Journal of the National Cancer Institute Advance Access originally published online on August 11, 2008
JNCI Journal of the National Cancer Institute 2008 100(16):1144-1154; doi:10.1093/jnci/djn255
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© The Author 2008. Published by Oxford University Press.
ARTICLES |
Radical Prostatectomy Versus Watchful Waiting in Localized Prostate Cancer: the Scandinavian Prostate Cancer Group-4 Randomized Trial
Affiliations of authors: Department of Urology (AB-A, FF, MH), Regional Oncologic Center (LH, HG), Department of Pathology (CB), University Hospital, Uppsala, Sweden; Department of Urology (MR), Department of Pathology (SN), Helsinki University Central Hospital, Helsinki, Finland; King's College London, School of Medicine, Division of Cancer Studies, London, UK (LH); Department of Urology (SOA, JEJ), Center for Assessment of Medical Technology (JEJ), Örebro University Hospital, Örebro, Sweden; Department of Urology, Borås Hospital, Borås, Sweden (SB); Department of Urology, Linköping University Hospital, Linköping, Sweden (AS); Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden (HOA, JP); Department of Epidemiology, Harvard School of Public Health, Boston, MA (HOA)
Correspondence to: Lars Holmberg, PhD, MD, Professor, King's College, Medical School, Division of Cancer Studies, Academic Oncology, 3rd Floor, Bermondsey Wing, Guy's Hospital, London SE1 9RT, UK (e-mail: lars.holmberg{at}kcl.ac.uk).
Background: The benefit of radical prostatectomy in patients with early prostate cancer has been assessed in only one randomized trial. In 2005, we reported that radical prostatectomy improved prostate cancer survival compared with watchful waiting after a median of 8.2 years of follow-up. We now report results after 3 more years of follow-up.
Methods: From October 1, 1989, through February 28, 1999, 695 men with clinically localized prostate cancer were randomly assigned to radical prostatectomy (n = 347) or watchful waiting (n = 348). Follow-up was complete through December 31, 2006, with histopathologic review and blinded evaluation of causes of death. Relative risks (RRs) were estimated using the Cox proportional hazards model. Statistical tests were two-sided.
Results: During a median of 10.8 years of follow-up (range = 3 weeks to 17.2 years), 137 men in the surgery group and 156 in the watchful waiting group died (P = .09). For 47 of the 347 men (13.5%) who were randomly assigned to surgery and 68 of the 348 men (19.5%) who were not, death was due to prostate cancer. The difference in cumulative incidence of death due to prostate cancer remained stable after about 10 years of follow-up. At 12 years, 12.5% of the surgery group and 17.9% of the watchful waiting group had died of prostate cancer (difference = 5.4%, 95% confidence interval [CI] = 0.2 to 11.1%), for a relative risk of 0.65 (95% CI = 0.45 to 0.94; P = .03). The difference in cumulative incidence of distant metastases did not increase beyond 10 years of follow-up. At 12 years, 19.3% of men in the surgery group and 26% of men in the watchful waiting group had been diagnosed with distant metastases (difference = 6.7%, 95% CI = 0.2 to 13.2%), for a relative risk of 0.65 (95% CI = 0.47 to 0.88; P = .006). Among men who underwent radical prostatectomy, those with extracapsular tumor growth had 14 times the risk of prostate cancer death as those without it (RR = 14.2, 95% CI = 3.3 to 61.8; P < .001).
Conclusion: Radical prostatectomy reduces prostate cancer mortality and risk of metastases with little or no further increase in benefit 10 or more years after surgery.
| CONTEXT AND CAVEATS Prior knowledge The Scandanavian Prostate Cancer Group (SPCG)-4 randomized trial began in 1989 in Sweden to compare the outcomes of prostate cancer patients who were assigned to watchful waiting vs radical prostatectomy. In the previous report in 2005, at a median 8.2 years of follow-up, men who underwent radical prostatectomy had better disease-specific survival rates than men in the watchful waiting group. Study design Continued follow-up of the SPCG-4 randomized trial. Contributions After a median follow-up of 10.8 years, 13.5% of men in the radical prostatectomy group and 19.5% of men in the watchful waiting group died from prostate cancer; at 12 years, the percentages were 12.5% and 17.9%, respectively. However, at 12 years, the overall mortality in the two arms was not statistically significantly different (32.7% vs 39.8%). Implications No increase in benefit of radical prostatecomy was observed after 10 years. Limitations It is unclear whether these results would apply to today's Western male populations, who, unlike the men in the SPCG-4 trial, are diagnosed with prostate cancer mainly by prostate-specific antigen screening. Quality of life comparisons were not performed. From the Editors
|
Manuscript received February 25, 2008; revised May 28, 2008; accepted June 20, 2008.
Editorial about this Article
Related Articles in JNCI
CiteULike 
Connotea 
Del.icio.us What's this?
J Natl Cancer Inst 2008 100: 1123-1125.
J Natl Cancer Inst 2008 100: 1119.
J Natl Cancer Inst 2008 100: 1119.
This article has been cited by other articles:
|
|
 |
|
  P. Albertsen Androgen Deprivation in Prostate Cancer -- Step by Step N. Engl. J. Med., June 11, 2009; 360(24): 2572 - 2574. [Full Text] [PDF]
|
|
|
|
 |
|
 E. P. Gelmann and S. M. Henshall Clinically Relevant Prognostic Markers for Prostate Cancer: The Search Goes On Ann Intern Med, May 5, 2009; 150(9): 647 - 649. [Full Text] [PDF]
|
|
|
|
 |
|
 K. L. Penney, C. A. Salinas, M. Pomerantz, F. R. Schumacher, C. A. Beckwith, G.-S. Lee, W. K. Oh, O. Sartor, E. A. Ostrander, T. Kurth, et al. Evaluation of 8q24 and 17q Risk Loci and Prostate Cancer Mortality Clin. Cancer Res., May 1, 2009; 15(9): 3223 - 3230. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Calonge, D. B. Petitti, and K. W. Lin Are Age-Based Criteria the Best Way to Determine Eligibility for Prostate Cancer Screening? Ann Intern Med, February 3, 2009; 150(3): 221 - 222. [Full Text] [PDF]
|
|
|
|
 |
|
 R. J. Schulz and A. R. Kagan Re: Prostatectomy vs Watchful Waiting in Localized Prostate Cancer: The Scandinavian Prostate Cancer Group-4 Randomized Trial J Natl Cancer Inst, January 21, 2009; 101(2): 124 - 124. [Full Text] [PDF]
|
|
|
|
|
|
M. J. Barry Screening for Prostate Cancer among Men 75 Years of Age or Older N. Engl. J. Med., December 11, 2008; 359(24): 2515 - 2516. [Full Text] [PDF]
|
|
|
|
 |
|
 Prostatectomy vs. Observation for Localized Prostate Cancer: Another Update Journal Watch (General), September 16, 2008; 2008(916): 6 - 6. [Full Text]
|
|
|
|
 |
|
 Radical Prostatectomy vs. Watchful Waiting Journal Watch Oncology and Hematology, September 16, 2008; 2008(916): 1 - 1. [Full Text]
|
|