Evaluating the use of radiotherapy followed by chemotherapy before surgery for locally-advanced rectal cancer.

This trial looked at the use of short-course radiotherapy (RT) followed by chemotherapy (CT) and delayed surgery to reduce distant metastases (tumor spread) in patients with locally advanced rectal cancer (LARC). The trial found that this treatment was more effective in controlling distant metastases when compared to standard chemoradiotherapy (CRT) followed by surgery and adjuvant CT (chemotherapy after surgery). 

Standard care for rectal cancer (cancer that begins in the rectum) consists of RT and CT at the same time (CRT) followed by surgery 6-8-weeks later. CT after surgery is also included in several countries in the standard care of rectal cancer. CT after surgery aims to reduce the chance of cancer returning.

Previous studies have shown that surgery can be delayed in order to deliver a short course of RT followed by a course of CT before surgery. However, the risk of metastasis and treatment failure when using RT and CT before delaying surgery compared to standard of care in patients with LARC remains under investigation. 

There were 912 patients with LARC enrolled in this trial. 462 patients 5 RT doses over 8 days, followed by 6-9 cycles of CT, followed by surgery after 2-4 weeks (group 1). 450 patients received standard RT and CT at the same time followed by surgery 6-10 weeks after the last RT dose (group 2). Group 2 also had the option of receiving CT after surgery. The average follow-up of this trial was 4.6 years.

After 3-years the risk of treatment failure was 23.7% in group 1 compared to 30.4% in group 2. The risk of treatment failure was 25% lower in group 1 compared to group 2. The probability of having distant metastases after 3 years was 20% in group 1 compared to 26.8% in group 2. The risk of developing distant metastases was 31% lower in group 1 compared to group 2. 

The chance of having all the tumor removed during surgery was 2.37 times higher in group 1 compared to group 2.

Patients in group 1 had a higher rate of side effects. Serious side effects occurred in 38% of group 1 compared to 34% of group 2. The most common side effect that occurred was diarrhoea. 

The authors found that in patients with LARC, short-curse RT followed by CT before surgery decreased the risk of treatment-failure and metastasis when compared to standard treatment.

Baseline imaging was not reported. This potentially could have led to errors in cancer staging. This has importance in monitoring the spread of tumors.