Age-Differentiated Responses to Rectal Cancer Treatment

The rate of rectal cancer is dropping in people over 50 years old while increasing in those under 50. We now know that potential biological differences in tumors exist in young patients compared with older patients. Other differences include a higher proportion of younger patients who are minority, female, on Medicaid, diagnosed at a later stage in the disease, and residing in an urban setting that is not near the medical facility where they were diagnosed.

Given the differences in the cancers themselves and the patient profiles, one might suspect that treatment therapies are not equally effective for the two age groups. Yet national treatment guidelines remain the same for all ages. In a recent study published in Cancer, Kolarich et al analyzed data from the National Cancer Database and found that treatment recommended by National Comprehensive Cancer Network (NCCN) for stage II and stage III cancer has a much lower rate of effectiveness in the under-50 population than in the over-50 population. Further, the effectiveness rate does not differ with how old these under-50 patients are.

In this 10-year retrospective review, some patients had been treated according to NCCN guidelines, which call for surgical resection alone for stage I disease, and for stage II and III, neoadjuvant chemoradiation (nCRT) followed by total mesorectal excision and then adjuvant chemotherapy. Others had not. The largest finding was that patients over 50 responded to their treatment (whether per NCCN guidelines or not) with a survival advantage, while those under 50 did not see this survival benefit.

Thoughts from a national leader

Cleveland Clinic colorectal surgeon Matthew Kalady, MD, who played an instrumental role in the development of the National Accreditation Program for Rectal Cancer, commented on the implications of this analysis in an editorial response submitted to Cancer. “I applaud the continuing conversation about growing number of young patients with rectal cancer,” says Dr. Kalady, Co-Director of Cleveland Clinic’s Comprehensive Colorectal Cancer Program. He cautions, however, that the study has significant limitations related to inclusion criteria, and does not segregate and analyze key variables such as tumor location and characteristics or data on local recurrence and disease-free recurrence, all critical to drawing conclusions. He calls for more research to connect the dots and inform treatment protocols for younger patients.

While the number of patients excluded for various reasons was significant (about 82 percent, leaving 43,106), Dr. Kalady finds value in the study. “I think the big takeaway is that it is true that younger patient populations clearly are not as well studied, but from what we see, perhaps these patients should be treated differently. Large clinical trials focusing on young patients with rectal cancer are not available, and any data that contribute to an improved understanding are encouraged.”

The overuse of nCRT

The Kolarich study also reveals the prevailing use of nCRT in stage I patients (excluded from the study due to the break from NCCN protocol), despite no evidence that it improves survival over surgery alone (41.9 percent of younger patients and 31.7 percent of older patients). Pelvic radiation can lead to severe side effects including radiation proctitis, decreased bowel function and decreased quality of life.

“These are necessary evils in advanced-stage cases for which there is treatment benefit, but not for stage I patients, and especially not for young patients,” Dr. Kalady explains. “Thus, nearly 1 of every 3 patients with stage I rectal cancer in the United States is receiving toxic therapy that is not beneficial.”

While awaiting sufficient evidence to inform guideline revisions, Kalady says that we need to be aggressive with the revised screening protocols. “Today, patients under 50 represent 21 percent of all rectal cancer victims, yet most are younger than the recommended screening age for colorectal cancer screening. It is becoming increasingly vital that we not only study the disparate treatment outcomes that flow from the current treatment guidelines, but also acknowledge the vast advantages to be gained from screening young people who have family histories or other high risk factors.”

A flexible sigmoidoscopy offers this screening option at a lower cost than colonoscopy, while retaining a fairly high detection rate. Dr. Kalady urges reform. “For the general population under 45 it remains challenging to recommend screening guidelines because the overall cancer rate is low. But for those at high risk, this is a cost-effective tool we have, with evidence to support its efficacy in prevention and early treatment.”