Sensitivity of next-generation Cologuard in precancer detection ‘numerically exceeded’ FIT
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Key takeaways:
- The next-generation Cologuard test was significantly more likely to detect cancer (94% vs. 67%) compared with FIT.
- The test also was more likely to detect precancerous lesions vs. FIT (43% vs. 23%).
VANCOUVER, British Columbia — A next-generation, multitarget stool DNA test detected colorectal cancer with 94% sensitivity and 91% specificity, outperforming fecal immunochemical testing, according to late-breaking data here.
“The next-generation Cologuard is different from FIT in that it has different markers,” Thomas F. Imperiale, MD, professor of medicine at Indiana University Medical Center, told Healio at the ACG Annual Scientific Meeting. “They’re all methylated DNA markers, as opposed to the current version where there were two methylated DNA markers and mutations in the KRAS gene.”
To evaluate the clinical performance of the next-generation, multitarget stool DNA test (Cologuard, Exact Sciences), Imperiale and colleagues conducted the BLUE-C study, which enrolled 26,758 participants scheduled for screening colonoscopy at 186 U.S. sites between November 2019 and January 2023.
Participants provided stool samples for testing with next-generation Cologuard and FIT prior to colonoscopy. Researchers categorized colonoscopy findings as CRC, advanced precancerous lesions (APL), no advanced neoplasia, and nonneoplastic or negative colonoscopy.
Of the enrolled population, 75.4% (mean age, 63 years; 53.2% women; 60.1% non-Hispanic white) had evaluable findings.
According to results, there were 98 cases of CRC, 2,144 APLs and 17,934 with no advanced neoplasia. The next-generation Cologuard demonstrated a specificity for absence of advanced neoplasia of 90.6% (95% CI, 90.1-91), while sensitivities for CRC, APL and APL with high-grade dysplasia were 93.9% (95% CI, 87.1-97.7), 43.4% (95% CI, 41.3-45.6) and 74.6% (95% CI, 65.6-82.3).
“The most important result was improved specificity, which is expected to reduce the false positive rate by 30% without losing any sensitivity,” Imperiale said. “With a lot of tests, when you improve specificity, you lose sensitivity and that didn’t happen here. Since the components of this next-generation test are different from the current version, sensitivity was preserved, or slightly improved, for both cancer and advanced precancerous lesions even with the improvement in specificity.”
In addition, next-generation Cologuard was significantly more likely to detect cancer (94% vs. 67%) or precancerous lesions (43% vs. 23%) than FIT, according to a related Exact Sciences press release.
“The most important of those advanced precancerous lesions, which are the ones with high grade dysplasia, were detected about 75% of the time, which is really excellent for a noninvasive test,” Imperiale told Healio. “This 75% sensitivity numerically exceeded that of FIT for CRC, which was 67.3%.”
Further, results showed specificity for nonneoplastic findings or negative colonoscopy was 92.7% (95% CI, 92.2-93.1).
“What patients and providers are going to recognize is fewer false positives and equal performance in detection of CRC and advanced precancerous lesions,” Imperiale said. “With fewer false positives there will be fewer people undergoing follow-up colonoscopy where nothing’s found that explains the positive result, which can generate worry and unnecessary testing.”
He added, “As far subsequent research, I think future studies will evaluate cost-effectiveness, as well as patient and provider acceptance.”
Reference:
- Next-generation Cologuard test demonstrates high sensitivity and specificity in pivotal BLUE-C study, significantly outperforming fecal immunochemical testing (FIT) for cancer and precancer detection. https://www.exactsciences.com/newsroom/press-releases/next-generation-cologuard-test-demonstrates-high-sensitivity-and-specificity-in-pivotal-blue-c-stud. Published Oct. 22, 2023. Accessed Oct. 24, 2023.
Perspective
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Mohamad Mouchli, MD
The next-generation Cologuard test remarkably outperformed FIT in detecting cancer and precancerous lesions. It also showed very good specificity for absence of advanced neoplasia, which could lead to less follow-up colonoscopy.
Although the results are encouraging, more research is needed to determine whether next-generation Cologuard has better false-positive rates in patients with increased age. It will also be great to know whether it will have better sensitivity to detect sessile serrated polyps compared with previous generation Cologuard testing, which is commonly missed with colonoscopy. The test is still not ready to be a gold-standard screening test to detect APL compared with colonoscopy, which has a sensitivity ranging from 75% to 93% for advanced polyps.
Challenges that need to be addressed in the future include cost, the need to provide stool samples, the need for follow-up colonoscopy after positive results, different screening recommendations by different societies, patients’ doubts and fears about negative results, and the fact that visual examination is not off the map as the best screening test.
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Imperiale TF, et al. Next-generation multitarget stool DNA test for colorectal cancer screening: A prospective clinical validation study (BLUE-C). Presented at: ACG Annual Scientific Meeting; Oct. 20-25, 2023; Vancouver, British Columbia (hybrid meeting).
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