The Norwegian Colorectal Cancer Prevention (NORCCAP) trial comparing colorectal cancer screening with flexible sigmoidoscopy vs no screening showed no reduction in colorectal cancer incidence or mortality after 7 years of follow-up. As reported by Øyvind Holme, MD, of Sorlandet Hospital Kristiansand, and colleagues in JAMA, the 11-year follow-up shows significant reductions in both incidence and mortality with screening.¹

Study Details

In the trial, individuals aged 50 to 64 years were randomly assigned to no screening (usual care) or once-only flexible sigmoidoscopy screening with or without fecal occult blood testing. Those randomized to screening were invited to undergo screening, performed in 1999 to 2000 in the 55- to 64-year age group and in 2001 in the 50- to 54-year age group. Participants with positive screening tests, consisting of cancer, adenoma, polyp ≥ 10 mm, or positive fecal occult blood test, were offered colonoscopy.

A total of 98,792 participants were included in the intention-to-screen analyses, consisting of 78,220 in the no-screening control group and 20,572 in the screening group. Of those in the screening group, 10,283 were randomly assigned to receive flexible sigmoidoscopy and 10,289 to receive flexible sigmoidoscopy and fecal occult blood testing.

Mean age was 57 years in the screening group and 56 years in the control group, with 34% and 47% aged 50 to 54 years and 66% and 53% aged 55 to 64 years. Half the participants in each group were women.  The screening adherence rate was 63%.

Colorectal Cancer Incidence

Colorectal cancer was diagnosed in 253 participants in the screening group vs 1,086 in the control group, yielding age-standardized rates of 112.6 vs 141.0 cases per 100,000 person-years (absolute rate difference = 28.4, 95% confidence interval [CI] = 12.1–44.7, hazard ratio [HR] = 0.80, 95% CI = 0.70–0.92). The number needed to invite for screening to prevent 1 colorectal cancer case over 10 years was 498.

Hazard ratios were 0.68 (95% CI = 0.49–0.94) in the 50- to 54-year age group and 0.83 (95% CI = 0.71–0.96) in the 55- to 64-year age group (P = .27 for heterogeneity),  0.73 (95% CI = 0.60–0.89) in men and 0.87 (95% CI = 0.72–1.06) in women (P  = .26 for heterogeneity), and  0.76 (95% CI = 0.63–0.92) for distal colorectal cancer and 0.90 (95% CI = 0.73–1.10) for proximal colorectal cancer. Hazard ratios were 0.72 (95% CI = 0.59–0.87) for sigmoidoscopy alone and 0.88 (95% CI = 0.74-1.05) for sigmoidoscopy plus fecal occult blood testing (P = .11 for heterogeneity). Screen-detected colorectal cancer was more frequently diagnosed at an earlier stage.

Overall, 19.5% of participants undergoing screening sigmoidoscopy and 21.3% of those who also had fecal occult blood testing were referred for colonoscopy, with 18.7% and 20.3% undergoing the procedure. Perforation or hospital admission for postpolypectomy bleeding occurred in none of the participants after sigmoidoscopy and in 10 after colonoscopy.

Colorectal Cancer Mortality

After a median of 10.9 years of follow-up, death due to colorectal cancer had occurred in 71 screening group participants and 330 control group participants, yielding age-standardized rates of 31.4 vs 43.1 deaths per 100,000 person-years (absolute rate difference = 11.7, 95% CI = 3.0–20.4, HR = 0.73, 95% CI = 0.56–0.94). The number needed to invite for screening to prevent 1 colorectal cancer death over 10 years was 1,547. 

Hazard ratios for colorectal cancer mortality were 0.74 (95% CI = 0.40–1.35) in the 50- to 54-year age group and 0.73 (95% CI = 0.55–0.97) in the 55- to 64-year age group, 0.58 (95% CI = 0.40–0.85) in men and 0.91 (95% CI, 0.64–1.30) in women (P  = .10 for heterogeneity), and 0.79 (95% CI = 0.55–1.11) for distal colorectal cancer and 0.73 (95% CI = 0.49–1.09) for proximal colorectal cancer. Hazard ratios were 0.84 (95% CI = 0.61–1.17) for flexible sigmoidoscopy and 0.62 (95% CI = 0.42–0.90) with sigmoidoscopy plus fecal occult blood testing (P = .20 for heterogeneity).

There was no difference between groups in all-cause mortality (HR = 0.97, 95% CI = 0.93–1.02).

Adjustment for Nonadherence

The intention-to-screen 10-year risk absolute difference was −0.22% (95% CI = −0.38% to −0.06%) for colorectal cancer incidence and −0.06% (95% CI = −0.14% to 0.03%) for colorectal cancer death in the entire population. After adjustment for nonadherence, the 10-year risk differences were −0.42% (95% CI = −0.69% to −0.15%) for incidence and −0.10% (95% CI = −0.25% to 0.05%) for death.

The investigators concluded: “In Norway, once-only flexible sigmoidoscopy screening or flexible sigmoidoscopy and [fecal occult blood testing] reduced colorectal cancer incidence and mortality on a population level compared with no screening. Screening was effective both in the 50- to 54-year and the 55- to 64-year age groups.” ■

Disclosure: NORCCAP was funded by grants from the Norwegian government and Norwegian Cancer Society. Work on the JAMA article was funded by grants from the Norwegian Cancer Society, Research Council of Norway, South-East Regional Health Authority of Norway, Fulbright Foundation, Sorlandet Hospital Kristiansand, and National Institutes of Health. For full disclosures of the study authors, visit jama.jamanetwork.com.

Reference

1. Holme Ø, Løberg M, Kalager M, et al: Effect of flexible sigmoidoscopy screening on colorectal cancer incidence and mortality: A randomized clinical trial.  JAMA 312:606-615, 2014.

See commentary by Aline Charabaty, MD, here.