Effect of Interval between Neoadjuvant Chemoradiotherapy and Surgery on Oncological Outcome for Rectal Cancer: A Systematic Review and Meta-Analysis

Abstract

Aim. To evaluate the influence of interval between neoadjuvant chemoradiotherapy (NCRT) and surgery on oncological outcome. Methods. A systematic search was conducted in PubMed, the Cochrane Library, and Embase databases for publications reporting oncological outcomes of patients following rectal cancer surgery performed at different NCRT-surgery intervals. Relative risk (RR) of pathological complete response (pCR) among different intervals was pooled. Results. Fifteen retrospective cohort studies representing 4431 patients met the inclusion criteria. There was a significantly increased rate of pCR in patients treated with surgery followed 7 or 8 weeks later (RR, 1.45; 95% CI, 1.18–1.78; and P < 0.01 and RR, 1.49; 95% CI, 1.15–1.92; and P = 0.002, resp.). There is no consistent evidence of improved local control or overall survival with longer or shorter intervals. Conclusion. Performing surgery 7-8 weeks after the end of NCRT results in the highest chance of achieving pCR. For candidates of abdominoperineal resection before NCRT, these data support implementation of prolonging the interval after NCRT to optimize the chances of pCR and perhaps add to the possibility of ultimate organ preservation.

Prognostic value of tumour regression grade in locally advanced rectal cancer: a systematic review and meta‐analysis

“…One of the confounding factors that will affect the rectal tumour response rate is the waiting time from cessation of neoadjuvant CRT to surgery. Supporting evidence was reported in two recent meta‐analyses, in which a longer interval of time to surgery (ideally 6–8 weeks) resulted in higher pCR rates compared with those who had surgery at 4–6 weeks with no added response rate beyond 9 weeks . This is not an issue in the current study as the majority reported interval times of 6–8 weeks after neoadjuvant CRT, with the exception of four studies, which reported minimum time to surgery of 4 weeks .…”

Pathological complete response due to a prolonged time interval between preoperative chemoradiation and surgery in locally advanced rectal cancer: analysis from the German StuDoQ|Rectalcarcinoma registry

“…Previous retrospective analysis due to the time interval of chemoradiation and surgery of rectal cancer have been made. All of them gained evidence for an increased rate of pCR by prolonging the time interval between neoadjuvant treatment and surgery without affecting perioperative morbidity [8][9][10][22][23][24][25]. These studies analyzed patients from the United States, the Netherlands or Belgium, whereas the number of patients was partly low (e.g.…”

“…The German guidelines for colorectal cancer recommend the oncological resection 6 to 8 weeks after completed preoperative chemoradiotherapy [7]. Recent studies have shown that a prolonged interval leads to higher rates of pathological complete response (pCR) and that this my even take longer than 16 weeks [8][9][10][11]. In addition, it was shown, that additional inclusion of chemotherapy cycles in the interval between radiochemotherapy and surgery enhance complete response rate without affecting surgical morbidity [12].…”

Road to organ preservation in locally advanced rectal cancer

“…The highest pCR rates were recorded in patients operated on beyond eight weeks after the end of chemoradiotherapy, which was associated with an approximately 49% higher chance for pCR compared to patients who were operated on earlier. Prolonging the interval beyond 10 or 12 weeks did not offer further advantages and also didn't affect survival or rate of sphincter spearing procedures [20].…”

“…According to their results, pCR improved by 5.8% when the interval to surgery was longer than six to eight weeks, without compromising OS and DFS and with similar complication rates and sphincter preservation. A systematic review and meta-analysis by Wang et al [20] included 15 retrospective studies with 4,431 patients and pCR ranging from 8.3% to 28%. The highest pCR rates were recorded in patients operated on beyond eight weeks after the end of chemoradiotherapy, which was associated with an approximately 49% higher chance for pCR compared to patients who were operated on earlier.…”