MIS-CYTO: A prospective, multi-center, observational study for validation of oncological adequacy of minimally invasive cytoreductive surgery for peritoneal malignancies with limited peritoneal spread at systematic mini-laparotomy by INDEPSO

Background The role of minimally-invasive cytoreductive surgery (MI-CRS) in low volume peritoneal disease has been explored but lacks robust evidence demonstrating oncological adequacy and non-inferiority to open CRS. The major challenges of MI-CRS are its technical complexity and chances of missing disease which could have detrimental oncological outcomes. The only means of resolving the dilemma of missed disease is to convert the procedure to open surgery and confirming the findings of MI approach. The Minimally InvaSive CYTOreductive surgery (MIS-CYTO) study is a prospective observational study that will evaluate the oncological adequacy of MI-CRS at systematic mini-laparotomy in patients with low volume peritoneal disease. Methods This single-arm study which will include 100 patients with primary and secondary peritoneal malignancies with a peritoneal cancer index (PCI)< 10 treated by MI-CRS. Patients will be recruited over 3 years and followed up for 5 years. All patients will undergo a staging laparoscopy (SL) with video documentation according to the study format. Patients who undergo subsequent MI-CRS will be included in the per-protocol population. At the end of MI-CRS video documentation of the resection sites is performed followed by a systematic mini-laparotomy for exploration of the abdominal cavity for any residual disease. The presence of residual disease will be confirmed on pathological evaluation. The primary end point is the incidence of missed disease during MI-CRS that is detected during mini-laparotomy. Quality assessment of SL and MI-CRS will be performed by an independent two-member committee. Patients undergoing conversion to open cytoreductive surgery will comprise the comparator group for studying the secondary end-point which include the sites of missed disease, perioperative outcomes and survival outcomes. Survival endpoints will be measured from the date of surgery to the event: overall survival (OS) will be defined by death due to any cause, and progression-free or relapse-free survival (PFS/RFS) by any recurrence or death whichever comes first. Ethics and Registration The study protocol is approved by the ethics committee of Shalby Cancer and Research Institute on 7th October 2024 (EC/069/02). The study is registered under the Clinical Trials Registry of India; subsidiary of clinicaltrials.gov (CTRI/2024/11/076312). Strengths and limitations The study will be the first to demonstrate the oncological adequacy or inadequacy of the MI-CRS The methodology and surgical protocol are robust and should minimize heterogeneity in surgical practices in the study If the oncological inadequacy of MI-CRS is not demonstrated, its use should be limited in patients with limited peritoneal disease. Two independent experts will review the adequacy of staging laparoscopy and MI-CRS both The stringent methodology could be a deterrent for surgeons/ centres to participate in the study, specifically performing a systematic mini-laparotomy for those surgeons who prefer to deliver specimens through a natural orifice.