Xia J, Gulati R, Au M, Gore JL, Lin DW, Etzioni REffects of screening on radical prostatectomy efficacy: the prostate cancer intervention versus observation trial. J Natl Cancer Inst 105: 546-550

Affiliations of authors: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA (JX, RG, RE)
Journal of the National Cancer Institute (Impact Factor: 12.58). 02/2013; 105(8). DOI: 10.1093/jnci/djt017
Source: PubMed


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.ResultsOn 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.

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    • "Conversely, the SPCG-4 study, from an unscreened Scandinavian population, demonstrated a significant survival benefit to radical prostatectomy (Bill-Axelson et al, 2011). Analyses of PIVOT trial data compared with SPCG-4 data suggest that PSA screening results in over diagnosis and lead-time effect (Xia et al, 2013). It has been estimated using the ERSPC data that this lead time is 11 years (Draisma et al, 2003). "
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    ABSTRACT: Background: Identification of men harbouring insignificant prostate cancer (PC) is important in selecting patients for active surveillance. Tools have been developed in PSA-screened populations to identify such men based on clinical and biopsy parameters. Methods: Prospectively collected case series of 848 patients was treated with radical prostatectomy between July 2007 and October 2011 at an English tertiary care centre. Tumour volume was assessed by pathological examination. For each tool, receiver operator characteristics were calculated for predicting insignificant disease by three different criteria and the area under each curve compared. Comparison of accuracy in screened and unscreened populations was performed. Results: Of 848 patients, 415 had Gleason 3+3 disease on biopsy. Of these, 32.0% had extra-prostatic extension and 50.2% were upgraded. One had positive lymph nodes. Two hundred and six (24% of cohort) were D'Amico low risk. Of these, 143 had more than two biopsy cores involved. None of the tools evaluated has adequate discriminative power in predicting insignificant tumour burden. Accuracy is low in PSA-screened and -unscreened populations. Conclusions: In our unscreened population, tools designed to identify insignificant PC are inaccurate. Detection of a wider size range of prostate tumours in the unscreened may contribute to relative inaccuracy.
    Full-text · Article · Apr 2014 · British Journal of Cancer
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    • "Improved treatment techniques as well as earlier diagnosis in recent years have certainly led to better results [3]. However, early diagnosis and/or early treatment of Pca has interestingly not improved the Pca specific survival or overall survival from Pca [4]. On the other hand, there is an everyday increasing number of publications dealing with new markers to detect Pca in the early stage [5]. "
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    ABSTRACT: Prostate cancer (PCa) is the commonest visceral cancer in men worldwide. Introduction of serum PSA as a highly specific biomarker for prostatic diseases has led to a dramatic increase in the diagnosis of early stage PCa in last decades. Guidelines underline that benefits as well as risks and squeals of early diagnosis and treatment should be discussed with patients. There are several new biomarkers (Pro-PSA, PCA-3 test, and TMPRSS2-ERG) available on the market but new ones are awaited in order to improve specificity and sensitivity. Investigators have also focused on identifying and isolating the gene, or genes, responsible for PCa. Current definitive treatment options for clinically localized PCa with functional and oncological success rates up to 95% include surgery (radical prostatectomy), external-beam radiation therapy, and interstitial radiation therapy (brachytherapy). Potential complications of overdiagnosis and overtreatment have resulted in arguments about screening and introduced a new management approach called "active surveillance." Improvements in diagnostic techniques, especially multiparametric magnetic resonance imaging, significantly ameliorated the accuracy of tumor localization and local staging. These advances will further support focal therapies as emerging treatment alternatives for localized PCa. As a conclusion, revolutionary changes in the diagnosis and management of PCa are awaited in the near future.
    Full-text · Article · Sep 2013 · The Scientific World Journal

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