Comparing early surgical outcomes between total neoadjuvant therapy and standard long course chemoradiotherapy for rectal cancer

Abstract

BACKGROUND

Total neoadjuvant therapy (TNT) has been proposed as an advancement over standard long-course chemoradiotherapy (LCCRT) for the treatment of locally advanced rectal cancer (LARC). It has been suggested that TNT enhances resectability, improves treatment compliance, increases the rate of pathological complete response, and reduces the risk of systemic recurrence. However, concerns have been raised that the prolonged interval to surgery associated with TNT, particularly in regimens such as the Rectal Cancer and Preoperative Induction Therapy Followed by Dedicated Operation (RAPIDO) protocol, may exacerbate fibrosis, leading to more technically challenging resections and poorer surgical outcomes.

AIM

To compare the early surgical outcomes of LARC patients treated with TNT-RAPIDO vs LCCRT.

METHODS

A single-center, retrospective cohort study was conducted of patients with LARC treated with TNT-RAPIDO or standard LCCRT followed by surgical resection between 2014 and 2024. A total of 99 patients with LARC were analyzed, including 29 treated with TNT-RAPIDO and 70 treated with standard LCCRT. Demographics, clinicopathological characteristics and early post-operative outcomes were compared between both groups.

RESULTS

Both groups were comparable in terms of demographics and clinicopathological characteristics. The median interval from initiation of neoadjuvant therapy to surgery was significantly longer in the TNT group compared to the LCCRT group (29.5 weeks vs 19.5 weeks, P < 0.001). Operative time and intraoperative complications were comparable. While the TNT group had a significantly higher lymph node harvest (40.7 vs 23.4, P < 0.001), the number of positive nodes was not significantly different. R0 resection rates were similar (93.1% vs 90%, P = 0.625). There was no difference in post-operative morbidity and 30-day mortality between both groups. The TNT group had a significantly shorter total stoma duration (27.1 weeks vs 42.5 weeks, P = 0.013) and a lower rate of permanent stoma formation (13.8% vs 35.7%, P = 0.013).

CONCLUSION

Compared with LCCRT, TNT-RAPIDO does not compromise operative time, complication rates, or oncological quality of resection and may confer a shorter total stoma duration and a lower permanent stoma rate.

Keywords: Locally advanced rectal cancer; Total neoadjuvant therapy; Rectal cancer and preoperative induction therapy followed by dedicated operation; Long course chemoradiotherapy; Early surgical outcomes; Retrospective cohort study

Core Tip: Rectal cancer and preoperative induction therapy followed by dedicated operation has emerged as a total neoadjuvant therapy strategy with improved oncological and functional outcomes. The impact of total neoadjuvant therapy on operative difficulty and short-term surgical outcomes, compared with long-course chemoradiotherapy, remains an area of ongoing debate. This cohort study of 99 patients demonstrated that the Rectal Cancer and Preoperative Induction Therapy Followed by Dedicated Operation (RAPIDO) protocol does not increase surgical difficulty or compromise early surgical outcomes compared with long-course chemoradiotherapy. It may also confer a shorter total stoma duration and a lower permanent stoma rate.