A total neoadjuvant therapy (TNT) approach could be an alternative to standard chemoradiotherapy (CRT) for patients with locally advanced rectal cancer, according to a phase 3 trial published in the Journal of Clinical Oncology.

TNT, which consisted of short-term radiotherapy (RT) followed by chemotherapy, proved noninferior to standard CRT with regard to disease-free survival (DFS). TNT was also associated with longer overall survival (OS) but a higher incidence of grade 3-4 toxicity.

Researchers compared these 2 regimens in the phase 3 STELLAR trial (ClinicalTrials.gov Identifier: NCT02533271). The trial included 599 patients with locally advanced rectal cancer. Patients were randomly assigned to receive TNT (n=302) or CRT (n=297), and baseline characteristics were well balanced between the arms.

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TNT consisted of short-term RT (25 Gy in 5 fractions over 1 week), followed by 4 cycles of capecitabine plus oxaliplatin (CAPOX). CRT consisted of RT (50 Gy in 25 fractions over 5 weeks) given concurrently with capecitabine.

The full-dose completion rates for preoperative treatment were 74.8% in the TNT arm and 93.2% in the CRT arm (P <.001). The rate of grade 3-4 toxicities was 26.5% and 12.6%, respectively (P <.001). 

Preoperative treatment was followed by total mesorectal excision and 2 additional cycles of CAPOX in the TNT arm or 6 cycles of CAPOX in the CRT arm. The rate of R0 resection was 91.5% in the TNT arm and 87.8% in the CRT arm (P =.189).

The median follow-up was 35 months, and the primary endpoint was 3-year DFS. There was no significant difference in 3-year DFS between the TNT and CRT arms — 64.5% and 62.3%, respectively (hazard ratio [HR], 0.883; P <.001 for noninferiority).

Similarly, there was no significant difference in metastasis-free survival (MFS) or locoregional recurrence (LRR) between the arms. The 3-year MFS rate was 77.1% in the TNT arm and 75.3% in the CRT arm (P =.475). The 3-year LRR rate was 8.4% and 11.0%, respectively (P =.461).

However, the 3-year OS rate was significantly longer in the TNT arm than in the CRT arm — 86.5% and 75.1%, respectively (HR, 0.67; P =.033).

“Short-term radiotherapy with preoperative chemotherapy followed by surgery was efficacious with acceptable toxicity and could be used as an alternative to CRT for locally advanced rectal cancer,” the researchers concluded.

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


Jin J, Tang Y, Hu C, et al. Multicenter, randomized, phase III trial of short-term radiotherapy plus chemotherapy versus long-term chemoradiotherapy in locally advanced rectal cancer (STELLAR). J Clin Oncol. Published online March 9, 2022. doi:10.1200/JCO.21.01667