Preoperative short-course radiotherapy (RT) followed by chemotherapy can decrease distant metastasis in patients with high-risk, locally advanced rectal cancer (LARC), according to research published in the European Journal of Cancer.

Researchers evaluated data from the RAPIDO trial and found that short-course RT plus chemotherapy can decrease distant metastasis, particularly liver metastasis, when compared with standard long-course chemo-RT.

The RAPIDO trial ( Identifier: NCT01558921) included 920 patients with LARC who had at least 1 high-risk criterion. The patients were randomly assigned to short-course RT followed by chemotherapy prior to surgery (n=462) or to long-course chemo-RT with optional postoperative chemotherapy (n=450).  

Continue Reading

Short-course RT (5 Gy in 5 fractions) was followed by 6 cycles of capecitabine plus oxaliplatin (CAPOX) or 9 cycles of folinic acid, fluorouracil, and oxaliplatin (FOLFOX4) and surgery after a recovery period of 2 to 4 weeks. 

Long-course RT (1.8-2.0 Gy in 28-25 fractions) was given concurrently with capecitabine and followed by surgery after roughly 8 weeks. Patients in this arm could also receive postoperative chemotherapy.

The median follow-up was 5.6 years. At 5 years, the cumulative probability of distant metastasis was 23% in the short-course arm and 30% in the standard arm (hazard ratio [HR], 0.72; 95% CI, 0.56-0.93; P =.011). 

The researchers noted that postoperative chemotherapy in the standard care arm did not influence the development of distant metastasis. The median time from randomization to distant metastasis was 1.4 years in the short-course arm and 1.3 years in the standard arm. 

Distant metastasis at 1 organ site occurred in 73% of patients in the short-course arm and 78% in the standard arm. Distant metastasis at 2 sites occurred in 22% and 17%, respectively. Five percent of patients in each arm had distant metastasis at 3 to 6 sites.

The incidence of liver metastasis was 9% in the short-course arm and 15% in the standard arm (P =.002). Lung metastases occurred in 13% and 12% of patients, respectively (P =.73). 

From the diagnosis of distant metastasis, the median overall survival was 2.6 years in the short-course arm and 3.2 years in the standard arm (HR, 1.39; 95% CI, 1.01-1.92; P =.04). 

Among all eligible patients, the 5-year overall survival rate was 82% in the short-course arm and 80% in the standard arm (HR, 0.91; 95% CI, 0.70-1.19; P =.50).

“To our knowledge, this study is the first to compare the first metastatic organ-site in LARC while comparing TNT [total neoadjuvant therapy] to conventional chemoradiotherapy, and to report a changed metastatic pattern with the different treatment regimens,” the researchers wrote. “Further research is needed to predict clinical response, eg, via biomarkers, and to define the optimal selection criteria for total neoadjuvant treatment.”

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Bahadoer RR, Hospers GAP, Mairjnen CAM, et al. Risk and location of distant metastases in patients with locally advanced rectal cancer after total neoadjuvant treatment or chemoradiotherapy in the RAPIDO trial. Eur J Cancer. Published online March 7, 2023.   doi:10.1016/j.ejca.2023.02.027

This article originally appeared on Cancer Therapy Advisor