for management should include the relative risk for the individual patient, adverse effects, and the patient's socioeconomic status.

"We recommend against initial treatment to prevent progression in men with low risk," said Dr. Roehrborn.