Cancer screening test: are they effective??

 A recent article assessed the actual years of lifetime gained from an array of approved cancer screening tests, finding minimal effect (see cancer screening not help much JAMAintmed2023 in dropbox, or https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2808648 ).

 

Details:
-- Assessment of mammography for breast cancer screening; colonoscopy, sigmoidoscopy, and fecal occult blood testing (FOBT, or guaiacs) for colorectal cancer;  low-dose CT (LDCT) for lung cancer in smokers; and PSA testing for prostate cancer

-- systematic review/meta-analysis of RCTs with more than 9 years of followup that reported all-cause mortality and estimated lifetime gained for these screening tests

-- 2,111,958 individuals involved

-- median followup:

    -- LDCT (3 studies), PSA (4 studies), colonoscopy (1 study): 10 years

    -- mammography (2 studies): 13 years

    -- sigmoidoscopy (4 studies) and FOBT (4 studies): 15 years

-- Main outcome: life-years gained, comparing individuals screened vs not screened

Results:
-- sigmoidoscopy: 110 days (0-274 days). the ONLY test with a significant lifetime gain

-- mammography: 0 days (-190 to 237 days)

-- PSA: 37 days (-37 to 73 days)

-- colonoscopy: 37 days (-146 to 146 days)

-- FOBT every year or every other year: 0 days (-70.7 to 70.7 days)

-- LDCT: 107 days (-286 to 430 days)

 

 

-- no difference in outcomes in post-hoc analysis of mammography screening that included women <50yo, or incorporating more trials that had been excluded for suboptimal randomization

 

-- as a contrasting reference point, bariatric surgery is associated with a 3.0-year increased life expectancy after 24 years of followup

Commentary:

-- pretty shocking that these standard cancer screening tools actually seem to have little effect on life expectancy

--  this study raises a few important issues:

    -- cancer screening has been integrated into our clinical practices, with flags in electronic medical records to make sure the screenings are done

    -- these screens are often hailed as markers of “quality of care”. I personally have an issue with this: seeing that the "box is checked" that a study has been done is a low-hanging fruit, one that is very easy to do (as opposed to a detailed medical record review to see if the patients are really getting standard-of-care therapies). I also have the same issue with A1C levels for diabetes, given that the most common cause of death in patients with diabetes is cardiovascular disease, and some meds (eg insulin, sulfonylureas) seem to hasten these bad outcomes and some (GLP-1, SGLT-2) decrease them (ie, A1C is a reasonable target but in the context of what meds are being given)

    -- BUT, we primary care providers are open to significant medicolegal consequences if a patient has a bad outcome and testing was not done (of course, even with testing, people can have bad outcomes)

-- also, the findings in this study are large-scale community data and reflects averages from aggregate data. Which means that some individual patients actually do much better than these numbers when early cancers are found that would otherwise progress to lethality, but a patient may also have a colon perforation by doing a colonoscopy (though it does happen more frequently with advancing age), or have a bad outcome from prostate cancer surgery/radiation, etc, which can also be lethal

-- It is important to remember that in assessing the risks of a screening test, it is not just from the test itself (eg doing a simple blood test or a colonoscopy) but the downstream evaluations and treatments (prostate or colon cancer treatments, for what might be an “overdiagnosis” where there is a finding of what looks like a cancer in the lab but does not go on to lead to increased mortality). And this is the reason that we really need to assess “all-cause mortality” and not just “cancer mortality”, the latter may hide the harms associated with the screening and treatments

-- this study did not include cervical cancer screening, since the researchers found no RCTs with cancer-specific or all-cause mortality and long-term followup

 

Limitations:

-- the length of followup may not reveal the true benefits: some of the cancers may not reveal benefit until well after the followup time in this study

    -- but, this study does question the approach of doing mammography, for example, if someone has a 10-year life expectancy, which has been advocated based on mathematical modeling

-- some of the screening tests were done based on very few studies, so might not pick up what could have been a significant benefit

    -- eg, there was only one study on colonoscopy, actually done by the author of this study above, of 85K people followed 10 years and finding an increased risk of colon cancer in those not screened, though no difference in death from colorectal cancer or all-cause mortality (see colonoscopy dec colon cancer incidence NEJM2022 in dropbox, or DOI: 10.1056/NEJMoa2208375)

    -- why, you might ask, does sigmoidoscopy beat out colonoscopy (besides the number of studies done), since one sees the whole colon with the latter and only a part with the former study?

        -- it turns out that right-sided lesions (missed by sigmoidoscopy) in many studies either have no benefit from their detection, or minimal benefit: they are harder to detect than left-sided lesions (more often have flat morphology), are more often big tumors, and are more often poorly-differentiated (the genetic makeup of these lesions are different from the left-sided ones: eg see https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6089587/)

 

-- it is hard to tease out the actual causes of death, since there is overlap between some cancer risk factors (eg obesity, high fat diets, diabetes, etc) and other causes of death from these same risk factors (eg heart disease). And these non-cancer causes would affect their estimates of the life-year calculations. similarly, if the cancer diagnosis leads to premature death from stress, suicide, accidents.

-- this study relied on intention-to-treat analysis (they could not get good per-protocol assessments), and there would be some nonadherence to protocols that would underestimate the efficacy of screening

 

So,

-- i am not concluding that we abandon all cancer screening, but i do think we need to have realistic expectations of the actual benefits of what the risks and benefits are. For example, for many patients, we may have a list of clinical items to address, and in some cases it is best to focus on the higher priority items. Perhaps the patient might be overwhelmed with a check-list that is very long. And this study would help us and the patients prioritize the most urgent interventions.

-- one issue that can be obscured/underplayed by focusing on screening test is the supreme importance of prevention

    -- assessing LDCT for smokers and finding “normal” findings has been shown in one study to lead patients to think that it is okay for them to smoke (though, of course, smokers overwhelmingly die from cardiovascular causes vs lung cancer)

    -- resources should be targeted more on preventing smoking or other targets shown to increase cancer risk than on picking up cancers (which may still be useful for some patients, but prevention is the real public health issue: eg targeting adolescents to decrease their risk of starting smoking, full-scale public health initiatives to get early adolescents get the HPV vaccine (preventing cervical cancer as well as oropharyngeal cancers in males and females), etc

 

 

geoff

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