"Both screening methods shifted cancer diagnoses to earlier stages, but the overall incidence of colorectal cancer and all-cause mortality remained similar across groups."
A large Swedish randomized controlled trial, SCREESCO, has reported that colorectal cancer screening in individuals around age 60 leads to increased detection of early-stage cancers. The trial compared two screening strategies—primary colonoscopy and fecal immunochemical testing (FIT)—against usual care.
While both methods shifted cancer diagnoses to earlier stages, the overall incidence of colorectal cancer and all-cause mortality remained similar across groups during a median follow-up period of approximately 4.8 years. Researchers plan to continue follow-up until 2030 to assess the long-term impact on colorectal cancer mortality.
The Trial Design
The SCREESCO (Screening of Swedish Colons) trial is a pragmatic, population-based study conducted across 18 Swedish regions. A total of 278,051 individuals aged 60 years were randomly assigned to one of three groups:
- Primary Colonoscopy Group: Participants were invited to undergo a once-only colonoscopy.
- FIT×2 Group: Participants were invited to complete two rounds of two-stool fecal immunochemical tests (FIT), performed two years apart, with a low positivity threshold of 10 μg hemoglobin per gram of feces. A colonoscopy was offered following a positive FIT result.
- Control Group (Usual Care): Participants received no screening invitation.
Outcomes were tracked using Swedish registers over a median follow-up of 4.8 years, from 2014 to 2020.
Results: Cancer Detection and Incidence
Earlier-Stage Cancer Detection
Both screening strategies led to a higher detection rate of early-stage colorectal cancer compared to the control group:
- Colonoscopy Group: Incidence rate ratio (IRR) for stage I–II CRC was 1.38 (95% CI 1.09–1.74), indicating a 38% increase in early-stage detection.
- FIT×2 Group: IRR for stage I–II CRC was 1.19 (95% CI 0.99–1.43), indicating a 19% increase.
Later-Stage Cancer
During the follow-up period, reductions in the detection of late-stage colorectal cancer (stage III–IV) were observed:
- Colonoscopy Group: IRR of 0.86 (95% CI 0.67–1.11), a directional but not statistically significant reduction.
- FIT×2 Group: IRR of 0.71 (95% CI 0.58–0.86), a statistically significant 29% reduction.
By the end of the follow-up period, 0.61% of participants in the FIT group developed colorectal cancer, compared to 0.73% in the control group. Cumulative curves suggested later-stage cancers became less frequent in both intervention arms after approximately 4 years, particularly in the FIT×2 group.
Overall Incidence and Mortality
- Overall CRC Incidence: No clear reduction was observed. The IRR for the colonoscopy group versus control was 1.08 (95% CI 0.91–1.28). For the FIT×2 group versus control, it was 0.92 (95% CI 0.81–1.05).
- All-Cause Mortality: There was no excess all-cause mortality in either screening group. The IRR was 0.96 for both the colonoscopy group and the FIT×2 group compared to controls.
Safety and Adverse Events
The study reported a slight increase in gastrointestinal and cardiovascular adverse events in the intervention groups during the first year after screening, rates that later converged with those of the control group.
- Colonoscopy-Specific Events: Serious adverse events directly linked to screening colonoscopies occurred at a rate of 0.2%. This included 2 bowel perforations and 15 major bleedings.
- FIT×2 Specific Findings: This group showed a higher rate of venous thromboembolism compared to controls (IRR 1.39, 95% CI 1.16–1.66), as well as higher rates of gastrointestinal events, primarily bleeding outcomes.
- Overall: Researchers noted that adverse events were overall infrequent, and all-cause mortality was consistent across all groups.
"Adverse events were overall infrequent, and all-cause mortality was consistent across all groups."
Context and Additional Findings
PSA Screening (Separate Study)
A separate Cochrane review, involving trials with approximately 790,000 men, reported that PSA screening may reduce prostate cancer-specific mortality by about 13% (approximately 2 fewer deaths per 1,000 men screened). However, it found no significant effect on overall survival. The review noted an increase in detection of early-stage cancers without a clear reduction in advanced disease, with overdiagnosis remaining a concern.
Implantable Immunotherapy for Ovarian Cancer (Separate Study)
A first-in-human Phase 1 trial tested AVB-001, a laparoscopic intraperitoneal implant delivering IL-2 locally for approximately one week, in 14 patients with platinum-resistant high-grade serous ovarian cancer. Results indicated increased CD8+ T cell and NK cell activity without an increase in regulatory T cells. The trial reported no dose-limiting toxicities or treatment-related deaths, and several patients achieved disease stabilization.
Conclusion
The SCREESCO trial's diagnostic-phase findings indicate that invitations to primary colonoscopy or low-cutoff FIT increase the detection of earlier-stage colorectal cancer compared to usual care, while also showing slight, temporary increases in adverse events. The reduction in later-stage cancers, particularly in the FIT×2 group, suggests a potential preventive effect from screening, possibly through the removal of cancerous precursors.
Longer follow-up is required to determine the definitive impact on colorectal cancer mortality. The trial's final endpoint—colorectal cancer-specific mortality—is scheduled to be reported after follow-up until December 31, 2030.