Age alone is not a barrier to efficacy of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastases: analysis of 1138 patients from the UK and Ireland Colorectal Peritoneal Metastases Registry.

BACKGROUND: The management of colorectal peritoneal metastases continues to be a challenge but recent evidence suggests cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) can improve survival. Uncertainty about the relationship between age and tumour biology makes patient selection challenging particularly when reported procedure related morbidity is high and impact on survival outcomes unknown. The UK and Ireland Colorectal Peritoneal Metastases Registry was reviewed to assess the influence of age on efficacy of CRS and HIPEC. METHODS: A review of outcomes from the UK and Ireland Colorectal Peritoneal Metastases Registry was performed. Data from 2000 to 2021 were included from five centres in the UK and Ireland, and the cohort were sub-divided into three age groups; <45 years, 45-65 years and >65 years old. Primarily, we examined post-operative morbidity and survival outcomes across the three age groups. In addition, we examined the impact that the completeness of cytoreduction, nodal status, or adverse pathological features had on long-term survival. RESULTS: During the study period, 1138 CPM patients underwent CRS HIPEC. 202 patients(17.8%) were <45 years, 549 patients(48.2%) aged 45-65 years and 387 patients(34%) >65 years. Overall, median length of surgery (CRS and HIPEC), median PCI score and rate of HIPEC administration was similar in all three groups, as was overall rates of major morbidity and/or mortality. Complete cytoreduction rates (CC0) were similar across the three cohorts; 77%, 80.6% and 81%, respectively. Median overall survival for all patients was 38 months following complete cytoreduction. CONCLUSION: Age did not appear to influence morbidity or long-term survival following CRS and HIPEC. When complete cytoreduction is achieved survival outcomes are good. The addition of HIPEC can be performed safely and may reduce local recurrence within the peritoneum.

Urinary tract involvement in peritoneal metastatic disease: Is this a contraindication to cytoreductive surgery and hyperthermic intraperitoneal chemotherapy?

Urinary tract involvement in resectable peritoneal malignancies might require extensive resections and reconstructions in the genitourinary tract during the performance of cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC), a fact which could impair the postoperative course and survival of these patients. We performed a review of the literature to assess whether urinary tract involvement in patients with peritoneal metastases undergoing CRS and HIPEC could affect the postoperative outcomes with respect to morbidity, mortality and survival rates, identifying a total of 6 retrospective studies addressing these clinical questions. Despite their heterogeneity, the existing studies demonstrate that despite a possible increase in postoperative complications when urological procedures are required as part of cytoreduction, survival outcomes do not seem to be affected. This review therefore concludes that urinary tract 6 in peritoneal metastatic disease is not a contraindication to CRS and HIPEC.

The Role of Neoadjuvant and Adjuvant Systemic Chemotherapy with Cytoreductive Surgery and Heated Intraperitoneal Chemotherapy for Colorectal Peritoneal Metastases: A Systematic Review.

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is an effective treatment for colorectal peritoneal metastases (CPM), increasing overall survival in selected patients. The aim of this systematic review was to assess the effect of neoadjuvant and adjuvant systemic chemotherapy on overall survival in patients with CPM undergoing CRS and HIPEC, compared with those who receive CRS and HIPEC alone. METHODS: A systematic literature review was performed using the PubMed database, and the preferred reporting items for systematic reviews and meta-analyses guidelines formed the structure of the review. Data regarding publication details, study design, patient pathology, treatments received, follow-up periods, overall survival and safety were collected and tabulated, and study quality was assessed using the MINORS score for non-randomized studies. RESULTS: Sixteen of 288 studies met the inclusion criteria. Seven publications related to the role of neoadjuvant chemotherapy, and there was no strong evidence for the efficacy of neoadjuvant chemotherapy. Of note, one study observed worse survival outcomes when neoadjuvant therapy was used. Fourteen studies investigated the role of adjuvant chemotherapy and there was limited evidence that adjuvant systemic chemotherapy improves survival following CRS and HIPEC. CONCLUSIONS: Systemic adjuvant chemotherapy may be associated with improved overall survival, but the role of systemic neoadjuvant chemotherapy cannot be determined by the currently available evidence. The delivery of a combination of the two modes of systemic chemotherapy has not been investigated in a randomized controlled trial to date. Further research designed to investigate the role of these modalities in the patient's treatment is required.

Management of colorectal cancer patients at high risk of peritoneal metastases.

PURPOSE: Colorectal cancer (CRC) has potential to spread within the peritoneal cavity, and this transcoelomic dissemination is termed "peritoneal metastases" (PM). Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is a radical strategy to treat selected CRC patients with PM. Studies suggest that identification of CRC patients at high risk of PM may lead to earlier treatment strategies and improve survival in this subset of patients. The aim of this article was to summarise the current evidence regarding CRC patients at high risk of PM. METHODS: A retrospective review of articles on CRC patients with high risk of PM published up to December 2014 in PubMed, Medline, Embase, and Ovid search engines was conducted. The following combination of search terms were used: "intraperitoneal chemotherapy", "HIPEC", "colorectal cancer", "peritoneal carcinomatosis", "peritoneal metastases", "high risk", "peritoneal recurrence". RESULTS: Although opinions differ, CRC patients identified as "high risk" of PM included: limited, synchronous PM completely resected with the primary tumor, ovarian metastases (synchronous or metachronous) and spontaneous or iatrogenic perforation of the bowel by the primary tumor. Aggressive early treatment strategies currently used are: CRS and HIPEC for high-risk primary tumors and second-look CRS and HIPEC often following systematic chemotherapy for the primary resection. Positive results have been shown with both approaches in a number of studies. With CRS/HIPEC for the primary tumor, the overall survival in the two groups (25 patients treated with CRS/HIPEC vs 50 treated with conventional surgery) was significantly improved (p<0.03), as was disease-free survival (p<0.04). For second look surgery, in 29 patients treated with CRS and HIPEC, this resulted in 14% morbidity and 0% mortality and a 2-year disease-free survival rate in excess of 50%. CONCLUSIONS: We are progressively moving to an era of individualised treatment strategies. The management of CRC patients with high risk of PM is ever evolving, with early detection and early treatment strategies showing promising results. The optimal timing of early surgery remains unclear and requires further evaluation. Should current and future randomized trials demonstrate long-term survival benefit, we may potentially see a change in treatment paradigm from current conventional surgery to a more aggressive, early radical approach as the standard of care.