JAMA had a population-based clinical trial in Norway of flexible sigmoidoscopy (sig) screening (see doi:10.1001/jama.2014.8266). 100K men and women aged 50-64 were randomized to once-only flex sig (10.2K people), combo of flex sig and fecal occult blood testing (FOBT, also 10.2K people) or control (78.2K), with screening in those 55-64 beginning in 1999-2000 and those 50-54 yo in 2001 and followed until 2012. Those with positive screen (cancer, adenoma, polyp>1cm, pos. FOBT) were offered colonoscopy.
Results:
–Adherence to screening was 63%
–After 10.9 yrs, 71 died from colorectal cancer in screened groups (31.4 deaths/100K person-yrs) and 330 in the control group (43.1 deaths/100K person-yrs), abs diff of 11.7 and HR of 0.73 (0.56-0.94). i.e., there was a difference of about 1 death/1000 individuals by sig screening
–Incidence of colon cancer in 253 in the screened group (112.6 cases/100K person-yrs) and 1086 in the controls (141.0 cases/100K person-yrs), abs diff of 28.4 and HR of 0.80 (0.70-0.92)
–Flex sig was beneficial in both age groups: cancer incidence in 50-54yo had HR of 0.68 (0.49-0.94) and in those 55-64 HR was 0.83 (0.71-0.96).
–Adding the FOBT did not change the results
–No complications of flex sig (done in 20.5K men and women), though of the 2816 colonoscopies done, (19.5% of those screened), there were 6 perforations and 4 were admitted for postpolypectomy bleeding
–Of note, there was no difference between screening and controls until 9 years later (for both mortality and cancer detection), which might suggest that the results would be more impressive with longer follow-up.
So, these hazard ratios are pretty comparable to the existing studies (although this was a truly population-based study, unlike the other trials which consisted of volunteers). Also first study to show benefit in those 50-54 years old. The big issue for us is that we tend to do colonoscopies as our first line, even though the complication rate is much higher (as in this study), and the only good data for cancer-specific mortality rate reductions are based on sigmoidoscopy studies. The issue, of course, is that sigs miss proximal tumors, and around 20% of patients with serious proximal lesions have no distal lesions (and therefore be missed by just doing sigs). The rationale for the FOBT is that proximal lesions bleed more than distal ones and FOBT might help uncover them, though the results above showed no benefit from adding FOBT. Also the clinical benefit of finding/resecting proximal tumors is significantly less than with distal tumors, in several studies. This study did find a 10% reduction in proximal colorectal cancer vs 24% reduction for distal cancers (proximal cancers presumably found on colonoscopy). The advent of stool DNA testing might shift the curve more away from routine colonoscopy screening. So, bottom line: we have largely adopted colonoscopy screening based on what makes sense (and to the delight of the gastroenterologists/hospitals — “scoping for dollars” as one of my GI friends put it), though sigs are reasonable alternatives. We should probably discuss this with patients, though there is an uphill battle given the dominant culture on this. Maybe will change with new tests in the future.
Geoff