Abstract 421P
Background
Preoperative chemoradiotherapy (preCRT) followed by total mesorectal excision is a standard treatment for locally advanced rectal cancer (LARC). However, preCRT shows a negative impact on anal function by intersphincteric resection (ISR) for low-lying rectal cancer. This study examined the efficacy and safety of neo-adjuvant chemotherapy (NAC) in patients (pts) with very low lying T3 stage LARC without preCRT.
Methods
Pts with tumors located within 5 cm from the anal verge were randomly assigned (1:1) to either NAC (NAC arm: pre-operative chemotherapy with 6 cycles of mFOLFOX6 or 4 cycles of CAPOX followed by ISR; then, post-operative identical regimen) or upfront surgery with ISR followed by post-operative chemotherapy (ISR arm: 12 cycles of mFOLFOX6 or 8 cycles of CAPOX). The primary endpoint was 3-year recurrence-free survival. Here, we report on short-term efficacy and safety results in the phase III part.
Results
One hundred thirty pts were enrolled from 2013 to 2019, and 127 pts were evaluable (NAC, n=65; ISR, n=62). Baseline characteristics were well-balanced between arms. All but one pt with early progression, completed pre-operative chemotherapy in the NAC arm, and all tumors in both arms were resected completely; in the NAC arm, all pts underwent anal preserving surgery (APS). In the ISR arm, 89% (55/62) of pts underwent APS; the remaining 11% (7/62) underwent abdominal perineal resection (anal preservation rate, p<0.01). There were no differences in ≥grade 3 post-operative complications between arms (20% NAC vs. 21% ISR [p=1.00]) or in chemo-associated ≥grade 3 adverse events (AEs) (28% NAC vs. 23% ISR [p=0.55]). Significant differences were observed in the occurrence of pathological T3/T4 tumors (48% NAC vs. 73% ISR, p<0.01) and pathological positive lymph nodes (26% NAC vs. 55% ISR, p<0.01). In the NAC arm, circumferential resection margin (CRM) positive rate (≤1 mm) was significantly lower (9%) than that in the ISR arm (26%, p=0.02).
Conclusions
For very low lying LARC, NAC achieved significant down-staging with lower CRM positive rate compared to upfront surgery, without increasing post-operative complications or chemotherapy-associated AEs.
Clinical trial identification
UMIN000009510 (release date: 20/12/2012).
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
The National Cancer Center Research and Development Fund (23-A-26).
Disclosure
H. Bando: Honoraria (self): Taiho pharmaceutical; Honoraria (self): Eli Lilly Japan. T. Yoshino: Research grant/Funding (institution): Novartis Pharma K.K; Research grant/Funding (institution): MSD.K.K.; Research grant/Funding (institution): Sumitomo Dainippon Pharma Co., Ltd.; Research grant/Funding (institution): Chugai Pharmaceutical Co., Ltd.; Research grant/Funding (institution): Sanofi K.K.; Research grant/Funding (institution): Daiichi Sankyo Company, Limited; Research grant/Funding (institution): Parexel International Inc.; Research grant/Funding (institution): Ono Pharmaceutical Co., Ltd.; Research grant/Funding (institution): GlaxoSmithKline K.K.. All other authors have declared no conflicts of interest.