HIPEC (Hyperthermic Intraperitoneal Chemotherapy)

Definition

HIPEC is the delivery of heated chemotherapy directly into the peritoneal cavity at the time of surgery, typically following cytoreductive surgery (CRS). It is the cornerstone treatment for peritoneal surface malignancies (PSM). - Fischer's Mastery of Surgery, 8th ed., p. 1013-1014

Rationale

The peritoneal cavity represents a natural barrier that limits systemic absorption, allowing high local drug concentrations with reduced systemic toxicity. Heat (41-43°C) enhances drug cytotoxicity and tissue penetration. HIPEC is administered using a heating perfusion apparatus that circulates the heated chemotherapy solution via an open or closed technique for a defined duration. - Fischer's Mastery of Surgery, p. 1014

Indications (Established and Investigational)

Tumor Type	Evidence Level
Pseudomyxoma peritonei	Strong - reference treatment
Peritoneal mesothelioma	Strong - reference treatment
Ovarian cancer (recurrent/initially unresectable)	Strong option
Colorectal peritoneal metastases	Established
Gastric cancer with peritoneal metastases	Investigational / selective

CRS + HIPEC is "today the reference treatment for pseudomyxoma peritonei and peritoneal mesothelioma, a strong option for treatment of initially nonresectable ovarian cancer." - Fischer's Mastery of Surgery, p. 1014

Peritoneal Cancer Index (PCI)

Before HIPEC, tumor burden is quantified using the PCI score (0-39), dividing the abdomen and small bowel into 13 regions (sites 0-12), each scored 0-3. PCI is the main prognostic factor and directs treatment sequencing. A high PCI in colorectal or gastric cancer is associated with no survival benefit from CRS/HIPEC. - Fischer's Mastery of Surgery, p. 1006

Commonly Used Drugs by Indication

Indication	HIPEC Drug
Ovarian	Cisplatin
Colorectal	Mitomycin-C / Oxaliplatin
Pseudomyxoma peritonei	Mitomycin-C / Oxaliplatin
Peritoneal mesothelioma	Cisplatin / Mitomycin-C
Gastric	Mitomycin-C / Oxaliplatin / Cisplatin

Other less commonly used agents include Paclitaxel, Gemcitabine, and Melphalan. - Fischer's Mastery of Surgery, Table 33.2

Cytoreductive Surgery (CRS)

CRS precedes HIPEC and involves all necessary procedures to achieve complete peritoneal resection: multivisceral resections, omentectomy, and peritonectomy (Sugarbaker technique). Leaving behind any residual disease has severe prognostic consequences. CRS + HIPEC must be performed by trained surgeons in specialized centers. - Fischer's Mastery of Surgery, p. 1013

The goal is CC-0 resection (complete cytoreduction - no visible residual tumor).

Contraindications

Extensive extraperitoneal (systemic) metastases
Unresectable disease
Poor performance status or inability to tolerate major surgery
Previous anaphylactic reaction to the chemotherapy agent
Severe renal or hepatic impairment
Myelosuppression
Severe myocardial insufficiency, recent MI, or arrhythmias

All patients must be evaluated by a specialized multidisciplinary tumor board. - Fischer's Mastery of Surgery, p. 1011

Preoperative Optimization

Given the invasiveness of CRS + HIPEC, prehabilitation is important:

Nutritional optimization (immunomodulatory supplements, enteral/parenteral nutrition in malnourished patients)
Respiratory physiotherapy
Hematologic optimization (preoperative systemic chemotherapy often causes bone marrow suppression)
Psycho-oncological support

Outcomes (Recent Evidence)

CRS + HIPEC is associated with significantly improved progression-free and overall survival vs. palliative chemotherapy alone for peritoneal carcinomatosis [Grainger & Allison's Diagnostic Radiology].
A 2024 systematic review and cost-effectiveness analysis (PMID: 39254852) evaluated HIPEC + CRS across tumor types including ovarian, colorectal, and gastric cancers.
A 2025 worldwide systematic review of national HIPEC guidelines (PMID: 40413333) analyzed recommendations from multiple countries, reflecting growing international consensus on indications and techniques.
For repeat CRS + HIPEC in colorectal peritoneal metastases, a 2024 systematic review (PMID: 38627808) found it is feasible in selected patients with acceptable morbidity.

PIPAC - Emerging Alternative

PIPAC (Pressurized Intraperitoneal Aerosol Chemotherapy) is a minimally invasive alternative for unresectable peritoneal disease - laparoscopic delivery of aerosolized chemotherapy under pressure. It does not attempt curative cytoreduction but allows repeated treatment, PCI assessment, and biopsies. Uses the same drug classes as HIPEC (e.g., oxaliplatin for colorectal, cisplatin + doxorubicin for ovarian). - Fischer's Mastery of Surgery, p. 1014

Summary

CRS + HIPEC represents a multimodal locoregional treatment strategy that can offer long-term survival or cure in carefully selected patients with peritoneal surface malignancies. Patient selection (especially PCI), surgical expertise, center volume, and complete cytoreduction (CC-0) are the key determinants of outcome.

This is a shared conversation. Sign in to Orris to start your own chat.