What are the risks associated with Hyperthermic Intraperitoneal Chemotherapy (HIPEC)?

Risk Profile of HIPEC

HIPEC carries moderate to substantial procedural risks with major complications occurring in 9-40% of patients and mortality rates of 0-7%, but recent high-quality trials demonstrate that when performed at experienced centers with appropriate patient selection, it does not significantly increase morbidity or mortality compared to cytoreductive surgery alone. 1

Mortality Risk

• Perioperative mortality (≤30 days) ranges from 0% to 7% across trials, though the most recent and highest-quality studies consistently report 0% procedure-related deaths. 1
• In gastric cancer specifically, the CYTO-CHIP study (277 patients) showed HIPEC added to cytoreductive surgery improved survival without increasing mortality. 1
• A phase II gastric cancer trial reported 90-day mortality of 0% despite 70% morbidity rate. 1
• In gastric cancer with peritoneal carcinomatosis, serious adverse events occurred in 14.7% of HIPEC patients versus 11.7% in surgery-alone patients (not statistically significant, P=0.839). 1

Major Complication Rates

• Major/severe complications occur in 9-40% of patients within 30 days of surgery, with significant variation across trials and centers. 1
• Complication rates have decreased over time at experienced centers as techniques have evolved and institutional experience has grown. 1
• The M06OVH-OVHIPEC trial (largest ovarian cancer study, n=245) showed no difference in grade 3-4 toxicities between HIPEC and control groups (27% vs 25%). 1

Specific Complications by System

Infectious complications include:

• Wound infections, sepsis, pneumonia, central line-associated infections, and intra-abdominal infections 1
• Abscesses and fistulas (various types) 1

Gastrointestinal complications include:

• Surgical wound dehiscence 1
• Bowel perforation 1
• Ileus 1
• Intestinal anastomotic leakage (no significant difference versus control in meta-analysis) 2

Cardiovascular and pulmonary complications include:

• Venous thromboembolism 1
• Myocardial infarction 1
• Pleural effusions and pneumothorax 1

Other major complications include:

• Hemorrhages requiring intervention 1
• Renal failure/insufficiency 1
• Excessive blood loss (common, with >50% requiring transfusions in some studies) 1

Procedural Burden

• Median procedure time ranges from 300-600 minutes (5-10 hours), significantly longer than cytoreductive surgery alone. 1
• Median hospital stay ranges from 8-24 days, though the M06OVH-OVHIPEC trial showed minimal difference (10 vs 8 days for HIPEC vs control). 1
• Many patients require additional procedures to manage complications, emphasizing the need for comprehensive perioperative care. 1

Critical Risk Mitigation Factors

Patient selection is paramount:

• HIPEC should be reserved for patients with high-volume intraperitoneal disease or peritoneal carcinomatosis who are at risk for widespread microscopic disease after resection. 1
• Patients with low peritoneal carcinomatosis index (PCI <7-10) have better outcomes and lower complication rates. 1
• Complete cytoreduction (R0 resection) is essential for benefit to outweigh risks; incomplete cytoreduction negates survival advantages. 1, 3
• Patients with distant extra-abdominal metastases should generally be excluded as intraperitoneal therapy will not address systemic disease. 1

Institutional experience matters:

• High-volume centers demonstrate lower complication rates as experience accumulates. 1
• Techniques have evolved to reduce complications, with both "open" and "closed" abdominal approaches tested. 1

Context-Specific Risk-Benefit Analysis

For ovarian cancer (interval debulking after neoadjuvant chemotherapy):

• HIPEC improved survival without increasing toxicity or affecting quality of life in the definitive M06OVH-OVHIPEC trial. 1
• Grade 3-4 toxicities were equivalent (27% vs 25%). 1

For gastric cancer with peritoneal metastases:

• CYTO-CHIP study showed HIPEC improved survival without increasing morbidity or mortality. 1
• However, the GASTRIPEC-I trial showed no overall survival benefit (HR 0.72, P=0.1647), though progression-free survival improved. 1
• A phase II trial reported 70% 90-day morbidity but 0% mortality. 1

For prophylactic HIPEC in advanced gastric cancer without peritoneal carcinomatosis:

• Meta-analysis shows improved 1-year and 3-year survival with reduced recurrence rates (RR 0.60) without increased complications. 3
• No statistically significant difference in complication rates (RR 1.15, P=0.51). 3

Common Pitfalls to Avoid

• Performing HIPEC in patients unlikely to achieve complete cytoreduction wastes resources and exposes patients to unnecessary risk without survival benefit. 1, 3
• Using HIPEC in patients with extensive disease (PCI >10) or extra-abdominal metastases where systemic disease will determine prognosis regardless of locoregional control. 1
• Inadequate institutional experience or volume leads to higher complication rates; this procedure should be performed at specialized centers. 1
• Failure to provide comprehensive perioperative support given the high rate of complications requiring additional interventions. 1