Locoregional control following TNT using short-course radiotherapy in rectal cancer: long-term results from the Swedish LARCT-US study

Abstract Introduction The Swedish prospective cohort trial LARCT-US previously reported a complete response rate of 24% and a locoregional recurrence (LRR) rate of 6% after R0/1 surgery following total neoadjuvant therapy (TNT) with an abbreviated RAPIDO schedule. This report aims to assess LRR with median follow-up >5 years. Method LARCT-US prospectively recorded 462 patients with locally advanced rectal cancer between 2016 and 2020. Inclusion criteria were cT4, cN2, MRF+, EMVI+ and/or enlarged lateral lymph nodes on MRI. Treatment consisted of 5Gy x5 followed by 4 cycles of CAPOX/6 cycles of FOLFOX. Patients with a clinical complete response could enter a watch-and-wait programme (W&W), otherwise surgery was performed. Result Overall, 56% patients were cT4 and 77% MRF+. Among the 462 recorded patients 25 (5%) developed early failure (i.e. non-resected, R2, and/or distant metastases) leaving 437 treated with curative intent. Some 62 patients (14%) entered W&W and 375 were operated (R0=92% and R1=8%). With a median follow-up of 5.8 years (4.5-8.5) the overall LRR rate was 6% (25/437). Distant metastases were detected in 107 (24%) patients. In operated patients with ypCR (n=61) no LRR was detected. Among patients entering W&W, regrowth within 1 year occurred in 14 patients, and additionally 7 during follow-up. After surgery for regrowth no LRR were detected in W&W patients. Discussion In contrast to results reported from the RAPIDO trial regarding LRR, the results from this nationwide cohort including even more advanced tumours indicate that TNT using 5Gy x5 not only yields favourable outcomes systemically but also provides excellent locoregional control.