Dana-Farber Tackles Rising Incidence of Young-Onset Colorectal Cancer

Leah H. Biller, MD

Medical Oncologist, Dana-Farber Cancer Institute, and Instructor in Medicine, Harvard Medical School

Kimmie, Ng, MD, MPH

Medical Oncologist, Codirector of the

Colon and Rectal Cancer Center,

Director of the Young-Onset Colorectal Cancer Center, and Director of Clinical

Research at the Gastrointestinal

Cancer Center, Dana-Farber Cancer

Institute. Ng is also an associate

professor of medicine at Harvard

Medical School.

Colorectal cancer (CRC) is the third-most-common cancer type and the third-most-common cause of cancer-related deaths in the United States, with 147,950 new cases and 53,200 CRC-related deaths projected for 2020.¹ However, approximately 10% to 11% of new cases and 6% to 7% of deaths are in patients under age 50 (defined as young-onset CRC).² The oncology community now recognizes that young-onset CRC may involve different environmental and genetic factors compared with CRC in older patients, but the data remain limited, and much is still unknown about this concerning phenomenon.

Overall, CRC screening with colonoscopy and stoolbased tests has revolutionized the prevention and early detection of CRC; nevertheless, rates of young-onset CRC have been rising.^2-5 The incidence of young-onset CRC grew by 22% from 2000 to 2013, and mortality increased by 13% between 2000 and 2014.² To address these alarming trends and detect CRC in more younger patients, the American Cancer Society included in its 2018 guidelines a qualified recommendation to initiate CRC screening at age 45 for average-risk individuals.⁶

The reasons for increased young-onset CRC remain uncertain, with a critical need for clarification.⁷ Genetic predisposition may be identified in 16% to 20% of patients with young-onset CRC; importantly, upward of 33% of patients without a concerning family history may still be carriers of genetic alterations, highlighting the importance of universal germline testing for this population.^8,9 Positive germline findings may have implications for risk stratification and surveillance of relatives via cascade testing, with important downstream effects on CRC prevention.

Investigators have conducted small studies to evaluate lifestyle factors associated with young-onset CRC. Most hypotheses have focused on obesity, a known risk factor for CRC overall, particularly because the rise in young-onset CRC has seemingly paralleled the increase in obesity in the United States.^10-12 Among 85,256 women followed prospectively in the Nurses’ Health Study II (NHSII), obese women (body mass index [BMI] 30) had a relative risk (RR) of 1.93 (95% CI, 1.15-3.25) for young-onset CRC compared with women with a BMI of 18.5 to 22.9.¹³ In fact, the RR was 1.20 for every 5-unit increase in BMI (95% CI, 1.05-1.38, P = .01). Another analysis of NHSII data found a similar, positive association between prolonged television viewing time (a marker for sedentary activity) and young-onset CRC.¹⁴

Differences in the clinical and molecular features of young-onset CRC also appear to exist. Younger patients are more likely to present with advanced (stage III/IV) disease compared with older patients.^15,16 Whether this is related to underlying biology, delays in diagnosis, or both is of ongoing interest, but tumors in younger patients may also have more aggressive pathology (including poorly differentiated and signet ring cell histologies).^15-17 Large national databases and patient-level registries have consistently found that the majority of tumors are in the distal colon and rectum; this is intriguing in light of recent data that suggest differences in treatment response and survival outcome by primary tumor site.^2,4,17-21 Among younger patients, BRAF V600 and NRAS mutations are less common, and the frequency of KRAS mutations and microsatellite instability is more variable.^17-20,22 Further investigation into these and other mutational patterns, with larger and more diverse cohorts, is required.

To better address these unmet clinical and research needs, Dana-Farber Cancer Institute of Boston, Massachusetts, launched the Young-Onset Colorectal Cancer Center, among the first of its kind, in March 2019. The center’s mission is 3-fold: (1) to provide expert and compassionate clinical care; (2) to promote scientific discovery and innovation to elucidate underlying biological mechanisms, identify risk factors, and facilitate development of novel therapies; and (3) to improve prevention and early detection by raising public awareness of the rising burden of CRC in young adults.

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To help patients navigate their cancer journey and cope with their diagnosis, the center has developed custom group programming initiatives (eg, support groups, webinars, seminars, and newsletters) tailored to this population. Finally, because many patients with young-onset CRC report feelings of isolation and a lack of contact with patient peers of similar age, the center aims to create a closeknit community of young patients and their supporters. The center’s inaugural Patient and Family Forum, scheduled for March 7, 2020, is an example of how the program is bringing young patients together.

The cornerstone of the Young-Onset Colorectal Cancer Center is a new research study called the Beyond CRC Project: Better Understanding of Young-Onset Colorectal Cancer (Figure). This multicenter, prospective, longitudinal cohort study is one of the first comprising exclusively patients with young-onset CRC. It is also designed to fill the gaps in existing patient cohorts, which are limited by small sample sizes, minimal racial and ethnic diversity, nonuniform collection of dietary and lifestyle data, and an absence of serial biospecimen collection, including stool samples for microbiome analyses. With comprehensive data and biospecimen collection, the Beyond CRC Project aims to identify the underlying risk factors and biology of young-onset CRC and leverage that knowledge to develop novel prevention, early detection, and treatment strategies.

One study estimates that in 2030, the incidence of young-onset CRC will increase by over 90% for individuals aged 20 to 34 and more than 27% for those aged 35 to 49.²³ Given that this phenomenon is only growing, focused and targeted investigation is imperative to both inform effective treatment strategies and stratify those most at risk who might benefit from additional screening. Additional dedicated centers are needed, and we welcome ongoing collaboration to better facilitate research endeavors and provide the best comprehensive care for our patients with young-onset CRC.

References

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The Young-Onset Colorectal Cancer Center offers several unique features and resources. All patients at the center receive multidisciplinary evaluation and up-front genetic counseling and testing at their initial visit. Each patient’s tumor is genomically profiled using the OncoPanel next-generation sequencing platform, the results of which are reviewed by a multidisciplinary molecular tumor board through a novel program called GI TARGET (Treatment Assistance Regarding Genomic Evaluations of Tumors). The result is a comprehensive report detailing personalized therapy options and clinical trial matches, which is shared with the treating oncologist to facilitate a precision medicine approach to care. The center has a dedicated research and program coordinator to help expedite referrals to critical support services (including fertility, sexual health, nutrition, and integrative medicine) and to act as the patient’s liaison to the clinical and research team. To provide comprehensive psychosocial support, the center also has its own social worker with clinical expertise in young patients with cancer.