Trials Confirm Preoperative Chemo-Radiation Improves Outcomes for Rectal Cancer

Cancer Connect

by Dr. C.H. Weaver M.D. updated 6/2020

Results from a large multi-institutional clinical trial continue to provide confirmatory evidence that treatment with pre-operative radiation significantly decreases local cancer recurrences in patients with rectal cancer that has not spread to distant sites and should be considered the standard of care for this disease.

The rectum comprises approximately the last 10 inches of the colon, or large intestine. Patients with rectal cancer that has not spread to distant sites in the body may be cured through the complete surgical removal (resection) of their cancer. Recently, results from previous clinical trials have demonstrated that radiation prior to surgery decreases cancer recurrences compared to treatment with surgery alone in rectal cancer. A decrease in cancer recurrences often correlates to improved long-term survival.

The concept behind the use of pre-operative radiation is to shrink cancer and kill undetectable cancer cells that may exist directly outside the site of cancer origin. Current detection methods are not able to find or measure small amounts of cancer cells that exist, therefore increasing the chance that they may be left behind following surgery. These cancer cells are responsible for cancer recurrences. In theory, through shrinking the site of cancer and killing nearby cancer cells, more complete surgical removal of the cancer may be obtained, resulting in fewer recurrences and improving chances for a cure.

According to the results of the phase 3 RAPIDO clinical trial released at the 2020 American Society of Clinical Oncology Annual Meeting pre-operative short-course radiation therapy (RT) followed by chemotherapy should be the new standard of care for treating locally advanced rectal cancer,

The objective of the RAPIDO clinical trial was to determine whether a short - course of RT followed by delayed surgery, and chemotherapy administered in the waiting period, would lead to better treatment outcomes

A total of 920 patients with locally advanced rectal cancer were enrolled in the study and treated between June 2011 and June 2016. One group of patients received short-course RT followed by 6 cycles of CAPOX or 9 cycles of FOLFOX4 chemotherapy followed by surgical removal of the cancer and this was compared to “standard” therapy consisting of capecitabine-based chemo-radiotherapy and surgery.

Patients participating in this trial have now been followed in excess of 4.5 years and the 3 years probability of disease-related treatment failure is 23.7% in the short course RT group compared to 30.4% in the standard treatment group. The improved outcomes were attributed to a lower rate of distant cancer spread and this resulted in a 3-year overall survival rate of 89% for those treated with the pre-surgery short-course RT followed by chemotherapy before surgery. (2)

This trial supports the results from previous multi-institutional clinical trials that compared neoadjuvant treatment with pre-operative radiation plus surgery to surgery alone in patients with rectal cancer that had not spread to distant sites. In an earlier pivotal trial local cancer recurrences had occurred in only 2.4% of patients treated with pre-opereative radiation plus surgery compared to 8.2% of patients treated with surgery alone.

A strategy that utilizes preoperative radiation and chemotherapy reduces the risk of local cancer recurrences in patients with rectal cancer that has not spread to distant sites.

References

  1. Hospers G, Bahadoer R,Dijkstra E, et al. Short-course radiotherapy followed by chemotherapy before TME in locally advanced rectal cancer: The randomized RAPIDO trial. Presented at: the 2020 ASCO Annual Meeting; May 29-31, 2020. Abstract 4006.
  2. New England Journal of Medicine, Vol 345, No. 9, pp 638-646, 2001
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