Efficacy And Safety Study Of Hyperthermic Intraperitoneal Chemotherapy After Colectomy In Patients With Colorectal Cancer At High Risk Of Peritoneal Carcinomatosis

Purpose:For patients with colorectal cancer with peritoneal metastasis,radical surgery plus HIPEC is the standard procedure in many countries.However,the safety and efficacy of RS,with or without HIPEC,in patients with a diagnosis of end-stage colorectal cancer remains controversial.There is a lack of prospective randomised controlled trials or retrospective clinical studies elucidating the safety and efficacy of RS combined with HIPEC.This retrospective study aimed to describe the safety and efficacy of RS with prophylactic HIPEC,in patients with T4 CRC.Method:Our study included two parts.The first part was a retrospective study.This study collected the hospital medical records of patients who were diagnosed as T4 CRC and received RS in Wuhan Union Medical College Hospital from January 2019 to April2021.The study subjects were selected according to the inclusion and exclusion criteria of the study,and were divided into HIPEC group and RS group according to whether the study subjects had HIPEC.PSM was used to reduce the effects of bias and confounding variables between the two groups.The incidence of postoperative complications,RFS and OS in the groups before and after PSM were analyzed.In the second part,retrospective study,hospital records of T4 CRC patients treated with RS combined with HIPEC from March 2019 to October 2020 in Wuhan Union Medical College Hospital were retrieved from our center’s prospective RCT database(NCT04845490)and screened according to the inclusion and exclusion criteria.Patients were divided into mitomycin and lobaplatin groups according to the grouping of drug classes that the study subjects received during HIPEC treatment.The incidence of postoperative complications,RFS and OS in the two groups before and after PSM were analyzed.Result:In the first part,a total of 417 patients with CRC were included,including165 patients in HIPEC group and 252 patients in RS group.There was no difference between HIPEC group and RS group in sex,age,height,weight,history,American Society of Anesthesiologists(ASA)classification,operation method,tumor location,maximum tumor diameter,tumor histological type,surgical margin,nerve invasion,vascular invasion,lymphatic metastasis,depth of invasion,preoperative complications.Those baseline data after PSM were comparable.There was no significant difference in postoperative complications between HIPEC group and RS group.The RFS(78.0vs.84.8%,P=0.252,χ~2=1.312)and OS(82.0 vs.88.5%,P=0.072,χ~2=3.242)of the overall cohort were not significantly different at 33 months.However,the RFS was significantly different between the two groups at 33 months in patients with stage T4b CRC(92.1%vs77.3%,P=0.0496,χ~2=3.854)and patients with tumor size≥5 cm(96.1 vs 76.0%,P=0.021,χ~2=5.353).In the second part,a total of 146 CRC patients treated with HIPEC were included,including 47 patients in the mitomycin group and 99 patients in the lobaplatin group,with no significant difference in the incidence of all adverse events between the two groups after PSM.There were no significant differences in OS(P=1.000,χ~2(27)0.001)and RFS(P=0.194,χ~2=1.688)at 22 months between the two groups,and there were no significant differences in OS and RFS between the two groups when stratified by T4A or T4b stage,tumor size≥5 cm or tumor location as rectum.In patients with colon cancer,the RFS was significantly different between the two groups(100.0%vs 63.2%,P=0.028,χ~2=4.824)at 22 months.Conclision:1.Prophylactic HIPEC did not increase the incidence of various complications after CRC,which was safe and feasible.2.Mitomycin versus lobaplatin,in the application of prophylactic HIPEC,there was no significant difference in the incidence of various complications after CRC surgery,with the same safety profile.3.Prophylactic HIPEC,for CRC with pathological stage T4b and tumor size≥5 cm,the 33 months cumulative RFS after RS combined with HIPEC was better than that of patients treated only with RS alone.4.Mitomycin,in the prophylactic HIPEC for colon cancer patients with pathological stage T4,the 22 months cumulative RFS was superior to that of patients who used lobaplatin as an intraperitoneal drug.5.The effect of HIPEC on long-term prognosis of CRC awaits prospective multicenter randomized controlled studies with high quality,large sample,and well-defined outcome measures.6.HIPEC has a promising future in the prevention of peritoneal metastasis of CRC,but the specific regimens of intraperitoneal hyperthermic perfusion chemotherapy,especially drug combinations,doses,patient selection,etc.,need to be provided in a prospective multicenter randomized controlled study to provide theoretical and technical support.