Hyperthermic Intraperitoneal Chemotherapy (HIPEC)
What HIPEC Is
HIPEC is a single intraoperative procedure that delivers heated chemotherapy (41-43°C) directly into the abdominal cavity for 30-90 minutes following cytoreductive surgery, achieving high intracellular drug concentrations at the peritoneal surface that systemic chemotherapy cannot reach. 1, 2
The procedure combines complete surgical removal of all visible tumor deposits from peritoneal surfaces with immediate perfusion of heated chemotherapy solution through the peritoneal cavity. 2 The goal is to achieve complete cytoreduction (CC-0 or CC-1 with <2.5mm residual disease) before HIPEC administration, as residual disease is the strongest predictor of overall survival. 1, 2
Indications by Malignancy Type
Ovarian Cancer (Strongest Evidence)
HIPEC is indicated ONLY after neoadjuvant chemotherapy and interval debulking surgery for stage III-IV epithelial ovarian cancer—NOT after primary debulking surgery. 1
- High-quality randomized trial evidence demonstrates improved recurrence-free survival and overall survival when HIPEC is added to interval cytoreduction in patients ineligible for primary cytoreductive surgery. 3, 4
- The National Comprehensive Cancer Network specifically recommends against using HIPEC after primary debulking surgery, as initial randomized trial data showed no benefit in this setting. 1
Colorectal Cancer (Evidence Does NOT Support Routine Use)
HIPEC is NOT recommended as standard of care for colorectal peritoneal metastases based on the PRODIGE 7 trial, which showed no survival benefit and increased late complications. 5
- The PRODIGE 7 phase III trial found no difference in overall survival (HR 1.00; 95% CI 0.63-1.58) or relapse-free survival when oxaliplatin-based HIPEC was added to cytoreductive surgery. 5
- Grade 3 or greater adverse events were more common at 60 days in the HIPEC group (RR 1.69; 95% CI 1.03-2.77). 5
- ASCO guidelines note that while one older trial showed survival benefit (HR 0.55; 95% CI 0.32-0.95), this could not rule out that aggressive cytoreduction alone was responsible for the effect. 5
- ESMO guidelines state this cannot be recommended as standard of care and should only be considered in selected patients with limited peritoneal metastasis at experienced high-volume centers. 5
Gastric Cancer (Limited Evidence)
Patients with gastric cancer and limited peritoneal metastases with Peritoneal Cancer Index (PCI) <10-20 may benefit from CRS-HIPEC. 2 The CYTO-CHIP study showed improved overall survival and recurrence-free survival versus CRS alone without increasing morbidity or mortality. 2
Other Malignancies
- Pseudomyxoma peritonei: Considered appropriate for CRS-HIPEC. 6, 7
- Peritoneal mesothelioma: May benefit from CRS-HIPEC in selected cases. 6, 7
Patient Selection Criteria
Mandatory Requirements
Complete cytoreduction must be achievable—if CC-0 or CC-1 cannot be accomplished, HIPEC should not be performed as suboptimal debulking negates potential benefits. 1, 2
Disease-Specific Criteria
- Peritoneal Cancer Index (PCI) <20 for colorectal cancer, with PCI <7-10 associated with better outcomes and lower complication rates. 2
- No extraperitoneal metastases (for colorectal cancer). 2
- Limited small bowel involvement (for colorectal cancer). 2
Patient Functional Status
- Normal renal function (critical given nephrotoxicity risk). 1
- Good performance status. 1, 2
- No pre-existing conditions that could worsen significantly with major surgery. 1
Critical Pitfall to Avoid
Do not proceed with HIPEC if complete cytoreduction cannot be achieved intraoperatively—incomplete cytoreduction negates survival advantages and increases risk. 1, 2
Chemotherapy Regimens and Dosing
Ovarian Cancer (Guideline-Endorsed)
Cisplatin 100 mg/m² is the standard HIPEC agent for ovarian cancer, perfused at 41-43°C for 90 minutes. 1
- The National Comprehensive Cancer Network specifically recommends cisplatin at this dose based on demonstrated improved disease-free survival and overall survival. 1
- Alternative dosing of 75-100 mg/m² is also guideline-endorsed. 1
Colorectal Cancer (Not Standardized)
- Oxaliplatin-based HIPEC was used in PRODIGE 7 (30-minute perfusion) but showed no benefit. 5
- Mitomycin-C is another commonly used agent, though PRODIGE 7 authors speculate results would not differ with this agent. 5
- Ongoing trials are evaluating mitomycin and different HIPEC procedures. 5
Gastric Cancer
Regimens vary by institution and are not standardized in guidelines. 2
Technical Parameters
- Temperature: 41-43°C maintained throughout perfusion. 1
- Duration: 30-90 minutes depending on agent and dose (90 minutes standard for cisplatin in ovarian cancer). 1
- Median procedure time: 300-600 minutes (5-10 hours) for combined cytoreductive surgery plus HIPEC. 1, 6
Perioperative Outcomes and Complications
Expected Hospital Course
- Median hospital stay: 8-24 days, with high-quality trials showing approximately 10 days. 1, 8
- Median time for gastrointestinal recovery: 5 days. 6
- Extended ICU stay required: 19.7% of patients. 6
Morbidity and Mortality
- Perioperative mortality: 0-8% across trials, with recent high-quality studies reporting 0% in experienced centers. 2
- Treatment-related mortality: 8% in some colorectal series. 5, 2
- Grade 3-4 complications: 9-40% within 30 days (27% in high-quality trials, similar to cytoreductive surgery alone). 1, 2
Most Common Complications
- Electrolyte abnormalities: Hypocalcemia (32.1%), hypokalemia (32.1%). 6
- Hematologic: Anemia (21.4-67%), thrombocytopenia (7.1%). 8, 6
- Renal: Creatinine elevation (15% vs 4% in controls). 8
- Major morbidity requiring surgical intervention: 8.9%. 6
Integration with Systemic Chemotherapy (Ovarian Cancer)
The standard neoadjuvant regimen is carboplatin AUC 5-6 plus paclitaxel 175 mg/m², with a minimum of 6 total cycles required (at least 3 cycles adjuvant after interval debulking surgery with HIPEC). 1
Delayed initiation of adjuvant chemotherapy after HIPEC is expected but should not prevent completion of the full treatment course. 1, 8
Post-Discharge Management
Antiemetic Regimen
Prescribe olanzapine 5-10 mg PO daily as first-line agent for breakthrough nausea/vomiting. 1, 8 Alternative agents include lorazepam, metoclopramide, or prochlorperazine. 1
Monitoring Requirements
- Renal function and hemoglobin: Arrange follow-up laboratory testing within 7-10 days of discharge. 8
- Fluid intake: Maintain at least 2 liters daily. 8
- Oncology follow-up: Schedule within 2-3 weeks to plan adjuvant therapy timing. 8
Red Flag Symptoms Requiring Immediate Evaluation
- Fever >38.5°C or signs of sepsis. 8
- Increasing abdominal pain or purulent drainage from incisions. 8
- Decreased urine output or dark urine. 8
- Signs of dehydration (decreased urine output, dizziness, dry mucous membranes). 8
Center Requirements
HIPEC should only be performed at high-volume centers with specialized expertise, as they demonstrate better outcomes and lower complication rates. 5, 2 The procedure requires a dedicated team of surgeons, anesthesiologists, and intensivists with proper infrastructure. 6