Top POEMs of 2012: Cancer Screening

Colonoscopy Less Acceptable Than FOBT; Finds More Adenomas, But Same Number of Cancers

Clinical question: What are the acceptability and cancer yield of colonoscopy and fecal occult blood testing?

Bottom line: Fecal occult blood testing every 2 years is more acceptable to patients than colonoscopy, and results in a similar cancer yield but a much lower yield of advanced adenomas. Although at this point the weight of observational evidence and limited clinical trial evidence supports colonoscopy every 10 years, for patients who are unwilling to undergo colonoscopy or who can't afford it, fecal occult blood testing (FOBT) is a good option. This study used semiquantitative fecal immunochemical testing (OC-Sensor). (LOE = 1b)

Reference: Quintero E, Castells A, Bujanda L, et al, for the COLONPREV Study Investigators. Colonoscopy versus fecal immunochemical testing in colorectal-cancer screening. N Engl J Med 2012;366(8):697-706.

Study design: Randomized controlled trial (double-blinded)

Funding source: Government

Setting: Outpatient (specialty)

Synopsis: This report is from a Spanish clinical trial that randomized 57,404 adults, aged 50 to 69 years, to an invitation for either a single colonoscopy or FOBT using an immunochemical test every 2 years. The final trial results of this "noninferiority" trial (ie, a trial that determines whether the 2 interventions are roughly the same) will not be available until 2021. Participants were excluded if they had hereditary or familial polyposis, previous colorectal cancer (CRC), or multiple first-degree relatives with CRC. Allocation was concealed, and analysis was by intention to screen and "as screened." Participants were allowed to cross over from one group to the other; this was more common for those initially assigned to colonoscopy (1628 vs 106). Participation rates, a sign of acceptability, were higher for FOBT than for colonoscopy (34.2% vs 24.6%; odds ratio = 0.62; 95% CI, 0.60 - 0.65). The yield of colorectal cancer was the same in both groups (0.1%), but colonoscopy identified significantly more advanced adenomas (1.9% vs 0.9%) and nonadvanced adenomas (4.2% vs 0.4%). The authors also looked at the results for those who ultimately had colonoscopy or FOBT, whether or not they were initially assigned to that group (the "as screened" analysis). In this analysis, there was a trend toward a higher percentage diagnosed with colorectal cancer in the colonoscopy group (0.5% vs 0.3%; P = .09). The number needed to scope to find one colorectal cancer was 191 in the colonoscopy group and only 18 in the FOBT group (positive FOBT results that lead to colonoscopy), so the FOBT strategy was less resource-intensive. This is the initial 2-year analysis from a 10-year study, so stay tuned for more results down the road.

Mark H. Ebell, MD, MS
Associate Professor
University of Georgia
Athens, GA

Prostate Cancer Screening: No Mortality Benefit After 13 Years of Follow-up (PLCO)

Clinical question: Does screening of asymptomatic men for prostate cancer improve mortality?

Bottom line: After more than a decade of follow-up from the Prostate, Lung, Colorectal, and Ovarian Cancer study (PLCO), there appears to be no mortality benefit to screening asymptomatic men for prostate cancer. (LOE = 1b)

Reference: Andriole GL, Crawford ED, Grubb RL 3rd, et al., for the PLCO Project Team. Prostate cancer screening in the randomized prostate, lung, colorectal, and ovarian cancer screening trial: mortality results after 13 years of follow-up. J Natl Cancer Inst 2012;104(2):125-132.

Study design: Randomized controlled trial (single-blinded)

Funding source: Government

Setting: Population-based

Synopsis: We have previously reported( on the first report from the PLCO study in which men between the ages of 55 years and 74 years at 10 centers were randomized to receive prostate cancer screening (annual PSA for 6 years plus digital rectal examination for 4 years) or no scheduled screening. The current study reports additional follow-up (up to 13 years). The authors report having 92% follow-up at 10 years after study enrollment but at the time of this publication, only 57% of the participants had 13 years of follow-up. The cumulative incidence rate of prostate cancer was 108 and 97 per 10,000 person-years in the screened and control groups, respectively. We would need to screen approximately 885 men annually to detect one additional prostate cancer. However, the cumulative mortality rates were virtually identical (3.7 and 3.4 per 10,000 person-years, respectively). Certainly, the 10-year data appear to be similar to the 13-year data. The authors found no difference in mortality whether men were screened before entering the trial, or by age or comorbidity. It appears that there is no overall mortality benefit to screening asymptomatic men for prostate cancer.

Henry C. Barry, MD, MS
Michigan State University
East Lansing, MI


Prostate Cancer Screening Increases Harm Risk Without Decreasing Mortality

Clinical question: Does screening for prostate cancer with prostate-specific antigen testing decrease prostate cancer-related mortality?

Bottom line: Like evaluating the quality of refereeing in sports, opinions differ based on where one sits. The authors of this evidence review concluded that prostate-specific antigen (PSA) testing provides a small reduction or no reduction in prostate cancer-specific mortality and increases the risk of harm. The journal editors' comments on the paper, however, conclude the clinical benefits of screening "remain uncertain." If there is a benefit to PSA screening, it is very small, and 1 in 8 men will have a false-positive result with regular testing, leading to more testing and treatment, which is likely to be harmful. The final recommendation of the United States Preventive Services Task Force is still pending at the organization's website, but the draft prior to the public comment period in late 2011 gave PSA screening a "D" recommendation, regardless of the patient's age (moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits). (LOE = 1a-)

Reference: Chou R, Croswell JM, Dana T, et al. Screening for prostate cancer: A review of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med 2011;155(11):762-771.

Study design: Meta-analysis (randomized controlled trials)

Funding source: Government

Setting: Various (meta-analysis)

Synopsis: This review of the evidence, which was completed some months ago, was slow to come to print given the firestorm that erupted following the recent less-than-enthusiastic assessment of screening for breast cancer. Ah, politics. To develop this evidence review, the Task Force searched MEDLINE and the Cochrane Library, along with a review of reference lists of identified articles, to identify the 5 studies that evaluated the effectiveness of PSA screening. Two reviewers independently evaluated each study for inclusion and one investigator abstracted the data with a second investigator reviewing the data for accuracy. Unfortunately, the 2 largest studies were rated as only "fair" quality and 3 other studies were rated as "poor." Neither of the fair studies found a benefit to prostate cancer screening with regard to mortality, though one (the European study) found a small benefit (0.07 percentage point) in men between the ages of 55 years and 69 years. Harm is common with screening: 12% to 13% of men will have at least one false-positive PSA screening result after 3 to 4 rounds of testing and approximately half these patients will have a resulting biopsy. Urinary retention or serious infections occur in approximately 1% of biopsies. Psychological harms from false-positive results or overdiagnosis are also reported but difficult to quantify. Regarding the benefits and harms of treatment for early-stage or screening-detected cancer, one good-quality trial found that prostatectomy for localized prostate cancer results in a 6.1% absolute risk reduction in prostate cancer-specific mortality. However, the numbers needed to treat to harm are on the order of 200 for perioperative death, 50 for cardiovascular events, 5 for urinary incontinence, and 3 for erectile dysfunction. There have been no randomized trials of radiation therapy versus watchful waiting, so the evidence for mortality benefit (although shown in multiple studies) comes from cohort research. Adverse effects associated with radiation therapy include erectile and bowel dysfunction.

Allen F. Shaughnessy, PharmD, MMedEd
Professor of Family Medicine
Tufts University
Boston, MA

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