MSK HIPEC Phase 2 Trial (NCT06057935)

Asbestos exposure causes most cases of mesothelioma, a cancer of the mesothelium lining the lungs, abdomen, heart, or testes. Approximately 80% of cases are pleural mesothelioma in the lung lining, 20% peritoneal in the abdomen, and less than 1% pericardial or testicular. Asbestos fibers inhaled or ingested irritate mesothelial cells, causing chronic inflammation, genetic mutations, and uncontrolled cell growth over 30-50 years. Asbestos also increases risks for lung, ovarian, laryngeal, and some gastrointestinal cancers, but mesothelioma is by far the most common.

Latency periods for malignant pleural mesothelioma after first asbestos exposure range from 14 to 72 years, with a mean of 48.7 years and median of 51 years in a study of 312 cases from Italy. Occupational groups with high-intensity exposure, such as insulators (mean 29.6 years) and dock workers (35.4 years), show shorter latencies than shipyard workers (49.4 years) or those with domestic exposure (51.7 years). Other studies report median latencies of 33.7 to 34 years, with 96% of cases occurring at least 20 years post-exposure. Factors like exposure intensity, duration, and type influence variability, though no single timeline applies universally.

There is no surgery to treat or cure asbestosis, a noncancerous lung scarring condition caused by asbestos exposure. Management focuses on medications, oxygen therapy, and pulmonary rehabilitation to relieve symptoms like shortness of breath. In rare cases of severe complications, such as lung transplantation, evidence shows limited applicability for people with advanced asbestosis, but long-term results remain poor.

Mesothelioma is incurable, with no known cure for any stage, and most people with the disease have a median survival of 12-21 months after diagnosis. Stage 4 mesothelioma, the most advanced stage, carries a median survival of about 12 months, though treatments like chemotherapy and immunotherapy can extend life and improve quality of life in some cases. While 12% of people with mesothelioma survive 5 years or more, the disease is generally considered terminal, especially when diagnosed late.

For some people with cancer limited to the lining of the abdomen, HIPEC has been associated with better survival than traditional chemotherapy alone, especially when surgeons can remove most or all visible disease. HIPEC also delivers chemotherapy directly to the abdomen, which can mean higher local drug levels and fewer whole-body side effects than IV chemotherapy. But the evidence is not uniform across all cancers, and some studies have found no overall survival advantage, even though toxicity was lower. So HIPEC is not broadly better in every situation, but it can be more effective for carefully selected people with peritoneal disease.

Evidence from large series shows that combined cytoreductive surgery and HIPEC is a major operation with reported overall complication (morbidity) rates around 30% to 70% and treatment‑related death (mortality) in roughly 0% to 18%, depending on cancer type, disease extent, and center experience. Common issues include abdominal pain, fatigue, digestive changes, low blood counts, infections, bleeding, and slower return of bowel function, while more serious but less common problems include blood clots, anastomotic leaks, organ injury, and pneumonia. HIPEC also carries specific risks from heated chemotherapy such as temporary kidney strain, fluid and electrolyte imbalance, and hematologic toxicity, which some studies describe in 4% to 39% of people. Long‑term risks can include scar tissue (adhesions) that cause chronic abdominal pain or bowel problems, and there remains a risk of cancer recurrence despite treatment. Outcomes and safety reported in the literature are generally better in high‑volume centers using strict protocols and in people with limited disease and good overall health.

Life expectancy after cytoreductive surgery with HIPEC varies widely, but large series report median overall survival around 3 to 4.5 years across mixed abdominal cancers. For people with peritoneal mesothelioma, several studies cited in cancer centers and mesothelioma advocacy sites describe an average survival of about 53 months (nearly 4.5 years), with some reports noting that many live 5 to 10 years or longer. Outcomes depend heavily on cancer type, stage, peritoneal cancer index (PCI), completeness of tumor removal, tumor biology, and overall health. Reported 5‑year survival rates after HIPEC range from roughly 36% to more than 69% in selected groups, and certain appendix or low‑grade peritoneal diseases can have median survivals approaching 20 years. These figures represent group averages, so individual trajectories for people with mesothelioma can be shorter or longer than published estimates.

HIPEC combined with cytoreductive surgery is often called the “mother of all surgeries” because it is extremely long, complex, and physically demanding. Reports from major centers describe operations that can last 6 to 16 hours or more, sometimes involving removal of multiple organs and meticulous scraping of tumor deposits from the peritoneum. After visible tumors are removed, surgeons circulate heated chemotherapy inside the abdomen to reach microscopic cancer cells, which adds time and technical difficulty. Complication rates can be significant, recovery is lengthy, and people with mesothelioma or other peritoneal cancers usually need intensive postoperative care. Despite these challenges, studies in cancers such as pseudomyxoma peritonei, appendix cancer, and ovarian cancer report improved survival for selected people when HIPEC is paired with extensive tumor removal.