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Pseudomyxoma peritonei describes extensive mucus accumulation within the peritoneum due to mucinsecreting tumor cells. Peritoneal carcinomatosis from non-ovarian malignancies has long been regarded as a terminal disease with limited survival. Mesotheliomas arise from the mesothelium lining potential spaces of the body, such as the peritoneum. In an attempt to prolong survival in these diseases, aggressive locoregional therapy, such as combining cytoreductive surgery (CRS) with perioperative intraperitoneal chemotherapy, has been used.
CRS and HIPEC
CRS consists of peritonectomy (ie, peritoneal stripping) procedures and multivisceral resections, depending on the extent of intra-abdominal tumor dissemination. The surgical procedure may be followed intraoperatively by the infusion of hyperthermic chemotherapy, most commonly mitomycin C. Inflow and outflow catheters are placed in the abdominal cavity, along with temperature probes to monitor temperature. The skin is then temporarily closed during the chemotherapy perfusion, which typically runs for 1 to 2 hours. This procedure is referred to as HIPEC.
Pseudomyxoma peritonei is a clinicopathologic entity characterized by the production of mucinous ascites and mostly originates from epithelial neoplasms of the appendix. Appendix cancer is diagnosed in fewer than 1,000 Americans each year; less than half are epithelial neoplasms. As mucin-producing cells of the tumor proliferate, the narrow lumen of the appendix becomes obstructed and subsequently leads to appendiceal perforation. Neoplastic cells progressively colonize the peritoneal cavity and produce copious mucin, which collects in the peritoneal cavity. Pseudomyxoma peritonei ranges from benign (disseminated peritoneal adenomucinosis) to malignant (peritoneal mucinous carcinomatosis), with some intermediate pathologic grades. Clinically, this syndrome ranges from early pseudomyxoma peritonei, fortuitously discovered on imaging or during a laparotomy performed for another reason, to advanced cases with a distended abdomen, bowel obstruction, and starvation. The conventional treatment of pseudomyxoma peritonei is surgical debulking repeated as necessary to alleviate pressure effects. However, repeated debulking surgeries become ever more difficult due to progressively thickened intra-abdominal adhesions, and this treatment is palliative, leaving visible or occult disease in the peritoneal cavity. Five-year overall survival (OS) depends on tumor histology and ranges from 6% for high-grade (HG) tumors to 75% for low-grade (LG) tumors.
Gastrointestinal Cancers (Colorectal, Gastric) and Peritoneal Carcinomatosis
Peritoneal dissemination develops in approximately 10–15% of patients with colon cancer, and despite the use of increasingly effective regimens of chemotherapy and biologic agents in the treatment of advanced disease, peritoneal metastases are associated with a median survival of 6 to 7 months.
Peritoneal carcinomatosis is detected in more than 30% of patients with advanced gastric cancer and is a poor prognostic indicator. Median survival is 3 months, and 5-year survival is less than 1%. Sixty percent of deaths from gastric cancer are attributed to peritoneal carcinomatosis. Current chemotherapy regimens are nonstandard, and peritoneal seeding is considered unresectable for cure.
Malignant mesothelioma is a relatively uncommon malignancy that may arise from the mesothelial cells lining the pleura, peritoneum, pericardium, and tunica vaginalis testis. In the U.S., 200-400 new cases of diffuse malignant peritoneal mesothelioma (DMPM) are registered every year, accounting for 10-30% of all-type mesothelioma. DMPM has traditionally been considered as a rapidly lethal malignancy with limited and ineffective therapeutic options. The disease is usually diagnosed at an advanced stage and is characterized by multiple variably sized nodules throughout the abdominal cavity. As the disease progresses, the nodules become confluent to form plaques, masses, or uniformly cover peritoneal surfaces. In most patients, death eventually occurs as a result of locoregional progression within the abdominal cavity. In historical case series, treatment by palliative surgery, systemic/intraperitoneal chemotherapy, and abdominal irradiation results in a median survival of approximately 12 months.
Surgical cytoreduction (resection of visible disease) in conjunction with hyperthermic intraperitoneal chemotherapy is designed to remove visible tumor deposits and residual microscopic disease. By delivering chemotherapy intraperitoneally, drug exposure to the peritoneal surface is increased some 20-fold compared to systemic exposure. In addition, prior animal and in vitro studies have suggested that the cytotoxicity of mitomycin C is enhanced at temperatures greater than 39 degrees Celsius (102.2°F).
Several different types of malignancies can arise in the ovary; epithelial carcinoma is the most common type, accounting for 90% of malignant ovarian tumors. Epithelial ovarian cancer is the fifth most common cause of cancer death in women in the United States. New cases and deaths from ovarian cancer in 2014 are estimated at 21,980 and 14,270, respectively. Most ovarian cancer patients (>70%) present with widespread disease, and annual mortality is approximately 65% of the incidence rate.
Current management of advanced epithelial ovarian cancer is CRS followed by combination chemotherapy. Treatment guidelines recommend intraperitoneal chemotherapy for patients with optimally debulked (<1 cm) stage 2 disease (pelvic extension of tumor) or stage 3 disease (peritoneal extension of tumor). Estimated median OS is 66 months with and 37 to 49 months without intraperitoneal chemotherapy, respectively. However, tumor recurrences are common, and prognosis for recurrent disease is poor.
CRS/HIPEC in combination with systemic chemotherapy is being studied for primary and recurrent disease. Because HIPEC is administered at the time of surgery, treatment-related morbidity may be reduced compared with intraperitoneal chemotherapy administered postoperatively.
Mitomycin, carboplatin, and other drugs used for HIPEC have not been U.S. Food and Drug Administration (FDA)‒approved for this indication. Cyclophosphamide and nitrogen mustard are FDA-approved for intraperitoneal administration, but neither drug is used regularly for this purpose.
Several peritoneal lavage systems (Product Code LGZ) have been FDA-cleared to provide “warmed, physiologically compatible sterile solution” (eg, Performer® HT perfusion system; RanD S.R.L., Medolla, Italy). None has received marketing approval or clearance to administer chemotherapy. FDA has issued warning letters to manufacturers of devices that are FDA-cleared for peritoneal lavage using sterile saline solutions when these devices are marketed for off-label use in HIPEC (eg, ThermaSolutions Inc., Minneapolis, MN; Belmont Instrument Corp., Billerica, MA).
Hyperthermia Therapy is addressed in a separate policy.
Cytoreductive surgery and perioperative intraperitoneal chemotherapy may be considered medically necessary for the treatment of:
Cytoreduction surgery and perioperative intraperitoneal chemotherapy is considered investigational for:
Medically Necessary is defined as those services, treatments, procedures, equipment, drugs, devices, items or supplies furnished by a covered Provider that are required to identify or treat a Member's illness, injury or Nervous/Mental Conditions, and which Company determines are covered under this Benefit Plan based on the criteria as follows in A through D:
A. consistent with the symptoms or diagnosis and treatment of the Member's condition, illness, or injury; and
B. appropriate with regard to standards of good medical practice; and
C. not solely for the convenience of the Member, his or her Provider; and
D. the most appropriate supply or level of care which can safely be provided to Member. When applied to the care of an Inpatient, it further means that services for the Member's medical symptoms or conditions require that the services cannot be safely provided to the Member as an Outpatient.
For the definition of Medically Necessary, “standards of good medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. BCBSMS makes no payment for services, treatments, procedures, equipment, drugs, devices, items or supplies which are not documented to be Medically Necessary. The fact that a Physician or other Provider has prescribed, ordered, recommended, or approved a service or supply does not in itself, make it Medically Necessary.
Investigative is defined as the use of any treatment procedure, facility, equipment, drug, device, or supply not yet recognized as a generally accepted standard of good medical practice for the treatment of the condition being treated and; therefore, is not considered medically necessary. For the definition of Investigative, “generally accepted standards of medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. In order for equipment, devices, drugs or supplies [i.e, technologies], to be considered not investigative, the technology must have final approval from the appropriate governmental bodies, and scientific evidence must permit conclusions concerning the effect of the technology on health outcomes, and the technology must improve the net health outcome, and the technology must be as beneficial as any established alternative and the improvement must be attainable outside the testing/investigational setting.
The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language.
POLICY HISTORY6/16/2008: Policy added
7/6/2009: Policy reviewed, no changes
12/30/2010: Added “Pseudomyxoma Peritonei” to the policy title. Policy description updated regarding disease prevalence and treatment approaches. Policy statement added to indicate that cytoreduction and hyperthermic intraperitoneal chemotherapy for the treatment of pseudomyxoma peritonei may be considered medically necessary; investigational policy statement clarified to specify that the indication considered is peritoneal carcinomatosis from colorectal cancer. CPT code 77605 moved from non-covered to covered. Added CPT code 96445 and ICD-9 code 197.6 as covered codes.
01/17/2012: Policy title changed from "Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy for the Treatment of Pseudomyxoma Peritonei and Peritoneal Carcinomatosis of Gastrointestinal Origin" to "Cytoreductive Surgery and Perioperative Intraperitoneal Chemotherapy for the Treatment of Pseudomyxoma Peritonei, Peritoneal Carcinomatosis of Gastrointestinal Origin, and Peritoneal Mesothelioma." Policy description updated. Policy statement added that cytoreductive surgery and perioperative intraperitoneal chemotherapy for the treatment of peritoneal mesothelioma may be considered medically necessary. Use of the term “hyperthermic” changed to “perioperative” in the title and policy statements to include early postoperative intraperitoneal chemotherapy. Use of the term “cytoreduction” changed to “cytoreductive surgery” to be more specific.
12/13/2012: Policy reviewed; no changes.
12/13/2013: Policy reviewed; no changes.
02/19/2015: Policy title changed from "Cytoreductive Surgery and Perioperative Intraperitoneal Chemotherapy for the Treatment of Pseudomyxoma Peritonei, Peritoneal Carcinomatosis of Gastrointestinal Origin, and Peritoneal Mesothelioma" to "Cytoreductive Surgery and Perioperative Intraperitoneal Chemotherapy for Select Intra-Abdominal and Pelvic Malignancies." Policy description updated regarding pseudomyxoma peritonei, gastrointestinal cancers and peritoneal carcinomatosis, and ovarian cancer. Medically necessary policy statements revised to combine both statements. Added gastric cancer, endometrial cancer, ovarian cancer, and all other indications, including goblet cell tumors of the appendix to the investigational policy statement. Policy guidelines updated to add medically necessary and investigative definitions. Added CPT code 77620 to the Code Reference section.
08/25/2015: Code Reference section updated to add ICD-10 codes. Added ICD-9 diagnosis codes 158.0-158.9. Removed deleted code CPT 96445 and replaced with CPT code 96446.
SOURCE(S)Blue Cross & Blue Shield of Association Policy # 2.03.07
CODE REFERENCEThis may not be a comprehensive list of procedure codes applicable to this policy.
The code(s) listed below are ONLY medically necessary if the procedure is performed according to the "Policy" section of this document.