Pre-operative short-course radiotherapy (RT) followed by chemotherapy should be the new standard of care for treating locally advanced rectal cancer, according to investigators who presented results of the phase 3 RAPIDO trial at the virtual 2020 ASCO Annual Meeting.

“Local control in locally advanced rectal cancer has improved. However, systemic relapses remain high even with postoperative chemotherapy, possibly due to low compliance,” wrote lead researcher Geke Hospers, MD, University Medical Center Groningen, The Netherlands, and colleagues.

The objective of the RAPIDO trial was to determine whether short-course RT followed by delayed surgery, and with chemotherapy administered in the waiting period, would lead to better compliance, downstaging, and fewer distant metastases.

A total of 920 patients with locally advanced rectal cancer were enrolled in the study and randomized to the experimental or standard arms between June 2011 and June 2016. The experimental arm consisted of short-course RT 5x5 Gy followed by 6 cycles of CAPOX or 9 cycles of FOLFOX4 followed by total mesorectal excision (TME). Standard therapy was comprised of capecitabine-based chemoradiotherapy (25-28 x 2.0-1.8 Gy) followed by TME.

The main end point of the study was a decrease in disease-related treatment failure via a reduced risk for systemic relapse.

The median follow-up time frame was 4.5 years. At 3 years, the cumulative probability of disease-related treatment failure was 23.7% in the experimental arm versus 30.4% in the standard treatment arm. This was attributed to a lower rate of distant metastases in the experimental versus standard treatment arm.

Data presented during the virtual ASCO meeting also showed that the 3-year overall survival rate was 89%, with no differences in overall health, quality-of-life, or endo-rectal functioning LARS score in the experimental arm.

Dr Hospers et al found that presurgery short-course RT followed by chemotherapy and before TME achieved a lower rate of disease-related treatment failure than conventional chemoradiotherapy. In addition, they observed that the experimental treatment arm had a pathologic complete response rate double that of the standard arm that contributed to organ preservation.

“This treatment can be considered as a new standard of care,” Dr Hospers and colleagues concluded.—Kaitlyn Manasterski

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.