Screening after 40: which tests have been shown to change outcomes, and which have not

Long “check-up after forty” lists often combine tests with very different levels of evidence about whether screening changes morbidity or mortality. A test that finds something is not the same as a test that changes outcomes. This article sorts the common screening tests for adults over forty by that second question — what randomised trials and the US Preventive Services Task Force (USPSTF) actually concluded — and says plainly where the evidence stops.

What "changes the outcome" means here

The strongest direct evidence for a screening test comes from randomised trials showing fewer deaths or serious illness in a defined population, but guideline bodies may also use indirect evidence and modelling and must weigh any expected benefit against false alarms, extra procedures and overdiagnosis. Detecting more early-stage disease is not enough on its own, as the ovarian cancer trial below shows.

The USPSTF grades preventive-service recommendations for people without obvious related symptoms: A and B mean “recommended”, C means “offer selectively”, D means “recommended against”, and I means the evidence is insufficient. Its statements are written for the United States; ages and intervals can differ elsewhere, so the applicable national guidance and individual risk need to be considered with a clinician.

Tests with trial or guideline support for adults over forty

• Blood pressure. The USPSTF recommends office blood-pressure screening for adults aged 18 or older who do not already have diagnosed hypertension, with diagnostic confirmation outside the clinic before treatment starts (grade A, 2021; PMID 33904861). Hypertension is often asymptomatic, which is part of the rationale for screening. More on the number itself: Blood pressure and longevity.

• Blood glucose. Screening for prediabetes and type 2 diabetes is recommended for asymptomatic, nonpregnant adults aged 35 to 70 in primary care who have overweight or obesity (grade B, 2021; PMID 34427594). When the two usual numbers do not agree, see When fasting glucose and HbA1c disagree.

• Colorectal cancer. For asymptomatic adults at average colorectal-cancer risk, screening is recommended from ages 50 to 75 (grade A) and 45 to 49 (grade B), with selective screening from 76 to 85 based on health, previous screening and preferences (grade C, 2021; PMID 34003218). Several test options are accepted, including stool-based tests and colonoscopy.

• Breast cancer. Biennial mammography is recommended for women and other persons assigned female at birth aged 40 to 74 who are at average risk of breast cancer (grade B, 2024; PMID 38687503). For people identified as having dense breasts on an otherwise negative mammogram, the USPSTF found the evidence insufficient to assess supplemental ultrasound or MRI (grade I; PMID 38687503).

• Cervical cancer. For asymptomatic people aged 30 to 65 with a cervix who are not in an excluded high-risk group, the current final USPSTF statement recommends cytology every three years, high-risk HPV testing every five years, or cotesting every five years (grade A, 2018; PMID 30140884). It recommends against screening after age 65 for people with adequate prior screening who are not otherwise at high risk (grade D; PMID 30140884).

• Lung cancer — only for a defined smoking history. Annual low-dose CT is recommended for adults aged 50 to 80 with at least 20 pack-years who currently smoke or quit within the past 15 years (grade B, 2021; PMID 33687470). This screening recommendation does not apply to people who have never smoked.

What the key trials actually measured

Colonoscopy — the NordICC trial. In the NordICC intention-to-screen analysis, 84,585 adults aged 55 to 64 in Poland, Norway and Sweden were randomised either to an invitation for a single screening colonoscopy or to no screening; 42.0% of those invited underwent screening (PMID 36214590). At 10 years, colorectal cancer had been diagnosed in 0.98% of the invited group and 1.20% of the usual-care group (PMID 36214590). At 10 years, the risk of death from colorectal cancer was 0.28% in the invited group and 0.31% in the usual-care group (risk ratio 0.90; 95% CI 0.64–1.16); the corresponding risks of death from any cause were 11.03% and 11.04% (risk ratio 0.99; 95% CI 0.96–1.04; PMID 36214590). The intention-to-screen analysis estimated the effect of an invitation in this population; because 42.0% of invitees underwent screening, it did not estimate the effect of undergoing colonoscopy (PMID 36214590).

Low-dose CT — the NLST trial. The NLST randomised 53,454 current or former smokers aged 55 to 74 with at least 30 pack-years, and no more than 15 years since quitting for former smokers, to three annual rounds of low-dose CT or chest X-ray (PMID 21714641). In this trial population, the observed lung-cancer mortality rates were 247 and 309 per 100,000 person-years in the CT and X-ray groups, respectively; the reported relative reduction was 20.0%, and all-cause mortality was 6.7% lower in the CT group (PMID 21714641). The same trial also reported that 96.4% of positive low-dose CT results across the three screening rounds were false positives (PMID 21714641).

Ovarian cancer — the UKCTOCS trial. UKCTOCS included 202,562 postmenopausal women aged 50 to 74 who were not at increased familial risk and assigned them to annual multimodal screening using longitudinal CA-125 with second-line ultrasound, annual transvaginal ultrasound, or no screening; median follow-up was 16.3 years (PMID 33991479). Screening with the blood-test strategy found more early-stage cancers, yet deaths from ovarian or tubal cancer were 0.6% in every group, with no significant difference. In this trial population, detecting more early-stage disease with multimodal screening did not coincide with lower ovarian- or tubal-cancer mortality (PMID 33991479).

Tests the USPSTF recommends against in people without symptoms

• Ovarian cancer screening in asymptomatic women not known to have a high-risk hereditary cancer syndrome (grade D, 2018; PMID 29450531).

• Thyroid cancer screening in the general population of asymptomatic adults; the statement does not cover people with relevant symptoms or specified high-risk histories (grade D, 2017; PMID 28492905).

• Pancreatic cancer screening in asymptomatic adults not known to be at high risk because of an inherited syndrome or familial pancreatic cancer (grade D, reaffirmed 2019; PMID 31386141).

• Carotid artery ultrasound to screen for stenosis in the general adult population without a history of transient ischaemic attack, stroke or other neurologic symptoms referable to the carotid arteries (grade D, 2021; PMID 33528542). This recommendation is about screening everyone; it does not cover people with symptoms or a specific clinical reason for the scan. For what a plaque finding means once it exists, see Stable atherosclerotic plaque: what the word means.

PSA for prostate cancer sits in between. For asymptomatic men aged 55 to 69 without a previous prostate-cancer diagnosis, the USPSTF calls PSA-based screening an individual decision after discussion of its small potential benefit and its risks of false positives, biopsy, overdiagnosis and treatment harms (grade C, 2018; PMID 29801017). For men aged 70 or older, it recommends against PSA-based screening (grade D; PMID 29801017).

Bundled check-ups: what the trials of "everything at once" found

A Cochrane review pooled randomised trials of general health checks — screening for several diseases or risk factors at once — in adults not selected for any disease. Across 11 trials with 233,298 participants, the total-mortality risk ratio was 1.00 (95% CI 0.97–1.03); cancer mortality was 1.01 (0.92–1.12), and fatal or non-fatal ischaemic heart disease was 0.98 (0.94–1.03) in the relevant trial subsets (PMID 30699470). Among adults not selected for disease in the included trials, general health checks had little or no effect on total or cancer mortality and probably little or no effect on cardiovascular mortality (PMID 30699470). These findings apply to bundled general health checks in those trial populations; they do not assess the effectiveness of every individual test included in such checks (PMID 30699470).

Where the evidence stops

A 2023 meta-analysis combined 18 randomised trials involving 2,111,958 participants from the populations eligible for six screening tests and estimated lifetime gained over 10 to 15 years of follow-up (PMID 37639247). For mammography, colonoscopy, stool blood testing, PSA and lung CT, the estimated lifetime gain was not statistically significant. Sigmoidoscopy was the only test for which the authors reported a statistically significant lifetime-gain estimate, but the estimate was imprecise and the published lower bound of its 95% confidence interval rounded to zero (PMID 37639247). Across the included trial populations, the confidence intervals for mammography, colonoscopy, stool blood testing, PSA and lung CT included no lifetime gain, so the analysis established neither a gain nor its absence for those tests (PMID 37639247). The authors described sigmoidoscopy as a possible exception (PMID 37639247).

What to do with this

The useful move is not "test more" but "know which tests apply to you and when each was last done". Age, anatomy, smoking exposure, body size, previous screening, personal and family history, inherited risk and overall health can all affect which screening recommendations apply. Symptoms fall outside the asymptomatic screening recommendations summarised here; family history or inherited risk may also place a person outside their stated populations, so the applicable condition-specific guidance should be reviewed with a clinician.

Keeping the dates of past tests and results in one place makes that conversation shorter: see Your health record in one place.

This material is for information only and does not replace a consultation with a doctor.

References

• US Preventive Services Task Force (2021). Screening for Colorectal Cancer: US Preventive Services Task Force Recommendation Statement. JAMA. PMID 34003218.

• US Preventive Services Task Force (2024). Screening for Breast Cancer: US Preventive Services Task Force Recommendation Statement. JAMA. PMID 38687503.

• US Preventive Services Task Force (2018). Screening for Cervical Cancer: US Preventive Services Task Force Recommendation Statement. JAMA. PMID 30140884.

• US Preventive Services Task Force (2021). Screening for Lung Cancer: US Preventive Services Task Force Recommendation Statement. JAMA. PMID 33687470.

• US Preventive Services Task Force (2021). Screening for Hypertension in Adults: US Preventive Services Task Force Reaffirmation Recommendation Statement. JAMA. PMID 33904861.

• US Preventive Services Task Force (2021). Screening for Prediabetes and Type 2 Diabetes: US Preventive Services Task Force Recommendation Statement. JAMA. PMID 34427594.

• US Preventive Services Task Force (2018). Screening for Prostate Cancer: US Preventive Services Task Force Recommendation Statement. JAMA. PMID 29801017.

• US Preventive Services Task Force (2018). Screening for Ovarian Cancer: US Preventive Services Task Force Recommendation Statement. JAMA. PMID 29450531.

• US Preventive Services Task Force (2017). Screening for Thyroid Cancer: US Preventive Services Task Force Recommendation Statement. JAMA. PMID 28492905.

• US Preventive Services Task Force (2019). Screening for Pancreatic Cancer: US Preventive Services Task Force Reaffirmation Recommendation Statement. JAMA. PMID 31386141.

• US Preventive Services Task Force (2021). Screening for Asymptomatic Carotid Artery Stenosis: US Preventive Services Task Force Recommendation Statement. JAMA. PMID 33528542.

• Bretthauer M. et al. (2022). Effect of Colonoscopy Screening on Risks of Colorectal Cancer and Related Death. New England Journal of Medicine. PMID 36214590.

• National Lung Screening Trial Research Team; Aberle D.R. et al. (2011). Reduced lung-cancer mortality with low-dose computed tomographic screening. New England Journal of Medicine. PMID 21714641.

• Menon U. et al. (2021). Ovarian cancer population screening and mortality after long-term follow-up in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a randomised controlled trial. Lancet. PMID 33991479.

• Krogsbøll L.T. et al. (2019). General health checks in adults for reducing morbidity and mortality from disease. Cochrane Database of Systematic Reviews. PMID 30699470.

• Bretthauer M. et al. (2023). Estimated Lifetime Gained With Cancer Screening Tests: A Meta-Analysis of Randomized Clinical Trials. JAMA Internal Medicine. PMID 37639247.