2025 JAMA 0602 Dominitz Illusion Simple ctDNA CRC Screening also McCabe.pdf
2025 NRCO McCabe Novel CRC Screening Challenges (also JAMA Dominitz).pdf
Summarize this pdf by McCabe only. Use paragraph form not bullets.
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In the article by McCabe and colleagues (2025) published in Nature Reviews Clinical Oncology, the authors critically examine the challenges posed by the rapid development and commercialization of novel blood-based tests for colorectal cancer (CRC) screening. While acknowledging the potential promise of these non-invasive tools, they caution against premature enthusiasm, particularly when such tests are promoted on the basis of unvalidated surrogate endpoints—such as cancer detection rates or stage shift—rather than proven reductions in CRC mortality or incidence. The authors emphasize that CRC screening is a mature field with several well-established, effective options (e.g., colonoscopy, FIT), and new entrants must demonstrate superiority or non-inferiority in clinical outcomes, not just convenience or intermediate markers.
McCabe et al. underscore that many new blood-based screening tests enter the market supported by single-arm studies and surrogate data, which do not adequately account for key biases such as lead-time and length bias. They argue that marketing claims based on early detection or stage distribution—without long-term outcome data—can mislead clinicians, patients, and payers. The article also highlights the risk that widespread adoption of less effective screening methods could dilute the public health impact achieved by current evidence-based modalities, particularly among underserved populations where screening uptake is already suboptimal.
The authors call for rigorous validation of these new tests through randomized controlled trials designed with appropriate endpoints, including CRC-specific mortality and incidence. They advocate for transparent regulatory pathways, thoughtful health policy, and careful consideration of downstream effects, such as overdiagnosis, false reassurance, and increased healthcare costs. In conclusion, McCabe and colleagues urge the oncology and public health communities to maintain high standards for evidence, especially when the stakes involve large-scale screening of healthy populations.
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In their June 2025 JAMA editorial, Dominitz, Patel, and Lieberman critically assess the growing enthusiasm for blood-based colorectal cancer (CRC) screening tests, warning against the "illusion of simplicity" they present. While these tests may appear more convenient and acceptable—particularly for individuals reluctant to complete colonoscopy or stool-based screening—they are far less effective at preventing CRC. This is due primarily to their poor sensitivity for detecting advanced precancerous lesions, which are the key targets for cancer prevention.
The authors focus on a recent clinical validation study of a novel circulating tumor DNA (ctDNA) test that showed decent sensitivity for CRC (79.2%) but very low sensitivity (12.5%) for advanced precancerous lesions, including only 7.6% for sessile serrated lesions. These findings are contrasted with stool-based tests like FIT, which are less sensitive for cancer per test but far superior at detecting precancerous lesions and are repeated more frequently. Modeling studies suggest that replacing colonoscopy or FIT with blood-based tests—particularly in adherent populations—would increase CRC cases and deaths.
Dominitz et al. do recognize a potential role for blood-based screening in individuals who categorically refuse existing screening options. However, they caution that this benefit hinges on follow-through with colonoscopy after an abnormal result—a step many patients currently skip, undermining screening effectiveness. They argue that while new tests may increase participation rates modestly, they risk diverting patients from proven, more effective strategies.
Ultimately, the editorial concludes that while blood-based tests represent a scientific advance, their widespread use as a first-line screening tool could paradoxically worsen public health outcomes. The authors urge clinicians to reserve them for nonadherent patients and to prioritize patient education about the strengths of colonoscopy and stool-based testing.
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ChatGPT said:
The articles by McCabe (Nature Reviews Clinical Oncology, 2025) and Dominitz (JAMA, 2025) both critically evaluate the emerging role of blood-based colorectal cancer (CRC) screening tests, and while they differ in emphasis and tone, they largely converge on key messages grounded in evidence and public health priorities.
Both articles emphasize that blood-based screening tests, while potentially more acceptable to patients, are currently inferior in clinical effectiveness compared to established modalities like colonoscopy and fecal immunochemical testing (FIT). McCabe et al. stress that blood tests often enter the market with surrogate endpoints (e.g., stage shift or cancer detection) rather than demonstrated mortality reduction. Similarly, Dominitz et al. highlight that while blood tests may show reasonable sensitivity for invasive cancers, they fail to detect advanced precancerous lesions—a shortfall that undermines their ability to prevent cancer rather than merely detect it.
A point of strong overlap is their shared concern about substitution effects. Both groups warn that if blood-based tests replace more effective options in adherent individuals, CRC incidence and mortality may rise. McCabe expresses this risk in the language of evidence standards and regulatory oversight, whereas Dominitz provides modeling-based quantification, noting that population benefit from blood-based screening occurs only under specific trade-offs: for every three people who would otherwise choose colonoscopy or FIT, at least two people who are completely unscreened must adopt blood-based screening to avoid a net harm.
In terms of divergence, McCabe’s article is more focused on regulatory and evidentiary rigor. It critiques the premature marketing and reimbursement of tests that lack validated endpoints and frames the issue as one of standards degradation in a mature screening field. Dominitz, by contrast, centers more on the clinical and behavioral dynamics, exploring why patients avoid current screening and how blood-based tests might improve adherence—albeit with caveats. His editorial gives greater attention to patient psychology, outreach interventions, and the complexities of integrating new tools without displacing superior ones.
Another subtle divergence lies in tone and framing: McCabe’s piece is policy-focused and somewhat cautionary in tone, positioning premature adoption as a systemic risk. Dominitz, while also cautionary, adopts a more pragmatic clinical lens, acknowledging a place for blood-based screening as a second-line option for those unlikely to pursue established methods.
In sum, both articles align in their critical stance toward overreliance on blood-based CRC screening in its current form, emphasizing the importance of rigorous evidence and proper integration into screening programs. They diverge slightly in focus—McCabe toward policy and evidentiary standards, Dominitz toward clinical implementation and patient behavior—but their core message is unified: simplicity must not substitute for effectiveness in CRC screening.
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