Meta-analysis of the effect of extending the interval after long-course chemoradiotherapy before surgery in locally advanced rectal cancer

Abstract

Background The current standard of care in locally advanced rectal cancer (LARC) is neoadjuvant long‐course chemoradiotherapy (nCRT) followed by total mesorectal excision (TME). Surgery is conventionally performed approximately 6–8 weeks after nCRT. This study aimed to determine the effect on outcomes of extending this interval. Methods A systematic search was performed for studies reporting oncological results that compared the classical interval (less than 8 weeks) from the end of nCRT to TME with a minimum 8‐week interval in patients with LARC. The primary endpoint was the rate of pathological complete response (pCR). Secondary endpoints were recurrence‐free survival, local recurrence and distant metastasis rates, R0 resection rates, completeness of TME, margin positivity, sphincter preservation, stoma formation, anastomotic leak and other complications. A meta‐analysis was performed using the Mantel–Haenszel method. Results Twenty‐six publications, including four RCTs, with 25 445 patients were identified. A minimum 8‐week interval was associated with increased odds of pCR (odds ratio (OR) 1·41, 95 per cent c.i. 1·30 to 1·52; P < 0·001) and tumour downstaging (OR 1·18, 1·05 to 1·32; P = 0·004). R0 resection rates, TME completeness, lymph node yield, sphincter preservation, stoma formation and complication rates were similar between the two groups. The increased rate of pCR translated to reduced distant metastasis (OR 0·71, 0·54 to 0·93; P = 0·01) and overall recurrence (OR 0·76, 0·58 to 0·98; P = 0·04), but not local recurrence (OR 0·83, 0·49 to 1·42; P = 0·50). Conclusion A minimum 8‐week interval from the end of nCRT to TME increases pCR and downstaging rates, and improves recurrence‐free survival without compromising surgical morbidity.

Population-based study of morbidity risk associated with pathological complete response after chemoradiotherapy for rectal cancer

“…Increasing the interval between nCRT and TME to a minimum of 8 weeks appears to increase pCR and downstaging rates, and improve disease‐free survival. It is unclear whether an increased interval leads to more tissue reaction and consequently complications.…”

Author response to: Comment on: Meta-analysis of the effect of extending the interval after long-course chemoradiotherapy before surgery in locally advanced rectal cancer

“…We would like to thank Hajibandeh and Hajibandeh for their close reading of our recent publication and commend them for drawing attention to the particularly important topic of the handling of survival outcome data in meta‐analysis.…”

Comment on: Meta-analysis of the effect of extending the interval after long-course chemoradiotherapy before surgery in locally advanced rectal cancer

“…We read with great interest the meta‐analysis by Ryan et al . which evaluated comparative outcomes for an interval of less than 8 weeks from the end of neoadjuvant long‐course chemoradiotherapy to total mesorectal excision and an interval of more than 8 weeks in patients with locally advanced rectal cancer.…”

“…Despite being a comprehensive meta‐analysis with robust methodological quality, there is an error in the analysis of recurrence‐free survival (RFS) which has led Ryan et al . to interpret the results incorrectly, and to make incorrect subsequent conclusions.…”