Locoregional and systemic control following total neoadjuvant therapy with short-course radiotherapy for locally advanced rectal cancer: long-term outcomes from the LARCT-US study

Introduction Total neoadjuvant treatment (TNT) results in more complete responses (CR) and less risk of distant metastasis (DM) compared with chemoradiotherapy in locally advanced rectal cancer (LARC). The best schedule and the most suitable patients are unknown. In Sweden, after the closure of the RAPIDO trial all hospitals in five out of six healthcare regions treated LARC patients with an abbreviated RAPIDO schedule, LARCT-US. Long-term data are reported. Methods Between July 2016 and June 2020, LARC patients with risk criteria for recurrence (cT4, cN2, MRF+, EMVI+, LN+) received TNT consisting of 5x5 Gy followed by 4 cycles of CAPOX/6 cycles of FOLFOX. Results Curatively treated patients (n=437 of 462 recorded) were analysed after median 6.5 years (IQR 5.9-7.2) follow-up. cT4 was seen in 54%. Sixty-two patients with a clinical CR (cCR) entered a watch-and-wait programme (21 patients with regrowth) and 375 patients had surgery. Of the 437 patients, locoregional recurrences (LRR) at 5 years occurred in 26 (6%, 95%CI 3.7-8.2) patients and DM in 108 (25%, 95%CI 20.7-28.7). The distal resection margin (DRM) was ≤10 mm in 8% after a sphincter-saving procedure, less than in RAPIDO. Among 109 patients (25%) with a CR (sustained cCR ≥1 year n=48, pathological CR n=61) showed excellent outcome with no LRR and few (13%) DM. Conclusion TNT with 5x5 Gy and 4 CAPOX/6 FOLFOX cycles yield excellent locoregional and distant control, despite inclusion of more advanced tumours than previous TNT studies. The low LRR risk in LARCT-US, could be explained by more adequate DRMs practiced at Swedish centres.