Jennifer Croswell

Screening for prostate cancer: a review of the evidence for the U.S. Preventive Services Task Force.

BACKGROUND Screening can detect prostate cancer at earlier, asymptomatic stages, when treatments might be more effective. PURPOSE To update the 2002 and 2008 U.S. Preventive Services Task Force evidence reviews on screening and treatments for prostate cancer. DATA SOURCES MEDLINE (2002 to July 2011) and the Cochrane Library Database (through second quarter of 2011). STUDY SELECTION Randomized trials of prostate-specific antigen-based screening, randomized trials and cohort studies of prostatectomy or radiation therapy versus watchful waiting, and large observational studies of perioperative harms. DATA EXTRACTION Investigators abstracted and checked study details and quality using predefined criteria. DATA SYNTHESIS Of 5 screening trials, the 2 largest and highest-quality studies reported conflicting results. One found that screening was associated with reduced prostate cancer-specific mortality compared with no screening in a subgroup of men aged 55 to 69 years after 9 years (relative risk, 0.80 [95% CI, 0.65 to 0.98]; absolute risk reduction, 0.07 percentage point). The other found no statistically significant effect after 10 years (relative risk, 1.1 [CI, 0.80 to 1.5]). After 3 or 4 screening rounds, 12% to 13% of screened men had false-positive results. Serious infections or urine retention occurred after 0.5% to 1.0% of prostate biopsies. There were 3 randomized trials and 23 cohort studies of treatments. One good-quality trial found that prostatectomy for localized prostate cancer decreased risk for prostate cancer-specific mortality compared with watchful waiting through 13 years of follow-up (relative risk, 0.62 [CI, 0.44 to 0.87]; absolute risk reduction, 6.1%). Benefits seemed to be limited to men younger than 65 years. Treating approximately 3 men with prostatectomy or 7 men with radiation therapy instead of watchful waiting would each result in 1 additional case of erectile dysfunction. Treating approximately 5 men with prostatectomy would result in 1 additional case of urinary incontinence. Prostatectomy was associated with perioperative death (about 0.5%) and cardiovascular events (0.6% to 3%), and radiation therapy was associated with bowel dysfunction. LIMITATIONS Only English-language articles were included. Few studies evaluated newer therapies. CONCLUSION Prostate-specific antigen-based screening results in small or no reduction in prostate cancer-specific mortality and is associated with harms related to subsequent evaluation and treatments, some of which may be unnecessary. PRIMARY FUNDING SOURCE Agency for Healthcare Research and Quality.

Cumulative Incidence of False-Positive Test Results in Lung Cancer Screening: A Randomized Trial

BACKGROUND Direct-to-consumer promotion of lung cancer screening has increased, especially low-dose computed tomography (CT). However, screening exposes healthy persons to potential harms, and cumulative false-positive rates for low-dose CT have never been formally reported. OBJECTIVE To quantify the cumulative risk that a person who participated in a 1- or 2-year lung cancer screening examination would receive at least 1 false-positive result, as well as rates of unnecessary diagnostic procedures. DESIGN Randomized, controlled trial of low-dose CT versus chest radiography. (ClinicalTrials.gov registration number: NCT00006382) SETTING Feasibility study for the ongoing National Lung Screening Trial. PATIENTS Current or former smokers, aged 55 to 74 years, with a smoking history of 30 pack-years or more and no history of lung cancer (n = 3190). INTERVENTION Random assignment to low-dose CT or chest radiography with baseline and 1 repeated annual screening; 1-year follow-up after the final screening. Randomization was centralized and stratified by age, sex, and study center. MEASUREMENTS False-positive screenings, defined as a positive screening with a completed negative work-up or 12 months or more of follow-up with no lung cancer diagnosis. RESULTS By using a Kaplan-Meier analysis, a persons cumulative probability of 1 or more false-positive low-dose CT examinations was 21% (95% CI, 19% to 23%) after 1 screening and 33% (CI, 31% to 35%) after 2. The rates for chest radiography were 9% (CI, 8% to 11%) and 15% (CI, 13% to 16%), respectively. A total of 7% of participants with a false-positive low-dose CT examination and 4% with a false-positive chest radiography had a resulting invasive procedure. LIMITATIONS Screening was limited to 2 rounds. Follow-up after the second screening was limited to 12 months. The false-negative rate is probably an underestimate. CONCLUSION Risks for false-positive results on lung cancer screening tests are substantial after only 2 annual examinations, particularly for low-dose CT. Further study of resulting economic, psychosocial, and physical burdens of these methods is warranted. PRIMARY FUNDING SOURCE National Cancer Institute.

Cumulative incidence of false-positive results in repeated, multimodal cancer screening

PURPOSE Multiple cancer screening tests have been advocated for the general population; however, clinicians and patients are not always well-informed of screening burdens. We sought to determine the cumulative risk of a false-positive screening result and the resulting risk of a diagnostic procedure for an individual participating in a multimodal cancer screening program. METHODS Data were analyzed from the intervention arm of the ongoing Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, a randomized controlled trial to determine the effects of prostate, lung, colorectal, and ovarian cancer screening on disease-specific mortality. The 68,436 participants, aged 55 to 74 years, were randomized to screening or usual care. Women received serial serum tests to detect cancer antigen 125 (CA-125), transvaginal sonograms, posteroanterior-view chest radiographs, and flexible sigmoidoscopies. Men received serial chest radiographs, flexible sigmoidoscopies, digital rectal examinations, and serum prostate-specific antigen tests. Fourteen screening examinations for each sex were possible during the 3-year screening period. RESULTS After 14 tests, the cumulative risk of having at least 1 false-positive screening test is 60.4% (95% CI, 59.8%–61.0%) for men, and 48.8% (95% CI, 48.1%–49.4%) for women. The cumulative risk after 14 tests of undergoing an invasive diagnostic procedure prompted by a false-positive test is 28.5% (CI, 27.8%–29.3%) for men and 22.1% (95% CI, 21.4%–22.7%) for women. CONCLUSIONS For an individual in a multimodal cancer screening trial, the risk of a false-positive finding is about 50% or greater by the 14th test. Physicians should educate patients about the likelihood of false positives and resulting diagnostic interventions when counseling about cancer screening.

Cancer Screening: The Clash of Science and Intuition*

The concept of early detection of cancer holds great promise and intuitive appeal. However, powerful biases can mislead clinicians when evaluating the efficacy of screening tests by clinical observation alone. Selection bias, lead-time bias, length-biased sampling, and overdiagnosis are counterintuitive concepts with critical implications for early-detection efforts. This article explains these biases and other common confounders in cancer screening. The most direct and reliable way to avoid being led astray by intuitions is through the use of randomized controlled trials.

Collaborative Modeling: Experience of the U.S. Preventive Services Task Force

Models can be valuable tools to address uncertainty, trade-offs, and preferences when trying to understand the effects of interventions. Availability of results from two or more independently developed models that examine the same question (comparative modeling) allows systematic exploration of differences between models and the effect of these differences on model findings. Guideline groups sometimes commission comparative modeling to support their recommendation process. In this commissioned collaborative modeling, modelers work with the people who are developing a recommendation or policy not only to define the questions to be addressed but ideally, work side-by-side with each other and with systematic reviewers to standardize selected inputs and incorporate selected common assumptions. This paper describes the use of commissioned collaborative modeling by the U.S. Preventive Services Task Force (USPSTF), highlighting the general challenges and opportunities encountered and specific challenges for some topics. It delineates other approaches to use modeling to support evidence-based recommendations and the many strengths of collaborative modeling compared with other approaches. Unlike systematic reviews prepared for the USPSTF, the commissioned collaborative modeling reports used by the USPSTF in making recommendations about screening have not been required to follow a common format, sometimes making it challenging to understand key model features. This paper presents a checklist developed to critically appraise commissioned collaborative modeling reports about cancer screening topics prepared for the USPSTF.