Effect of dutasteride on prostate biopsy rates and the diagnosis of prostate cancer in men with lower urinary tract symptoms and enlarged prostates in the combination of avodart and tamsulosin trial

UROLOGICAL SURVEY

UROLOGICAL ONCOLOGY

Effect of dutasteride on prostate biopsy rates and the diagnosis of prostate cancer in men with lower urinary tract symptoms and enlarged prostates in the combination of avodart and tamsulosin trial

Roehrborn CG; Andriole GL; Wilson TH; Castro R; Rittmaster RS

Department of Urology, UT Southwestern Medical Center, Dallas, TX, USA

Eur Urol. 2011; 59: 244-9

BACKGROUND: A 23% relative risk reduction (RRR) in prostate cancer (PCa) was shown in men receiving dutasteride in the 4-yr Reduction by Dutasteride of Prostate Cancer Events study, in whom biopsies were protocol dependent.

OBJECTIVE: Our aim was to explore PCa risk reduction in men with benign prostatic hyperplasia (BPH) from the Combination of Avodart and Tamsulosin (CombAT) study, in which biopsies were undertaken for cause.

DESIGN, SETTING, AND PARTICIPANTS: CombAT was a 4-yr randomized double-blind parallel group study in 4844 men > 50 yr of age with clinically diagnosed moderate to severe BPH, International Prostate Symptom Score > 12, prostate volume > 30mL, and serum prostate-specific antigen (PSA) 1.5-10 ng/mL. Men underwent annual PSA measurement and digital rectal examination (DRE), and prostate biopsies were performed for cause.

INTERVENTION: All patients took tamsulosin 0.4mg/d, dutasteride 0.5mg/d, or a combination of both.

MEASUREMENTS: The primary end point was incidence of PCa. Secondary end points included postbaseline prostate biopsy rates and Gleason score of cancers.

RESULTS AND LIMITATIONS: Dutasteride (alone or in combination with tamsulosin) was associated with a 40% RRR of PCa diagnosis compared with tamsulosin monotherapy (95% confidence interval, 16-57%; p=0.002) and a 40% reduction in the likelihood of biopsy. There were similar reductions in low- and high-grade Gleason score cancers. The biopsy rate in the groups receiving dutasteride trended toward a higher diagnostic yield (combination: 29%, dutasteride: 28%, tamsulosin: 24%). One limitation was the lack of a standardized approach to PCa diagnosis and grading.

CONCLUSION: Dutasteride, alone or in combination with tamsulosin, significantly reduced the relative risk of PCa diagnosis in men with BPH undergoing annual DRE and PSA screening. Consistent with the increased usefulness of PSA for PCa detection, men receiving dutasteride had a numerically lower biopsy rate and higher yield of PCa on biopsy.

TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT00090103 (http://www.clinicaltrials.gov/ct2/show/NCT00090103).

Editorial Comment

This report from a large trial of dutasteride and/or tamsulosin (CombAT) focuses upon the cohort of men in which biopsies were undertaken for cause (suspicion of prostate cancer, PCa).

Men either received dutasteride, tamsulosin or both drugs. Thus, the results of the tamsulosin group may be seen as a control group for the effect of dutasteride. Altogether, PCa was detected in 2.3% in the combination group, in 2.6% in the dutasteride group and in 3.9% in the tamsulosin group. This may not seem impressive, but in pooling the dutasteride arm, there was a 1.5% absolute and a 40% relative risk reduction. Even more interestingly, Gleason sum scores were not significantly different between the groups (means Gleason scores were 6.3 in the combination group, 6.8 in the dutasteride group and 6.7 in the tamsulosin group; p = 0.12). In conclusion, these data underscore the clinical usefulness of dutasteride and even more, an important step toward the reduction of risk for prostate cancer.

Dr. Andreas Bohle

Professor of Urology

HELIOS Agnes Karll Hospital

Bad Schwartau, Germany

E-mail: [e-mail]

Publication Dates

• Publication in this collection
  30 May 2011
• Date of issue
  Apr 2011