Radical Prostatectomy versus Watchful Waiting in Early Prostate Cancer

Anna Bill-Axelson, M.D., Lars Holmberg, M.D., Ph.D., Mirja Ruutu, M.D., Ph.D., Michael Häggman, M.D., Ph.D., Swen-Olof Andersson, M.D., Ph.D., Stefan Bratell, M.D., Ph.D., Anders Spångberg, M.D., Ph.D., Christer Busch, M.D., Ph.D., Stig Nordling, M.D., Ph.D., Hans Garmo, Ph.D., Juni Palmgren, Ph.D., Hans-Olov Adami, M.D., Ph.D., Bo Johan Norlén, M.D., Ph.D., Jan-Erik Johansson, M.D., Ph.D., for the Scandinavian Prostate Cancer Group Study No. 4

ABSTRACT

Background In 2002, we reported the initial results of a trial comparing radical prostatectomy with watchful waiting in the management of early prostate cancer. After three more years of follow-up, we report estimated 10-year results.

Methods From October 1989 through February 1999, 695 men with early prostate cancer (mean age, 64.7 years) were randomly assigned to radical prostatectomy (347 men) or watchful waiting (348 men). The follow-up was complete through 2003, with blinded evaluation of the causes of death. The primary end point was death due to prostate cancer; the secondary end points were death from any cause, metastasis, and local progression.

Results During a median of 8.2 years of follow-up, 83 men in the surgery group and 106 men in the watchful-waiting group died (P=0.04). In 30 of the 347 men assigned to surgery (8.6 percent) and 50 of the 348 men assigned to watchful waiting (14.4 percent), death was due to prostate cancer. The difference in the cumulative incidence of death due to prostate cancer increased from 2.0 percentage points after 5 years to 5.3 percentage points after 10 years, for a relative risk of 0.56 (95 percent confidence interval, 0.36 to 0.88; P=0.01 by Gray's test). For distant metastasis, the corresponding increase was from 1.7 to 10.2 percentage points, for a relative risk in the surgery group of 0.60 (95 percent confidence interval, 0.42 to 0.86; P=0.004 by Gray's test), and for local progression, the increase was from 19.1 to 25.1 percentage points, for a relative risk of 0.33 (95 percent confidence interval, 0.25 to 0.44; P<0.001 by Gray's test).

Conclusions Radical prostatectomy reduces disease-specific mortality, overall mortality, and the risks of metastasis and local progression. The absolute reduction in the risk of death after 10 years is small, but the reductions in the risks of metastasis and local tumor progression are substantial.

Saw Palmetto for Benign Prostatic Hyperplasia

Stephen Bent, M.D., Christopher Kane, M.D., Katsuto Shinohara, M.D., John Neuhaus, Ph.D., Esther S. Hudes, Ph.D., M.P.H., Harley Goldberg, D.O., and Andrew L. Avins, M.D., M.P.H.

ABSTRACT

Background Saw palmetto is used by over 2 million men in the United States for the treatment of benign prostatic hyperplasia and is commonly recommended as an alternative to drugs approved by the Food and Drug Administration.

Methods In this double-blind trial, we randomly assigned 225 men over the age of 49 years who had moderate-to-severe symptoms of benign prostatic hyperplasia to one year of treatment with saw palmetto extract (160 mg twice a day) or placebo. The primary outcome measures were changes in the scores on the American Urological Association Symptom Index (AUASI) and the maximal urinary flow rate. Secondary outcome measures included changes in prostate size, residual urinary volume after voiding, quality of life, laboratory values, and the rate of reported adverse effects.

Results There was no significant difference between the saw palmetto and placebo groups in the change in AUASI scores (mean difference, 0.04 point; 95 percent confidence interval, –0.93 to 1.01), maximal urinary flow rate (mean difference, 0.43 ml per minute; 95 percent confidence interval, –0.52 to 1.38), prostate size, residual volume after voiding, quality of life, or serum prostate-specific antigen levels during the one-year study. The incidence of side effects was similar in the two groups.

Conclusions In this study, saw palmetto did not improve symptoms or objective measures of benign prostatic hyperplasia. (ClinicalTrials.gov number, NCT00037154 [ClinicalTrials.gov] .)

Cumulative Association of Five Genetic Variants with Prostate Cancer

S. Lilly Zheng, M.D., Jielin Sun, Ph.D., Fredrik Wiklund, Ph.D., Shelly Smith, M.S., Pär Stattin, M.D., Ph.D., Ge Li, M.D., Hans-Olov Adami, M.D., Ph.D., Fang-Chi Hsu, Ph.D., Yi Zhu, B.S., Katarina Bälter, Ph.D., A. Karim Kader, M.D., Ph.D., Aubrey R. Turner, M.S., Wennuan Liu, Ph.D., Eugene R. Bleecker, M.D., Deborah A. Meyers, Ph.D., David Duggan, Ph.D., John D. Carpten, Ph.D., Bao-Li Chang, Ph.D., William B. Isaacs, Ph.D., Jianfeng Xu, M.D., D.P.H., and Henrik Grönberg, M.D., Ph.D.

ABSTRACT

Background Single-nucleotide polymorphisms (SNPs) in five chromosomal regions — three at 8q24 and one each at 17q12 and 17q24.3 — have been associated with prostate cancer. Each SNP has only a moderate association, but when SNPs are combined, the association may be stronger.

Methods We evaluated 16 SNPs from five chromosomal regions in a Swedish population (2893 subjects with prostate cancer and 1781 control subjects) and assessed the individual and combined association of the SNPs with prostate cancer.

Results Multiple SNPs in each of the five regions were associated with prostate cancer in single SNP analysis. When the most significant SNP from each of the five regions was selected and included in a multivariate analysis, each SNP remained significant after adjustment for other SNPs and family history. Together, the five SNPs and family history were estimated to account for 46% of the cases of prostate cancer in the Swedish men we studied. The five SNPs plus family history had a cumulative association with prostate cancer (P for trend, 3.93x10^–28). In men who had any five or more of these factors associated with prostate cancer, the odds ratio for prostate cancer was 9.46 (P=1.29x10^–8), as compared with men without any of the factors. The cumulative effect of these variants and family history was independent of serum levels of prostate-specific antigen at diagnosis.

Conclusions SNPs in five chromosomal regions plus a family history of prostate cancer have a cumulative and significant association with prostate cancer.

Alfuzosin and Symptoms of Chronic Prostatitis–Chronic Pelvic Pain Syndrome

J. Curtis Nickel, M.D., John N. Krieger, M.D., Mary McNaughton-Collins, M.D., Rodney U. Anderson, M.D., Michel Pontari, M.D., Daniel A. Shoskes, M.D., Mark S. Litwin, M.D., Richard B. Alexander, M.D., Paige C. White, M.D., Richard Berger, M.D., Robert Nadler, M.D., Michael O'Leary, M.D., Men Long Liong, M.D., Scott Zeitlin, M.D., Shannon Chuai, Ph.D., J. Richard Landis, Ph.D., John W. Kusek, Ph.D., Leroy M. Nyberg, M.D., Anthony J. Schaeffer, M.D., for the Chronic Prostatitis Collaborative Research Network

ABSTRACT

Background In men with chronic prostatitis–chronic pelvic pain syndrome, treatment with alpha-adrenergic receptor blockers early in the course of the disorder has been reported to be effective in some, but not all, relatively small randomized trials.

Methods We conducted a multicenter, randomized, double-blind, placebo-controlled trial to evaluate the efficacy of alfuzosin, an alpha-adrenergic receptor blocker, in reducing symptoms in men with chronic prostatitis–chronic pelvic pain syndrome. Participation in the study required diagnosis of the condition within the preceding 2 years and no previous treatment with an alpha-adrenergic receptor blocker. Men were randomly assigned to treatment for 12 weeks with either 10 mg of alfuzosin per day or placebo. The primary outcome was a reduction of at least 4 points (from baseline to 12 weeks) in the score on the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) (range, 0 to 43; higher scores indicate more severe symptoms). A 4-point decrease is the minimal clinically significant difference in the score.

Results A total of 272 eligible participants underwent randomization, and in both study groups, 49.3% of participants had a decrease of at least 4 points in their total NIH-CPSI score (rate difference associated with alfuzosin, 0.1%; 95% confidence interval, –11.2 to 11.0; P=0.99). In addition, a global response assessment showed similar response rates at 12 weeks: 33.6% in the placebo group and 34.8% in the alfuzosin group (P=0.90). The rates of adverse events in the two groups were also similar.

Conclusions Our findings do not support the use of alfuzosin to reduce the symptoms of chronic prostatitis–chronic pelvic pain syndrome in men who have not received prior treatment with an alpha-blocker. (ClinicalTrials.gov number, NCT00103402 [ClinicalTrials.gov] .)