Guideline-driven treatment fails to prolong OS among younger patients with rectal cancer

Treatment directed by current National Comprehensive Cancer Network guidelines for rectal cancer did not prolong OS among patients aged younger than 50 years, according to a retrospective review of the National Cancer Database published in Cancer.

“Our findings support the notion that rectal cancer in young patients may be biologically different from older patients, with differing response to treatment, as has been previously shown in colon cancer,” Atif Iqbal, MD, professor of medicine at University of Florida College of Medicine said in a press release. “These findings may help stimulate future research trial proposals focused on the younger patient population.”

Iqbal and colleagues compared survival patterns in different age groups of 43,106 patients with stage I to stage III rectal cancer using 2004 to 2014 data from the National Cancer Database. Researchers compared the differences between patients aged younger than 50 years (n = 9,126; men, 58.5%; white, 85.5%) and those aged older than 50 years (n = 33,980; men, 63.9%; white, 87.9%) by subgroups based on care directed by NCCN guidelines.

Younger patients were more likely to be female (41.5% vs. 36.1%) and of an ethnic or racial minority (14.5% vs. 12.1%) than older patients.

A greater proportion of patients aged younger than 50 years earned $63,000 per year or more (35.4% vs. 30.6%). Further, more patients in this age group were more likely to live in a metropolitan area (83.6% vs. 79.8%) and to be treated at an integrated or academic center (52.6% vs. 46.9%).

Younger patients also appeared more likely to be diagnosed at a later stage (stage III, 40% vs. 31%; P < .001), and to have signet ring cell lesions (1.2% vs. 0.5%), as well as poorly differentiated lesions (13% vs. 11.3%).

Younger patients appeared more likely to receive radiation therapy than older patients for all disease stages including radiation therapy for stage 1 disease (41.9% vs. 31.7%; P < .001) and chemoradiation for stage II and III disease (93.6% vs 88.1%; P < .001).

“Thus, fewer patients in the younger cohort received NCCN guideline-directed therapy for stage I disease, but a greater percentage received it for stage II and III disease,” the researchers wrote.

Older patients had worse outcomes for both the 30-day mortality rate (2% vs. 0.2%; P < .001) and the 90-day mortality rate (3.7% vs 0.5%; P < .001). This difference became more pronounced at 3, 5 and 10 years.

Researchers then evaluated survival by age and receipt of NCCN guideline-driven care.

Survival improved among older adults with stage II and stage III disease who receive guideline-driven care, as demonstrated by an 11% survival benefit in 10-year OS.

However, NCCN guideline-driven care resulted in “significantly reduced survival” among patients aged younger than 45 years who had stage II to stage III disease (P < .03). Further, guideline-driven care did not provide any survival benefit until age 50 years or older. This benefit did not become statistically significant until patients were aged older than 54 years.

“This article should open the eyes of physicians treating rectal cancer and of those making treatment guideline recommendations and screening policies,” Matthew F. Kalady, MD, vice chairman in the department of colorectal surgery at Cleveland Clinic, wrote in an accompanying editorial. “The alarming trend of increased colorectal cancer in the young population should make us stand up and take notice. We need to evaluate why this is happening and explore the unique characteristics that define this population and potential differences in comparison with older age rectal cancers.” – by Andy Polhamus

Disclosures: Iqbal reports no relevant financial disclosures. One author reports consulting roles with Bayer and Merck, as well as support to his institution from Astra Zeneca/Med-Immune, Bayer, Bristol-Myers Squibb, Incyte, NewLink and Tesaro. Kalady reports no relevant financial disclosures.