Impact of Preoperative Radiotherapy on Anastomotic Leakage and Stenosis After Rectal Cancer Resection: Post Hoc Analysis of a Randomized Controlled Trial.
BACKGROUND
Evidence regarding the effect of preoperative radiotherapy on anastomotic integrity remains conflicting in rectal cancer surgery. Prospective comparisons with appropriate controls are needed.


OBJECTIVE
This study aimed to assess the impact of preoperative radiotherapy on anastomotic leakage and stenosis after rectal cancer resection.


METHODS
This was a post hoc analysis of a randomized controlled trial (NCT01211210).


METHODS
Data were retrieved from the leading center of the trial, which is a tertiary hospital.


METHODS
The full analysis population of 318 patients was included.


METHODS
Patients were randomly assigned to receive preoperative radiation (50 Gy per 25 fractions) and 5-fluorouracil infusion, alone (arm A) or combined with oxaliplatin (arm B), or preoperative chemotherapy with 5-fluorouracil and oxaliplatin without radiation (arm C).


METHODS
The rates of anastomotic leakage and stenosis were calculated for each treatment arm. Multivariate analysis was used to verify the effect of preoperative radiotherapy.


RESULTS
The treatment arms were comparable in terms of most baseline characteristics, but more diversions were used in the chemoradiotherapy arms. Anastomotic leakage occurred in 20.2% of patients in arm A, 23.6% of patients in arm B, and 8.5% of patients in arm C (p = 0.007). The corresponding rates of stenosis were 17.0%, 18.9%, and 6.8% (p = 0.02). Multivariate analysis confirmed the correlation between preoperative radiotherapy and clinical leakage (p = 0.02), which was associated with delayed stenosis (p < 0.001). For patients undergoing chemoradiotherapy, radiation proctitis was identified as an independent risk factor for clinical leakage (p = 0.01) and stenosis (p < 0.001).


CONCLUSIONS
The main limitations were discrepancies in stoma creation and chemotherapy regimen among the treatment arms.


CONCLUSIONS
Preoperative radiotherapy increases the risk of anastomotic leakage and stenosis after rectal cancer resection. Clinical leakage independently contributes to the development of stenosis.
1 Department of Colorectal Surgery, Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China 2 Department of Oncology, Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China 3 Department of Radiotherapy, Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China 4 Department of Radiology, Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China 5 Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Sun Yat-sen University, Guangzhou, Guangdong, China.
Qiyuan
Q
Qin
Tenghui
T
Ma
Yanhong
Y
Deng
Jian
J
Zheng
Zhiyang
Z
Zhou
Hui
H
Wang
Lei
L
Wang
Jianping
J
Wang
D000230:Adenocarcinoma / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D000328:Adult; D000368:Aged; D000714:Anastomosis, Surgical / Q000009:adverse effects / Q000379:methods; D057868:Anastomotic Leak / Q000209:etiology / Q000517:prevention & control; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects; D059248:Chemoradiotherapy / Q000009:adverse effects* / Q000379:methods; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects* / Q000379:methods; D003082:Colectomy / Q000379:methods; D003251:Constriction, Pathologic / Q000175:diagnosis / Q000209:etiology; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D010043:Outcome and Process Assessment, Health Care; D000077150:Oxaliplatin; D011300:Preoperative Care / Q000009:adverse effects / Q000379:methods; D011349:Proctitis / Q000175:diagnosis / Q000209:etiology; D011829:Radiation Dosage; D011832:Radiation Injuries / Q000175:diagnosis*; D012004:Rectal Neoplasms / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D005472:Fluorouracil