The effect of study arm on prostate cancer treatment in the large screening trial ERSPC

Prostate cancer (PC) mortality is the most valid end‐point in screening trials, but could be influenced by the choice of initial treatment if treatment has an effect on mortality. In this study, PC treatment was compared between the screening and control arms in a screening trial. Data were collected from the European Randomized Study of Screening for Prostate Cancer (ERSPC). The characteristics and initial treatment of PC cases detected in the screening and the control arm were compared. Polytomous logistic regression analysis was used to assess the influence of study arm on treatment, adjusting for potential confounders and with statistical imputation of missing values. A total of 8,389 PC cases were detected, 5,422 in the screening arm and 3,145 in the control arm. Polytomous regression showed that trial arm was associated with treatment choice after correction for missing values, especially in men with high‐risk PC. A control subject with high‐risk PC was more likely than a screen subject to receive radiotherapy (OR: 1.43, 95% CI: 1.01–2.05, p = 0.047), expectant management (OR: 2.92, 95% CI: 1.33–6.42, p = 0.007) or hormonal treatment (OR: 1.77, 95% CI: 1.07–2.94, p = 0.026) instead of radical prostatectomy. However, trial arm had only a minor role in treatment choice compared to other variables. In conclusion, a small effect of trial arm on treatment choice was seen, particularly in men with high‐risk PC. Therefore, differences in treatment between arms are unlikely to play a major role in the interpretation of the results of the ERSPC.

[1]  T. Tammela,et al.  Tumor characteristics in a population-based prostate cancer screening trial with prostate-specific antigen. , 2003, Clinical cancer research : an official journal of the American Association for Cancer Research.

[2]  B A Miller,et al.  The role of increasing detection in the rising incidence of prostate cancer. , 1995, JAMA.

[3]  H. D. de Koning,et al.  Low all-cause mortality in the volunteer-based Rotterdam section of the European randomised study of screening for prostate cancer: self-selection bias? , 2004, Journal of medical screening.

[4]  S B Malkowicz,et al.  Biochemical Outcome After Radical Prostatectomy , External Beam Radiation Therapy , or Interstitial Radiation Therapy for Clinically Localized Prostate Cancer , 2000 .

[5]  Roderick J. A. Little,et al.  Statistical Analysis with Missing Data , 1988 .

[6]  M. Roobol,et al.  The story of the European Randomized Study of Screening for Prostate Cancer , 2003, BJU international.

[7]  Harry J de Koning,et al.  Comparison of screen detected and clinically diagnosed prostate cancer in the European randomized study of screening for prostate cancer, section rotterdam. , 2005, The Journal of urology.

[8]  S. Fosså,et al.  Endocrine treatment, with or without radiotherapy, in locally advanced prostate cancer (SPCG-7/SFUO-3): an open randomised phase III trial , 2009, The Lancet.

[9]  C. Parker.  Active surveillance: towards a new paradigm in the management of early prostate cancer. , 2004, The Lancet. Oncology.

[10]  B E Hillner,et al.  Factors that determine the treatment for local and regional prostate cancer. , 1996, Medical care.

[11]  T. Tammela,et al.  Lead-time in prostate cancer screening (Finland) , 2002, Cancer Causes & Control.

[12]  B. G. Blijenberg,et al.  Screening and prostate-cancer mortality in a randomized European study. , 2009, The New England journal of medicine.

[13]  P. Smith,et al.  The Data Monitoring Committee – bridging the gap between urology and public health epidemiology , 2003, BJU international.

[14]  Hans Lilja,et al.  Results of a randomized, population‐based study of biennial screening using serum prostate‐specific antigen measurement to detect prostate carcinoma , 2004, Cancer.

[15]  C.J.H. Mann,et al.  Clinical Prediction Models: A Practical Approach to Development, Validation and Updating , 2009 .

[16]  Harry J de Koning,et al.  Lead times and overdetection due to prostate-specific antigen screening: estimates from the European Randomized Study of Screening for Prostate Cancer. , 2003, Journal of the National Cancer Institute.

[17]  J. Hugosson,et al.  Prostate cancer screening decreases the absolute risk of being diagnosed with advanced prostate cancer--results from a prospective, population-based randomized controlled trial. , 2007, European urology.

[18]  C. Bangma,et al.  Overdiagnosis and overtreatment of early detected prostate cancer , 2007, World Journal of Urology.

[19]  Ewout W Steyerberg,et al.  Survival estimates of a prognostic classification depended more on year of treatment than on imputation of missing values. , 2006, Journal of clinical epidemiology.

[20]  T. H. van der Kwast,et al.  Tumour features in the control and screening arm of a randomized trial of prostate cancer. , 2006, European urology.

[21]  A. Gottschalk.  Commentary on Endocrine treatment, with or without radiotherapy, in locally advanced prostate cancer (SPCG-7/SFUO-3): An open randomized phase III trial , 2009 .

[22]  Roderick J. A. Little,et al.  Statistical Analysis with Missing Data: Little/Statistical Analysis with Missing Data , 2002 .

[23]  Nicole A. Lazar,et al.  Statistical Analysis With Missing Data , 2003, Technometrics.

[24]  Jacques Bernier,et al.  Long-term results with immediate androgen suppression and external irradiation in patients with locally advanced prostate cancer (an EORTC study): a phase III randomised trial , 2002, The Lancet.