A large retrospective study has found that early-onset colorectal cancers are clinically and genomically indistinguishable from average-onset colorectal cancers. In addition, the study found that more aggressive treatment based solely on the patient’s age at diagnosis is neither necessary nor effective. However, the study did find that younger patients most often presented with left-sided disease, rectal bleeding, and abdominal pain. Results of this retrospective comparison were published by Andrea Cercek, MD, and colleagues in the Journal of the National Cancer Institute.

Excluding skin cancers, colorectal cancer is the third most common cancer diagnosed in both men and women in the United States, and the third leading cause of cancer-related deaths. This year, it is estimated that nearly 150,000 new cases of colon and rectal cancer will be diagnosed, and about 53,000 people will die from the disease.

While the incidence of colorectal cancer has decreased overall since the mid-1980s (dropping by about 1% each year between 2013 and 2017, largely due to additional screening and treatment improvements), most of that progress has been in older adults. For adults aged 50 years or younger, the incidence of colorectal cancer has been steadily increasing by 1% to 2% annually since the mid-1990s. By 2030, it is estimated that 10.9% of all colon cancers and 22.9% of all rectal cancers will be diagnosed in patients younger than 50, compared with 4.8% and 9.5%, respectively, in 2010, although the reasons why the disease is increasing in younger adults are unclear.

Study Methodology

The researchers used a patient database from Memorial Sloan Kettering Cancer Center to identify patients younger than age 50 with a pathologic diagnosis of colorectal cancer between 2014 and 2019. In total, 759 patients with early-onset colorectal cancer (age ≤ 35 years, n = 151; 36–49 years, n = 608) and 687 patients with average age-onset colorectal cancer (age ≥ 50 years) were included in the study.

For all comparisons, patients with early-onset disease were further stratified by age at diagnosis: 35 years and younger vs 36 to 49 years, enabling a separate analysis in the 35 and younger group, where the incidence of colorectal cancer is increasing the most and where more aggressive tumor biology has been suggested.

Patients with mismatch repair–deficient tumors, colorectal cancer–related hereditary syndromes, and inflammatory bowel disease were excluded from all but the germline analysis. All statistical tests were two-sided.

Results

The researchers found that patients with early-onset colorectal cancer were more likely to have left-sided tumors (35 years and younger = 80.8%; 36–49 years = 83.7%; average-onset = 63.9%; P < .001 for both comparisons). Rectal bleeding (35 years and younger = 41.1%; 36–49 years = 41.0%; average-onset = 25.9%; P = .001 and P < .001, respectively) and abdominal pain (35 years and younger = 37.1%; 36­­–49 years = 34.0%; average-onset = 26.8%; P = .01 and
P = .005, respectively) were more common in early-onset colorectal cancer.

Among microsatellite-stable tumors, the researchers found no differences in histopathologic tumor characteristics. Initially, differences in TP53 and receptor tyrosine kinase signaling pathway (RTK-RAS) alterations were noted by age. However, on multivariate analysis, including somatic gene analysis and tumor sidedness, no statistically significant differences at the gene or pathway level were demonstrated.

Among advanced microsatellite-stable colorectal cancers, chemotherapy response and survival were equivalent by age cohorts. Pathogenic germline variants were identified in 23.3% of patients aged 35 years and younger vs 14.1% of those with average-onset colorectal cancer  (P = .01).

“Early-onset colorectal cancers are more commonly left-sided and present with rectal bleeding and abdominal pain, but are otherwise clinically and genomically indistinguishable from average-onset colorectal cancers. Aggressive treatment regimens based solely on the age at colorectal cancer diagnosis are not warranted,” concluded the study authors.

Disclosure: Funding for this study was provided by the National Cancer Institute, the National Institutes of Health, Stand Up To Cancer, Memorial Sloan Kettering Cancer Center, and the Romeo Milio Lynch Syndrome Foundation. For full disclosures of the study authors, visit academic.oup.com/jnci.