Approach Considerations
The decision to proceed with surgery depends on the symptoms, elevation of tumor markers, and imaging findings specific for peritoneal cancer. One should have high suspicion for peritoneal mesothelioma in any individual with evidence of a diffuse malignant process in the abdomen on imaging. Multimodality therapy is currently the most commonly accepted therapeutic approach to peritoneal mesothelioma.
For patients without extraperitoneal spread of diffuse malignant peritoneal mesothelioma who have a good performance status, cytoreduction surgery (CRS) and hyperthermic intraoperative peritoneal perfusion with chemotherapy is recommended. This includes using the combination of surgical cytoreduction, intraperitoneal perioperative chemotherapy, and hyperthermia.
Medical Care
Intraperitoneal chemotherapy greatly enhances drug concentrations in the peritoneal cavity and decreases its systemic toxicity. See the videos below.
First-line chemotherapy for peritoneal cancer is a platinum agent with a taxane. A 2006 multiple-treatment meta-analysis that included 60 trials in women showed that a platinum-taxane combination improved survival when compared with taxane. If patients are found to have breast cancer susceptibility gene 1 or 2 (BRCA1/2)) mutations (BRCA carriers), olaparib maintenance therapy is recommended.
In addition to the intraoperative use of heated chemotherapeutic drugs such as cisplatin, mitomycin, or doxorubicin, newer techniques include adding immunotherapeutic agents such as interleukins and interferons. While the median survival with traditional therapeutic options ranges from 4 to 12 months, the application of multimodality therapy has shown promising results with increased survival approaching 60 months. [22]
For patients with unresectable or recurrent malignant mesothelioma, palliative systemic chemotherapy (with different regimens such as cisplatin plus pemetrexed) should be considered. Other antineoplastic agents that may be used include cisplatin plus paclitaxel or mitomycin, doxorubicin, and irinotecan. Preclinical trails have shown a possible role of phosphatidylinositol-3-kinase (P13K) in peritoneal mesothelioma, and P13K inhibitors are a potential therapy. In 2017, the FDA approved pembrolizumab, a programmed death 1 (PD-1) inhibitor, for patients with mesothelioma that is refractory to other treatment options.
Primary peritoneal carcinoma is treated similarly to ovarian cancer, with cytoreduction and chemotherapy. Multimodality treatment consisting of tumor debulking followed by chemotherapy regimens based on 5-fluorouracil, doxorubicin, or cisplatin has been shown to have high response rate and improvement of median survival. Furthermore, the use of newer antineoplastic agents such as taxanes, topoisomerase I inhibitors, gemcitabine, and vinorelbine, alone or in combinations (eg, gemcitabine/cisplatin, irinotecan/cisplatin, docetaxel/gemcitabine, gemcitabine/carboplatin) has increased median survival to 8-11 months. In addition to chemotherapeutic agents, antiangiogenic drugs such as bevacizumab and erlotinib have shown some benefit.
In 2014, the FDA approved bevacizumab (Avastin) for platinum-resistant, recurrent, epithelial ovarian cancer in patients who received no more than two prior chemotherapy regimens. It is indicated for use in combination with paclitaxel, pegylated liposomal doxorubicin, or topotecan. [23] In 2016, bevacizumab’s indication was expanded to include treatment of platinum-sensitive recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, in combination with carboplatin and either paclitaxel or gemcitabine, followed by bevacizumab alone. [24, 25]
It is generally accepted that all patients with good performance status should be considered for a trial of empiric chemotherapy, preferably with a regimen containing newer drugs. The combination of paclitaxel and carboplatin is a reasonable first-line therapy with the addition of a third agent (etoposide or gemcitabine) providing possible benefit. Supportive measures should be considered in patients with poor performance status.
Secondary peritoneal carcinomatosis of unknown primary site usually responds to chemotherapy regimens that are effective in the treatment of advanced epithelial ovarian cancer.
Surgical Care
Treatment of primary peritoneal carcinoma consists of total abdominal hysterectomy and bilateral salpingo-oophorectomy as needed, with debulking of tumor and follow-up chemotherapy.
Cytoreductive surgery (CRS) is the removal of macroscopic peritoneal tumors. It may involve multiple peritonectomy and visceral resection procedures. Electrosurgery is used to limit bleeding from the vascular peritoneal surface. [12]
Treatment of malignant peritoneal mesothelioma consists primarily of surgical palliation. Complete surgical resection is rarely, if ever, feasible and has not been shown to afford a survival benefit in the absence of additional therapy. If laparoscopy is used to help make the initial diagnosis, confine port sites to the abdominal midline because port site recurrence has been described, requiring extensive abdominal wall resection. [26]
Benign cystic mesothelioma tends to recur even with aggressive surgical removal; however, among recorded cases, no deaths have been attributable to this disorder.
In patients with desmoplastic small cell tumors, the combination of aggressive surgical debulking and systemic chemotherapy with cyclophosphamide, doxorubicin, and vincristine interspersed with ifosfamide, etoposide, and mesna (P6 protocol) appears to lead to an improved outcome. However, surgical excision is recommended only for nonmetastatic disease. [27]
Treatment of peritoneal and GI hemangiomas has involved surgical removal.
Consultations
Patients strongly suspected to have peritoneal carcinoma should be referred to a gynecologic oncologist.
Long-Term Monitoring
Follow up to evaluate patients for complications of the cancer, spread of the cancer, and possible complications of therapy. Screening for known associated cancers and cancer syndromes is essential.
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Dr. Oliver Zivanovic, MD, PhD, discusses the role of hyperthermic intraperitoneal chemotherapy in ovarian cancer. Courtesy of Memorial Sloan-Kettering Cancer Center.
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Dr. Oliver Zivanovic, MD, PhD, demonstrates hyperthermic intraperitoneal chemotherapy for ovarian cancer. Courtesy of Memorial Sloan-Kettering Cancer Center.
