Skipping colonoscopy after a positive stool test sharply raises colorectal cancer risk

JAMA Network Open / Karolinska Institutet

A positive fecal occult blood test (FOBT) is not a cancer diagnosis. It is a flag — a signal that something in the gut is bleeding and warrants a closer look via colonoscopy. But a significant number of people who receive that flag never follow through. And according to a new study published March 19 in JAMA Network Open, those individuals form a distinctly high-risk group for developing colorectal cancer.

The study also delivered better news for the other side of the screening equation: among people who did follow up with colonoscopy and received negative results, colorectal cancer incidence declined over time. The decrease was more pronounced in men than in women, a finding the authors say supports the growing push toward risk-based, individualized screening schedules.

Two populations, two very different trajectories

Colorectal cancer screening in many countries follows a two-step process. First, a noninvasive stool test — either a guaiac-based FOBT or a newer fecal immunochemical test (FIT) — checks for hidden blood. If that test is positive, the patient is referred for a diagnostic colonoscopy to determine the source of bleeding.

The system works well when people complete both steps. But adherence to follow-up colonoscopy after a positive stool test is a persistent problem in every healthcare system that uses this model. Estimates of nonadherence vary, but rates of 20% to 50% have been reported in different populations.

This study, led by Hanna Heyman, MD, at Karolinska Institutet, quantified the consequences of that gap. Among individuals who did not adhere to follow-up colonoscopy after a positive FOBT, colorectal cancer risk was significantly elevated. The researchers were able to identify this nonadherent group as a target for interventions aimed at improving early detection.

Negative colonoscopy as a strong reassurance — especially for men

For individuals who completed the screening pathway and received a negative colonoscopy result, the picture was more encouraging. Cancer incidence decreased over the study period, suggesting that the screening process itself — by removing precancerous polyps and surveilling the colon — reduces subsequent risk.

The reduction was greater in men. The reasons for this sex-based difference are not fully explained by the study, but may relate to differences in polyp prevalence, polyp biology, or the types of lesions detected and removed during screening colonoscopies. Men generally have higher baseline rates of colorectal cancer and higher rates of advanced adenomas, which means screening may have more opportunity to intervene.

This sex difference has practical implications for how screening intervals are set. Current guidelines typically recommend the same follow-up schedule for men and women after a negative colonoscopy, but the data suggest that risk-stratified approaches — accounting for sex along with other factors — could improve efficiency without sacrificing safety.

Why people skip the follow-up

The reasons for nonadherence to follow-up colonoscopy are well-documented in the literature, though this particular study does not examine them directly. Fear of the procedure, discomfort with bowel preparation, lack of symptoms ("I feel fine, so it can't be serious"), scheduling barriers, cost, and distrust of the medical system all play roles.

What this study adds is the outcome data. Skipping the follow-up is not a neutral decision. A positive FOBT selects for a population already at elevated risk, and declining the diagnostic step that could catch cancer early — or prevent it entirely by removing precancerous polyps — leaves that risk unaddressed.

The researchers argue that identifying this nonadherent population enables targeted interventions: patient navigation programs, reminder systems, alternative screening strategies like CT colonography for those who refuse traditional colonoscopy, or simply more effective communication about what a positive stool test means and does not mean.

Limitations worth noting

The study is observational, so it cannot prove that nonadherence caused higher cancer rates — only that the two are associated. People who skip colonoscopy may differ from those who comply in ways that independently affect cancer risk, including other health behaviors, socioeconomic factors, and comorbidities.

The study population and setting are not described in detail in the available summary, which limits assessment of generalizability. Screening programs vary substantially between countries in terms of test type, age ranges, invitation systems, and follow-up protocols, all of which affect adherence rates and outcomes.

The finding that men benefited more from negative colonoscopy is suggestive but requires further investigation to determine whether it reflects biology, screening behavior, or statistical artifact.

What the data do make clear is that the weakest link in the two-step screening chain is not the stool test and not the colonoscopy. It is the gap between them.