This Clinician's View is written by Christopher Aquina, MD colon and rectal surgeon and surgical oncologist at AdventHealth Orlando.
Colon and Rectal Surgeon and Surgical Oncologist
Several cancers can cause peritoneal carcinomatosis, including peritoneal mesothelioma and primary peritoneal cancer as well as secondary cancers that have metastasized from the gastrointestinal (GI) tract — appendiceal, colon, rectal, and gastric cancers – or from the ovaries. In fact, approximately 60,000 patients in the U.S. are diagnosed with peritoneal metastases each year. When the cancer is confined to the peritoneal cavity or there are limited extraperitoneal metastases, cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) has emerged as a safe and viable treatment option for certain patients, improving both their survival and quality of life. AdventHealth began offering this treatment modality in 2022.
Treating Peritoneal Surface Malignancy with CRS/HIPEC
Treatment of peritoneal surface malignancy has always presented a challenge, requiring a careful balance of eradicating or managing the cancer while minimizing morbidity. CRS/HIPEC takes a very targeted approach to eliminate or at least minimize many of the obstacles.
First, the patient is carefully evaluated preoperatively to determine if they are potential candidates for CRS/HIPEC. Assessment of the patient’s functional status, tumor histology, and disease burden with the use of cross-sectional imaging and diagnostic laparoscopy is performed. For patients in which optimal cytoreduction (elimination of all visible disease or debulking down to minimal residual disease) appears feasible, the patient is taken for exploratory laparotomy under general anesthesia, and the surgeon removes all tumor nodules directly or with organ resection, which may include omentectomy, appendectomy, small bowel resection, colectomy, proctectomy, splenectomy, cholecystectomy, hysterectomy, hepatectomy, and/or cystectomy. Immediately following the CRS, a sterile chemotherapy solution heated to 42 degrees Celsius is circulated throughout the peritoneal cavity for 90-100 minutes. This hyperthermia helps increase the chemotherapy’s cytotoxicity to the cancer cells.
Specific benefits of HIPEC compared to systemic chemotherapy include the following:
- Higher concentration of chemotherapy delivered directly to the cancer cells
- Improved drug absorption due to direct delivery
- Minimal chemotherapy absorption into the bloodstream, resulting in decreased toxic side effects
Improved Safety and Effectiveness of CRS/HIPEC
In 1980, Dr. John Spratt first introduced the basic concept of HIPEC when he treated a patient with pseudomyxoma peritonei with intraperitoneal thiotepa followed by hyperthermic intraperitoneal methotrexate. Throughout the 1980s and 1990s, physicians continued to explore this approach, attempting a combination of CRS and HIPEC to treat peritoneal metastasis. However, they struggled with high mortality and morbidity rates. Since that time, we have significantly advanced the approach to CRS/HIPEC, improving surgical technique and optimizing patient selection to achieve better outcomes. In a large cohort study that included 1,200 consecutive patients who underwent CRS/HIPEC between 1994 and 2014, the rate of complete cytoreduction increased from 61% to 80%, the rate of major complications halved from 14% to 7%, and the perioperative mortality rate decreased from 3% to 0.7% over the study period.
A multi-institutional outcome study of 1,822 patients who received CRS/HIPEC was published in JAMA Network in 2019, and found the procedure to be safe across the full range of National Surgical Quality Improvement Project safety metrics when compared with other high-risk oncologic procedures, such as esophagectomy, hepatectomy, and pancreaticoduodenectomy. Additional prospective studies and randomized controlled trials have demonstrated the safety and survival benefit of CRS/HIPEC. Key findings from these studies included the following:
- Overall 30-day mortality was lower with CRS/HIPEC (1.1%) compared to pancreaticoduodenectomy (2.5%), right lobe hepatectomy (2.9%), esophagectomy (3.0%), and trisegmental hepatectomy (3.9%).
- In colorectal cancer peritoneal metastases, median overall survival following CRS+/- HIPEC was 41 months compared to only 16 months with systemic chemotherapy alone.
- In peritoneal mesothelioma and appendiceal cancer peritoneal metastases, CRS/HIPEC significantly improved 5-year survival from less than 10% to 50-90%.
Selecting Candidates for CRS/HIPEC
When we evaluate a patient for CRS/HIPEC, we take into consideration patient fitness, the specific tumor type and histology, the locations and volume of peritoneal metastases as measured by the peritoneal carcinomatosis index (PCI), and the ability to achieve optimal cytoreduction. The multidisciplinary Chicago Consensus Working Group has established the following treatment consensus guidelines for the management of peritoneal surface malignancies:
In general, all patients with peritoneal surface malignancy from low-grade appendiceal mucinous neoplasm (LAMN), pseudomyxoma peritonei, or peritoneal mesothelioma and those with appendiceal or colorectal cancer adenocarcinoma with limited or no extraperitoneal metastatic disease should be referred to a peritoneal surface malignancy specialist.
Looking Ahead
Peritoneal carcinomatosis remains a challenging diagnosis. However, through the increased use of CRS/HIPEC as appropriate, we can provide some patients with a highly targeted, effective treatment option that can bring them both improved survival and quality of life. Other modalities, such as prophylactic HIPEC in patients at high risk for development of peritoneal metastases and pressurized intraperitoneal aerosolized chemotherapy (PIPAC) for patients who are initially not candidates for CRS/HIPEC due to burden of disease, are currently under investigation and may become additional treatment options in the future.
