HIPEC: Evaluation and Treatment Process
Overview of HIPEC Technique
HIPEC is a specialized intraoperative procedure where heated chemotherapy (typically 41-43°C) is perfused throughout the peritoneal cavity for 60-90 minutes immediately following cytoreductive surgery, designed to treat microscopic residual peritoneal disease through enhanced drug penetration and heat-induced tumor cell sensitization. 1
The technique involves delivering chemotherapy in a heated solution that increases drug penetration at the peritoneal surface and enhances cancer cell sensitivity by inhibiting DNA repair mechanisms 1. Both "open" and "closed" abdominal techniques exist, with procedure times ranging from 300-600 minutes and hospital stays of 8-24 days 1.
Disease-Specific Indications
Ovarian Cancer (Strongest Evidence)
For stage III epithelial ovarian, fallopian tube, or primary peritoneal cancer, HIPEC should be considered ONLY at interval debulking surgery (IDS) after neoadjuvant chemotherapy (NACT), NOT at primary debulking surgery. 1
Specific Patient Selection Criteria:
- Stage III disease with extensive abdominal involvement requiring NACT 1
- Response or stable disease after 3 cycles of NACT (preferred) or 4-6 cycles (acceptable) 1
- Complete or optimal cytoreduction (R0 resection) achieved at IDS 1
- Exclude patients treated with primary debulking surgery without NACT - randomized trials show no PFS or OS benefit in this population 1
NCCN-Recommended Protocol:
- Cisplatin 100 mg/m² as the HIPEC agent 1
- Carboplatin (AUC 5-6) + paclitaxel (175 mg/m²) for NACT and postoperative chemotherapy 1
- Minimum 6 total cycles of chemotherapy, including at least 3 cycles after IDS 1
Outcomes Data:
The M06OVH-OVHIPEC trial (n=245) demonstrated improved recurrence-free survival and overall survival with HIPEC versus surgery alone, with comparable toxicity rates (grade 3-4: 27% vs 25%) and no differences in quality of life metrics 1.
Gastric Cancer (Limited Evidence)
For gastric cancer with peritoneal metastases, HIPEC with cytoreductive surgery can be considered ONLY in highly selected patients with limited peritoneal disease (low PCI score) at experienced centers, but evidence remains insufficient for standard-of-care recommendation. 1, 2
Evaluation Requirements:
- Diagnostic laparoscopy with peritoneal washings is mandatory for all stage IB-III potentially resectable gastric cancers to detect occult peritoneal disease 1, 2
- Document peritoneal disease using Peritoneal Carcinomatosis Index (PCI) 1, 2
- Lower PCI scores correlate with better prognosis and may identify HIPEC candidates 1, 2
- Positive peritoneal cytology (CY+) without visible implants should be considered M1 disease - surgery not recommended as initial treatment 2
Critical Caveat:
The NCCN guidelines do not recommend surgery as initial treatment for patients with positive peritoneal cytology, and the additional value of HIPEC needs establishment in ongoing clinical trials 1.
Colorectal Cancer (Experimental Only)
For colorectal cancer with peritoneal metastases, there is insufficient evidence to recommend HIPEC with cytoreductive surgery outside of clinical trials. 1, 3
ESMO Position:
- Complete cytoreductive surgery can be considered for peritoneal-only metastases 1
- HIPEC addition is experimental and cannot be recommended outside clinical trial settings 1
- Risks must be balanced carefully against uncertain benefits 1
Pan-Asian Guidelines:
Complete cytoreductive surgery and HIPEC can be considered for patients with limited peritoneal metastases only in centers experienced with HIPEC (Level III, C evidence) 1.
Preoperative Evaluation Algorithm
Step 1: Imaging Assessment
- Contrast-enhanced CT thorax/abdomen/pelvis for staging 1
- Note: CT has limited sensitivity (28-51%) for peritoneal metastases despite high specificity (97-99%) 2
- FDG-PET/CT not routinely recommended - detects only 3% of occult peritoneal metastases versus 19% by diagnostic laparoscopy 2
Step 2: Invasive Staging (Disease-Specific)
- For gastric cancer stage IB-III: Mandatory diagnostic laparoscopy with peritoneal washings 1, 2
- Direct visualization of peritoneal surfaces with targeted biopsies 2
- Peritoneal washing cytology to identify occult carcinomatosis 2
- Document PCI score 1, 2
Step 3: Patient Fitness Assessment
- Experienced gynecologic oncologist evaluation (for ovarian cancer) 1
- Multidisciplinary tumor board discussion mandatory 1
- Assessment of ability to achieve complete cytoreduction (R0 resection) 1
Step 4: Exclusion Criteria Identification
- Extra-abdominal metastases (contraindication in most protocols) 1
- Bulky retroperitoneal disease 1
3 sites of bowel obstruction 1
- Parenchymal liver metastases (disease-specific) 1
- Inability to achieve optimal cytoreduction 1
Surgical Procedure Requirements
Cytoreductive Surgery Goals
The primary goal is complete removal of all macroscopic disease (R0 resection) - residual disease after debulking is the strongest predictor of overall survival. 1
- Optimal cytoreduction rates in trials: 45-91% of patients 1
- Complete cytoreduction (R0) achieved in 30-59% of patients 1
- Procedures include TAH/BSO, omentectomy, and additional procedures based on disease extent 1
HIPEC Administration
- Perfusion duration: 60-90 minutes depending on agent and dose 1
- Intraperitoneal temperature: 41-43°C 1
- Administered immediately after cytoreduction as part of same procedure 1
Complications and Safety Profile
Expected Morbidity
- Major/severe complications occur in 9-40% of patients within 30 days 1
- Intraoperative/postoperative mortality: 0-7% (most recent trials report 0%) 1
- Median hospital stay: 8-24 days 1
- Excessive blood loss common - >50% require transfusions in some studies 1
Common Major Complications
- Fistulas (various types), abscesses, infections (wound, sepsis, pneumonia, intra-abdominal) 1
- Surgical wound dehiscence, bowel perforation, ileus 1
- Hemorrhages, venous thromboembolism, myocardial infarction 1
- Pleural effusions, pneumothorax, renal failure/insufficiency 1
- Additional procedures frequently needed to manage complications 1
Ovarian Cancer-Specific Toxicity
- Grade 3-4 toxicities: 27% with HIPEC versus 25% without (no significant difference) 1
- Increased anemia (67% vs 50%, p=0.025) and creatinine elevation (15% vs 4%, p=0.026) 1
- No differences in hospital stay (median 10 vs 8 days) or ability to complete postoperative chemotherapy 1
Postoperative Management
Chemotherapy Requirements
All patients receiving HIPEC must complete systemic chemotherapy postoperatively. 1
- Minimum 6 total cycles of treatment (NACT + postoperative) 1
- At least 3 cycles of adjuvant therapy after IDS required 1
- Same regimen as NACT typically continued (carboplatin/paclitaxel for ovarian cancer) 1
Critical Practice Pitfalls
Do NOT Offer HIPEC For:
- Ovarian cancer at primary debulking surgery (no NACT) - no survival benefit demonstrated 1
- Patients with disease progression during NACT 1
- Extra-abdominal metastatic disease 1
- Inability to achieve optimal cytoreduction 1
- Colorectal or gastric cancer outside clinical trials (insufficient evidence) 1, 3