Early-onset patients diagnosed with worse disease, but also more likely to receive systemic treatment

Patients diagnosed with colorectal cancer (CRC) before the age of 50 had a modest survival advantage over those who were diagnosed with the same malignancy between ages 51-55, but only when adjusted for disease stage on diagnosis, a large, nationally representative cancer database indicated.

On multivariable adjustment—most notably with adjustment for disease stage—overall mortality was 5% lower among patients with early-onset CRC at a Hazard Ratio (HR) of 0.95 (95% CI, 0.93-0.96; P<0.001) compared with patients diagnosed with CRC at an older age, En Cheng, MD, PhD, Yale School of Public Health, New Haven, Connecticut, and colleagues reported in JAMA Network Open. And, in a model adjusted for stage alone, overall mortality was 11% lower for those with early-onset CRC at a HR of 0.89 (95% CI, 0.88-0.90; P<0.001) compared to those with later-onset CRC, investigators added.

“Understanding the survival among individuals with early-onset CRC compared with those aged 50 years and older is fundamental to informing treatment approaches and understanding the unique biological distinctiveness within early-onset CRC,” Cheng and colleagues wrote.

Out of 769,871 individuals identified with CRC in the National Cancer Database, 13.3% had early-onset CRC, defined as CRC in patients under the age of 50 years. Another 10.2% of registrants had later-onset CRC, defined as those who were diagnosed with CRC between 51 and 55 years of age.

In the overall study cohort, almost half (49.15) were female, and the majority (82.7%) were White.

Patients with early-onset CRC were more likely to be diagnosed with stage IV cancer at 27.8% compared with 24.1% of those with later-onset cancer (P<0.001) as well as with rectal tumors at 29.3% compared with 28.7% (P=0.004), respectively.

However, more early-onset patients were likely to receive systemic treatment than older patients:

  • Radiation therapy: 24.7% versus 22.1% (P<0.001).
  • Chemotherapy: 68% versus 59.2% (P<0.001).
  • Immunotherapy: 3.3% versus 2.7% (P<0.001).

In contrast, slightly more later-onset CRC patients were likely to have surgery at 86.8% compared with 86.4% for younger-onset patients, investigators noted.

“Compared with individuals diagnosed with CRC at ages 51 to 55 years, individuals with early-onset CRC experienced inferior overall survival (log-rank P<0.001) for all years,” researchers found. “Specifically, compared with individuals diagnosed with CRC from ages 51 to 55 years, individuals 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<0.001) in the unadjusted Kaplan-Meier analysis.”

Nevertheless, “stratified by stage, individuals with early-onset CRC had higher survival rates across all years of follow-up,” they added. “The corresponding adjusted HRs for stages I to IV were 0.87 (95% CI, 0.81-0.93; P<0.001), 0.86 (95% CI, 0.82-0.90; P< .001), 0.98 (95% CI, 0.95-1.01; P=0.15), and 0.96 (95% CI, 0.94-0.98; P<0.001).”

The survival advantage was greatest for patients diagnosed with CRC between 35 to 39 years of age, where it was 12% longer (HR 0.88; 95% CI, 0.84-0.92; P<0.001), although this was largely limited to patients diagnosed with stage I and II CRC.

“[A]fter adjustment for stage at diagnosis, individuals with early-onset CRC actually had better survival, with a relative 5% reduction in mortality,” the authors pointed out. “This may reinforce the importance of early CRC detection in the younger population, especially given that we are in the midst of a shift in the recommended age for CRC screening. However, considering that younger people are generally healthier, with more years remaining to live, the survival advantage should be interpreted cautiously, especially given that the advantage has a small magnitude and is heterogeneous by ages and stage,” they cautioned.

Commenting on the findings, lead editorialist Kirbi Yelorda, MD, Standard University, Stanford, California, and colleagues pointed out that rates of CRC diagnoses in patients under the age of 50 increased by 22% from 2000-2013 while mortality from CRC increased by 13% over the same interlude.

“The United States Preventive Services Task Force (USPSTF) recently reduced the CRC screening age to 45 years from 50 years in their 2020 draft recommendation statement” they noted. “This recommendation was based on modeling analyses suggesting more life-years gained, fewer CRC-related deaths, and a favorable balance of benefit and harms when screening begins at age 45 years.”

Nevertheless, the editorialists suggested that there are several factors that should be taken into consideration when interpreting the results from Cheng and colleagues.

“First, CRC remains rare in the population younger than 45 years, at 25 new cases diagnosed per 100,000 people per year,” they wrote. “Individuals with early-onset CRC typically present with higher-risk pathology and more advanced or distal disease compared with patients older than 50 years; yet these patients also have higher cancer-specific survival. This may be partially attributed to fewer comorbidities. Additionally, patients with early-onset CRC tend to undergo more aggressive treatment, including greater lymph node harvest (>12 lymph nodes examined), and commence systemic therapy within 6 months of diagnosis. While there is no difference in management recommendations between early-onset and late-onset CRC, the differences in clinical practice, and thus potentially survival, may reflect patient and clinician age-related bias.”

Yelorda and colleagues concluded that, while CRC diagnoses in patients under age 45 years continue to represent a small portion of overall CRC cases, the findings by Cheng and colleagues “provide optimism about treatment outcomes in these patients.” However, they added that “More information is needed to understand how the updated USPSTF CRC screening recommendations could impact mortality inpatients screened between the ages of 45 and 50 years.”

  1. Patients diagnosed with CRC before the age of 50 had a modest survival advantage compared with those diagnosed with CRC between 51 and 55 years of age, but only after adjusting for disease stage on diagnosis.

  2. More early-onset CRC patients had stage IV disease and rectal tumors, but they were still more likely to receive systemic treatment than later-onset CRC patients.

Pam Harrison, Contributing Writer, BreakingMED™

The study was funded by the National Institutes of Health and Cancer Dream Team Translational Research Grant.

Cheng had no disclosures to make.

The editorialists had no relevant financial disclosures.

Cat ID: 23

Topic ID: 78,23,730,16,23,192,925