Patients younger than 50 years may not derive any overall survival (OS) benefit from the National Comprehensive Cancer Network (NCCN) recommended treatment guidelines for stage II or III rectal cancer, leading study authors to suspect younger patients may have a biologically different disease than older patients, according to a study published in Cancer.

The incidence and survival outcomes of rectal cancer has been improving among patients older than 50 years — most likely due to advancing therapies and screening protocol — but has been on the rise among younger patients.

For this retrospective review, authors accessed the National Cancer Data Base to analyze the outcomes of 43,106 patients who underwent curative-intent transabdominal resections with negative surgical margins for stage I-III rectal cancer. In total, 9126 (21%) of evaluated patients were younger than 50 years. Younger patients were significantly more likely to be female and minorities (African American, Asian, Hispanic), uninsured, and have fewer comorbidities. Younger patients were also significantly more likely to have more advanced disease (stage III, 40% vs 31%) at diagnosis compared with older patients.

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Results showed that patients younger than 50 were more likely to receive radiotherapy compared with older patients regardless of disease stage (contrary to NCCN guidelines for surgical resection alone for stage I disease), and also that chemoradiation, the NCCN guideline-recommended treatment for stage II and III disease, did not lead to any OS benefit.

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Survival analyses demonstrated that younger patients had better short- and long-term outcomes compared with older patients. The 30-day mortality rate was 2.0% compared with 0.2% among older patients and younger patients respectively (P <.001), and the 90-day mortality rate was 3.7% and 0.5%, respectively (P <.001); this difference in survival advantage for younger patients widened at 3, 5, and 10 years. No differences in survival were observed by deciles among patients younger than 50, but after age 50, the prognosis worsened by each decile.

The authors concluded that “this analysis supports the notion that early‐onset rectal cancer may differ in its biology and response to therapy, as has been previously shown in colon cancer. These data may help to stimulate future trial proposals to investigate the possibility of the exclusion or selective use of adjuvant therapies for stage II and III disease in the younger cohort to help to decrease treatment toxicity.”


Kolarich A, George TJ, Hughes SJ, et al. Rectal cancer patients younger than 50 years lack a survival benefit from NCCN guideline-directed treatment for stage II and III disease [published online July 9, 2018]. Cancer. doi: 10.1002/cncr.31527