In the 1930s and 1940s, when the American Cancer Society [ACS] first brought forth the message that early cancer detection saves lives, it was a broad brushstroke and an appropriate message. The problem now is that new technology enables us to find [tumors that would never progress to invasive cancers], and suddenly the message isn’t so simple anymore,” said Otis W. Brawley, MD, Chief Medical Officer and Executive Vice President, Research and Cancer Control Science at the American Cancer Society and Professor of Hematology, Medical Oncology, Medicine, and Epidemiology at Emory University, Atlanta.
Series of Controversies
The value of using population-wide screening tests on asymptomatic people to detect cancer early, when it is presumably easier to cure, has come into question and ignited a fierce debate among physicians—and confusion among the public. The first controversy erupted in 2008, when a draft report from the U.S. Preventive Services Task Force (USPSTF) of an analysis of data on the prostate-specific antigen (PSA) test—the most common screening tool—showed that PSA testing in asymptomatic men is not necessary.
The following year, the USPSTF advised that healthy women get routine breast cancer screenings biannually beginning at age 50 and stopping at age 74, instead of its previous recommendation that mammograms should be obtained annually and begin at age 40. According to the Task Force findings, to save the life of one woman in her 40s, 1,904 would have to undergo annual screening, which would result in a number of false-positives, psychological distress, and unnecessary surgery.
In May, the Task Force issued its final recommendations against regular prostate cancer screenings for men of all ages, saying that in this test, too, the collateral damage from overscreening far outweighs the potential benefit. According to the Task Force, one man in every 1,000 screened may avoid death as a result of the PSA test, while one man in every 3,000 tested will die as a result of complications from prostate cancer surgery and dozens more will suffer from erectile dysfunction, incontinence, pain, infection, and emotional distress.
Evolving Concept
“The conceptual model of cancer screening is super-compelling: Find the cancer early and cure it; don’t find the cancer and the person dies. But with the possible exception of the Pap test, cancer screening is not that simple,” said Peter B. Bach, MD, Director of the Center for Health Policy and Outcomes at Memorial Sloan-Kettering Cancer Center.
What is proving to be more advantageous are screenings for people at increased risk for cancer. A review of 21 studies on the benefits and harms of low-dose computed tomography screening for lung cancer recently published in the Journal of the American Medical Association found that such screening does benefit individuals at high risk for lung cancer due to smoking.1 However, the review also found a relatively high risk of false-positives, with approximately 20% of the people screened requiring further testing, including biopsies, but only 1% had lung cancer. Still, said Dr. Bach, the lead author of the JAMA report, the evidence shows that when screening is done in high-risk individuals such as smokers, “the risk/benefit tradeoff does seem to favor benefit.”
What Is Cancer?
Even when abnormal cell growth is found during routine screenings, it doesn’t mean that a cancer will become invasive and lead to death. “An overwhelming issue here is our definition of what cancer is,” said Dr. Brawley. Rudolf Virchow, a mid-19th century physician and pathologist who discovered that leukemia was caused by the rapid proliferation of abnormal white cells, was the first person to define cancer as a process in which healthy cells mutate and then reproduce. This definition led to the notion that early detection of these mutating cells leads to cure. But Dr. Virchow could never have imagined the advancements in medicine that now make it possible to detect tiny cancers at such early stages, noted Dr. Brawley.
“Virchow never saw cancer on an x-ray, CT, or MRI scan or diagnosed it with a fine-needle biopsy, but pathologists today still use the same hematoxylin and eosin (H&E) stains he used to diagnose cancer. Now, for example, we may see cells that look like breast cancer, but does that mean that those cells are genomically programmed to grow, spread, and metastasize? No, it doesn’t. In fact, we know that between 10% and 30% of localized breast cancers found on mammograms will not progress,” said Dr. Brawley.
Other Groups Weigh In
A host of medical organizations, including the ACS, the American College of Radiology, the American Society of Breast Disease, and the American Medical Association, have all come out against the new mammography screening guidelines from the USPSTF. These groups all support mammography screening beginning at age 40.
There is slightly more support for the USPSTF recommendations on PSA screening, with the ACS, the American Urological Association (AUA), and the American College of Preventive Medicine agreeing that there is insufficient evidence to recommend routine PSA screening for average-risk men in any age group. However, the ACS advises that average-risk men with at least a 10-year life expectancy receive information on screening and have the opportunity to make an informed decision beginning at age 50. The AUA recommends that screening information be conveyed to men aged 40 and older who have a life expectancy of more than 10 years.
In July, ASCO released a new evidence-based provisional clinical opinion (PCO) on the use of PSA screenings, which recommends that physicians discuss the benefits and risks of PSA testing with asymptomatic patients who have life expectancies greater than 10 years.2 The PCO notes that the risks of testing outweigh the benefits for men with shorter life expectancies.
Interpreting Cancer-screening Statistics
All the publicity surrounding the debate over the benefits and risks associated with cancer screenings has failed to dissuade people from seeking them. A study published in the April 25, 2012, issue of JAMA found that despite the 2008 USPSTF recommendation against prostate cancer screening in men aged 75 or older, PSA screening rates did not change.3
One reason for the consistency in screening rates may be that physicians do not understand cancer-screening statistics, and as a consequence, provide misleading information to their patients. A study published earlier this year in the Annals of Internal Medicine, which included a survey of over 400 primary care physicians in the United States, found that the majority of respondents could not distinguish between relevant and irrelevant or even misleading information when it comes to cancer screenings and whether they save lives.4 According to the findings, 47% of physicians incorrectly said that finding more cases of cancer in screened as opposed to unscreened populations “proves that screening saves lives.” And 76% said that better survival rates prove that screening saves lives.
Refining the Message
“The role of screening is clear in individuals who are at high risk for developing cancer based on either their genetics or family histories,” said Frank L. Meyskens, Jr, MD, Director, Chao Family Comprehensive Cancer Center at the University of California, Irvine, and Chair-Elect of ASCO’s Cancer Prevention Committee. “Once you go beyond that to an asymptomatic general population, it becomes difficult to justify, because either during the risk phase where there are no pathologic changes or even when there are early pathologic changes, it’s very difficult to predict who is going to go on to develop cancer and who isn’t. Once cancer is invasive, it’s easy to make recommendations about what to do, but up until then, it’s difficult. Progress in validating genomic and nongenomic biomarkers may help refine screening and early detection recommendations, but we are not there yet.”
According to Dr. Bach, improving the public’s understanding of the role of cancer screenings and changing physicians’ reliance on them will take time, but progress is being made. “Reports in the media on the benefits and risks of screening tests are starting to be more balanced. An important part of the messaging to the public is that cancer screening tests themselves don’t make you healthier—they just have the potential to make you healthier—and that they only make sense if you are meaningfully at risk of cancer.” Shifting physicians’ attitudes may take longer.
“There’s a cognitive dissonance between the practice of evidence-based medicine and how we train doctors to make clinical decisions. And they are fundamentally different,” said Dr. Bach. “I think that this is going to be a generational change. As we shift to doctors who are brought up more on the ability to evaluate and utilize comparative effectiveness research when making clinical decisions, rather than relying on personal experience or intuition, the use of cancer screening tests will become more strategic.” ■
Disclosure: Drs. Bach, Brawley, and Meyskens, Jr, reported no potential conflicts of interest.
References
1. Bach PB, Mirkin JN, Oliver TK, et al: Benefits and harms of CT screening for lung cancer: A systematic review. JAMA 307:2418-2429, 2012.
2. Basch E, Oliver TK, Vickers A, et al: Screening for prostate cancer with prostate-specific antigen testing: American Society of Clinical Oncology provisional clinical opinion. J Clin Oncol. July 16, 2012 (early release online).
3. Prasad SM, Drazer MW, Huo D, et al: 2008 US Preventive Services Task Force recommendations and prostate cancer screening rates. JAMA 307:1692-1694, 2012.
4. Wegwarth O, Schwartz LM, Woloshin S, et al: Do physicians understand cancer screening statistics? A national survey of primary care physicians in the United States. Ann Intern Med 156:340-349, 2012.
