International Expert Consensus on Defining Textbook Oncologic Outcomes in Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Colorectal Peritoneal Metastasis.

BACKGROUND: Textbook oncologic outcome (TOO) is a composite metric shown to correlate with improved survival after curative intent oncologic procedures. Despite increasing use among disciplines in surgical oncology, no consensus exists for its definition in cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). STUDY DESIGN: An international consensus-based study employed a Delphi methodology to achieve agreement. Fifty-four senior surgeons from the peritoneal surface malignancies field received a questionnaire comprising TOO parameters divided into 3 surgical domains: operative, short-term, and long-term postoperative outcomes. Two online meetings with participants defined the new criteria. Consensus was achieved when 75% of agreement rate was reached. Clinical data of patients who underwent CRS and HIPEC for colorectal peritoneal metastasis between 2010 and 2022 from 1 designated center (Sheba Medical Center) were collected, the consensus definition applied and outcomes analyzed. RESULTS: Thirty-eight surgeons (70%) participated. Expert consensus TOO parameters for colorectal peritoneal metastasis CRS and HIPEC included the absence of unplanned reoperations during 30 days postoperation, absence of severe postoperative complications (Clavien-Dindo ≥III), absence of unplanned readmissions during 30 days postoperation, 90-day postoperative mortality, and absence of contraindications for chemotherapy within 12 weeks from operation, and included the achievement of complete cytoreduction (CC0). The study cohort consisted of 251 patients, and 151 (60%) met TOO criteria. Patients who achieved TOO had significantly better overall survival (median 67.5 months, 95% CI) vs patients who did not achieve TOO (median 44.6 months, 95% CI, p < 0.001) and significantly improved disease-free survival (median, 12 months, 95% CI, vs 9 months, 95% CI, p = 0.01). CONCLUSIONS: Achievement of TOO as defined by consensus statement is associated with improved survival.

Perioperative and Oncological Outcomes of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Metastasis of Rectal Origin.

BACKGROUND: The peritoneum is a common metastatic site of colorectal cancer (CRC) and associated with worse oncological outcomes. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) has been shown to improve outcomes in selected patients. Studies have demonstrated significant difference in survival of patients with primary colon and rectal tumors both in local and in metastatic setting; but only few assessed outcomes of CRS/HIPEC for rectal and colon tumors. We studied the perioperative and oncological outcomes of patients undergoing CRS/HIPEC for rectal cancer. METHODS: A retrospective analysis of a prospectively maintained database between 2009 and 2021 was performed. RESULTS: 199 patients underwent CRS/HIPEC for CRC. 172 patients had primary colon tumors and 27 had primary rectal tumors. Primary rectal location was associated with longer surgery (mean 4.32, hours vs 5.26 h, p = 0.0013), increased blood loss (mean 441cc vs 602cc, p = 0.021), more blood transfusions (mean 0.77 vs 1.37units, p = 0.026) and longer hospitalizations (mean 10 days vs 13 days, p = 0.02). Median disease-free survival (DFS) was shorter in rectal primary group; 7.03 months vs 10.9 months for colon primaries (p = 0.036). Overall survival was not statistically significant; 53.2 months for rectal and 60.8 months for colon primary tumors. Multivariate analysis indicated origin (colon vs rectum) and Peritoneal Cancer Index to be independently associated with DFS. CONCLUSIONS: Patients with rectal carcinoma undergoing CRS/HIPEC for peritoneal metastasis had worse peri-operative and oncological outcomes. Overall survival was excellent in both groups. This data may be used for risk stratification when considering CRS/HIPEC for patients with rectal primary.

Pelvic Peritonectomy Poorly Affects Outcomes in Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Colorectal Metastases.

BACKGROUND: Constraints of pelvic anatomy render complete cytoreduction (CRS) challenging. The aim of this study is to investigate the impact of pelvic peritonectomy during CRS/HIPEC on colorectal peritoneal metastasis (CRPM) patients' outcomes. METHODS: This is a retrospective analysis of a prospectively maintained CRS/hyperthermic intraperitoneal chemotherapy (HIPEC) database. The analysis included 217 patients with CRPM who had a CRS/HIPEC between 2014 and 2021. We compared perioperative and oncological outcomes of patients with pelvic peritonectomy (PP) (n = 63) to no pelvic peritonectomy (non-PP) (n = 154). RESULTS: No differences in demographics were identified. The peritoneal cancer index (PCI) was higher in the PP group with a median PCI of 12 vs. 6 in the non-PP group (p < 0.001). Operative time was 4.9 vs. 4.3 h in the PP and non-PP groups, respectively (p = 0.63). Median hospitalization was longer in the PP group at 12 vs. 10 days (p = 0.007), and the rate of complications were higher in the PP group at 57.1% vs. 39.6% (p = 0.018). Pelvic peritonectomy was associated with worse disease-free (DFS) and overall survival (OS) with 3-year DFS and OS of 7.3 and 46.3% in the PP group vs. 28.2 and 87.8% in the non-PP group (p = 0.028, p .> 0.001). The univariate OS analysis identified higher PCI (p = 0.05), longer surgery duration (p = 0.02), and pelvic peritonectomy (p < 0.001) with worse OS. Pelvic peritonectomy remained an independent prognostic variable, irrespective of PCI, on the multivariate analysis (p < 0.001). CONCLUSIONS: Pelvic peritonectomy at the time of CRS/HIPEC is associated with higher morbidity and worse oncological outcomes. These findings should be taken into consideration in the management of patients with pelvic involvement.

Natural History and Management of Small-Bowel Obstruction in Patients After Cytoreductive Surgery and Intraperitoneal Chemotherapy.

BACKGROUND: Small-bowel obstruction (SBO) after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is a common complication associated with re-admission that may alter patients' outcomes. Our aim was to characterize and investigate the impact of bowel obstruction on patients' prognosis. METHODS: This was a retrospective analysis of patients with SBO after CRS/HIPEC (n = 392). We analyzed patients' demographics, operative and perioperative details, SBO re-admission data, and long-term oncological outcomes. RESULTS: Out of 366 patients, 73 (19.9%) were re-admitted with SBO. The cause was adhesive in 42 (57.5%) and malignant (MBO) in 31 (42.5%). The median time to obstruction was 7.7 months (range, 0.5-60.9). Surgical intervention was required in 21/73 (28.7%) patients. Obstruction eventually resolved (spontaneous or by surgical intervention) in 56/73 (76.7%) patients. Univariant analysis identified intraperitoneal chemotherapy agents: mitomycin C (MMC) (HR 3.2, p = 0.003), cisplatin (HR 0.3, p = 0.03), and doxorubicin (HR 0.25, p = 0.018) to be associated with obstruction-free survival (OFS). Postoperative complications such as surgical site infection (SSI), (HR 2.2, p = 0.001) and collection (HR 2.07, p = 0.015) were associated with worse OFS. Multivariate analysis maintained MMC (HR 2.9, p = 0.006), SSI (HR 1.19, p = 0.001), and intra-abdominal collection (HR 2.19, p = 0.009) as independently associated with OFS. While disease-free survival was similar between the groups, overall survival (OS) was better in the non-obstruction group compared with the obstruction group (p = 0.03). CONCLUSIONS: SBO after CRS/HIPEC is common and complex in management. Although conservative management was successful in most patients, surgery was required more frequently in patients with MBO. Patients with SBO demonstrate decreased survival.

Outcomes of Stable Lung Colorectal Metastases on Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: Cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) have demonstrated benefit in patients with colorectal peritoneal metastases (CRPM). Traditionally, extraperitoneal disease is considered a contraindication to CRS/HIPEC. Stable lung metastases in patients with colorectal cancer often have an indolent course, while the presence of untreated peritoneal metastases poorly affects short-term survival. We sought to evaluate the outcomes of patients undergoing CRS/HIPEC for peritoneal disease with known stable lung metastases. METHODS: We retrospectively reviewed our prospectively maintained CRS/HIPEC database. In 2017, we adopted a policy of considering patients with stable lung metastases for CRS/HIPEC as part of multidisciplinary treatment. We compared the oncologic outcome and safety of CRS/HIPEC with peritoneal only (PM) against patients with peritoneal and lung metastases (PLM). RESULTS: Our database includes 570 patients with CRS/HIPEC of which 174 with CRPM that underwent CRS/HIPEC, 18 with preoperatively diagnosed peritoneal and lung metastases. The demographics of the PM and PLM group were similar with the exception of operative time that was longer in the PLM group. Median PCI of the cohort was 7, similar in both groups (p = 0.89). Three-year overall survival (OS) of PLM patients was 68%, compared to 71% in PM (p = 0.277). Three-year progression-free survival (PFS) rate was 20% in PLM and 23% in PM (p = 0.688). CONCLUSIONS: Presence of stable lung metastases from colorectal cancer in patients with CRPM does not appear to affect the outcomes of CRS/HIPEC. Patients with stable lung disease should be considered for CRS/HIPEC after multidisciplinary discussion.

The impact of gastrointestinal anastomotic leaks on survival of patients undergoing cytoreductive surgery and heated intraperitoneal chemotherapy.

BACKGROUND: Gastrointestinal (GI) leaks after cytoreductive surgery and hyperthermic Intraperitoneal Chemotherapy (CRS/HIPEC) is a known life-threatening complication that may alter patients' outcomes. Our aim is to investigate risk factors associated with GI leaks and evaluate the impact of GI leaks on patient's oncological outcomes. METHODS: A retrospective analysis of perioperative and oncological outcomes of patients with and without GI leaks after CRS/HIPEC. RESULTS: Out of 191 patients included in this study, GI leaks were identified in 17.8% (34/191) of patients. Small bowel anastomoses were the most common site (44%). Most of the GI leaks were managed conservatively and re-operation was needed in 44.1% of cases. Univariate analysis identified higher PCI (p = 0.03), higher number of packed cells transfused (p = 0.036), pelvic peritonectomy (p = 0.013), high number of anastomoses (p = 0.003) and colonic resection (p = 0.042) as factors associated with GI leaks. Multivariate analysis identified stapled anastomoses (OR 2.59, p = 0.001) and pelvic peritonectomy (OR 2.33, p = 0.044) as independent factors associated with GI leaks. Disease-free survival tended to be worse in the leak group but did not reach statistical significance (p = 0.235). The 3- and 5-year OS was 73.2% and 52.9% in the leak group compared to 75.8% and 73.2% in the non-leak group (p = 0.236). CONCLUSIONS: GI leak showed no impact on overall and disease free survival after CRS/HIPEC.Avoidance of stapled reconstruction in high risk patients with high tumor burden and large number of anastomoses may yield improved outcomes.

Ratio of Pathological Response to Preoperative Chemotherapy in Patients Undergoing Complete Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy for Metastatic Colorectal Cancer Correlates with Survival.

BACKGROUND: Pathological response of colorectal peritoneal metastasis (CRPM) may affect prognosis. We investigated the relationship between oncological outcomes and pathological response to chemotherapy of CRPM following cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: We conducted a retrospective analysis of a prospectively maintained Peritoneal Surface Malignancies database between 2015 and 2020. Analysis included patients with CRPM who underwent a CRS/HIPEC procedure (n = 178). The cohort was divided into three groups according to the response ratio (ratio of tumor-positive specimens to the total number of specimens resected): Group A, complete response; Group B, high response ratio, and Group C, low response ratio. RESULTS: The group demographics were similar, but the overall complication rate was higher in Group C (65.2%) compared with Groups A (55%) and B (42.8%) [p = 0.03]. Survival correlated to response ratio; the estimated median disease-free survival of Group C was 9.1 months (5.97-12.23), 14.9 months (4.72-25.08) for Group B, and was not reached in Group A (p = 0.001). The estimated median overall survival in Group C was 35 months (26.69-43.31), and was not reached in Groups A and B (p = 0.001). CONCLUSIONS: The pathological response ratio to systemic therapy correlates with survival in patients undergoing CRS/HIPEC. This study supports the utilization of preoperative therapy for better patient selection, with a potential impact on survival.

Perioperative and Oncological Outcomes of Combined Hepatectomy with Complete Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy for Metastatic Colorectal Cancer.

BACKGROUND: Synchronous peritoneal and liver metastasis in colorectal cancer is a relative contraindication for curative surgery. We aimed to evaluate the safety and oncological outcomes of combined treatment of peritoneal and liver metastasis. METHODS: We conducted a retrospective analysis of metastatic colorectal cancer patients from two prospective databases: peritoneal surface malignancy (n = 536) and hepatobiliary (n = 286). We compared 60 patients treated with cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC) and hepatectomy; 80 patients treated with cytoreduction and HIPEC only; and 63 patients treated with hepatectomy alone. RESULTS: No differences in demographics were observed between the groups. Median hospital and intensive care unit (ICU) stay was shorter in group C (7 and 1 days, respectively) versus groups A and B (13 and 1 days, and 12 and 1 days, respectively; p < 0.001). Postoperative complications were not significantly different. Median follow-up was 18.6, 23.1, and 30.6 months for groups A, B, and C, respectively. Estimated 5-year overall survival (OS) was 48.8% (group A), 55.4% (group B), and 60.2% (group C) [p = 0.043 for group A vs. group C], and estimated 5-year disease-free survival (DFS) was 14.2% (group A), 23.0% (group B), and 18.6% (group C). Five-year OS was superior in group C compared with group A (p = 0.043), and DFS was superior in group C compared with groups A and B (p = 0.043 and 0.03, respectively). The peritoneum was the site of first recurrence in groups A and B (23.3% and 32.5%, respectively), and the liver was the site of first recurrence in group C (44.4%). CONCLUSIONS: We report favorable perioperative and oncological outcomes in combined cytoreduction/HIPEC and hepatectomy for patients with peritoneal and liver metastasis. Surgical intervention after multidisciplinary discussion should be considered in patients with both peritoneal and hepatic lesions when complete cytoreduction is feasible.