- Researchers evaluated the long term efficacy of once only sigmoidoscopy screening on colorectal cancer incidence and mortality after twenty three years.
- This randomized controlled trial analyzed 98,654 Norwegian participants aged 50 to 64 years assigned to screening or no screening groups.
- Screening reduced colorectal cancer risk by 1.7 percentage points in men and 0.5 percentage points in women (CI, -1.0 to -0.01).
- The researchers concluded that sigmoidoscopy screening significantly reduced cancer incidence in both sexes but reduced mortality only in men.
- Clinicians should consider these sex based differences in long term outcomes when discussing colorectal cancer screening options with their patients.
Durability of Sigmoidoscopy in Colorectal Cancer Prevention
Colorectal cancer remains a leading cause of malignancy-related mortality globally, necessitating robust screening strategies to detect and remove precancerous adenomatous polyps [1, 2]. While various modalities exist, including fecal immunochemical testing and full colonoscopy, flexible sigmoidoscopy is often utilized due to its lower resource intensity and reduced procedural risk [3, 4]. Previous meta-analyses of randomized controlled trials have established that sigmoidoscopy effectively reduces both the incidence and mortality of distal colorectal cancer for at least 15 years [5, 6]. However, clinical uncertainty persists regarding the absolute duration of this protection and whether the benefits are sustained equally across different patient demographics [7, 8]. A new longitudinal analysis of the Norwegian Colorectal Cancer Prevention trial now extends our understanding of these outcomes by evaluating the clinical impact of a single screening event over 23 years, revealing striking sex-based differences in long-term mortality benefits.
The NORCCAP Trial Design and Population
The Norwegian Colorectal Cancer Prevention (NORCCAP) study, registered as trial NCT00119912, was designed to evaluate the long-term efficacy of flexible sigmoidoscopy. The study population was drawn from Oslo and Telemark County, Norway, and specifically targeted persons aged 50 to 64 years who were free of colorectal cancer at the time of randomization. This age range represents a critical window for the detection of adenomatous polyps before they progress to invasive malignancy. By utilizing national registries for follow-up, the researchers ensured a comprehensive longitudinal assessment of patient outcomes over a 23-year period. A total of 100,210 persons were randomly assigned to the trial, with 98,654 individuals ultimately included in the intention-to-screen analyses (a rigorous statistical approach that evaluates patients based on their initial randomized group, regardless of whether they actually completed the screening). The study architecture divided these participants into two primary cohorts: a screening group consisting of 20,552 individuals and a no-screening group consisting of 78,102 individuals. The screening intervention involved a once-only sigmoidoscopy, which was administered either as a standalone procedure or in combination with a single fecal immunochemical test (a noninvasive assay used to detect trace amounts of human hemoglobin in the stool). This design allowed the authors to determine if the addition of fecal occult blood testing provided any incremental benefit over endoscopic visualization alone. The clinical utility of any screening program is heavily dependent on patient adherence, and the NORCCAP trial reported robust engagement from the target population. Participation rates for screening were 61.4 percent in men and 64.7 percent in women, providing a substantial dataset for sex-based subgroup analysis. These high rates of uptake facilitated a precise calculation of risk differences for both colorectal cancer incidence and mortality over more than two decades of clinical follow-up.
Divergent Long-Term Incidence and Mortality Outcomes
The longitudinal data collected through national registries over a 23-year period revealed a significant disparity in how a single sigmoidoscopy affects long-term cancer risk between the sexes. In men, the 23-year cumulative risk for colorectal cancer was 4.3 percent in the screening group, compared to 6.0 percent in the no-screening group. This represents a risk difference for colorectal cancer incidence of -1.7 percentage points (95 percent CI, -2.2 to -1.2 percentage points). While women also saw a reduction in cancer rates, the magnitude of the benefit was notably smaller. Among female participants, the 23-year cumulative risk for colorectal cancer was 4.2 percent in the screening group versus 4.7 percent in the no-screening group, resulting in a risk difference of -0.5 percentage points (CI, -1.0 to -0.01 percentage points). The divergence in outcomes was even more pronounced when examining mortality rates, where the survival benefit of screening was essentially absent in the female cohort. In men, the 23-year cumulative risk for colorectal cancer death was 1.4 percent in the screening group versus 2.2 percent in the no-screening group, which corresponds to a risk difference for colorectal cancer death of -0.8 percentage points (CI, -1.1 to -0.5 percentage points). Conversely, the mortality data for women showed no statistically significant clinical benefit from the intervention. In the female cohort, the 23-year cumulative risk for colorectal cancer death was 1.3 percent in the screening group versus 1.4 percent in the no-screening group, yielding a risk difference of only -0.1 percentage points (CI, -0.3 to 0.1 percentage points). For practicing physicians, this stark contrast indicates that while a single sigmoidoscopy provides durable, two-decade protection against cancer death for men, the same intervention does not significantly alter the long-term mortality trajectory for women.
Anatomical Specificity and Adjunctive Testing
The researchers observed that the protective effect of a single sigmoidoscopy was not uniform across the large intestine. The reduction in colorectal cancer risk was most pronounced in the rectosigmoid region, which comprises the distal portion of the colon and the rectum. This anatomical specificity aligns with the physical reach of the flexible sigmoidoscope, which typically allows for the visualization and removal of precancerous lesions only in the lower segments of the bowel. Because the intervention directly addresses pathology in these distal areas, the long-term reduction in both cancer incidence and mortality is concentrated in the segments most accessible to the clinician during the procedure. In addition to evaluating sigmoidoscopy as a standalone intervention, the trial investigated whether the addition of fecal blood testing to sigmoidoscopy improved clinical outcomes. Participants were randomized to receive either sigmoidoscopy alone or sigmoidoscopy combined with a single fecal immunochemical test. The findings indicated that the addition of fecal blood testing did not change screening benefits regarding colorectal cancer incidence or mortality. For clinicians, this suggests that the primary driver of the observed 23-year protection is the direct endoscopic visualization and subsequent polypectomy, rather than the supplementary biochemical screening provided by a one-time fecal test. The NORCCAP trial, which provides some of the most extensive longitudinal data available for endoscopic screening, was funded by the Norwegian government and the Norwegian Cancer Society. Ultimately, these results underscore the necessity of considering sex-specific outcomes when designing colorectal cancer screening protocols. While a single sigmoidoscopy offers substantial, two-decade protection for men, the lack of a mortality benefit in women suggests that alternative strategies, such as full colonoscopy to visualize the proximal colon or more frequent stool-based testing, may be required to achieve comparable long-term survival outcomes in the female population.
References
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