Early-Onset Colorectal Cancer Is Not Distinguishable From Average-Onset CRC

Genomic tumor profiles and clinical outcome data showed that early-onset colorectal cancer (EO-CRC) is not biologically different from average-onset colorectal cancer (AO-CRC) – after adjusting for known variables – in contrast to previous reports.

“Our results demonstrate that clinical outcomes and response to chemotherapy are the same and that aggressive treatment regimens based solely on the age at CRC diagnosis are not warranted,” the authors wrote in a study published in the Journal of the National Cancer Institute.

The retrospective analysis looked at 759 patients younger than 50 with a CRC diagnosis from Memorial Sloan Kettering Cancer Center (MSKCC) between January 2014 and June 2019. Most patients had stage 4 disease.

“It's just important to keep in mind that Memorial Sloan Kettering Cancer Center is an amazing institution, it's a very prominent institution. But if you look at the data, the majority of patients were Caucasian, so we do have to take that into account,” said Dr. Cathy Eng, who penned an accompanying editorial to the study and is the David H. Johnson Chair in Surgical and Medical Oncology at Vanderbilt-Ingram Cancer Center (VICC), Professor of Medicine and Director of the VICC Young Adult Cancers Initiative, in an interview with CURE®.

“You're going to have a very narrowed ethnicity in regard to the sample, or the cohort that was evaluated, as well as you're going to also have a narrowed perspective of psychosocial class,” Eng added. “But I just want to make sure that the take home point when people read the data, is that they have to understand is from the perspective of a single institution.”

The researchers compared the patients with EO-CRC with a group of patients with AO-CRC treated during a similar timeframe at MSKCC. They found that while the presence of hypertension, diabetes and smoking history progressively increased with diagnosis age, rectal bleeding and abdominal pain or bloating were more common in patients with EO-CRC. These patients were also less likely to be anemic and have left-sided tumors or rectal cancer.

In terms of clinical outcomes, it was discovered that first-line chemotherapy use and type as well as site of first metastases and metastasectomy (surgery to remove metastases) frequency didn’t differ among age groups or confound survival outcomes. The radiographic responses to chemotherapy and median overall survival (OS) did not differ.

After germline analysis, the highest prevalence of mutation occurred in the younger age group.

“Among patients with very early-onset CRC, the prevalence of germline mutations was especially high at 23% because of a near doubling of mutations in high-penetrance cancer susceptibility genes,” the authors wrote. There was no substantial difference in tumor grade between the EO- and AO-CRC groups.

The study authors also noted that the patients with AO-CRC had higher rates of chronic diseases like diabetes, obesity and hypertension, while it appears likely that external or environmental factors may affect earlier CRC development. Although several risk factors have been established, the question still remains as to what the direct cause of the increasing incidence of EO-CRC.

“I think many of us are recognizing that these young adults need additional support, not only just to reverse to treatment, but in regard to all the psychosocial issues that arise with being diagnosed with colorectal cancer at such a young age,” Eng said. “And I think that in and of itself helps the young adult in regard to their overall prognosis – talking about fertility, depression, coping and insomnia, anxiety. These things are real, and they need to be discussed, and I think people weren't as comfortable before discussing it with the young adults.”

Patients should also listen to their bodies, and communicate with their care teams, whether it be daily issues with sleeping or sexual dysfunction and bowel motility issues – “If anything is on your mind, no question is stupid,” Eng said. She also stressed that many organizations have free counseling services and other resources that a provider can help patients find access to.

The earlier age for CRC screening guidelines is also a good step forward, Eng said, but not the complete answer to the issue. As the authors concluded in the study, there is still need for additional research among diverse populations identifying potential environmental risk factors.

Read more: Additional Efforts Necessary to Implement New Recommended Age Range for Colorectal Cancer Screenings

“When you're diagnosed (with CRC) as a young patient, please ask your doctor to make sure that they've sent off tumor mutation testing on your tumor, because that can help guide your therapy, not necessarily upfront – it could – but also could be very helpful to your oncologist to determine subsequent lines of therapy and how you should be followed up in the future. So I take it for granted that everyone knows that but sometimes I see patients as a second opinion in my clinic, and I find that it's not being done 100% of the time, and it should be done.”

For more news on cancer updates, research and education, don’t forget to subscribe to CURE®’s newsletters here.