Colorectal cancer screening by peripheral blood testing? This cell-free DNA assay had an 83% sensitivity and 90% specificity for advanced neoplasia. However, the issue is that this does not detect precancerous lesions well. Colonoscopy has its obvious advantages as it can both diagnose colorectal cancer as well as eradicate precancerous lesions.
Colorectal cancer is the third most diagnosed cancer in adults in the United States. Early detection could prevent more than 90% of colorectal cancer–related deaths, yet more than one third of the screening-eligible population is not up to date with screening despite multiple available tests. A blood-based test has the potential to improve screening adherence, detect colorectal cancer earlier, and reduce colorectal cancer–related mortality.
We assessed the performance characteristics of a cell-free DNA (cfDNA) blood-based test in a population eligible for colorectal cancer screening. The coprimary outcomes were sensitivity for colorectal cancer and specificity for advanced neoplasia (colorectal cancer or advanced precancerous lesions) relative to screening colonoscopy. The secondary outcome was sensitivity to detect advanced precancerous lesions.
The clinical validation cohort included 10,258 persons, 7861 of whom met eligibility criteria and were evaluable. A total of 83.1% of the participants with colorectal cancer detected by colonoscopy had a positive cfDNA test and 16.9% had a negative test, which indicates a sensitivity of the cfDNA test for detection of colorectal cancer of 83.1% (95% confidence interval [CI], 72.2 to 90.3). Sensitivity for stage I, II, or III colorectal cancer was 87.5% (95% CI, 75.3 to 94.1), and sensitivity for advanced precancerous lesions was 13.2% (95% CI, 11.3 to 15.3). A total of 89.6% of the participants without any advanced colorectal neoplasia (colorectal cancer or advanced precancerous lesions) identified on colonoscopy had a negative cfDNA blood-based test, whereas 10.4% had a positive cfDNA blood-based test, which indicates a specificity for any advanced neoplasia of 89.6% (95% CI, 88.8 to 90.3). Specificity for negative colonoscopy (no colorectal cancer, advanced precancerous lesions, or nonadvanced precancerous lesions) was 89.9% (95% CI, 89.0 to 90.7).
In an average-risk screening population, this cfDNA blood-based test had 83% sensitivity for colorectal cancer, 90% specificity for advanced neoplasia, and 13% sensitivity for advanced precancerous lesions. (Funded by Guardant Health; ECLIPSE ClinicalTrials.gov number, NCT04136002.)
Overall survival (OS) improvement was not statistically significant in the study arm but is a non-chemotherapy option. Patients here had tumors with MSS.
Less maintenance is NOT NON-inferior, so it is inferior in patients with wild type BRAF metastatic colon cancer. So it is better to keep on the full regimen. Although, quality of life is better.
This is a nice, practical study showing that when considering liver directed therapy, options in metastatic CRC, CT’s alone are insufficient and contrasted MRI can be helpful. More than 30% of patients had care that was impacted using MRI prior to any therapeutic decisions.
Negative study for the use of HIPEC in the adjuvant setting of high-risk or locally advanced colorectal cancers, including those with perforation and peritoneal invasion. HIPEC doesn’t seem to reduce the risk of peritoneal recurrence after potentially curative resection.
Another KRAS G12C inhibitor. Congrats to FCS Director of Drug Development Manish Patel, MD, one of the authors. Durable responses with less adverse events.
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