Direct surgery with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for patients with colorectal peritoneal metastases

Abstract

Introduction: Neoadjuvant chemotherapy is widely used in treatment of peritoneal metastases from colorectal cancer, but there is little scientific evidence for this approach. This study aimed to study survival in patients treated with direct surgery with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC), i.e. without neoadjuvant chemotherapy. Material and methods: Patients with histopathologically confirmed peritoneal metastases from colorectal cancer that underwent first-time CRS-HIPEC with complete cytoreduction (CC0 or 1) at Karolinska University Hospital 2012e2019 were included. Patients with synchronous extraperitoneal metastases were excluded if not treated before end of follow-up. Factors associated with overall survival (OS) and disease-free survival (DFS) were evaluated using the Kaplan-Meier method and Cox regression models. The multivariable models were adjusted for sex, age, synchronous/metachronous peritoneal metastases, peritoneal carcinomatosis index (PCI), extraperitoneal metastases and the pathological tumor (T) and lymph node (N) stage of the primary tumor. Results: In all, 131 patients underwent complete CRS-HIPEC for peritoneal metastases without neoadjuvant chemotherapy. The median OS and DFS were 40.3 months and 12.5 months, respectively, in patients treated with direct surgery. In the multivariable model, PCI16 was the only variable associated with decreased OS, whereas elevated PCI, metachronous development of peritoneal metastases and synchronous extraperitoneal metastases were associated with decreased DFS. Age was not associated with an impaired prognosis. Conclusion: Patients who underwent direct surgery with CRS-HIPEC had a good prognosis, with a median OS of more than 3 years. The results from this study question the need of neoadjuvant chemotherapy in all patients eligible for CRS-HIPEC.

Comprehensive Treatment Algorithms of the Swiss Peritoneal Cancer Group for Peritoneal Cancer of Gastrointestinal Origin

“…It found no survival benefit for CRS HIPEC performed with high-dose oxaliplatin ip and 5-FU/leucovorin iv, except for patients with a peritoneal cancer index of 11–15 in a post-hoc analysis [ 22 ]. The latter point is consistent with a prior finding suggesting that patients with a peritoneal cancer index of up to 16 and/or limited small bowel involvement benefit most from CRS HIPEC [ 96 , 97 , 98 , 99 ]. Much has been written on the strength and weakness of the PRODIGE-7 trial, which was first presented in June 2018 at the American Society of Clinical Oncology meeting and included contemporary systemic chemotherapy and targeted therapy.…”

“…In addition, the extension of PC of colorectal origin matters beyond mere resectability with a threshold peritoneal cancer index of 20 and below most commonly reported. Indeed, many expert centers today set the bar for CRS HIPEC at a peritoneal cancer index of 16 [ 96 , 97 , 98 , 99 , 110 , 111 ] to maximize cure, while avoiding large resection of small bowel to prevent a short bowel syndrome. Peritoneal recurrence after CRS HIPEC is common with a median time to recurrence of 33 months [ 112 , 113 , 114 ].…”

Sex differences in metastatic surgery following diagnosis of synchronous metastatic colorectal cancer

“…However, to our knowledge, no study has described any gender differences in tumor burden in patients with mCRC. In a recent study on curatively treated patients with CRC with peritoneal metastases there were no gender differences in tumor burden (information from the author) 37 . Another study showed that primary tumor location affected the burden of liver metastases, 38 a factor adjusted for in all multivariable models.…”

“…In a recent study on curatively treated patients with CRC with peritoneal metastases there were no gender differences in tumor burden (information from the author). 37 Another study showed that primary tumor location affected the burden of liver metastases, 38 a factor adjusted for in all multivariable models. In the present study, there was no gender difference in the presence of multiple metastatic locations, which is in line with a previous study.…”

The Impact of Neoadjuvant Chemotherapy on the Surgical Management of Colorectal Peritoneal Metastases: A Systematic Review and Meta-Analysis

“…30 Similarly from Sweden, a recent retrospective study of 131 consecutive patients reported a median OS of 40 months after complete cytoreduction, with 60% of the study population receiving adjuvant chemotherapy. 31 The authors question the need for NAC due to the favourable reported survival. Perhaps, for the purposes of survival, the timing of systemic chemotherapy is inconsequential.…”