Colon to Rectum

J Clin Oncol. 2022;40(15):1681–92

Jin J, Tang Y, Hu C, Jiang LM, Jiang J, Li N, Liu WY, Chen SL, Li S, Lu NN, Cai Y, Li YH, Zhu Y, Cheng GH, Zhang HY, Wang X, Zhu SY, Wang J, Li GF, Yang JL, Zhang K, Chi Y, Yang L, Zhou HT, Zhou AP, Zou SM, Fang H, Wang SL, Zhang HZ, Wang XS, Wei LC, Wang WL, Liu SX, Gao YH, Li YX

Multicenter, randomized, phase 3 trial of short-term radiotherapy plus chemotherapy versus long-term chemoradiotherapy in locally advanced rectal cancer (STELLAR)

Purpose: To ascertain if preoperative short-term radiotherapy followed by chemotherapy is not inferior to a standard schedule of long-term chemoradiotherapy (CRT) in patients with locally advanced rectal cancer.
Materials and methods: Patients with distal or middle-third, clinical primary tumor stage 3–4 and/or regional lymph node-positive rectal cancer were randomly assigned (1:1) to short-term radiotherapy (25 Gy in 5 fractions over 1 week) followed by 4 cycles of chemotherapy (total neoadjuvant therapy [TNT]) or CRT (50 Gy in 25 fractions over 5 weeks, concurrently with capecitabine [CRT]). Total mesorectal excision was undertaken 6–8 weeks after preoperative treatment, with 2 additional cycles of CAPOX (intravenous oxaliplatin [130 mg/m², once daily] on day 1 and capecitabine [1000 mg/m², twice daily] from days 1–14) in the TNT group and 6 cycles of CAPOX in the CRT group. The primary end point was 3-year disease-free survival (DFS).
Results: Between August 2015 and August 2018, a total of 599 patients were randomly assigned to receive TNT (n = 302) or CRT (n = 297). At a median follow-up of 35 months, 3-year DFS was 64.5% and 62.3% in TNT and CRT groups, respectively (hazard ratio = 0.883, 1-sided 95% confidence interval, not applicable to 1.11; pnon-inferiority < 0.001). There was no significant difference in metastasis-free survival or locoregional recurrence, but the TNT group had better 3-year overall survival than the CRT group (86.5% vs. 75.1%; p = 0.033). Treatment effects on DFS and overall survival were similar regardless of prognostic factors. The prevalence of acute grade III–V toxicities during preoperative treatment was 26.5% in the TNT group versus 12.6% in the CRT group (p < 0.001).

Conclusion: Short-term radiotherapy with preoperative chemotherapy followed by surgery was efficacious with acceptable toxicity and could be used as an alternative to chemoradiotherapy for locally advanced rectal cancer.

DOI: 10.1200/jco.21.01667