Does cancer screening help us live longer?

We’ve all heard that “cancer screening saves lives.” If you read this blog regularly, you know that’s sort of true. For certain cancer screenings like mammogram and colonoscopy, screening prevents some cancer-related deaths, but we don’t have evidence that it reduces overall mortality (death from any cause).

Does screening give us more years of life?

A new meta-analysis in JAMA Internal Medicine provides more information on the relationship between cancer screening and overall lifespan. Researchers from the University of Oslo looked at 18 long-term randomized clinical trials of six common cancer screening tests (Mammography screening for breast cancer; colonoscopy, sigmoidoscopy, or fecal occult blood testing for colorectal cancer; CT screening for lung cancer in smokers and former smokers; and prostate-specific antigen testing for prostate cancer) to see the impact of screening on how long participants lived. All trials had at least ten years of follow-up. In total the trials included 2.1 million participants.

The authors found that one test, sigmoidoscopy for colorectal cancer, showed a significant increase in life gained of 110 days for people who were screened, compared to those who were not screened. But the other screening tests did not show a statistically significant increase in lifespan in the screening group.

The limitations of this analysis are important to note. The meta-analysis included only randomized controlled trials that measured all-cause mortality (many do not, because it requires more participants) and had long enough follow-up, which limited it to 18 studies (a small fraction of the cancer screening trials that exist). One of the included mammogram trials was recently found to be inaccurately randomized, Yale School of Medicine Dr. F. Perry Wilson pointed out in a Medscape op-ed. However, one could argue the small sample of trials included shows a limitation of the research landscape itself– ideally we would have many more long-term randomized trials of cancer screening that are powered to detect all-cause mortality.

Why life-years gained from screening is low

How could it be that many cancer screenings don’t have an impact on overall lifespan? While screenings prevent some deaths from cancer, they don’t prevent all. For example, with no screening, an estimated 28 women out of 1,000 will die from breast cancer over their lifetime; with biennial screening starting at age 50, 21 will still die from breast cancer.

At the same time, cancer screenings have associated harms such as false positive results, overdiagnosis, and overtreatment (not to mention the financial cost of all these cascade events). Of 1,000 women who get screened for breast cancer every other year starting at age 50, we can expect there to be 1,021 false positive results, 148 unnecessary biopsies, and 10 cases of overdiagnosis. Some of these will be relatively innocuous, but others could lead to increased stress, harm from radiation, and even financial toxicity, all which can impact overall health. It could be that the benefits of screening that some people receive get washed out by the harms that others experience when looking at screening on a population level.

There are other reasons why cancer screenings may not have as large an impact on overall mortality. Treatments for some cancers have improved over the years, making it more likely that someone diagnosed with cancer will survive. And other causes of death such as heart disease have a greater impact on overall mortality than cancer.

What does this mean for me?

Do the results of this study mean that no one should get screened for cancer? The short answer is no. Even if screening has not been shown to increase lifespan on average, there will still be patients that benefit from screening and avoid early death from cancer. However, before undergoing screening, people should be aware that they are much more likely to experience a false positive or overtreatment than they are to have their life saved by the screening. Given that knowledge, many people will still choose screening, but some may not.

This risk-benefit calculation also changes based on one’s particular risk factors for cancer, as well as the type of screening. For example, colonoscopy is not just a screening test but a preventive measure as polyps are removed.

Researchers are also working on ways to increase the benefits and reduce harms from screening, so that the decision to get screened is easier. For example, Dr. Laura Esserman, a surgeon and breast cancer oncologist at the University of California San Francisco and Dr. Scott Eggener, a surgeon and urologic oncologist at the University of Chicago, suggest in a New York Times op-ed that we use personalized screening for breast cancer “based on such factors as age, genetics, lifestyle, health history and breast density.”

Esserman and Eggner recommend that very low-risk diagnoses such as ductal carcinoma in situ or a 6 on the Gleason scale be treated with active surveillance (“watch and wait” strategy”) rather than with aggressive treatment right away. They note that the classification of non-invasive, low-risk diagnoses as “cancer” adds unnecessary pressure to patients to pursue aggressive treatment, and suggest using different terminology other than the “dreaded C-word.”

Can we stop the screening train?

If cancer screening has minimal impact on overall lifespan, why is screening so prevalent? In an accompanying editorial in JAMA Internal Medicine, three of the meta-analysis authors explain that it’s hard to stop screening programs once they’ve become commonplace, because they are a win-win for many stakeholders. Screening increases volume and feeds the healthcare industry engine, creating jobs and boosting the incomes of physicians and the medical device industry. And it’s easier for policymakers to support screening programs rather than take more difficult but potentially impactful actions to prevent cancer such as regulate pollutants and other carcinogens.

Cancer screening is also unique in that there are fewer requirements for implementation compared to drug approvals. “Cancer screening—now also including novel multicancer early detection tests—can be rolled out as full-scale human experiments before basic information about test performance, benefits, harms, and cost-effectiveness is available,” the authors write.

Before we throw all our eggs in the basket for these new “liquid biopsy” tests, we have to be sure that there is a mortality benefit– a feasible ask for a multi-cancer screening test — and that conflicts of interest don’t tip the scales in the decisions to approve or cover these tests.