Baseline PSA, TRUS volumes suggest best BPH therapy

September 1, 2004

San Francisco--Baseline PSA and transrectal ultrasound volumes may predict the best medical therapy for BPH, according to investigators involved in the Medical Therapy of Prostatic Symptoms (MTOPS) trial. Similar to the initial findings of MTOPS, this secondary analysis suggests a role for different drug regimens based on patients' level of risk.

San Francisco-Baseline PSA and transrectal ultrasound volumes may predict the best medical therapy for BPH, according to investigators involved in the Medical Therapy of Prostatic Symptoms (MTOPS) trial. Similar to the initial findings of MTOPS, this secondary analysis suggests a role for different drug regimens based on patients' level of risk.

"Completely different patterns emerge in the placebo, doxazosin, finasteride, and combination groups," said lead author Claus G. Roehrborn, MD, professor and chairman of the department of urology, University of Texas Southwestern Medical Center, Dallas.

Previous studies have found that serum PSA correlates with both total and transition zone prostate volume, Dr. Roehrborn said. And PSA has been shown to predict episodes of retention and the need for surgery (Urology 2001; 58:210-6).

In MTOPS, a double-blind, multicenter clinical trial, 3,047 BPH patients were randomized to receive placebo, doxazosin mesylate (Cardura), finasteride (Proscar), or a combination of finasteride and doxazosin, and treated for an average of 5 years. The primary results of MTOPS were published last year (N Engl J Med 2003; 349:2387-98).

In the current analysis, investigators stratified the MTOPS population by treatment group, then divided each group by baseline volume, transition volume, and PSA. They then calculated baseline, change from baseline, and endpoint values for the tracked parameters.

Pre-protocol population According to Dr. Roehrborn, investigators concentrated on the pre-protocol population because patients at higher risk for progression-those with larger glands and higher PSAs-have a greater risk of reaching the endpoint and crossing over to active therapy. The magnitude of the response in that group of patients could be contaminated in the intent-to-treat analysis, he said. A pre-protocol population analysis, on the other hand, could be expected to demonstrate a significant drop-off in response, particularly in the higher-risk patients.

Analyzing the pre-protocol population, researchers found that the higher the prostate volume, the less the placebo response for all four parameters: IPSS, BPH Impact Index, quality-of-life score, and maximum flow rate. Transition zone volume and PSA were also inversely correlated with placebo response.

However, the pattern changed in the other treatment arms. In the doxazosin group, researchers noted a significant drop-off in all four longitudinal parameters in those with the largest volume, transition volume, and in the second and third PSA tertiles. But the same drop-off did not take place for finasteride in any of the four outcome parameters. And flow rate, symptom score, BPH Impact Index, and quality-of-life responses were flat across all risk categories with combination therapy.

In low-risk patients-those with the lowest volume, transition volume, and PSA tertiles-the investigators found that doxazosin outperformed not only placebo, but also finasteride. And it performed as well as combination therapy in the low-risk group. In high-risk patients-those in the highest volume, transition value, and PSA tertiles-finasteride was superior to doxazosin, and combination therapy was superior to all other treatment arms.

Patient recommendations Dr. Roehrborn said the analysis supports three clinical recommendations:

"The moderate-risk patients require further analysis-undoubtedly a multivariate analysis-to understand the impact of those volumes and PSA on outcomes," Dr. Roehrborn said.

In general, these findings parallel the initial recommendations based on MTOPS, which also considered baseline volume and PSA, but used symptom progression and surgery as endpoints.

MTOPS was funded by the National Institutes of Health. Dr. Roehrborn reported affiliations with GlaxoSmithKline, Merck, and Sanofi.