Hyperthermic Intraperitoneal Chemotherapy for Select Intra-Abdominal and Pelvic Malignancies

POLICY NUMBER

A.2.03.07

DESCRIPTION

Cytoreductive surgery (CRS) includes peritonectomy (ie, peritoneal stripping) procedures and multivisceral resections, depending on the extent of intra-abdominal tumor dissemination. Cytoreductive surgery may be followed by infusion of intraperitoneal chemotherapy with or without heating, which is intended to improve the tissue penetration of the chemotherapy. When heated, this is referred to as hyperthermic intraperitoneal chemotherapy (HIPEC). Cytoreductive surgery and HIPEC have been proposed for a number of intra-abdominal and pelvic malignancies such as pseudomyxoma peritonei and peritoneal carcinomatosis from colorectal, gastric, or endometrial cancer.

Pseudomyxoma Peritonei

Pseudomyxoma peritonei is a clinicopathologic disease 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. The incidence of pseudomyxoma peritonei is estimated at 2 cases per 1 million individuals. 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, usually discovered during imaging or laparotomy performed for another reason, to advanced cases with a distended abdomen, bowel obstruction, and starvation.

TreatmentThe conventional treatment of pseudomyxoma peritonei is surgical debulking repeated as necessary to alleviate pressure effects. However, repeated debulking surgeries become more difficult due to progressively thickened intra-abdominal adhesions, and this treatment is palliative, leaving visible or occult disease in the peritoneal cavity.

Peritoneal Carcinomatosis of Colorectal Origin

Peritoneal dissemination develops in 10% to 15% of patients with colon cancer.

TreatmentDespite the use of increasingly effective regimens of chemotherapy and biologic agents to treat advanced disease, peritoneal metastases are associated with a median survival of 6 to 7 months.

Peritoneal Carcinomatosis of Gastric Origin

Peritoneal carcinomatosis is detected in more than 30% of patients with advanced gastric cancer and is a poor prognostic indicator. The 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.

TreatmentCurrent chemotherapy regimens are nonstandard, and peritoneal seeding is considered unresectable for a cure.

Peritoneal Mesothelioma

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 United States, 200 to 400 new cases of diffuse malignant peritoneal mesothelioma are registered every year, accounting for 10% to 30% of all-type mesothelioma. Diffuse malignant peritoneal mesothelioma has traditionally been considered 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 results from locoregional progression within the abdominal cavity. In historical case series, treatment by palliative surgery, systemic or intraperitoneal chemotherapy, and abdominal irradiation has resulted in a median survival of 12 months.

TreatmentSurgical cytoreduction (resection of visible disease) in conjunction with hyperthermic intraperitoneal chemotherapy (HIPEC) 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 with systemic exposure. In addition, previous animal and in vitro studies have suggested that the cytotoxicity of mitomycin C is enhanced at temperatures greater than 39°C (102.2°F).

Ovarian Cancer

Several different types of malignancies can arise in the ovaries; epithelial carcinoma is the most common, 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. Most ovarian cancer patients (>70%) present with widespread disease, and annual mortality is 65% of the incidence rate. In addition, African American women reportedly have a higher prevalence of presenting with more advanced tumors, being undertreated or untreated, and having shorter disease-free survival compared to other racial groups.

TreatmentCurrent management of advanced epithelial ovarian cancer is cytoreductive surgery (CRS) followed by combination chemotherapy. Tumor recurrences are common, and the prognosis for recurrent disease is poor.

Cytoreductive surgery plus 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, oxaliplatin, carboplatin, and other drugs used for HIPEC have not been approved by the U.S. Food and Drug Administration (FDA) for this indication.

Several peritoneal lavage systems (FDA product code: LGZ) have been cleared for marketing by the FDA through the 510(k) process to provide “warmed, physiologically compatible sterile solution” (eg, Performer® HT perfusion system; RanD; Warrior Blood and Fluid Warmer; X-FLO Fluid Management System). None has received marketing approval or clearance to administer chemotherapy. The FDA has issued warnings 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.

Hyperthermic Intraperitoneal Lavage Devices Cleared by the U.S. Food and Drug Administration

Hyperthermia Therapy  is addressed in a separate policy.

POLICY

Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (HIPEC) at the time of surgery may be considered medically necessary for the treatment of:

• pseudomyxoma peritonei; and

• diffuse malignant peritoneal mesothelioma.

The use of HIPEC may be considered medically necessary in newly diagnosed epithelial ovarian or fallopian tube cancer at the time of interval cytoreductive surgery when ALL of the following criteria are met:

• The individual has stage III disease (see Policy Guidelines);

• The individual is not eligible for primary cytoreductive surgery or surgery had been performed but was incomplete and will receive neoadjuvant chemotherapy and subsequent interval debulking surgery (see Policy Guidelines); and

• It is expected that complete or optimal cytoreduction can be achieved at time of the interval debulking surgery (see Policy Guidelines).

The use of HIPEC in all other settings to treat ovarian cancer, including but not limited to stage IIIC or IV ovarian cancer, is considered investigational.

Cytoreductive surgery plus HIPEC is considered investigational for:

• peritoneal carcinomatosis from colorectal cancer, gastric cancer, or endometrial cancer;

   and

• all other indications, including goblet cell tumors of the appendix.

POLICY EXCEPTIONS

None

POLICY GUIDELINES

The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language.

Ovarian cancer staging is as follows:

• Stage I: The cancer is confined to the ovary or fallopian tube.

• Stage II: The cancer involves one or both ovaries with pelvic extension.

• Stage III: The cancer has spread within the abdomen.

• Stage IV: The cancer is widely spread throughout the body.

Eligibility for neoadjuvant chemotherapy and interval debulking surgery is based on a high perioperative risk profile (ie, the individual is a poor candidate to withstand an aggressive initial cytoreductive procedure) or a low likelihood of achieving cytoreduction to less than 1 cm (ie, the individual has extensive disease that precludes upfront optimal cytoreduction) or surgery has been performed but was incomplete (ie, after surgery, one or more residual tumors measuring >1 cm in diameter were present).

Complete cytoreduction is defined as no visible disease and optimal cytoreduction as one or more residual tumors measuring 10 mm or less in diameter remaining.

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 Mental Health Disorders, 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 medical necessity, “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. 

POLICY HISTORY

6/16/2008: 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.

06/06/2016: Policy number A.2.03.07 added.

07/27/2016: Policy description updated. Policy statements unchanged.

08/07/2017: Policy description updated regarding hyperthermic intraperitoneal chemotherapy. Policy statements unchanged.

02/01/2019: Policy title changed from "Cytoreductive Surgery and Perioperative Intraperitoneal Chemotherapy for Select Intra-Abdominal and Pelvic Malignancies" to "Hyperthermic Intraperitoneal Chemotherapy for Select Intra-Abdominal and Pelvic Malignancies." Policy description updated regarding conditions in which CRS and HIPEC are being evaluated. First policy statement updated to state that cytoreductive surgery plus HIPEC at the time of surgery may be considered medically necessary for the conditions listed. Added policy statement that the use of HIPEC may be considered medically necessary in newly diagnosed epithelial ovarian or fallopian tube cancer at the time of interval cytoreductive surgery when certain criteria are met. Added statement that the use of HIPEC in all other settings to treat ovarian cancer, including but not limited to stage IIIC or IV ovarian cancer, is considered investigational. Fourth policy statement updated to change "perioperative intraperitoneal chemotherapy" to "HIPEC." Policy Guidelines updated to add information regarding ovarian cancer, neoadjuvant chemotherapy and interval debulking surgery, and complete and optimal cytoreduction. Code Reference section updated to add ICD-10 diagnosis codes C56.1 - C56.9 and C57.00 - C57.02.

09/27/2019: Code Reference section updated to add new ICD-10 procedure code 3E0M30Y, effective 10/01/2019.

11/13/2019: Policy description updated regarding devices. Policy statements unchanged.

11/18/2020: Policy description updated regarding pseudomyxoma peritonei and devices. Policy statements unchanged.

08/27/2021: Policy reviewed. Policy statements unchanged. Policy Guidelines updated to change "Nervous/Mental Conditions" to "Mental Health Disorders" and "Medically Necessary" to "medical necessity."

08/08/2022: Policy description updated regarding ovarian cancer. Policy statements and Policy Guidelines updated to change "patient" to "individual."

08/08/2023: Policy reviewed; no changes.

12/21/2023: Code Reference section updated to add new 2024 CPT codes 96547 and 96548. Revised the code description for CPT code 96446, effective 01/01/2024.

08/05/2024: Policy description updated regarding devices. Policy statements unchanged.

08/27/2025: Policy reviewed; no changes.

SOURCE(S)

Blue Cross & Blue Shield of Association Policy # 2.03.07

CODE REFERENCE

This 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.

Covered Codes

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