Why Do Younger Colorectal Cancer Patients Have Better Outcomes Despite More Aggressive Disease?

Canadian Cancer Trials Group investigators say it's unclear if disease biology is different in younger patients or if older ones are more likely to undergo screening.

Although younger patients with colorectal cancer (CRC) are being diagnosed with more aggressive or advanced disease, they are experiencing improved outcomes compared with older patients, according to the results of a new study published in Clinical Colorectal Cancer.

According to Laura Rodriguez, from the Canadian Cancer Trials Group, and colleagues from Queen’s University, Kingston, Canada, “it is unclear if this is driven by fundamental differences in disease biology, or whether it simply reflects the fact that older patients are more likely to have CRC screening.”

“Further work is needed to understand if this apparent disconnect is explained by intrinsic differences in tumor biology,” the researchers wrote.

For their study, Rodriguez and her colleagues used data on 6,775 patients from the Ontario Cancer Registry. All patients had stage I–III colon cancer and had been treated with surgery during 2002–2008. Patients were divided into groups according to age: younger than 40 years (2%), age 41–50 (5%), age 51–60 (14%), and older than 60 years (79%).

The researchers identified several features of aggressive disease that occurred more commonly in younger patients. Compared with patients older than 60, younger patients were more likely to have lymphovascular invasion (35% vs 27%; P = .005), T3/4 tumors (88% vs 79%; P = .005), and node-positive disease (58% vs 41%; P < .001).

In addition, younger patients were significantly more likely to be diagnosed with stage II disease compared with older ones (58% vs 41%; P < .001).

“This may be explained by the fact that current screening guidelines do not recommend routine screening for this seemingly low-risk population,” the researchers wrote. “This could result in younger patients being diagnosed once [they have become] symptomatic and, thus, at a later stage.”

Younger patients were significantly more likely to undergo adjuvant chemotherapy than their older counterparts for both stage II (50% vs 13%; P < .001) and stage III disease (> 92% vs 57%; P < .001).

Despite having more aggressive characteristics, patients 40 years of age or younger had improved survival (hazard ratio [HR], 0.32; 95% CI, 0.21–0.49) and cancer-specific survival (HR, 0.41; 95% CI, 0.26–0.64) compared with patients 60 years and older.

“The paradoxical observation that younger patients have superior survival may relate to less comorbidity, fewer complications related to surgery, improved tolerance of adjuvant chemotherapy, or intrinsic differences in tumor biology,” Rodriguez and colleagues wrote.