BACKGROUND: The Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) trial showed that radical prostatectomy (RP) reduced prostate cancer deaths with an absolute mortality difference (AMD) between the RP and watchful waiting arms of 6.1% (95% confidence interval [CI] = 0.2% to 12.0%) after 15 years. In the United States, the Prostate Cancer Intervention Versus Observation Trial (PIVOT) produced an AMD of 3% (95% CI = -1.1% to 6.5%) after 12 years. It is not known whether a higher frequency of screen detection in PIVOT explains the lower AMD. METHODS: We assumed the SPCG-4 trial represents RP efficacy and prostate cancer survival in an unscreened population. Given the fraction of screen-detected prostate cancers in PIVOT, we adjusted prostate cancer survival using published estimates of overdiagnosis and lead time to project the effect of screen detection on disease-specific deaths. RESULTS: On the basis of published estimates, we assumed that 32% of screen-detected cancers were overdiagnosed and a mean lead time among non-overdiagnosed cancers of 7.7 years. When we adjusted prostate cancer survival for the 76% of case patients in PIVOT who were screen detected, we projected that the AMD after 12 years would be 2.0% (95% CI = -1.6% to 5.6%) based on variation in published estimates of overdiagnosis and mean lead time in the United States. CONCLUSIONS: If RP efficacy and prostate cancer survival in the absence of screening are similar to that in the SPCG-4 trial, then overdiagnosis and lead time largely explain the lower AMD in PIVOT. If these artifacts of screening are the correct explanation, then there is a subset of case subjects that should not be treated with RP, and identifying this subset should lead to a clearer understanding of the benefit of RP in the remaining cases.
RCT Entities:
BACKGROUND: The Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) trial showed that radical prostatectomy (RP) reduced prostate cancer deaths with an absolute mortality difference (AMD) between the RP and watchful waiting arms of 6.1% (95% confidence interval [CI] = 0.2% to 12.0%) after 15 years. In the United States, the Prostate Cancer Intervention Versus Observation Trial (PIVOT) produced an AMD of 3% (95% CI = -1.1% to 6.5%) after 12 years. It is not known whether a higher frequency of screen detection in PIVOT explains the lower AMD. METHODS: We assumed the SPCG-4 trial represents RP efficacy and prostate cancer survival in an unscreened population. Given the fraction of screen-detected prostate cancers in PIVOT, we adjusted prostate cancer survival using published estimates of overdiagnosis and lead time to project the effect of screen detection on disease-specific deaths. RESULTS: On the basis of published estimates, we assumed that 32% of screen-detected cancers were overdiagnosed and a mean lead time among non-overdiagnosed cancers of 7.7 years. When we adjusted prostate cancer survival for the 76% of case patients in PIVOT who were screen detected, we projected that the AMD after 12 years would be 2.0% (95% CI = -1.6% to 5.6%) based on variation in published estimates of overdiagnosis and mean lead time in the United States. CONCLUSIONS: If RP efficacy and prostate cancer survival in the absence of screening are similar to that in the SPCG-4 trial, then overdiagnosis and lead time largely explain the lower AMD in PIVOT. If these artifacts of screening are the correct explanation, then there is a subset of case subjects that should not be treated with RP, and identifying this subset should lead to a clearer understanding of the benefit of RP in the remaining cases.
Authors: Timothy J Wilt; Michael K Brawer; Karen M Jones; Michael J Barry; William J Aronson; Steven Fox; Jeffrey R Gingrich; John T Wei; Patricia Gilhooly; B Mayer Grob; Imad Nsouli; Padmini Iyer; Ruben Cartagena; Glenn Snider; Claus Roehrborn; Roohollah Sharifi; William Blank; Parikshit Pandya; Gerald L Andriole; Daniel Culkin; Thomas Wheeler Journal: N Engl J Med Date: 2012-07-19 Impact factor: 91.245
Authors: Anna Bill-Axelson; Lars Holmberg; Mirja Ruutu; Hans Garmo; Jennifer R Stark; Christer Busch; Stig Nordling; Michael Häggman; Swen-Olof Andersson; Stefan Bratell; Anders Spångberg; Juni Palmgren; Gunnar Steineck; Hans-Olov Adami; Jan-Erik Johansson Journal: N Engl J Med Date: 2011-05-05 Impact factor: 91.245
Authors: Roman Gulati; Elisabeth M Wever; Alex Tsodikov; David F Penson; Lurdes Y T Inoue; Jeffrey Katcher; Shih-Yuan Lee; Eveline A M Heijnsdijk; Gerrit Draisma; Harry J de Koning; Ruth Etzioni Journal: Cancer Epidemiol Biomarkers Prev Date: 2011-05 Impact factor: 4.254
Authors: Timothy J Wilt; Michael K Brawer; Michael J Barry; Karen M Jones; Young Kwon; Jeffrey R Gingrich; William J Aronson; Imad Nsouli; Padmini Iyer; Ruben Cartagena; Glenn Snider; Claus Roehrborn; Steven Fox Journal: Contemp Clin Trials Date: 2008-08-23 Impact factor: 2.226
Authors: Gerrit Draisma; Ruth Etzioni; Alex Tsodikov; Angela Mariotto; Elisabeth Wever; Roman Gulati; Eric Feuer; Harry de Koning Journal: J Natl Cancer Inst Date: 2009-03-10 Impact factor: 13.506
Authors: Björn L D M Brücher; Gary Lyman; Richard van Hillegersberg; Raphael E Pollock; Florian Lordick; Han-Kwang Yang; Toshikazu Ushijima; Khay-Guan Yeoh; Tomas Skricka; Wojciech Polkowski; Grzegorz Wallner; Vic Verwaal; Alfredo Garofalo; Domenico D'Ugo; Franco Roviello; Hans-Ulrich Steinau; Timothy J Wallace; Martin Daumer; Nitah Maihle; Thomas J Reid; Michel Ducreux; Yuko Kitagawa; Alexander Knuth; Bruno Zilberstein; Scott R Steele; Ijaz S Jamall Journal: BMC Cancer Date: 2014-03-14 Impact factor: 4.430
Authors: G L Shaw; B C Thomas; S N Dawson; G Srivastava; S L Vowler; V J Gnanapragasam; N C Shah; A Y Warren; D E Neal Journal: Br J Cancer Date: 2014-04-10 Impact factor: 7.640