Dec. 15, 2022
Colorectal cancer (CRC) is the third most common and second most lethal cancer in the United States. Since 1988, researchers have documented a significant increase in the incidence of CRC in adults under age 50, throughout the United States and in other high-income countries. Early-onset CRC now accounts for approximately 10% of all new diagnoses of this cancer, and researchers also have observed an increase in CRC-related mortality among younger patients during the past decade.
In a review published in the New England Journal of Medicine in 2022, author Frank A. Sinicrope, M.D., discusses current evidence related to the phenotype and diagnosis of early-onset CRC and strategies to address the increasing incidence of this disease. Dr. Sinicrope is a gastroenterologist and medical oncologist at Mayo Clinic in Rochester, Minnesota.
Clinical phenotype
Dr. Sinicrope notes that the clinical features of early-onset colorectal cancer differ from those of later onset disease in some specific ways.
- Early-onset colorectal cancers are most commonly detected in the rectum and the left colon.
- Patients with early-onset CRC typically have more-advanced disease at diagnosis than patients with later onset colorectal cancer.
- Symptoms most commonly associated with early-onset CRC include hematochezia (fresh blood per rectum), abdominal or pelvic pain and bloating, and a change in bowel habits.
"We are still uncertain whether the advanced stage of early-onset cancers signals the presence of a more aggressive tumor biology, or if it is related to delayed diagnosis," notes Dr. Sinicrope. "Studies suggest that patients with early-onset disease have had a longer duration of symptoms at presentation and a longer delay in the time to diagnosis than do older patients."
According to Dr. Sinicrope, multiple factors can contribute to a delayed diagnosis. These include a lack of awareness about early-onset disease and its symptoms, which are often attributed to a benign condition, and the fact that many patients under age 50 are less likely to have a primary care provider.
Current screening guidelines
Experts now recommend beginning colorectal cancer screening at age 45 for individuals considered to be at average risk of colorectal cancer. Screening options for patients at average risk include a fecal immunohistochemical test (FIT), multitarget stool DNA testing, colonoscopy, sigmoidoscopy alone or combined with FIT, and a guaiac-based fecal occult blood test. Colonoscopy is the standard for colorectal cancer screening, and it also facilitates the immediate identification and removal of precancerous polyps.
Strategies to reduce the incidence of early-onset CRC
Approximately half the patients with early-onset colorectal cancer receive the diagnosis before age 45, before most people undergo their first routine colonoscopy. For this reason, Dr. Sinicrope and others recommend taking an individualized approach to colorectal cancer screening, based on family history when such information is available.
"Patients who have a first-degree family member diagnosed with colorectal cancer or advanced adenoma before age 60, or anyone with two first-degree relatives who receive this diagnosis at any age, should be advised to begin undergoing screening colonoscopy at age 40, or at an age 10 years less than the age of the family member with the earliest diagnosis," says Dr. Sinicrope.
About 25% of patients between ages 40 and 49 who have been diagnosed with early-onset CRC meet family history criteria for screening before age 45. "If this individualized approach had been applied to these patients, they would have undergone earlier screening, making an earlier diagnosis at a premalignant stage more possible," says Dr. Sinicrope.
It is important to note that the majority of early-onset colorectal cancers are sporadic in that they occur in the absence of any known hereditary cancer syndrome. However, one should consider an inherited condition and exclude it in these patients.
In recent studies that have tested for heritable mutations in cancer susceptibility genes, pathogenic germline variants were identified in 1 in 6 patients with early-onset CRC, half of which were in DNA mismatch repair genes associated with Lynch syndrome. Lynch syndrome is the most common type of hereditary colon cancer. Although it occurs in about 3% of the general population, the risk of Lynch syndrome is increased in those with early-onset colorectal cancer. For this reason, Dr. Sinicrope notes that genetic risk counseling and evaluation, including germline multigene panel testing, is recommended for all patients with colorectal cancer who are under age 50.
It's also essential to address factors that can improve patients' adherence to CRC screening guidelines, including patients' test preferences. Dr. Sinicrope adds that the best CRC screening test is the one that the patient will comply with. And the most important factor in getting screened is a physician recommendation. "Improving access to care and increasing public awareness about the rising incidence of early-onset CRC may result in more individuals undergoing screening," says Dr. Sinicrope.
For more information
Sinicrope FA. Increasing incidence of early-onset colorectal cancer. New England Journal of Medicine. 2022;386;1547.
Refer a patient to Mayo Clinic.