Cancer Screening: Limited Power to Reduce Death at 10 Years?

EBM Focus - Volume 18, Issue 30

Reference: JAMA Intern Med. 2023 Aug 28 early online

Practice Point: Does cancer screening really make no difference? Headlines are intended to turn heads. Just make sure you look at the details before changing your practice.

EBM Pearl: All-cause mortality may be a perfect, but not practical, metric by which to measure the effectiveness of cancer screening.

Have any of your patients asked about full body screening MRIs yet? Brace yourself. Full body MRIs are being promoted by celebrities on social media as preventative medicine for the elite. To date, no evidence supports this. There are however, many screening modalities which are widely used and recommended, although their ability to extend lifespan is uncertain. A recent systematic review and meta-analysis(es) in JAMA sought to address this question regarding common cancer screenings.

Authors searched MEDLINE and the Cochrane database for randomized clinical trials and meta-analyses comparing cancer screening with no screening. Included trials had > 9 years of follow-up with end-points of cancer-specific and all-cause mortality. The search covered screening tests at frequencies per guideline recommendations: mammography for breast cancer starting at age 50, fecal occult blood test (FOBT), sigmoidoscopy, and colonoscopy for colon cancer, prostate specific antigen (PSA) for prostate cancer, CT chest for lung cancer, and pap smear for cervical cancer. Observational studies and extrapolated data were excluded.

Data from more than 2.1 million individuals in 18 randomized clinical trials evaluating various screening tests with a median follow-up of 10 to 15 years were included in this systematic review and what equates to 6 separate meta-analyses. Based on these analyses, sigmoidoscopy was the only screening test associated with a significant increase in life-span (110 days; 95% CI, 0-274 days)*. No significant lifetime gain was observed with mammography, PSA, colonoscopy, FOBT, or CT chest screenings. There were no eligible trials for cervical cancer screening.

So, should we order sigmoidoscopies and abandon all other screening tests? No. The ability to detect a difference where one exists is proportional to the length of a study and the size of a study. This may explain why sigmoidoscopy, a procedure which is essentially a lesser version of colonoscopy, but with more available trial data (4, compared to 1 with colonoscopy) and longer follow-up (15 vs 10 years) was found to extend life while colonoscopy did not. The patient-years studied for sigmoidoscopy here are many more than for the other tests.

An additional consideration regarding power is that the included trials were individually powered to detect disease-specific mortality, not all-cause mortality, despite that being the primary outcome for the current meta-analyses. So that’s even more reason to question whether the lack of statistically significant findings for the other screening modalities means absence of effect or that we still need bigger, longer, randomized controlled trials to find an effect if one does exist. The reality is, however, that once screening guidelines are in place, it becomes challenging to complete randomized trials of screening – hence the relative lack of data on colonoscopies and pap smears.

Ultimately, though all-cause mortality is obviously an important metric, it may just not be a practical metric to evaluate cancer screening. So what do we do with this information? Continue to keep the individual in front of you in mind during shared-decision making regarding cancer screening. In addition to all-cause mortality, cancer-specific mortality, morbidity, and harms of screening must be considered. Though this evidence may add some nuance to the conversation, for now we are not making any changes to our practice because of it.

*Statistical significance was set at whether 95% CI crossed 0.

For more information, see the topic Adult Preventative Health in DynaMed.

DynaMed EBM Focus Editorial Team

This EBM Focus was written by Nicole Jensen, MD, Family Physician at WholeHealth Medical. Edited by Alan Ehrlich, MD, Executive Editor at DynaMed and Associate Professor in Family Medicine at the University of Massachusetts Medical School; Katharine DeGeorge, MD, MS, Senior Deputy Editor at DynaMed and Associate Professor of Family Medicine at the University of Virginia; Dan Randall, MD, Deputy Editor at DynaMed; Vincent Lemaitre, PhD, Medical Editor at DynaMed; Elham Razmpoosh, PhD, Postdoctoral fellow at McMaster University; and Sarah Hill, MSc, Senior Associate Editor at DynaMed.