Ruth Etzioni

American Cancer Society Guideline for the Early Detection of Prostate Cancer: Update 2010

In 2009, the American Cancer Society (ACS) Prostate Cancer Advisory Committee began the process of a complete update of recommendations for early prostate cancer detection. A series of systematic evidence reviews was conducted focusing on evidence related to the early detection of prostate cancer, test performance, harms of therapy for localized prostate cancer, and shared and informed decision making in prostate cancer screening. The results of the systematic reviews were evaluated by the ACS Prostate Cancer Advisory Committee, and deliberations about the evidence occurred at committee meetings and during conference calls. On the basis of the evidence and a consensus process, the Prostate Cancer Advisory Committee developed the guideline, and a writing committee drafted a guideline document that was circulated to the entire committee for review and revision. The document was then circulated to peer reviewers for feedback, and finally to the ACS Mission Outcomes Committee and the ACS Board of Directors for approval. The ACS recommends that asymptomatic men who have at least a 10‐year life expectancy have an opportunity to make an informed decision with their health care provider about screening for prostate cancer after they receive information about the uncertainties, risks, and potential benefits associated with prostate cancer screening. Prostate cancer screening should not occur without an informed decision‐making process. Men at average risk should receive this information beginning at age 50 years. Men in higher risk groups should receive this information before age 50 years. Men should either receive this information directly from their health care providers or be referred to reliable and culturally appropriate sources. Patient decision aids are helpful in preparing men to make a decision whether to be tested. CA Cancer J Clin 2010;60:70–98.

Estimating health care costs related to cancer treatment from SEER-Medicare data.

Background. Cancer-specific medical care costs are used by health service researchers, medical decision analysts, and health care policymakers. The SEER-Medicare database is a unique data resource that makes it possible to derive incidence- and prevalence-based estimates of cancer-related medical care costs by site and stage of disease, by treatment approach, and for age and gender strata for individuals older than 65 years. Objectives. This paper describes the cost-related data available in the SEER-Medicare database, and discusses techniques and methods that have been used to derive various cost estimates from these data. The limitations of SEER-Medicare data as a source of cost estimates are also discussed. Results. Examples of cost estimates for colorectal and breast cancer derived from SEER-Medicare are presented, including estimates of incidence-based cost (average cost per patient) by the initial, terminal, and continuing care phases of cancer treatment. Estimates of cancer-related treatment costs, costs by type of treatment, and long-term costs are presented, as are prevalence-based costs (aggregate Medicare and national expenditures) by cancer type.

American Cancer Society lung cancer screening guidelines

Answer questions and earn CME/CNE

Quality of life in survivors of colorectal carcinoma

Colon carcinoma is a common malignancy that accounts for a substantial share of all cancer‐related morbidity and mortality. However, little is known with regard to general and disease specific quality of life in survivors of colorectal carcinoma, particularly from community‐based samples of cases across stage and survival times from diagnosis.

Overdiagnosis and Overtreatment of Prostate Cancer

CONTEXT Although prostate cancer (PCa) screening reduces the incidence of advanced disease and mortality, trade-offs include overdiagnosis and resultant overtreatment. OBJECTIVE To review primary data on PCa overdiagnosis and overtreatment. EVIDENCE ACQUISITION Electronic searches were conducted in Cochrane Central Register of Controlled Trials, PubMed, and Embase from inception to July 2013 for original articles on PCa overdiagnosis and overtreatment. Supplemental articles were identified through hand searches. EVIDENCE SYNTHESIS The lead-time and excess-incidence approaches are the main ways used to estimate overdiagnosis in epidemiological studies, with estimates varying widely. The estimated number of PCa cases needed to be diagnosed to save a life has ranged from 48 down to 5 with increasing follow-up. In clinical studies, generally lower rates of overdiagnosis have been reported based on the frequency of low-grade minimal tumors at radical prostatectomy (1.7-46.8%). Autopsy studies have reported PCa in 18.5-38.5%, although not all are low grade or low volume. Factors influencing overdiagnosis include the study population, screening protocol, and background incidence, limiting generalizability between settings. Reported rates of overtreatment vary widely in the literature, although contemporary international studies suggest increasing use of conservative management. CONCLUSIONS Epidemiological, clinical, and autopsy studies have been used to examine PCa overdiagnosis, with estimates ranging widely from 1.7% to 67%. Correspondingly, estimates of overtreatment vary widely based on patient features and may be declining internationally. Careful patient selection for screening and reducing overtreatment are important to preserve the benefits and reduce the downstream harms of prostate-specific antigen testing. Because all of these estimates are extremely population and context specific, this must be considered when using these data to inform policy. PATIENT SUMMARY Screening reduces spread and death from prostate cancer (PCa) but overdiagnoses some low-risk tumors that may not have caused harm. Because treatment has potential side effects, it is critical that not all patients with PCa receive aggressive treatment.

Quantifying the role of PSA screening in the US prostate cancer mortality decline

ObjectiveTo quantify the plausible contribution of prostate-specific antigen (PSA) screening to the nearly 30% decline in the US prostate cancer mortality rate observed during the 1990s.MethodsTwo mathematical modeling teams of the US National Cancer Institute’s Cancer Intervention and Surveillance Modeling Network independently projected disease mortality in the absence and presence of PSA screening. Both teams relied on Surveillance, Epidemiology, and End Results (SEER) registry data for disease incidence, used common estimates of PSA screening rates, and assumed that screening, by shifting disease from distant to local-regional clinical stage, confers a corresponding improvement in disease-specific survival.ResultsThe teams projected similar mortality increases in the absence of screening and decreases in the presence of screening after 1985. By 2000, the models projected that 45% (Fred Hutchinson Cancer Research Center) to 70% (University of Michigan) of the observed decline in prostate cancer mortality could be plausibly attributed to the stage shift induced by screening.ConclusionsPSA screening may account for much, but not all, of the observed drop in prostate cancer mortality. Other factors, such as changing treatment practices, may also have played a role in improving prostate cancer outcomes.

Substantial interindividual and limited intraindividual genomic diversity among tumors from men with metastatic prostate cancer

Tumor heterogeneity may reduce the efficacy of molecularly guided systemic therapy for cancers that have metastasized. To determine whether the genomic alterations in a single metastasis provide a reasonable assessment of the major oncogenic drivers of other dispersed metastases in an individual, we analyzed multiple tumors from men with disseminated prostate cancer through whole-exome sequencing, array comparative genomic hybridization (CGH) and RNA transcript profiling, and we compared the genomic diversity within and between individuals. In contrast to the substantial heterogeneity between men, there was limited diversity among metastases within an individual. The number of somatic mutations, the burden of genomic copy number alterations and aberrations in known oncogenic drivers were all highly concordant, as were metrics of androgen receptor (AR) activity and cell cycle activity. AR activity was inversely associated with cell proliferation, whereas the expression of Fanconi anemia (FA)-complex genes was correlated with elevated cell cycle progression, expression of the E2F transcription factor 1 (E2F1) and loss of retinoblastoma 1 (RB1). Men with somatic aberrations in FA-complex genes or in ATM serine/threonine kinase (ATM) exhibited significantly longer treatment-response durations to carboplatin than did men without defects in genes encoding DNA-repair proteins. Collectively, these data indicate that although exceptions exist, evaluating a single metastasis provides a reasonable assessment of the major oncogenic driver alterations that are present in disseminated tumors within an individual, and thus may be useful for selecting treatments on the basis of predicted molecular vulnerabilities.

Prostate-specific antigen testing in black and white men: an analysis of medicare claims from 1991–1998

OBJECTIVES To describe the trends in prostate-specific antigen (PSA) use and associated cancer detection among black and white Medicare beneficiaries older than 65 years during the calendar period from January 1991 through December 1998. METHODS Medicare claims data were linked with cancer registry data from the Surveillance, Epidemiology and End Results program of the National Cancer Institute. Data from a 5% random sample of men without a diagnosis of prostate cancer were combined with data from prostate cancer cases diagnosed during the calendar period from 1991 to 1998. PSA tests conducted after a diagnosis of prostate cancer were excluded. RESULTS PSA use has stabilized among white men, reaching an annual rate of 38% by 1995 and remaining at this level through 1998. The annual rate of use among black men reached 31% by 1998, but was still increasing at that time. By 1996, at least 80% of tests in both blacks and whites were second or later tests. By the end of 1996, 35% of white men and 25% of black men were undergoing testing at least biannually or more frequently. In 1996, 83% of diagnoses in whites and 77% in blacks were preceded by a PSA test. CONCLUSIONS Older black men lag slightly behind older white men in their use of the PSA test; however, annual testing rates in blacks have yet to stabilize. In both race groups, an overwhelming majority of diagnoses are associated with a PSA test, whether for screening or diagnostic purposes. Regular screening rates in blacks are substantially lower than in whites, but the regular screening rates are relatively low in both race groups. Should PSA screening prove efficacious, efforts to promote regular use among both black and white men will likely be needed.

Associations of demographic and lifestyle characteristics with prostate-specific antigen (PSA) concentration and rate of PSA increase

The objective of this study was to examine whether demographic and lifestyle characteristics are associated with prostate‐specific antigen (PSA) levels and the rate of PSA increase (PSA velocity).

Comparative Effectiveness of Alternative Prostate-Specific Antigen–Based Prostate Cancer Screening Strategies: Model Estimates of Potential Benefits and Harms

BACKGROUND The U.S. Preventive Services Task Force recently concluded that the harms of existing prostate-specific antigen (PSA) screening strategies outweigh the benefits. OBJECTIVE To evaluate comparative effectiveness of alternative PSA screening strategies. DESIGN Microsimulation model of prostate cancer incidence and mortality quantifying harms and lives saved for alternative PSA screening strategies. DATA SOURCES National and trial data on PSA growth, screening and biopsy patterns, incidence, treatment distributions, treatment efficacy, and mortality. TARGET POPULATION A contemporary cohort of U.S. men. TIME HORIZON Lifetime. PERSPECTIVE Societal. INTERVENTION 35 screening strategies that vary by start and stop ages, screening intervals, and thresholds for biopsy referral. OUTCOME MEASURES PSA tests, false-positive test results, cancer detected, overdiagnoses, prostate cancer deaths, lives saved, and months of life saved. RESULTS OF BASE-CASE ANALYSIS Without screening, the risk for prostate cancer death is 2.86%. A reference strategy that screens men aged 50 to 74 years annually with a PSA threshold for biopsy referral of 4 µg/L reduces the risk for prostate cancer death to 2.15%, with risk for overdiagnosis of 3.3%. A strategy that uses higher PSA thresholds for biopsy referral in older men achieves a similar risk for prostate cancer death (2.23%) but reduces the risk for overdiagnosis to 2.3%. A strategy that screens biennially with longer screening intervals for men with low PSA levels achieves similar risks for prostate cancer death (2.27%) and overdiagnosis (2.4%), but reduces total tests by 59% and false-positive results by 50%. RESULTS OF SENSITIVITY ANALYSIS Varying incidence inputs or reducing the survival improvement due to screening did not change conclusions. LIMITATION The model is a simplification of the natural history of prostate cancer, and improvement in survival due to screening is uncertain. CONCLUSION Compared with standard screening, PSA screening strategies that use higher thresholds for biopsy referral for older men and that screen men with low PSA levels less frequently can reduce harms while preserving lives. PRIMARY FUNDING SOURCE National Cancer Institute and Centers for Disease Control and Prevention.