Surgical and short-term oncological safety of total neoadjuvant therapy in high-risk locally advanced rectal cancer.

Abstract

Management for locally advanced rectal cancer (LARC) conventionally comprises long-course chemoradiotherapy (LCCRT), total mesorectal excision (TME), and adjuvant chemotherapy. However, the RAPIDO study published in 2021 showed that total neoadjuvant therapy (TNT) led to better oncological outcomes without increased toxicity. We review the surgical and short-term oncological outcomes of patients with high-risk LARC who underwent TNT or LCCRT before TME. Patients with high-risk LARC who underwent TNT or LCCRT before TME between 2021 and 2022 were reviewed. Thirty-five patients (66%) had TNT as per RAPIDO whilst 18 underwent LCCRT. Median follow-up was 16 months (range 5-25). Of the patients who had TNT, median age was 65 years old (range 44-79), 34 (97%) had clinical Stage 3 LARC and median height FAV was 5 cm (range 0.5-14). Nine (26%) required a dose delay/reduction due to treatment toxicity. Seven (50%) showed resolution of previously enlarged lateral nodes. Three (9%) had pathological complete response. Postoperative major morbidity was 23%, of which 4 patients required a reoperation. Six (17%) patients had disease-related treatment failure, with two having disease progression during TNT, two developed local recurrence, and two developed distal metastasis following surgery. Median duration to surgery following completion of chemotherapy was significantly shorter with TNT (36 days versus 74 days) (P < 0.001). There were no other significant differences in outcomes. TNT is clinically safe in high-risk LARC patients with no significant difference to surgical and short-term oncological outcomes compared to LCCRT, although a higher incidence of early surgical morbidity was observed.