Background: Anastomotic leakage is a major complication of rectal cancer surgery. The aim of this study was to investigate risk factors associated with symptomatic anastomotic leakage after total mesorectal excision (TME). Methods: Between 1996 and 1999, patients with operable rectal cancer were randomized to receive short-term radiotherapy followed by TME or to undergo TME alone. Eligible Dutch patients who underwent an anterior resection (924 patients) were studied retrospectively. Results: Symptomatic anastomotic leakage occurred in 107 patients (11·6 per cent). Pelvic drainage and the use of a defunctioning stoma were significantly associated with a lower anastomotic failure rate. A significant correlation between the absence of a stoma and anastomotic dehiscence was observed in both men and women, for both distal and proximal rectal tumours. In patients with anastomotic failure, the presence of pelvic drains and a covering stoma were both related to a lower requirement for surgical reintervention. Conclusion: Placement of one or more pelvic drains after TME may limit the consequences of anastomotic failure. The clinical decision to construct a defunctioning stoma is supported by this study.

Objective: To analyze risk and patterns of locoregional failure (LRF) in patients of the RAPIDO trial at 5 years. Background: Multimodality treatment improves local control in rectal cancer. Total neoadjuvant treatment (TNT) aims to improve systemic control while local control is maintained. At 3 years, LRF rate was comparable between TNT and chemoradiotherapy in the RAPIDO trial. Methods: A total of 920 patients were randomized between an experimental (EXP, short-course radiotherapy, chemotherapy, and surgery) and a standard-care group (STD, chemoradiotherapy, surgery, and optional postoperative chemotherapy). LRFs, including early LRF (no resection except for organ preservation/R2 resection) and locoregional recurrence (LRR) after an R0/R1 resection, were analyzed. Results: Totally, 460 EXP and 446 STD patients were eligible. At 5.6 years (median follow-up), LRF was detected in 54/460 (12%) and 36/446 (8%) patients in the EXP and STD groups, respectively (P=0.07), in which EXP patients were more often treated with 3-dimensional-conformed radiotherapy (P=0.029). In the EXP group, LRR was detected more often [44/431 (10%) vs. 26/428 (6%); P=0.027], with more often a breached mesorectum (9/44 (21%) vs. 1/26 (4); P=0.048). The EXP treatment, enlarged lateral lymph nodes, positive circumferential resection margin, tumor deposits, and node positivity at pathology were the significant predictors for developing LRR. Location of the LRRs was similar between groups. Overall survival after LRF was comparable [hazard ratio: 0.76 (95% CI, 0.46–1.26); P=0.29]. Conclusions: The EXP treatment was associated with an increased risk of LRR, whereas the reduction in disease-related treatment failure and distant metastases remained after 5 years. Further refinement of the TNT in rectal cancer is mandated.

Background: Neoadjuvant chemotherapy for early breast cancer can avoid mastectomy by shrinkage of tumour volume. This review assesses the effectiveness of neoadjuvant chemotherapy on clinical outcome. Methods: All randomized trials comparing neoadjuvant and adjuvant chemotherapy for early breast cancer were reviewed systematically and meta-analyses were performed. Results: Fourteen studies randomizing 5500 women were eligible for analysis. Overall survival was equivalent in both groups. In the neoadjuvant group, the mastectomy rate was lower (relative risk 0·71 (95 per cent confidence interval (c.i.) 0·67 to 0·75)) without hampering local control (hazard ratio 1·12 (95 per cent c.i. 0·92 to 1·37)). Neoadjuvant chemotherapy was associated fewer adverse effects. Conclusion: Neoadjuvant chemotherapy is an established treatment option for early breast cancer.