Response: Reading Between the Lines of Cancer Screening Trials Using Modeling to Understand the Evidence
Fred Hutchinson Cancer Research Center, Seattle WA.Medical care (Impact Factor: 3.23). 04/2013; 51(4):304-306. DOI: 10.1097/MLR.0b013e31828a7e1a
In our article about limitations of basing screening policy on screening trials, we offered several examples of ways in which modeling, using data from large screening trials and population trends, provided insights that differed somewhat from those based only on empirical trial results. In this editorial, we take a step back and consider the general question of whether randomized screening trials provide the strongest evidence for clinical guidelines concerning population screening programs. We argue that randomized trials provide a process that is designed to protect against certain biases but that this process does not guarantee that inferences based on empirical results from screening trials will be unbiased. Appropriate quantitative methods are key to obtaining unbiased inferences from screening trials. We highlight several studies in the statistical literature demonstrating that conventional survival analyses of screening trials can be misleading and list a number of key questions concerning screening harms and benefits that cannot be answered without modeling. Although we acknowledge the centrality of screening trials in the policy process, we maintain that modeling constitutes a powerful tool for screening trial interpretation and screening policy development.
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ABSTRACT: ABSTRACT This review, based on published papers, aims to describe the costs of prostate cancer screening and to examine whether prostate cancer screening is cost effective. The estimated cost per cancer detected ranged from €1299 in The Netherlands to US$44,355 in the USA. The estimated cost per life-year saved ranged from US$3000 to US$729,000, while the cost per quality-adjusted life year (QALY) was AU$291,817 and Can$371,100. The most appropriate data for economic evaluation of prostate cancer screening should be the cost per QALY gained. The estimated costs per QALY gained by prostate cancer screening were significantly higher than the cost-effectiveness threshold, suggesting that even when based on favorable randomized controlled trials in younger age groups, prostate cancer screening is still not cost effective.
Article: Prostate cancer[Show abstract] [Hide abstract]
ABSTRACT: Much progress has been made in research for prostate cancer in the past decade. There is now greater understanding for the genetic basis of familial prostate cancer with identification of rare but high-risk mutations (eg, BRCA2, HOXB13) and low-risk but common alleles (77 identified so far by genome-wide association studies) that could lead to targeted screening of patients at risk. This is especially important because screening for prostate cancer based on prostate-specific antigen remains controversial due to the high rate of overdiagnosis and unnecessary prostate biopsies, despite evidence that it reduces mortality. Classification of prostate cancer into distinct molecular subtypes, including mutually exclusive ETS-gene-fusion-positive and SPINK1-overexpressing, CHD1-loss cancers, could allow stratification of patients for different management strategies. Presently, men with localised disease can have very different prognoses and treatment options, ranging from observation alone through to radical surgery, with few good-quality randomised trials to inform on the best approach for an individual patient. The survival of patients with metastatic prostate cancer progressing on androgen-deprivation therapy (castration-resistant prostate cancer) has improved substantially. In addition to docetaxel, which has been used for more than a decade, in the past 4 years five new drugs have shown efficacy with improvements in overall survival leading to licensing for the treatment of metastatic castration-resistant prostate cancer. Because of this rapid change in the therapeutic landscape, no robust data exist to inform on the selection of patients for a specific treatment for castration-resistant prostate cancer or the best sequence of administration. Moreover, the high cost of the newer drugs limits their widespread use in several countries. Data from continuing clinical and translational research are urgently needed to improve, and, crucially, to personalise management.
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