Hyperthermic Intraperitoneal Chemotherapy and Cytoreductive Surgery in the Management of Peritoneal Carcinomatosis

Rahul Rajeev, MBBS; Kiran K. Turaga, MD

Disclosures

Cancer Control. 2016;23(1):36-46. 

In This Article

Abstract and Introduction

Abstract

Background: Malignant peritoneal disease can lead to significant debility due to bowel obstructions, ascites, and cancer cachexia. Moreover, inadequate imaging techniques can lead to the suboptimal detection of disease, and the poor vascularity of tumors can lead to a poor response to systemic chemotherapy. However, combination cytoreductive surgery/hyperthermic intraperitoneal chemotherapy (HIPEC) is a promising novel treatment for patients with this disease.

Methods: The medical literature focusing on diagnostic updates and the management of peritoneal disease was reviewed. The application principles of HIPEC for use in peritoneal disease were also summarized.

Results: Improvements in imaging and the application of laparoscopic techniques have significantly increased the rate of diagnosis of early peritoneal disease with consequently less morbid cytoreductive procedures. Appropriate patient selection based on prognostic scores along with complete cytoreduction can identify a cohort of patients likely to derive durable benefit from this combination treatment.

Conclusions: Advances in diagnostic and therapeutic techniques, including surgical cytoreductive techniques, have demonstrated significant survival gains in patients with peritoneal disease. Although HIPEC can be used for the management of various types of histologies, further development of high-level evidence is necessary to advance the field.

Introduction

Peritoneal metastases represent an advanced stage of abdominal cancers and often present with disseminated disease. The incidence of peritoneal metastases varies from 60% in ovarian cancers to 20% in gastric cancer and 8% to 17% colorectal cancer.[1,2] An estimated 134,490 cases of colorectal cancer, 26,370 cases of gastric cancer, and 22,280 cases of ovarian cancer are expected to be diagnosed in 2016 in the United States alone, with estimated deaths from these cancers to reach 74,160.[3]

Many mechanisms of peritoneal spread have been proposed.[4–7] Invasion of the luminal wall by invasive cancer or a perforation of the wall by a noninvasive tumor may lead to a direct spread to the peritoneum.[4] Adherence molecules on free cancer cells may aid in peritoneal implantation.[5] Iatrogenic spread during surgery, when tumor emboli are released from blood vessels and the lymphatics, is also a possible cause. When untreated, peritoneal carcinomatosis rapidly progresses to malignant ascites, acute bowel obstruction, and perforation requiring aggressive palliative chemotherapy or surgery. Although patients with extraperitoneal metastases undergoing interventions of curative intent now have acceptable survival rates, peritoneal surface disease was historically considered an incurable entity and palliative therapy resulted in a median survival rate of a few months to less than 1 year.[6,7]

The magnitude of the burden of peritoneal metastasis is often underappreciated due to the low sensitivity rate of common imaging techniques for peritoneal disease.[8] The rate of sensitivity of computed tomography in identifying peritoneal disease depends on the location in the abdomen, the size of individual nodules, and the morphology of the disease. The rate of sensitivity of computed tomography is 11% for visualizing peritoneal nodules less than 0.5 cm in size in the setting of colorectal disease, a rate that is unacceptable in clinical practice.[8] However, use of advanced imaging for the detection of peritoneal carcinomatosis outside referral centers is infrequent, and many cases may go unreported.[9] Consequently, peritoneal metastases are rarely included in clinical trials of systemic chemotherapy because the disease and its progression are often not detected by imaging standards set in the trials.[2]

Conventional antineoplastic strategies for visceral metastasis are not effective for peritoneal cancer. Although systemic chemotherapy has become more successful for use in visceral metastases, a secondary analysis of 2 phase 3 trials on systemic chemotherapy in metastatic colorectal cancer demonstrated that peritoneal metastases incur a 30% reduction in rate of overall survival (OS) than nonperitoneal metastases, even after adjusting for other prognostic factors (Fig 1).[2] This lower rate of survival in peritoneal carcinomatosis suggests an inherent unfavorable biology.[2]

Figure 1.

Overall survival rate by CRC-PC status. RC-PC = colorectal cancer/peritoneal carcinomatosis.
From Franko J, Shi Q, Goldman CD, et al. Treatment of colorectal peritoneal carcinomatosis with systemic chemotherapy: a pooled analysis of north central cancer treatment group phase III trials N9741 and N9841. J Clin Oncol. 2012;30(3):263–267. Reprinted with permission. © 2012 American Society of Clinical Oncology. All rights reserved.

Cytoreductive surgeries in solid organ metastases have been useful as a curative therapy, whereas its use has been evolving over time for peritoneal disease. For patients with isolated metastasis to the peritoneum, cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) yields improved rates of survival and quality of life.[10,11] This multidisciplinary therapy is based on the concept of the peritoneum as an organ and hypothesizes that improved prognosis is achieved with complete removal of disease from the peritoneum.

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