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Multicancer Detection: The Need for Clinical Guidance

November 2021, Vol 11, No 11
Jaffer A Ajani, MD
Professor, Gastrointestinal Medicine
The University of Texas M.D.
Anderson Cancer Center
Houston, TX
Al B Benson III, MD
Professor, Medicine
Northwestern University
Feinberg School of Medicine
Robert H. Lurie Comprehensive
Cancer Center
Chicago, IL
Mary B Daly, MD, PhD, FACP
Professor, Clinical Genetics
Fox Chase Cancer Center
Philadelphia, PA
David S Ettinger, MD
Professor, Oncology
Johns Hopkins Sidney Kimmel
Comprehensive Cancer Center
Baltimore, MD
Maria M Ho, PhD
Scientific Director
Mc-Givney Global Advisors
Wayne, PA

Cancer remains the leading cause of death in individuals aged <80 years in the United States, and was responsible for nearly 10 million deaths worldwide in 2020.1,2 According to the National Cancer Institute, the 5-year survival rate for individuals diagnosed with localized cancer of any type is 89%.3 However, this rate drops to only 21% for those diagnosed with metastatic disease,3 highlighting the detrimental impact of late-stage diagnosis on patient outcomes.

Although early detection may result in higher rates of treatment success, single-organ screening programs are only available for a few types of cancer. This is not surprising as it is challenging to justify population-wide screening programs for each cancer type given the low individual prevalence. On the other hand, we continue to face a somber statistic: more than 60% of cancer diagnosis and deaths can be attributed to cancers that were not detectable via screening.4

Conceptually, multicancer detection provides a tremendous potential to bridge that clinical gap. Tests that have the ability to detect multiple cancer types may overcome the barriers of single-organ tests by combining cancer prevalence to provide a clinically impactful, efficient, and cost-effective detection strategy. Ideally, these tests will be noninvasive (eg, blood, urine, saliva), sensitive for the detection of a wide range of cancers at an early stage when long-term cure is more feasible, highly specific, and affordable.

The advancement of multicancer detection is upon us, thanks to the convergence of genomic knowledge and sophisticated analytic techniques. There is a robust and growing pipeline of these tests in development, and some may be available in the near future. Examples include blood tests based on DNA mutations and protein biomarkers,5 methylation of circulating tumor DNA,6,7 or fragmentation patterns of cell-free DNA across the genome.8 Because these detection tools are less invasive and more convenient, they have the potential to improve screening or early detection rates and bolster acceptance across populations at risk.

Although these tests can potentially change the paradigm of cancer detection, the following questions must be addressed:

  • Should these tests be applied only to individuals at high risk for developing (multiple) cancer, at least initially? If so, what risk factors are the most important? Should the focus be on factors that overlap across multiple cancers (eg, age, weight, comorbidities, lifestyle choices, genetic conditions)?
  • When should detection tests begin and what should be the frequency?
  • How should multicancer detection integrate with existing single-organ screenings or detection methods?
  • What are the psychological effects of multicancer detection and how should they be monitored and addressed?
  • What is the diagnostic follow-up protocol for patients with a positive test result?
  • Should these tests be applied to patients in remission?
  • What evidence will be needed to further inform and refine the use of these tests?

Industry can develop new technology, but it is up to the oncology community to apply clinical perspectives on its appropriate use to maximize benefit for patients. Currently, clinical guidelines are available for the detection or screening of individual cancer types, such as breast, colorectal, lung, and prostate.9 There is a growing need, however, for clinical guidance on how a multicancer detection approach should be addressed, integrated, and communicated across relevant tumor types for optimum patient management and evidence-based payer coverage. Clinical guidelines developed by cancer experts are key to providing a framework for appropriate applications of innovative tests and a platform for educating clinicians, patients, and other stakeholders.

As practicing oncologists, we propose the following principles on providing clinical guidance on a multicancer approach:

Principle 1: Use of an Effective and Efficient Platform

Clinical guidelines developed for multicancer detection should be comprehensive, up-to-date, and widely available for use by patients and physicians.

Principle 2: Expert Collaboration Reflecting Scientific Evidence

Clinical guidelines for multicancer detection should be developed in consultation with current screening and disease experts, and patient advocates. Guidelines should be based on expert consensus on scientific evidence.

Principle 3: Defined Scope of Relevant Tumor Types Addressed by Multicancer Detection Tests

It makes sense to first define the scope of the guidelines to key cancer types addressed by multicancer detection tests. The initial disease focus of clinical guidelines for multicancer detection should be based on the performance characteristics of available assays and include high-mortality cancers that can be detected at an early state. The scope may be expanded to include more tumor types with experience and data accumulation.

Principle 4: Comprehensive Recommendations Across the Patient Care Spectrum

Clinical guidelines for multicancer detection should include risk stratification, test start-time and intervals, integration with current screening and detection methods, recommendations for follow-up on test results, monitoring of patients in remission, monitoring of treatment response or resistance, and the importance of psychological support for patients.

Principle 5: Widespread Awareness and Utilization

Publication of clinical guidelines for multicancer detection should have widespread dissemination and communication throughout the clinical, patient, and payer communities. Collaboration should occur across specialties beyond oncology, such as primary care, to create awareness and facilitate access.

We believe that application of these principles to the development of multicancer detection clinical guidelines will foster efficiency in the use of evidence-based and consensus-driven recommendations as the field of multicancer detection tests matures. It is imperative that we initiate the discussion on how to develop a framework to guide usage of these multicancer detection tests. Hopefully, we will be prepared to harness the full potential of such tests when they become available.

References

  1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020;70:7-30.
  2. Ferlay J, Ervik M, Lam F, et al. Global cancer observatory: cancer today. https://gco.iarc.fr/today. Accessed April 21, 2021.
  3. National Cancer Institute. SEER cancer statistics review (CSR) 1975-2015. Updated September 10, 2018. http://seer.cancer.gov/csr/1975_2015. Accessed April 21, 2021.
  4. Sarma EA, Kobrin SC, Thompson MJ. A proposal to improve the early diagnosis of symptomatic cancers in the United States. Cancer Prev Res (Phila). 2020;13:715-720.
  5. Lennon AM, Buchanan AH, Kinde I, et al. Feasibility of blood testing combined with PET-CT to screen for cancer and guide intervention. Science. 2020;369:eabb9601.
  6. Liu MC, Oxnard GR, Klein EA, et al; for the CCGA Consortium. Sensitive and specific multi-cancer detection and localization using methylation signatures in cell-free DNA. Ann Oncol. 2020;31:745-759.
  7. Chen X, Gole J, Gore A, et al. Non-invasive early detection of cancer four years before conventional diagnosis using a blood test. Nat Commun. 2020;11:3475.
  8. Cristiano S, Leal A, Phallen J, et al. Genome-wide cell-free DNA fragmentation in patients with cancer. Nature. 2019;570:385-389.
  9. National Comprehensive Cancer Network. NCCN guidelines. www.nccn.org/guidelines/category_1. Accessed April 1, 2021.

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