Locoregional and systemic control after total neoadjuvant therapy with short-course radiotherapy for locally advanced...

Total neoadjuvant treatment (TNT) results in more complete responses 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.

Between July 2016 and June 2020, LARC patients with at least one high-risk criterion for recurrence according to staging MRI (cT4, cN2, mesorectal fascia involvement <1 mm, extramural vascular involvement, lateral node involvement) received TNT consisting of 5 × 5 Gy followed by four cycles of CAPOX/six cycles of FOLFOX.

Curatively treated patients (437 of 462) were analysed after a median of 6.5 (interquartile range 5.9-7.2) years of follow-up. cT4 was seen in 53.5%. Sixty-two patients with a cCR entered a watch-and-wait programme (21 patients with regrowth) and 375 patients underwent primary surgery. At 5 years, of the 437 patients, locoregional recurrence (LRR) occurred in 26 patients (5.9% (95% c.i. 3.7% to 8.2%)) and DM occurred in 108 patients (24.7% (95% c.i. 20.7% to 28.7%)). The distal resection margin was ≤10 mm in 8.3% of patients after a sphincter-saving procedure (a lower percentage than in RAPIDO). The 109 patients (24.9%) with a complete response (48 patients with a cCR sustained for >1 year after the start of radiotherapy and 61 patients with a pCR) had excellent outcomes (0% with LRR and 3.7% with DM).

TNT consisting of 5 × 5 Gy followed by four cycles of CAPOX/six cycles of FOLFOX resulted in 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 distal resection margins practiced at Swedish centres.