Shifting the Cancer Screening Paradigm: Developing a Multi-Biomarker Class Approach to Multi-Cancer Early Detection Testing.

Guideline-recommended screening programs exist for only a few cancer types. Although all these programs are understood to lead to reductions in cancer-related mortality, standard-of-care screening tests vary in accuracy, adherence and effectiveness. Recent advances in high-throughput technologies and machine learning have facilitated the development of blood-based multi-cancer cancer early detection (MCED) tests. MCED tests are positioned to be complementary to standard-of-care screening and they may broaden screening availability, especially for individuals who are not adherent with current screening programs and for individuals who may harbor cancers with no available screening options. In this article, we outline some key features that should be considered for study design and MCED test development, provide an example of the developmental pathway undertaken for an emerging multi-biomarker class MCED test and propose a clinical algorithm for an imaging-based diagnostic resolution strategy following MCED testing.

Outcomes Following a False-Positive Multi-Cancer Early Detection Test: Results from DETECT-A, the First Large, Prospective, Interventional MCED Study.

Guideline recommended standard of care screening is available for four cancer types; most cancer-related deaths are caused by cancers without standard of care screening. DETECT-A is the first prospective interventional trial evaluating a multi-cancer early detection (MCED) blood test (CancerSEEK) in women without a history of cancer, providing the first opportunity to assess the long-term outcomes of individuals with false-positive (FP) MCED results. This prospective analysis of DETECT-A participants with FP results evaluates the performance of an imaging-based diagnostic workflow and examines cancer risk following a FP result. This analysis included all DETECT-A participants with a positive CancerSEEK test and subsequent flourine-18 fluorodeoxyglucose positron emission tomography-IV contrast-enhanced computed tomography (18-F-FDG PET-CT) imaging and clinical workup indicating no evidence of cancer within 1 year of enrollment (n = 98). Medical records, study interactions, and study surveys were used to assess cancer incidence, treatments, and clinical outcomes through August 2023. Ninety-five of 98 participants with a FP result remained cancer-free with a median follow-up of 3.6 years (IQR: 2.5-4.1) from determination of FP status. Three incident cancers were observed over the follow-up period. One bilateral stage IIIC ovarian cancer was diagnosed 1.9 years after determination of FP status; two stage I breast cancers were diagnosed 0.1 and 1.6 years from determination of FP status. The annual incidence rate of cancer during follow-up from FP determination was 1.0% (95% confidence interval, 0.2%-2.8%). Participants with a positive CancerSEEK test who underwent 18-F-FDG PET-CT and clinical workup without cancer findings had low risk for cancer over the following several years. Prevention Relevance: This study provides multiyear clinical outcomes data following a false-positive multi-cancer early detection test for individuals participating in a prospective interventional trial. It provides a preliminary performance assessment of an imaging-based diagnostic workflow following a false-positive multi-cancer early detection test.

Outcomes following a false positive multi-cancer early detection (MCED) test: Results from DETECT-A, the first large, prospective, interventional MCED study.

Guideline recommended standard of care (SoC) screening is available for four cancer types; most cancer-related deaths are caused by cancers without SoC screening. DETECT-A is the first prospective interventional trial evaluating an MCED blood test (CancerSEEK) in women without a history of cancer, providing the first opportunity to assess the long-term outcomes of individuals with false positive (FP) MCED results. This prospective analysis of DETECT-A participants with FP results evaluates the performance of an imaging-based diagnostic workflow and examines cancer risk following a FP result. This analysis included all DETECT-A participants with a positive CancerSEEK test and subsequent flourine-18 fluorodeoxyglucose positron emission tomography-IV contrast enhanced computed tomography (18-F-FDG PET-CT) imaging and clinical workup indicating no evidence of cancer within one year of enrollment (n=98). Medical records, study interactions, and study surveys were used to assess cancer incidence, treatments, and clinical outcomes through August 2023. Ninety-five of 98 participants with a FP result remained cancer-free with a median follow-up of 3.6 years (IQR: 2.5-4.1) from determination of FP status. Three incident cancers were observed over the follow-up period. One bilateral stage IIIC ovarian cancer was diagnosed 1.9 years after determination of FP status; two stage I breast cancers were diagnosed 0.1 and 1.6 years from determination of FP status. The annual incidence rate of cancer during follow-up from FP determination was 1.0% (95% CI: 0.2%-2.8%). Participants with a positive CancerSEEK test who underwent 18-F-FDG PET-CT and clinical workup without cancer findings had low risk for cancer over the following several years.

Multiyear Clinical Outcomes of Cancers Diagnosed Following Detection by a Blood-Based Multicancer Early Detection Test.

In the US, <20% of cancers are diagnosed by standard-of-care (SoC) screening. Multicancer early detection (MCED) tests offer the opportunity to expand cancer screening. Understanding the characteristics and clinical outcomes of MCED-detected cancers is critical to clarifying MCED tests' potential impact. DETECT-A is the first prospective interventional trial of an MCED blood test (CancerSEEK). CancerSEEK, coupled with diagnostic PET-CT, identified cancers including those not detected by SoC screening, the majority of which were localized or regional. We report multiyear outcomes in patients with cancers diagnosed following a positive CancerSEEK test. Nine cancer types were diagnosed in 26 participants whose cancers were first detected by CancerSEEK. Information on cancer diagnoses, treatments, and clinical outcomes was extracted from medical records through November 2022. Data collection occurred at a median of 4.4 years (IQR: 4.1-4.6) following study enrollment. Thirteen of 26 (50%) participants were alive and cancer-free [ovarian (4), thyroid (1), uterine (2), breast (1), colorectal (2), and lung (3)]; 7/13 (54%) had cancers without recommended SoC screening modalities. All eight treated stage I or II participants (8/8, 100%) and 12/14 (86%) surgically treated participants were alive and cancer-free. Eligibility for surgical treatment was associated with favorable multiyear outcomes (P = 0.0002). Half of participants with MCED-detected cancers were alive and cancer-free after 4.4 years median follow-up. Most were diagnosed with early-stage cancers and were treated surgically. These results suggest that early cancer detection by CancerSEEK may have facilitated curative-intent treatments and associated positive clinical outcomes in some DETECT-A participants. Prevention Relevance: This study provides preliminary evidence of the potential of multicancer early detection testing as an effective screening tool for detecting cancers without standard-of-care (SoC) screening modalities and complementing SoC cancer screening.