Speaking with One Voice on Cancer Screening
As a general internist, cancer screening is part of my job. However, it is a part of my job that can torture me. I know we save hundreds of thousands of people each year with screening tests but I also know that we:
we falsely reassure some people by telling them that they do not have disease when they do;
we chase down false positive screening tests to prove that people don’t have disease we didn’t think they had until we screened them;
and, in some people, we diagnosis and treat disease that would never have caused problems.
Adding to these issues, is the problem that we cannot even agree on whom to screen and how often. Here, Dr. Jarva Chow and I address this last problem.
A recent trial on colon cancer screening[i] raised important questions about cancer screening. What is the ultimate goal of cancer screening? Is cancer screening intended to lower overall mortality, cause specific mortality, or prevent cancer? How large a number needed to screen is too large for a test to be acceptable? Because these questions have not been answered, there continues to be debate about the advisability of cancer screening in general, and the manner and frequency in particular.[ii] Important differences in recommendations for cancer screening between the USPSTF, ACS, and specialty societies[iii],[iv] is perhaps the clearest manifestation of this issue. If we are to reach agreement on the benefit of cancer screening, thus enabling guideline committees to speak with one voice, we must agree on what constitutes an effective screening test and on how much we, as a nation, are willing to pay for it.
Why does variation exist in guidelines?
Guideline variation exists because different committees, as well as different doctors and patients, require different levels of evidence and the promise of different benefits to accept that screening is advisable. This includes the type of data (clinical trials vs. observational studies) and which endpoints are improved and by what degree. The Nordicc trial highlighted these differences. The trial demonstrated that screening colonoscopy reduced the risk of future colon cancer but had neither an effect on colon cancer related mortality (a benefit in this endpoint has been shown in other colon cancer screening trials[v]) nor on overall mortality (which has not been consistently demonstrated[vi]). Different guideline producing groups, working off this same data, could come up with very different recommendations.
The presence of variation may be due to the disagreement over how to interpret data or value endpoints, but it raises the possibility, and at the very least, the appearance that conflicts of interests play a role. In an effort to remove conflicts of interest that could bias care, physicians are no longer allowed to receive gifts from pharmaceutical companies. Yet, many societies that offer physicians guidance receive significant compensation from industry. The American Cancer Society lists in its 2020 Annual Report contributions of over $1 million from Merck & Co, Genentech, and Pfizer to name a few.[vii] Cancer screening typically involves a large asymptomatic patient population. Diagnostic labs and procedures are associated with risk or physical harm, cost money, and may be of limited benefit. The evidence supporting screening guidelines should arguably be more robust than other medical interventions given the otherwise healthy patient population.
Reaching Guideline Accord: A Starting Point
Ideally, an effective screening test should find cancer early, decrease the rate of dying from the cancer it seeks to find, and increase the overall survival of the people being screened. Recommended screening tests do detect cancer earlier and most of those recommended have also been shown to decrease disease specific mortality. Few screening tests, however, have demonstrated improved overall survival.6 This, of course, does not mean that all screening tests are ineffective, leading to tangential harms that balance out intended benefits. Trials powered to show overall survival benefits are hugely expensive, requiring large populations followed for years. Yet without evidence of overall survival benefit we really do not know the benefits of a screening test. The best data would show measured benefits, allow calculation of a number needed to screen, and cost benefit analysis.
Reaching Guideline Accord: A Proposal
The first step to developing guidelines that can be supported by all interested parties is to agree on “specific cancer agnostic” requirements. We would expect that most parties could agree that a minimum data requirement is controlled trial data demonstrating a disease specific mortality benefit. We would suggest that there should be agreement that harms of screening are unlikely to prevent overall mortality benefits. The next step is to agree on costs. Taking into account the cost of the test, lost income, and diagnostic evaluations of false positives, what is the cost of screening to prevent a single death from the disease of interest over a specified period of time? Lastly, just because a screening test is proven effective at one time does not mean that it will always be effective. As populations and treatments evolve what was once a cost-effective screening test might become unnecessary. These topics should be revisited every 5-10 years.
As a nation and profession, we have agreed that cancer screening is a worthy place to spend healthcare dollars. However, for screening to be successful, physicians and guideline producing societies should speak with one voice. This requires we agree on how to answer difficult questions regarding evidence base, cost, and the balance of harm and benefits. These answers, however, will offer clarity in how to guide clinicians and patients about cancer screening.
Jarva Chow, MD, MPH, is a critical care physician and anesthesiologist practicing at the University of Chicago. Her interests include exposing conflicts of interest, evidence-based medicine, and, when time allows, practicing wushu.
[i] Bretthauer M, Løberg M, Wieszczy P, et al. Effect of Colonoscopy Screening on Risks of Colorectal Cancer and Related Death. N Engl J Med. 2022;387(17):1547-1556. doi:10.1056/NEJMoa2208375
[ii] Clift AK, Dodwell D, Lord S, et al. The current status of risk-stratified breast screening. Br J Cancer. 2022;126(4):533-550. doi:10.1038/s41416-021-01550-3
[iii] Siu AL; U.S. Preventive Services Task Force. Screening for Breast Cancer: U.S. Preventive Services Task Force Recommendation Statement [published correction appears in Ann Intern Med. 2016 Mar 15;164(6):448]. Ann Intern Med. 2016;164(4):279-296. doi:10.7326/M15-2886
[iv] Oeffinger KC, Fontham ET, Etzioni R, et al. Breast Cancer Screening for Women at Average Risk: 2015 Guideline Update From the American Cancer Society [published correction appears in JAMA. 2016 Apr 5;315(13):1406]. JAMA. 2015;314(15):1599-1614. doi:10.1001/jama.2015.12783
[v] Shaukat A, Mongin SJ, Geisser MS, et al. Long-term mortality after screening for colorectal cancer. N Engl J Med. 2013;369(12):1106-1114. doi:10.1056/NEJMoa1300720
[vi] Lin JS, Perdue LA, Henrikson NB, Bean SI, Blasi PR. Screening for Colorectal Cancer: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force [published correction appears in JAMA. 2021 Jul 20;326(3):279]. JAMA. 2021;325(19):1978-1998. doi:10.1001/jama.2021.4417
[vii] American Society of Cancer. 2020 Annual Report. https://www.cancer.org/about-us/financial-governance-information/stewardship-report.html . Accessed November 8, 2022.