Early-Onset CRC Associated With Longer Survival

Will Pass

June 28, 2021

Individuals diagnosed with primary colorectal cancer (CRC) at less than 50 years of age have better survival outcomes than individuals diagnosed at 51-55 years, based on data from more than 750,000 patients.

This finding emphasizes the importance of early CRC detection in younger individuals, reported lead author En Cheng, MD, PhD, of Yale University, New Haven, Conn., and colleagues.

"Early-onset CRC (i.e., CRC diagnosed at age less than 50 years) has been characterized by unique clinical, genetic, and epigenetic characteristics, and thus it may be associated with different survival from CRC diagnosed among individuals older than 50 years," the investigators wrote in JAMA Network Open. Previous studies comparing survival times across age groups have yielded inconsistent results.

To gain a better understanding, the investigator conducted a retrospective study using data from the National Cancer Database. Excluding patients with primary CRC who had concomitant diagnosis, history of other malignant tumors, noninvasive adenocarcinoma, or missing data, the final dataset included 769,871 patients. Early-onset CRC was defined by age less than 50 years, whereas later-onset CRC was defined by ages 51-55 years.

"Individuals diagnosed at age 50 years were excluded to minimize an apparent screening detection bias at age 50 years in our population, given that these individuals disproportionately presented with earlier stages," the investigators wrote.

Initial comparisons across groups revealed several significant differences. Individuals in the early-onset group were more often women (47.3% vs. 43.8%; P < .001), members of races in the "other" category (6.9% vs. 5.9%; P < .001), and Medicaid patients (12.3% vs. 10.3%; P < .001). They were also more likely to be diagnosed with stage IV cancer (27.8% vs 24.1%; P < .001) and have rectal tumors (29.3% vs. 28.7%; P = .004).

In the unadjusted Kaplan-Meier analysis, patients with early-onset CRC had a lower 10-year survival rate (53.6%; 95% CI, 53.2%-54.0% vs. 54.3%; 95% CI, 53.8%-54.8%; P < .001). The fully adjusted model revealed significantly higher survival for early-onset patients, compared with later-onset patients (adjusted hazard ratio, 0.95; 95% CI, 0.93-0.96; P < .001) . This disparity deepened when adjusting only for stage (HR, 0.89; 95% CI, 0.88-0.90; P < .001).

Survival was longest among patients 35-39 years (aHR, 0.88; 95% CI, 0.84-0.92; P < .001), compared with those aged 51-55, and among early-onset individuals with stage I disease (a HR, 0.87; 95% CI, 0.81-0.93; P < .001) or stage II disease (a HR, 0.86; 95% CI, 0.82-0.90; < .001), compared with those having the same stages of later-onset CRC. No survival advantage was observed among patients diagnosed at age 25 or younger or those with stage III or IV disease.

"Interestingly, hereditary nonpolyposis colorectal cancer, owing to underlying mismatch repair deficiency, is associated with superior survival and is often diagnosed in individuals from ages 35-45 years," the investigators noted. "In contrast, adenomatous polyposis coli syndrome is more common in individuals who are diagnosed with CRC at age younger than 20 years (10%), compared with those diagnosed at later ages (0.1%), and adenomatous polyposis coli syndrome is not associated with a survival advantage. These high penetrance syndromes could partly account for the relative heterogeneity in survival across ages among individuals with early-onset CRC."

Cautious About Interpretation

Cheng and colleagues concluded their publication with a disclaimer: "Our finding of a survival advantage associated with early-onset CRC among younger individuals should be interpreted cautiously, given that the advantage had a small magnitude and was heterogeneous by age and stage," they wrote. "Further study is needed to understand the underlying heterogeneity of survival by age and stage among individuals with early-onset CRC."

Kirbi L. Yelorda, MD, of Stanford (Calif.) University, and colleagues, had a similar interpretation.

"These results offer support for effectiveness of treatment in patients diagnosed with CRC at younger ages; however, they must be interpreted within the context of epidemiological and biological factors," Yelorda and colleagues wrote in an accompanying editorial.

The findings also suggest that the recent reduction in recommended screening age by the U.S. Preventive Services Task Force – from 50 years to 45 years – is warranted, they added, but screening younger patients remains unnecessary.

"While these results do not suggest that screening should start for patients younger than 45 years, they do support the benefit of early detection in young patients," Yelorda and colleagues wrote, noting a "fairly low incidence rate" among individuals younger than 45, which is insufficient to justify the risk-to-benefit ratio and increased costs associated with expanded screening.

Important but Not Surprising

It's "not surprising" that early-onset patients typically have better survival than later-onset patients, according to Joseph C. Anderson, MD, associate professor at White River Junction Veterans Affairs Medical Center, Hartford, Vt.; Geisel School of Medicine at Dartmouth, Hanover, N.H.; and the University of Connecticut, Farmington.

"They're younger, have less comorbidities, and can tolerate chemotherapy," Anderson said in an interview. "It's not surprising that people do poorly with later stages. Younger people are no exception."

Anderson, who previously coauthored an editorial weighing the pros and cons of earlier screening, noted that earlier screening is needed because of the rising incidence of late-stage diagnoses among younger patients, which, as the study found, are associated with worse outcomes.

Beyond adherence to screening recommendations, Anderson urged clinicians to be aggressive when doing a workup of CRC symptoms in younger patients, among whom delayed diagnoses are more common.

"We can't just say it's something more benign, like hemorrhoids, like we used to," Anderson said. "Somebody who's 30 years old and having rectal bleeding needs to be evaluated promptly – there can't be a delay."

The study was supported by the National Institutes of Health and Stand Up To Cancer (grant administered by the American Association for Cancer Research). The investigators disclosed relationships with Evergrande Group, Janssen, Revolution Medicines, and others. One editorialist reported serving as a member of the USPSTF when the guideline for colorectal cancer was developed, and being a coauthor on the guideline. No other disclosures were reported among editorialists. Anderson reported no relevant conflicts of interest.

This article originally appeared on MDedge.com, part of the Medscape Professional Network.


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