- Use of annual supplemental multi-cancer early detection testing led to a 45% decrease in stage IV diagnoses, relative to standard of care, in a modeling study.
- The largest absolute reductions in stage IV diagnoses were in lung, colorectal, and pancreatic cancers, while the largest relative reductions were in cervical, liver, and colorectal cancers.
- Supplementing standard of care with multi-cancer testing increased diagnoses by just 2.8%, suggesting overdiagnosis is not a concern.
Supplemental use of multi-cancer early detection (MCED) testing has the potential to substantially reduce late-stage cancer diagnoses, according to results from a modeling study.
Over the course of 10 years, use of annual supplemental MCED testing led to a 10% increase in stage I diagnoses, a 20% increase in stage II diagnoses, a 34% increase in stage III diagnoses, and a 45% decrease in stage IV diagnoses, relative to standard of care alone, reported Jagpreet Chhatwal, PhD, of Massachusetts General Hospital and Harvard Medical School in Boston, and colleagues in Cancer.
The largest absolute reductions in stage IV diagnoses were in lung (400 vs 765 per 100,000), colorectal (96 vs 236 per 100,000), and pancreatic (89 vs 211 per 100,000) cancers. The largest relative reductions were in cervical (83%), liver (74%), and colorectal (59%) cancers.
"Our breakdown of stage IV reductions by cancer type further emphasizes the clinical utility of MCED testing as the cancer types that had the largest absolute reductions ... are among the most aggressive cancer types with the poorest survival rates," the authors wrote.
"Our study shows that MCED testing has the potential to substantially reduce stage IV cancer incidence, particularly for cancer types that lack routine screening programs," they concluded. "Although further research is needed to validate these findings in real-world settings, our results suggest that MCED testing could transform cancer diagnosis and improve patient outcomes across a broad range of cancer types."
Chhatwal and colleagues determined that the cumulative number of diagnoses was 8,669 with standard of care and 8,910 with supplemental MCED testing, translating into an increase of just 2.8% (241 per 100,000), which suggests that "overdiagnosis may not be an issue with this technology."
"This is a critical finding because it mitigates concerns that MCED testing could lead to a surge in unnecessary cancer diagnoses and treatment," they wrote.
When the time horizon was extended to 20 years, the stage IV reduction remained at 45%. In a scenario with just one-time testing in year 1, stage IV reduction dropped "drastically" to 7%, Chhatwal and team pointed out.
However, in an editorial accompanying the study, Özge Karanfil, PhD, of Koç University in Istanbul, and colleagues noted that while the reduction with a one-time MCED test was small, it still represented a "meaningful reduction in cancer mortality through stage shift -- an important insight for assessing feasibility."
The study authors explained that although MCED tests are promising, "real-world data on their long-term effectiveness will not be available for many years," thus the need for simulation modeling to predict the performance of these tests.
They developed a microsimulation model of 14 solid tumor cancer types -- breast, cervical, colorectal, endometrial, esophageal, gastric, head and neck, kidney, liver, lung, ovarian, pancreatic, prostate, and urinary bladder -- that account for nearly 80% of cancer incidence and mortality.
The model was designed to reproduce annual incidence rates reported in the Surveillance, Epidemiology, and End Results database, with a simulated cohort consisting of 5 million adults ages 50 to 84 without a cancer diagnosis, whose demographic features were consistent with that of the U.S. population in 2015.
A cancer diagnosis could arise from standard-of-care procedures or annual MCED testing. Diagnosis under standard of care encompassed existing routine screening procedures, incidental detection, and symptomatic presentation.
In the model's base case, the MCED test was administered annually at the beginning of each calendar year with the assumption of 100% uptake and 100% adherence.
In their editorial, Karanfil and colleagues noted that the model's base case was optimistic, but added that a more realistic setting, such as 70% uptake, could "still project very meaningful reductions in late-stage cancers."
The editorialists also pointed out that the study did not address false-positives or subsequent diagnostic workup, "which -- though not directly related to stage shift -- are critical for policy evaluation because of their implications for additional testing, anxiety, and healthcare costs."
Disclosures
The study was funded by Exact Sciences Corporation.
Chhatwal reported ownership in Value Analytics Labs.
Several co-authors reported employment with Exact Sciences, and others reported multiple relationships with industry.
The editorialists had no disclosures.
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