What qualifies a patient for Hyperthermic Intraperitoneal Chemotherapy (HIPEC)?

HIPEC Qualification Criteria

For ovarian cancer, HIPEC should be offered at interval debulking surgery (IDS) in patients with stage III epithelial ovarian, fallopian tube, or primary peritoneal cancer who have received neoadjuvant chemotherapy (NACT) and demonstrate response or stable disease, with the critical requirement that complete or optimal cytoreduction is achievable. 1

Primary Indication: Ovarian Cancer with NACT

The NCCN Guidelines, based on the M06OVH-OVHIPEC trial (n=245), establish the clearest evidence-based indication for HIPEC 1:

• Stage III disease (FIGO stage III primary epithelial ovarian, fallopian tube, or peritoneal cancer) 1
• Neoadjuvant chemotherapy completed: 3 cycles preferred, but 4-6 cycles allowed 1
• Response or stable disease after NACT (patients with disease progression during NACT are excluded) 1
• Interval debulking surgery planned (not primary debulking surgery) 1
• Achievable complete cytoreduction: Maximum effort to achieve R0 resection (no macroscopic residual disease) is essential, as residual disease is the strongest predictor of overall survival 1

Critical exclusion: HIPEC is NOT recommended for patients undergoing primary debulking surgery (PDS) without NACT, as randomized trials showed no improvement in progression-free survival or overall survival in this population 1

Disease-Specific Considerations

Ovarian Cancer

• No additional selection criteria beyond stage III disease with NACT and IDS are required, as the M06OVH-OVHIPEC trial showed consistent benefit across subgroups (age, histologic type, prior surgery, extent of disease) 1
• Patients with splenic metastases and pleural effusion may be included 1
• Exclude: Liver metastases, supraclavicular metastatic adenopathy, extra-abdominal metastases, complete intestinal obstruction 1

Colorectal Peritoneal Carcinomatosis

• Insufficient evidence to recommend HIPEC with cytoreductive surgery outside of clinical trials 2
• If considered experimentally: Peritoneal Cancer Index (PCI) <20, complete cytoreduction achievable, no extra-abdominal metastases 3, 4

Appendiceal Neoplasms

• Should be referred to HIPEC specialty centers for assessment as part of research protocols, not standard of care 2
• Historical data show acceptable outcomes in selected patients 5

Gastric Peritoneal Carcinomatosis

• Insufficient evidence to recommend outside clinical trials 2

Malignant Peritoneal Mesothelioma

• Should be referred to HIPEC specialty centers for research protocol assessment, not standard of care 2
• Some institutional series show feasibility 5

Gallbladder Carcinoma with Peritoneal Metastases

• CRS with HIPEC should only be considered in highly selected patients with limited peritoneal disease (PCI <20), complete cytoreduction achievable, good performance status, and no extra-abdominal metastases 3
• This approach remains experimental and should only be performed in specialized centers within clinical trials 3

Essential Patient Selection Criteria (All Tumor Types)

Performance Status

• Good performance status required (ECOG 0-1 or Karnofsky ≥50) 3
• Patients must be stable enough to tolerate extensive surgery and postoperative chemotherapy 3

Disease Burden

• High-volume intraperitoneal disease with peritoneal carcinomatosis, at risk for widespread residual microscopic disease even after resection 1
• No distant extra-abdominal metastases (intraperitoneal therapy ineffective for extraperitoneal disease) 1
• Resectable disease: Complete or optimal cytoreduction must be achievable 1, 5

Surgical Feasibility

• Completeness of cytoreduction score 0 (CC-0) or optimal cytoreduction achievable (residual disease <1 cm) 1, 5
• Patients with less extensive disease are excluded because potential benefit unlikely to outweigh procedural risks 1

Specialized Center Requirements

• Treatment must occur at specialized centers with expertise in cytoreductive surgery and HIPEC 4, 2
• The PRODIGE 7 trial achieved 91% complete cytoreduction rates due to center expertise 4
• Institutional experience correlates with decreased complication rates over time 6

Postoperative Requirements

• All patients must receive postoperative chemotherapy (typically 3 cycles) after NACT and IDS with HIPEC 1
• The NCCN-recommended HIPEC agent is cisplatin 100 mg/m² (as used in M06OVH-OVHIPEC) 1

Common Pitfalls to Avoid

• Do not offer HIPEC for primary debulking surgery in ovarian cancer without NACT—evidence shows no benefit 1
• Do not proceed if complete cytoreduction cannot be achieved—residual disease is the strongest predictor of poor outcomes 1, 5
• Do not offer to patients with extra-abdominal metastases—intraperitoneal therapy will not address systemic disease 1
• Do not perform in centers without specialized expertise—morbidity ranges from 9-40% for major complications, and outcomes depend heavily on surgical skill 1, 4

Repeat HIPEC Considerations

• Repeat CRS with HIPEC can be considered in highly selected patients with peritoneal-only recurrence after initial CRS/HIPEC 6, 7
• Median interval between procedures: 20-26 months 6, 7
• Requires same selection criteria: complete cytoreduction achievable, no extra-abdominal disease, good performance status 6, 7
• Can be performed with acceptable morbidity (14-33% grade 3-4 complications) and no 30-day mortality in experienced centers 6, 7