Objective: To evaluate the safety and feasibility of neoadjuvant chemotherapy prior elective surgery following self-expanding metallic stents (SEMS) for complete obstructive left hemicolon cancer.
Methods: This prospective, multicenter, open-labelled trial was approved by the Ethics Committee of Beijing Chaoyang Hospital, Capital Medical University(2016-ke-161-1) and registered in Clinicaltrials.gov (NCT02972541).
Inclusion criteria: (1)age between 18 and 75 years old;(2) adenocarcinoma confirmed by pathology;(3) left hemicolon cancer confirmed by clinical manifestations and imaging examinations with the distance to anal verge > 15 cm; (4) resectable cancer evaluated by imaging examination without distant metastasis; (5) Eastern Cooperative Oncology Group (ECOG) score ≤ 1 or Karnofsky Performance Scale (KPS) > 70, indicating tolerance of neoadjuvant chemotherapy and operation; (6) absence of chemotherapy or radiotherapy within past six months; (7) bone marrow system and hepatorenal function: hemoglobin ≥ 90 g/L, neutrophil ≥ 1.5×109/L, platelet ≥ 80×109/L, total bilirubin ≤ 1.5×ULN(upper limits of normal), serum transaminase ≤ 2.5×ULN, serum creatinine ≤ 1.0×ULN, endogenous creatinine clearance rate > 50 ml/min; (8) sign for informed consent.
Exclusion criteria: (1) multiple primary colorectal cancer; (2) rejection of operation;(3) presenting peritonitis or bowel perforation before SEMS; (4) unqualified conditions proved by inspector from registration data. According to inclusion criteria, 62 consecutive patients receiving neoadjuvant chemotherapy prior to elective surgery following SEMS for complete obstructive left hemicolon cancer from Beijing Chaoyang Hospital of Capital Medical University (n=31), Qilu Hospital of Shandong University (n=14), the Third Xiangya Hospital of Central South University (n=13), Zhongnan Hospital of Wuhan University (n=2), the Fourth Hospital of Hebei Medical University (n=2) between December 2015 and December 2017 were prospectively enrolled in this study. Patients were divided into neoadjuvant chemotherapy group and elective surgery group according to the investigator's clinical experience and patient's preference. Patients in the elective surgery group received surgery within one to two weeks after SEMS placement without neoadjuvant chemotherapy. Those in the neoadjuvant chemotherapy group received 2 cycles of CapeOX or 3 cycles of mFOLFOX6 neoadjuvant chemotherapy within one to two weeks after SEMS placement, and then underwent surgery within 3 weeks after finishing neoadjuvant chemotherapy. Data between groups were compared using Student t-test, chi-square analysis or Fisher exact test analysis, including basic clinical informations, operational conditions and postoperative complications. The adverse reactions during the neoadjuvant chemotherapy were recorded. Surgical difficulty was assessed using visual analog scales ranging from 1 to 10, where 1 represented the lowest and 10 the highest degree of surgical difficulty, as judged by the surgeon.
Results: The study included 38 males and 24 females with mean age of (64.8±8.8) years. The clinical baseline data between 2 groups were not significantly different (all P>0.05) except the average time interval between SEMS and surgery was significantly longer in neoadjuvant chemotherapy group [(61.6±13.5) days vs. (10.4±5.2) days, t=16.679, P<0.001]. There was no stent migration in either group. Three patients had perforation in the elective surgery group; one patient had perforation and one had obstruction in the neoadjuvant chemotherapy group; and all these patients received emergent surgery. Adverse reactions of neodajuvant chemotherapy were mainly degree 1 and 2 except one patient with degree 3 diarrhea. Patients in neoadjuvant chemotherapy group had significantly lower rate of stoma [4.8%(1/21) vs. 34.1%(14/41), χ²=6.538, P=0.011], higher rate of laparoscopic surgery [71.4%(15/21) vs. 36.6%(15/41), χ²=6.751, P=0.009], shorter mean operative time (147 minutes vs. 178 minutes, t=-3.255, P=0.002), less mean intraoperative blood loss (47 ml vs. 127 ml, t=-4.129, P<0.001), lower degree of surgical difficulty(3.3 vs. 5.6, t=-5.091, P<0.001), shorter mean postoperative exhausting time (56.2 hours vs. 69.0 hours, t=-2.891, P=0.006), and shorter mean postoperative hospital stay (8.5 days vs. 13.5 days, t=-2.246, P=0.028) as compared with patients in the elective surgery group. Surgical site infection rate and anastomotic leakage rate did not differ significantly between two groups(all P>0.05).
Conclusion: Neoadjuvant chemotherapy prior elective surgery following SEMS is a relatively safe and feasible approach in the treatment for obstructive left hemicolon cancer, and is associated with less stoma, more laparoscopic surgery, shorter operative time, less blood loss, lower surgical difficulty, and faster postoperative recovery as compared with conventional elective surgery.