Rx Guidelines Do Not Benefit Younger Rectal Cancer Patients

Pam Harrison

July 11, 2018

Patients younger than 50 years with stage II or III rectal cancer do not appear to benefit from guideline-driven treatment recommendations in terms of overall survival compared with older patients who do benefit from those recommendations, a retrospective view of the National Cancer Data Base (NCDB) indicates.

Lead author Atif Iqbal, MD, University of Florida College of Medicine, Gainesville, and colleagues explain that the "National Comprehensive Cancer Network (NCCN) guidelines define the current standard of care for the intended cure of rectal cancer as surgical resection alone for stage I disease and as neoadjuvant chemoradiation therapy with subsequent surgical resection and systemic chemotherapy for stage II and III disease."

"For stage II and III disease, younger patients are more likely to receive NCCN guideline-driven care...but this does not seem to affect their survival," the researchers add.

"In contrast, older patients show a large and significant survival benefit from it," they add.

The study was published online July 9 in Cancer.

This is a finding that should "open the eyes" of all involved in the treatment of rectal cancer, in view of the "alarming trend" of an increase in diagnoses of colorectal cancer in younger patients, comments the author of an accompanying editorial.

Study Details

Data analyzed for the study included all patients diagnosed with rectal cancer from 2004 through 2014. The final analysis included 5591 rectal cancer patients younger than 50 years and 19,348 rectal cancer patients aged 50 to 75 years.

"The younger cohort had better short-term mortality and long-term survival rates than their older counterparts," the investigators note. The 30-day mortality rate was 2% for older patients vs 0.2% for younger patients; the 90-day mortality rate was 3.7% for older patients vs 0.5% for younger patients (P < .001 for both endpoints).

"This difference became more pronounced with 3-, 5-, and 10-year survival rates...and it persisted independently for stage I, II, and II disease," the investigators add.

Table. Proportion of Patients Surviving, Based on Age (Stage I, II, and III Disease Combined)

  At 3 Years At 5 Years At 7 Years At 10 Years
Age 20-29 years 83.1% 75.5% 72.6% 67.6%
Age 30-39 years 87.7% 81.3% 77.5% 72.3%
Age 40-49 years 88.0% 79.5% 74.5% 68.9%
Age 50-75 years 81.8% 72.3% 64.3% 51.4%


Among older patients with stage II or III disease, the survival benefit for those who received stage-appropriate treatment was 14% at 5 years; that survival benefit persisted to 10 years.

Younger patients with stage I disease gained a survival benefit when treated according to guideline-driven care.

In contrast, guideline-driven care did not confer a survival benefit among younger patients with stage II or III disease, the investigators emphasize.

"Our data suggest that patients younger than 50 years with rectal cancer differ at presentation in comparison with the more aged cohort," the team states.

For example, such patients are more likely to be female, belong to a minority group, and lack insurance.

They are also more likely to present with a higher stage of disease and have worse tumor characteristics compared with older patients.

"This study uses a large national cancer database to demonstrate that patients younger than 50 years diagnosed with rectal cancer represent a unique demographic group in which the survival advantage of receiving NCCN guideline-driven therapy for stage II and III disease does not materialize," the investigators state.

"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," they suggest.

"Time to Take Notice"

In an accompanying editorial, Matthew Kalady, MD, Cleveland Clinic, Ohio, suggests that this study should "open the eyes" of all involved in the treatment of rectal cancer as well as those who make recommendations to help guide therapy and formulate screening policies.

"The alarming trend of increased CRC [colorectal cancer] in the young population should make us stand up and take notice," Kalady writes.

"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," he adds.

The fact that most recommendations for the management of rectal cancer are based on studies of older patients may explain at least part of treatment response observed among younger patients in the current study, Kalady suggests.

But the lack of survival benefit seen in younger patients treated according to NCCN guidelines may also have something to do with limitations inherent in the database that was used in the analysis.

As Kalady points out, "half of all patients with rectal cancer in the NCDB were excluded from the analysis because of missing data; including one-third of the patients without clinical stage information, which is the key determinant in treatment planning," he points out.

Information such as the location of the tumor within the rectum, circumferential margins, lymph node involvement, and the quality of the surgical specimen was also not available, "all of which influence cancer outcomes," Kalady also notes.

The current analysis also does not examine either the risk for local recurrence or disease-free recurrence, both of which are important endpoints in rectal cancer outcomes in addition to overall survival.

"[I]t is our responsibility to continually evaluate our approach to CRC prevention, screening, and treatment," Kalady writes.

"Furthermore, there needs to be a concerted effort not just for the care of patients with rectal cancer (young and old) but also toward understanding the differences in the biology of these tumors, if there are any," he suggests.

"It is time to take notice," Kalady concludes.

The study was supported in part by funds from the National Institutes of Health, the American Cancer Society, the National Cancer Institute, Elekta AB, the National Center for Research Resources, and the National Center for Advancing Translational Sciences. Dr Iqbal has disclosed no relevant financial relationships. Coauthor Thomas J. George Jr, MD, has acted as a consultant for Merck and Bayer for work performed outside of the current study. His institutional research has been supported by Incyte, Bristol-Myers Squibb, Bayer, Merck, NewLink, AstraZeneca/Med-Immune, and Tesaro. Dr Kalady has disclosed no relevant financial relationships.

Cancer. Published online July 9, 2018. Abstract, Editorial

For more from Medscape Oncology, follow us on Twitter: @MedscapeOnc


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as: