Cathy Eng, MD

Cathy Eng, MD, FACP, FASCO, a professor of Medicine, co-leader of the VICC Gastrointestinal Cancer Research Program, David H. Johnson chair in Surgical and Medical Oncology, co-director in GI Oncology, and director of the VICC Young Adults Program at Vanderbilt University Medical Center, and a co-chair of the NCI Gastrointestinal Steering Committee, discusses what can be done in order to integrate biomarker testing for anal cancer into clinical practice.

According to Eng, the role of biomarkers is largely exploratory and in the anal cancer space, it is an area of active research, explains Eng. The biomarker one that has been most heavily explored is PD-L1 expression in multiple malignancies where immune checkpoint inhibitors are being considered as it showed promise in other solid tumors as a predictor of response to immune checkpoints inhibitors.

In anal cell carcinoma specifically, more research is needed to be done in order to integrate biomarkers. Moreover, there needs to be an increased consideration of immune checkpoint inhibitors, according to Eng. Because HPV plays such a large role in the development of this rare disease, Eng specifically believes that HPV circulating-tumor DNA should be considered in clinical trials moving forward in order to provide patients with the best treatment.

 What can be done at this point to integrate biomarkers, I think is increased recognition of immune checkpoint inhibition. I know there's a lot of interest in it currently, obviously in multiple cancers, but we've seen some benefit in this rare cancer as well. We're also looking at it in the adjuvant setting, in EA2165 for high-risk recurrent patients. I think what we can learn from this is that for immune checkpoint inhibitors, we don't have the best answers in regard to biomarkers for our patient populations, we need to think about other aspects. Because HPV has such a large role in the development of anal carcinoma, I think consideration for HPV circulating-tumor DNA really should be considered in all clinical trials moving forward, as well as trying our best to identify other biomarkers as well although.

 Once again, for all metastatic patients next generation sequencing should be completed when thinking about steps moving forward, should they need alternative treatment options. I always encourage in the metastatic setting, next generation sequencing. In current studies, both early stage and late stage, I'm hoping that they will also incorporate HPV circulating-tumor DNA. I think that's very promising right now.

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Cathy Eng, MD, discusses what can be done in order to integrate biomarker testing for anal cancer into clinical practice.

Biomarker Testing for Anal Cancer 

Historically, colorectal cancer (CRC) has been viewed as a common cancer among elderly patients. The average age at diagnosis of patients with CRC in the United States is 67 years,

in which a screening colonoscopy remains the gold standard of care for prevention and is recommended for all individuals >50 years of age.

Recent literature has suggested, however, that there will be an unexpected rise in the incidence of CRC, notably of left-sided tumors of the descending colon and rectum, in young adults (<50 years of age) over the next decade.

The recognition of the rising incidence of CRC in young adults was initially reported by Bailey and colleagues.

This was a retrospective cohort study of patients with colon or rectal cancer using the Surveillance, Epidemiology, and End Results (SEER) database. The SEER database reports on the incidence, survival, and prevalence of cancer and represents approximately 28% of the United States patient population. Data were reviewed from January 1, 1975, through December 31, 2010 (n = 393,241). The incidence of cancer was predicted for 2020 and 2030 compared with 2010. Despite an expected sharp decline in the diagnosis of colon cancer for individuals >75 years of age, the incidence of colon cancer is expected to dramatically increase by 90% for those between 20 to 34 years of age by the year 2030. Similar findings were noted in left-sided tumors, specifically in rectosigmoid and rectal cancer, with an increase of 124% for young adults aged 20 to 34 years.

Rebecca L. Siegel, MPH, conducted an updated review of the SEER database from 1974 through 2013 (n = 490,305).

When compared with individuals born before 1950, those born after 1990 have double the risk of colon cancer and quadruple the risk of rectal cancer. The investigators noted that from the mid-1980s and on, rates of colon cancer rose by 2.4% per year for individuals aged 20 to 29 years and by 1.0% for those 30 to 39 years of age.

Based on my own clinical experience and when speaking to CRC advocacy groups, it is not uncommon to hear that many young adults had reported earlier signs or symptoms but had often ignored their symptoms or attributed their bowel irregularity to hemorrhoids. Other patients reported that despite their symptoms, their primary care provider either did not pursue a full evaluation or misdiagnosed them with hemorrhoids or irritable bowel disease. As a result of the increased recognition of the expected rise in CRC in young adults and with the support of advocacy groups, CRC screening at a younger age is being considered. As of 2018, the American Cancer Society is now recommending CRC screening to start at age 45.6 However, an earlier age of screening remains controversial and is not supported at this time by the United States Preventive Services Task Force or the American Society of Gastroenterology.

Regardless of screening protocols, the etiology for this unexpected rise of CRC in young adults remains unknown at this time, is likely multifactorial, and continues to be under investigation.

For all patients, cancer treatment can be daunting. For a young adult who is about to embark on an independent life with a new career, a new relationship, or a new home, however, a diagnosis of CRC is especially shocking. Although many hospitals have an adolescent young adult program, it is often associated with a pediatric program. Often, young adults <45 years of age neither fit the description of an adolescent young adult nor fit in with the average age of the elderly CRC population. Furthermore, most hospitals do not have a specific treatment approach for young adult patients and often manage these individuals in a similar fashion to their average age elderly patients.

Despite our best intentions to cure patients, there are both acute and chronic toxicities associated with therapy. The treatment of CRC often requires surgery for curative intent. The consideration of chemotherapy and/or chemoradiation therapy is also often part of the treatment plan. Examples of typical acute toxicities include postoperative discomfort, change in bowel habits, nausea, vomiting, mouth sensitivity, fatigue, and possibly peripheral neuropathy. Of greater concern, however, is the period after completing therapy, as the chronic toxicities may include bowel and urinary dysfunction, sexual dysfunction, lingering neuropathy, etc.

With an expected rise in CRC in young adults over the next decade, health care providers must be educated to recognize these patients&rsquo; unmet needs and the concerns and difficulties they face.

Facets that caregivers should consider for generalized aspects of cancer care in young adults with CRC are listed as follows:

Reproductive health and sexuality counseling

Genetics and possible referral to a high-risk genetics clinic

Hopefully, cancer care providers will increase their efforts to recognize the needs of our young adult patients. Recognition will only optimize the overall patient outcome.

Cancer Stats Facts: Colorectal cancer. Surveillance, Epidemiology, and End Results Program website. seer.cancer.gov/statfacts/html/ colorect.html. Accessed October 24, 2019.

U.S. Preventive Services Task Force. Archived. Colorectal cancer: screening. https://bit.ly/2JZ9Xvy. Published 2008. Accessed October 24, 2019.

Final recommendation statement, colorectal cancer: screening. https://bit.ly/2NUVTUO. Updated June 2016. Accessed October 24, 2019.

Bailey CE, Hu CY, You YN, et al. Increasing disparities in the age-related incidences of colon and rectal cancers in the United States, 1975-2010. JAMA Surgery. 2015;150(1):17-22. doi: 10.1001/ jamasurg.2014.1756.

Siegel RL, Fedewa SA, Anderson WF, et al. Colorectal cancer incidence patterns in the United States, 19742013. J Natl Cancer Inst. 2017;109(8). doi: 10.1093/jnci/djw322.

American Cancer Society updates colorectal cancer screening guidelines. American Cancer Society. cancer.org/latest-news/ american-cancer-society-updates-colorectal-cancer-screening-guideline.html. Published May 30, 2018. Accessed October 24, 2019.

Rex DK, Boland R, Dominitz JA, et al. Colorectal cancer screening: recommendations for physicians and patients from the U.S. multi-society task force on colorectal cancer. Gastrointest Endosc. 2017;86(1):18-33. doi: 10.1016/j. gie.2017.04.003.

Articles

Historically, colorectal cancer has been viewed as a common cancer among elderly patients. The average age at diagnosis of patients with colorectal cancer in the United States is 67 years,&nbsp;in which a screening colonoscopy remains the gold standard of care for prevention and is recommended for all individuals &gt;50 years of age.

Meeting the Unmet Needs of Young Adults With Colorectal Cancer

Cathy Eng, MD, professor of gastrointestinal medical oncology, The University of Texas MD Anderson Cancer Center, discusses how the PRODIGE 7 trial, though negative, provided valuable evidence to the field for treatment of patients with metastatic colorectal cancer (mCRC) with peritoneal carcinomatosis.

This was the first trial in 15 years looking at treatment options for this patient population. While the results were negative, Eng says this is still an important trial because it highlighted the need to move forward in the field of mCRC.

Cathy Eng, MD, discusses how the PRODIGE 7 trial, though negative, provided valuable evidence to the field for treatment of patients with metastatic colorectal cancer with peritoneal carcinomatosis.

Cathy Eng, MD | Authors

Articles

Biomarker Testing for Anal Cancer

Meeting the Unmet Needs of Young Adults With Colorectal Cancer

Expert Discusses How Negative Trial Impacted Field of mCRC