Second-look surgery plus hyperthermic intraperitoneal chemotherapy versus surveillance in patients at high risk of developing colorectal peritoneal metastases (PROPHYLOCHIP–PRODIGE 15): a randomised, phase 3 study

Clinical Efficacy and Safety of Hyperthermic Intraperitoneal Chemotherapy in Colorectal Cancer Patients at High Risk of Peritoneal Carcinomatosis: A Systematic Review and Meta-Analysis

“…The use of HIPEC therapy in CRC patients at high risk of PM may be a relatively extreme approach, since the existing published RCT research conclusions are similar to ours, and preventive HIPEC does not benefit the long-term survival of the target populations. This conclusion may provide some reference value for other ongoing RCT studies (27,28). Intriguingly, the incidence of PM was significantly reduced by HIPEC treatment compared to control treatments.…”

“…The characteristics of all included studies are presented in Table 1. Six clinical studies (4 observational studies and 2 RCTs) involving 603 patients were enrolled in this systematic review and meta-analysis (23)(24)(25)(26)(27)(28)(29)(30). Among all included studies, 2 studies administered HIPEC treatment only in the experimental group, while the remaining 4 studies conducted treatment by HIPEC combined with curative surgery or adjuvant systemic chemotherapy in the intervention group.…”

Mid-Term Audit of a National Peritoneal Surface Malignancy Program Implementation in a Low Middle Income Country: The Moroccan Experience

“…[17,18] For PM originating from colorectal malignancies, the Oxaliplatin-HIPEC (PRODIGE-7) randomized study did not illustrate a significant overall survival benefit to the addition of HIPEC for patients undergoing CRS [19]. Moreover, the PROPHYLOCHIP-PRODIGE 15 trial also showed no improvement to disease-free survival in case of systematic second-look surgery plus oxaliplatin-HIPEC compared to standard surveillance for patients at high risk of developing colorectal PM [20]. As regards peritoneal carcinomatosis of gastric origin, there is scarce evidence supporting the use of HIPEC in addition to CRS [21,22].…”

Diagnostic and therapeutic algorithm for colorectal peritoneal metastases. A consensus of the peritoneal surface malignancies onco-team of the Italian society of surgical oncology

“…Patients treated for synchronous PM in non-specialized centers, even those with complete resection, should be referred to a PTRC. In a significant quote of patients who underwent resection of PM at the time of primary treatment, a second look surgery allows to discover and treat further peritoneal metastatic nodules with similar outcomes of one-stage curative treatment [28,29]. If the tumor load is high, with multiple and diffuse nodules, a simple histological confirmation after an accurate intra-operative staging (PCI and unresectability causes) is the best choice, before sending the patient to a PTRC (statement 3).…”

“…However, one-stage curative treatment with HIPEC in referral centers is preferable whenever possible 3 PM can be an unexpected event during surgery for primary CRC. If the tumor load is high, with multiple and diffuse nodules, a simple histological confirmation and an accurate intra-operative staging (PCI and unresectability causes) is the best choice, before sending the patient to a peritoneal referral center 4 If the patient is symptomatic and peritoneal metastases is suspected, surgery should be performed according to the urgency to intervene before sending the patient to a peritoneal referral center 5 In case of obstruction, perforation or bleeding, when radical resection of the primary can be carried out safely and limited nodules are present, resection of the primary combined with peritoneal metastases is an acceptable option before sending the patient to a peritoneal referral center 6 When surgery is emergent and peritoneal metastases are diffuse, a limited palliation (primary resection only, stoma formation) with peritoneal biopsy and staging (PCI and unresectability causes) are indicated, before sending the patient to a peritoneal referral center 7 Every patient potentially eligible for CRS-HIPEC should be evaluated by a referral centre and discussed in dedicated colorectal multidisciplinary meetings 8 During colorectal multidisciplinary meetings a complete medical history, abdominal/thoracic CT scan and blood tumor markers should be available 9 CT scan with contrast enhancement medium represents the gold standard for stage patients with colorectal peritoneal metastases 10 MRI and PET scan should be considered complementary imaging for stage patients with colorectal peritoneal metastases 11 Laparoscopy is a complementary method for stage patients with colorectal peritoneal metastases and It is crucial that is performed by surgeons with experience in CRS-HIPEC 12 Only patients with pre-operative Peritoneal Cancer Index <16 and with the possibility of obtain a CC0/1 resection should be selected for CRS-HIPEC 13 Molecular gene mutation testing (RAF/RAS mutation) and microsatellite status (stable or not) are important selection factors for CRS-HIPEC 14 Performance status, extraperitoneal metastases (liver, lymph nodes), tumor site (right versus left colon) tumor differentiation, signet ring histology, ascites, symptoms of obstruction and lymph node status (N2a) of the primary in case of metachronous PM should be carefully considered potentially exclusion criteria for CRS-HIPEC 15 In patients selected for CRS-HIPEC Mitomycin C based regimen is recommended 16 Before selecting patients to CRS-HIPEC pre-operative chemotherapy should be always considered especially in presence of synchronous disease 17 Peritoneal progression during systemic chemotherapy should not be considered an absolute contraindication for CRS-HIPEC, if the selection criteria are still met 18 In very selected patients with limited metachronous peritoneal metastases and no risk factors, perioperative systemic chemotherapy could be omitted in favour of a front-line CRS-HIPEC 19 In the sub-group of patients with peritoneal metastases who have mismatch repair-deficient (dMMR) and/or microsatellite instability-high (MSI-H), the treatment with immune checkpoint inhibitor should be considered as first choice for confirming the diagnosis of peritoneal involvement, allowing a histological definition of all suspected nodules [29]. Laparoscopic exploration can assess the peritoneal cancer index (PCI) more accurately then preoperative radiological investigations [36].…”