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MP 2.03.07 Cytoreductive Surgery and Perioperative Intraperitoneal Chemotherapy for the Treatment of Pseudomyxoma Peritonei, Peritoneal Carcinomatosis of Gastrointestinal Origin, and Peritoneal Mesothelioma

Medical Policy    
Section
Medicine
 
Original Policy Date
6/27/05
 
Last Review Status/Date
Reviewed with literature search/10:2012
Issue
10:2012
  Return to Medical Policy Index

Disclaimer

Our medical policies are designed for informational purposes only and are not an authorization, or an explanation of benefits, or a contract.  Receipt of benefits is subject to satisfaction of all terms and conditions of the coverage.  Medical technology is constantly changing, and we reserve the right to review and update our policies periodically.


Description

Peritoneal carcinomatosis from non-ovarian malignancies has long been regarded as a terminal disease with limited survival. In an attempt to prolong survival, aggressive locoregional therapy, such as combining cytoreductive surgery with perioperative intraperitoneal chemotherapy, has been used.

Pseudomyxoma peritonei

Pseudomyxoma peritonei is a clinicopathologic entity characterized by the production of mucinous ascites and mostly originates from epithelial neoplasms of the appendix. As the tumor grows, the narrow lumen of the appendix becomes obstructed and subsequently leads to appendiceal perforation. The neoplastic cells progressively colonize the peritoneal cavity and copious mucin production builds up in the peritoneal cavity. Appendix tumors causing pseudomyxoma peritonei range from a benign pathologic appearance (disseminated peritoneal adenomucinosis) to malignant pathologic findings (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. (1)

Colorectal cancer 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.

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 U.S., 200-400 new cases of diffuse malignant peritoneal mesothelioma (DMPM) are registered every year, accounting for 10-30% of all-type mesothelioma. (2) DMPM has traditionally been considered as a rapidly lethal malignancy with limited and ineffective therapeutic options. (2) 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. (2)

Surgical cytoreduction in conjunction with hyperthermic intraperitoneal chemotherapy is designed to remove visible tumor deposits with intraperitoneal chemotherapy to address remaining 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.

Cytoreductive surgery (CRS) consists of peritonectomy procedures and multivisceral resections, depending on the extent of intra-abdominal tumor dissemination. (3) 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 the 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 hyperthermic intraperitoneal chemotherapy (HIPEC). Other methods of intraperitoneal chemotherapy include early postoperative intraperitoneal chemotherapy (EPIC).


Policy

Cytoreductive surgery and perioperative intraperitoneal chemotherapy for the treatment of pseudomyxoma peritonei may be considered medically necessary.

Cytoreductive surgery and perioperative intraperitoneal chemotherapy for the treatment of diffuse malignant peritoneal mesothelioma may be considered medically necessary.

Cytoreductive surgery and perioperative intraperitoneal chemotherapy is considered investigational for peritoneal carcinomatosis from colorectal cancer.


Policy Guidelines

Coding

The coding for this overall procedure would likely involve codes for the surgery, the intraperitoneal chemotherapy, and the hyperthermia.

Cytoreduction

There is no specific CPT code for the surgical component of this complex procedure. It is likely that a series of CPT codes would be used describing exploratory laparotomies of various components of the abdominal cavity, in addition to specific codes for resection of visceral organs, depending on the extent of the carcinomatosis.

Intraperitoneal Chemotherapy

CPT code 96446 identifies “chemotherapy administration into the peritoneal cavity via indwelling port or catheter.” When performed using a temporary catheter or performed intraoperatively, the unlisted code 96549 (unlisted chemotherapy procedure) would be reported.

Hyperthermia

CPT code 77605 identifies, “Hyperthermia, externally generated; deep.”


Benefit Application

BlueCard/National Account Issues

Cytoreduction and intraperitoneal hyperthermic chemotherapy is a specialized procedure and may be offered at limited centers. Therefore, out of network referral may be requested.


Rationale

Pseudomyxoma peritonei

A retrospective, multicenter cohort study evaluated the toxicity and prognostic factors after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) and/or early postoperative intraperitoneal chemotherapy (EPIC), for diffuse peritoneal disease from malignancies of multiple different histologic origins. (4) The study included 1,290 patients from 25 institutions who underwent 1,344 procedures between 1989 and 2007. HIPEC was performed in 1,154 procedures. Postoperative mortality was 4.1%. The principal origin of peritoneal carcinomatosis was pseudomyxoma peritonei in 301 patients. Exclusion criteria were perioperative chemotherapy performed greater than 7 days after surgery and the presence of extra-abdominal metastases. Median overall survival (OS) for patients with pseudomyxoma peritonei was not reached (median OS for all patients was 34 months).

Elias and colleagues report a large case series treating pseudomyxoma peritonei with CRS and intraperitoneal chemotherapy. (5) Their multicenter study included 301 patients treated between 1993 and 2007. Complete CRS was achieved in 219 patients (73%), and hyperthermic intraperitoneal chemotherapy was performed in 255 (85%). The primary tumor site was the appendix in 91% of patients, the ovary in 7%, and the origin was unknown in 2%. Tumor histology was disseminated peritoneal adenomucinosis in 51%, intermediate in 27%, and peritoneal mucinous carcinomatosis in 22%. Postoperative mortality was 4% and morbidity, 40%. Mean follow-up was 88 months. The 1-, 3-, and 5-year OS rates were 89.4%, 84.8%, and 72.6%, respectively. The 10-year survival rate was 54.8%. Median survival had not yet been reached but will be longer than 100 months. The disease-free survival (DFS) rate was 56% at 5 years, and the median duration of DFS was 78 months. A multivariate analysis identified 5 prognostic factors: the extent of peritoneal seeding (p=0.004), the center (p=0.0004), the pathologic grade (p=0.03), gender (p=0.02), and the use of hyperthermic intraperitoneal chemotherapy (p=0.04). When only the 206 patients with complete CRS were considered, the extent of peritoneal seeding was the only significant prognostic factor (p=0.004).

Vaira and colleagues report their experience managing pseudomyxoma peritonei with cytoreduction and hyperthermic intraperitoneal chemotherapy in a single institution in 60 patients, 53 of whom had final follow-up data. (6) The postoperative morbidity rate was 45%; no postoperative deaths were observed. The primary tumor was appendiceal adenocarcinoma in 72% of patients and appendiceal adenoma in 28%. Approximately one-half of the patients with adenocarcinoma had received previous systemic chemotherapy. Five- and 10-year OS were 94% and 85%, respectively, and 5- and 10-year DFS were 80% and 70%, respectively. Significant differences in improved OS were observed in patients who experienced complete surgical cytoreduction (p<0.003) and in those with histologic type disseminated peritoneal adenomucinosis versus those with peritoneal mucinous carcinomatosis (p<0.014).

Chua and colleagues report the long-term survival of 106 patients with pseudomyxoma peritonei treated between 1997 and 2008 with cytoreductive surgery and intraperitoneal chemotherapy. (7) Sixty-nine percent of patients had complete cytoreduction. Seventy-three patients had disseminated peritoneal adenomucinosis, 11 had peritoneal mucinous carcinomatosis, and 22 had mixed tumors. The mortality rate was 3% and the severe morbidity rate was 49%. The median follow-up was 23 months (range: 0–140 months). The overall median survival was 104 months with a 5-year survival rate of 75%. PFS was 40 months with 1-, 3-, and 5-year PFS rates of 71%, 51%, and 38%, respectively. Factors influencing survival included histopathologic type of tumor, with the best survival in patients with disseminated peritoneal adenomucinosis and the worst in patients with peritoneal mucinous carcinomatosis (p=0.002), and completeness of cytoreduction (p=0.002).

In 2008, Elias and colleagues reported the results of 105 consecutive patients with pseudomyxoma peritonei treated between 1994 and 2006 with CRS and hyperthermic intraperitoneal chemotherapy. (1) The primary tumor was the appendix in 93 patients, ovary in 3, urachus in 1, pancreas in 1, and indeterminate in 7. Tumor histology was disseminated peritoneal adenomucinosis in 48% of patients, intermediate in 35% and peritoneal mucinous carcinomatosis in 17%. At the end of surgery, 72% of patients had no visible residual peritoneal lesions. Postoperative mortality was 7.6% and morbidity, 67.6%. Median follow-up was 48 months, and 5-year OS and DFS were 80% (95% confidence interval [CI]: 68–88%) and 68% (95% CI: 55–79%), respectively. Two factors were identified on multivariate analysis that had a negative influence on DFS: a CA 19.9 level greater than 300 units/mL and nondisseminated peritoneal adenomucinosis tumor histology.

Yan and colleagues conducted a systematic review on the efficacy of CRS and intraperitoneal chemotherapy for all relevant studies from 1996 to 2006. (8) There were no randomized controlled trials (RCTs) or comparative studies. Ten studies were included (with a total of 863 patients) and were observational without control groups. Two of the studies had relatively long-term follow-up of 48 and 52 months, and the remaining studies had median follow-up times of less than 3 years (range: 19-35 months). Median survival across all studies ranged from 51 to 156 months. One-, 2-, 3-, and 5-year survival rates varied from 80–100%, 76–96%, 59–96%, and 52–96%, respectively. Overall mortality rates varied from 0-18% and morbidity from 33–56%.

Peritoneal carcinomatosis from colorectal cancer

Reviews from 2009 and 2010 (3, 9, 10) summarize the experience in the literature for treatment of colorectal peritoneal carcinomatosis with CRS and hyperthermic intraperitoneal chemotherapy (HIPEC), some of which is included in the section below. There has been an RCT with a second publication after 8 years of follow-up, (11, 12) one comparative study, (13) and numerous observational studies. Across studies, overall median survival after CRS and hyperthermic intraperitoneal chemotherapy in patients with peritoneal dissemination from colon cancer has ranged from 13 to 63 months (median: approximately 18 months). The study that showed 63 months survival (14) may be explained by the use of more contemporary chemotherapeutic regimens in the treatment of advanced stage colon cancer compared to prior studies in which previous standard therapy was used. (3) For comparison, published studies reporting the outcome after systemic treatment of metastatic colon cancer with polychemotherapy with or without biologic agents range from 14.8 months to 22.6 months (median: 19.2 months). (3)

A single institution study was undertaken that randomly assigned 105 patients with peritoneal carcinomatosis to receive standard treatment with systemic chemotherapy (fluorouracil and leucovorin) and palliative surgery, if necessary (i.e., treatment of bowel obstruction), or to a second arm consisting of aggressive cytoreduction and intraperitoneal chemotherapy followed by standard systemic chemotherapy. (12) Patients with other sites of metastases, i.e., lung or liver, were excluded. The cytoreductive procedure consisted of stripping the parietal peritoneum and resection of infiltrated viscera, if possible. Most often, resection of the gall bladder, parts of the stomach, and spleen were performed. The greater omentum was also routinely removed. At the completion of resection, the presence of residual tumor was assessed. Hyperthermic mitomycin C was then administered intraperitoneally for 90 minutes. The most important complications were small bowel leakage and abdominal sepsis, but a total of 24% of patients suffered from severe or life-threatening complications, such as heart failure, arrhythmias, or renal failure. A total of 8 patients (16%) died as the result of treatment at 30 days. The main endpoint was survival, measured from the time of randomization to death from any cause. After a median follow-up of 21.6 months, 20 of 51 patients in the standard therapy group were still alive compared to 30 of 54 patients in the cytoreduction group. Median survival in the control group was 12.6 months compared to 22.4 months in the cytoreduction group. Subgroup analysis revealed that survival was particularly poor among patients with either residual tumor measuring greater than 2.5 mm or in patients with tumor involvement in 6 or more regions in the abdomen. In these groups, median survival was only approximately 5 months, compared to 29 months in patients with no residual tumor.

An editorial on this randomized trial commented that while this study shows that CRS and HIPEC with systemic chemotherapy nearly doubles survival compared to systemic chemotherapy alone, it does not show how much of this benefit is derived from the surgery and how much from the HIPEC, (15) and in a letter to the editor, Markman points out that the reported survival benefit may be primarily related to the cytoreduction, with added chemotherapy only contributing to increased morbidity. (16) Finally, new targeted systemic treatment options have emerged for colon cancer, specifically cetuximab and bevacizumab, which offer additional palliative options for colon cancer, whereas the chemotherapy used in the randomized trial is no longer considered standard.

Aside from the issues of the trial methodology, the results of the trial present complicated risk benefit questions that are not adequately addressed. If the main rationale for CRS is to provide a curative option, data regarding disease recurrence would be important. It is not known whether the survivors in either group are alive with or without disease. If the main rationale for the therapy is palliation in terms of prolonging life or relieving specific symptoms (e.g., related to ascites or bowel obstruction), it is important to determine the quality of life associated with the 10-month improvement in median survival. Quality-of-life data were not reported in this randomized trial; however, the high incidence of major complications, and the reported mean length of hospitalization of 29 days suggest that this aggressive surgical approach has a significant impact on quality of life. Quality of life was addressed in a separate case series of 64 patients undergoing CRS and intraperitoneal chemotherapy. (17) The Functional Assessment of Cancer Therapy - Colon (FACT-C), activities of daily living, the brief pain inventory, and depression scales comprised the quality-of-life instruments used. A total of 48 patients completed the assessment prior to and at a mean of 12 days after surgery; 16 of the original 64 patients did not complete the survey either due to death (n=11) or missed appointments. By 6 months’ follow-up, only 39 patients were available, either due to death or continuing dropout. Among the respondents, the overall quality of life decreased significantly from baseline to postsurgery but improved to greater than baseline at 3 months. However, these data are difficult to interpret without a control group and owing to the large number of dropouts due to death.

The randomized study (12) reported an 8-year follow-up of all patients still alive until 2007. (11) This update had a minimum follow-up of 6 years for all patients (median: 94 months; range: 72–115 months). During the follow-up, 1 patient crossed over from the standard arm to the hyperthermic intraperitoneal chemotherapy arm after recurrent disease at 30 months after randomization (the standard arm being systemic chemotherapy only and the hyperthermic intraperitoneal chemotherapy arm including systemic chemotherapy, CRS, and HIPEC). At the time of this long-term follow-up, in the standard arm, 4 patients were still alive, 2 with disease and 2 without disease, and in the HIPEC arm, 5 patients were still alive, 2 with disease and 3 without disease. Disease-specific survival was reported as 12.6 months in the standard arm and 22.2 months in the HIPEC arm (p=0.028), and progression-free survival (PFS) was 7.7 months in the standard arm and 12.6 months in the hyperthermic intraperitoneal chemotherapy arm (p=0.02).

A retrospective, multicenter cohort study evaluated the toxicity and prognostic factors after CRS and HIPEC and/or EPIC, for diffuse peritoneal disease from malignancies of multiple different histologic origins. (4) The study included 1,290 patients from 25 institutions who underwent 1,344 procedures between 1989 and 2007. HIPEC was performed in 1,154 procedures. Postoperative mortality was 4.1%. The principal origin of peritoneal carcinomatosis was colorectal adenocarcinoma in 523 patients. Exclusion criteria were perioperative chemotherapy performed greater than 7 days after surgery and the presence of extra-abdominal metastases. The overall median survival for patients with a colorectal primary was 30 months. Independent prognostic indicators in multivariate analysis were institution, histologic origin of the tumor, completeness of CRS, extent of carcinomatosis, and lymph node involvement.

Elias and colleagues compared 48 patients in the French Multicentric Database with peritoneal carcinomatosis arising from colon cancer who received palliative systemic oxaliplatin or irinotecan-based chemotherapy to 48 patients who underwent additional cytoreduction and HIPEC. (14) The chemotherapeutic regimen and the duration of systemic chemotherapy were comparable in both groups. The results showed a significant improvement of long-term survival after complete macroscopic cytoreduction followed by HIPEC compared to systemic treatment alone. The median survival was 23.9 months in the control group versus 62.7 months in the HIPEC group. The 5-year survival rates were 13% and 51%, respectively.

vanLeeuwen and colleagues reported on the experience in a Swedish series of 103 patients treated between 2003 and 2006. (18) This study was to explore factors associated with postoperative morbidity and survival. While postoperative mortality in this center was less than 1%, postoperative morbidity was 56%. Tumor type and optimal cytoreduction influenced survival. In this uncontrolled series, at 2 years, OS was estimated at 72% and DFS was 34%.

Glehen and colleagues reported on a retrospective multi-institutional case series involving 28 institutions and 506 patients. (19) The study population consisted of patients with peritoneal carcinomatosis related to colorectal cancer who underwent the procedure between 1987 and 2002. Patients with extra-abdominal metastases were excluded. A variety of protocols for intraperitoneal operative chemotherapy were used; mitomycin C was the most common. Some patients also received intraperitoneal chemotherapy in the early postoperative procedure, sometimes after a prior operative infusion. In the early postoperative setting, fluorouracil was most common. A total of 20 patients (4%) died postoperatively. Major complications occurred in 116 patients (22.9%); digestive fistula was the most common major complication, occurring in 8.3% of patients, and was the cause of death in the 7 of the 20 patients who died. At a mean follow-up of 53 months, the morbidity and mortality rates were 22.9% and 4%, respectively, with a median survival of 19.2 months. Subgroup analysis of outcomes based on the completeness of resection reported that patients with complete resection of macroscopic disease had a median survival of 32.4 months compared to only 8 months in those cases for which complete resection was not possible. The completeness of resection was the most significant prognostic indicator. The overall recurrence rate was 73.3%, with peritoneal recurrences noted in 41.9% of patients. The authors concluded that these results echoed those reported in small case series.

Peritoneal mesothelioma

A 2011 systematic review by Baratti and colleagues searched the PubMed literature from 1979-2010 for studies on the clinical management of diffuse malignant peritoneal mesothelioma (DMPM). (2) The review included 14 studies with a total of 427 patients; 289 of whom underwent CRS with HIPEC, EPIC in 2, or both in 106. Series that included patients with well-differentiated or low-grade types of mesothelioma were excluded. All of the included series were prospective non-randomized observational case-series studies without control groups. Mean patient age ranged from 49 to 55.7 years. All of the centers used peritonectomy procedures and multivisceral resections to remove all visible disease. HIPEC protocols varied widely among institutions in terms of technique, drugs, carriers, timing and temperature. Operative mortality and morbidity were reported in 11 mono-institutional series. Operative death rates ranged from 0% to 10.5%. Overall, it occurred in 11 of 373 assessable patients (3.1%). In a multi-institutional series, mortality was 2.2%. Severe and life-threatening complications were analyzed. Morbidity varied from 20 to 41%. For the patients who underwent CRS and HIPEC, median overall survival ranged from 29.5 to 92 months. It was not reached in 3 series, being longer than 100 months in one. The 1-, 2-, 3-, and 5-year overall survival rates varied from 43% to 88%, 43% to 77%, 43% to 70%, and 33% to 68%, respectively. In 4 series, median PFS ranged from 7.2 to 40 months.

The largest series in the systematic review was from an international registry study, for which 401 patients (99%) had complete follow-up. (20) Of the 401 patients, 92% received HIPEC. Reasons for not receiving HIPEC included EPIC being given instead, intraoperative hemodynamic instability, and reason unclear. The median and 1-, 3-, and 5-year survival were 53 months, 81%, 60%, and 47%, respectively.

The review acknowledges the possibility of patient selection bias as an explanation for the superior survival noted with aggressive treatment over more conventional treatment modalities, since patients with poor performance status are generally excluded from CRS and HIPEC. The authors conclude that, even in the absence of controlled data, the evidence suggests that the use of CRS and HIPEC in the treatment of DMPM should be the benchmark against which other treatments should be evaluated.

A retrospective, multicenter cohort study evaluated the toxicity and prognostic factors after CRS and HIPEC and/or EPIC, for diffuse peritoneal disease from malignancies of multiple different histologic origins. (4) The study included 1,290 patients from 25 institutions who underwent 1,344 procedures between 1989 and 2007. HIPEC was performed in 1,154 procedures. Postoperative mortality was 4.1%. Principal origin of tumor was peritoneal mesothelioma in 88 patients. Exclusion criteria were perioperative chemotherapy performed greater than 7 days after surgery and the presence of extra-abdominal metastases. Median survival for the patients with mesothelioma was 41 months. Independent prognostic indicators in multivariate analysis were institution, origin of peritoneal carcinomatosis, completeness of CRS, extent of carcinomatosis, and lymph node involvement.

National Comprehensive Cancer Network (NCCN) Guidelines and National Cancer Institute (NCI) Physician Query Database (PDQ)

NCCN clinical practice guidelines in oncology for colon cancer (v.1.2013) consider the treatment of disseminated carcinomatosis with cytoreductive surgery and perioperative hyperthermic intraperitoneal chemotherapy to be investigational and do not endorse such therapy outside of a clinical trial. (21)

NCCN guidelines that specifically address the treatment of appendiceal tumors, pseudomyxoma peritonei and peritoneal mesothelioma are not identified.

Two randomized Phase III trials were identified and are outlined in the following paragraphs.

A Phase III randomized study of systemic chemotherapy with versus without intraperitoneal chemohyperthermia in patients undergoing surgery for peritoneal carcinomatosis originating from colorectal cancer is of unknown status (NCT00769405). Primary outcome is OS. Secondary outcome measures include recurrence-free survival (RFS), treatment toxicity, morbidity from surgical complications, and prognostic factors of survival. Expected enrollment is 264, with a trial start date of February 2008.

A Phase III randomized pilot study of standard systemic therapy with versus without cytoreduction surgery and hyperthermic intraperitoneal mitomycin C in patients with advanced limited peritoneal dissemination of colon adenocarcinoma is ongoing. (NCT01167725) Primary outcome is OS. Secondary outcomes include PFS, quality of life, toxicity burden of these regimens, survival according to patient's peritoneal surface tumor genotype, and comparisons of circulating tumor cells in patients treated with these regimens. Expected enrollment is 340, and estimated primary completion date is May 2014.

Practice Guidelines and Position Statements

In 2007, the Society of Surgical Oncology issued a consensus statement on cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the management of peritoneal surface malignancies of colonic origin. (22) Their recommendation is that patients with peritoneal carcinomatosis without distant disease, in whom complete cytoreduction is possible, undergo hyperthermic intraperitoneal chemotherapy prior to systemic therapy. As of September 2012, an updated consensus statement has not been identified.

Summary

Pseudomyxoma peritonei

Several case studies and a systematic review on the use of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy have been published. Although no randomized trials or comparative studies have been published, the data have shown consistent, long-term DFS and OS with the use of this technique as compared to historic controls. Therefore, cytoreductive surgery and hyperthermic intraperitoneal chemotherapy may be considered medically necessary for this indication.

Peritoneal carcinomatosis from colorectal cancer

Numerous studies with different levels of evidence support the safety and feasibility of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy, and existing data suggest a possible improvement in long-term survival of select patients. However, prospective randomized trials are needed to compare best available systemic therapy with and without cytoreductive surgery and hyperthermic intraperitoneal chemotherapy to determine the exact effects of each step, which are currently unknown. An ongoing Phase III trial (NCT00769405) addresses this question of how much of the survival benefit is derived from the cytoreduction and how much from hyperthermic intraperitoneal chemotherapy, as patients will be randomly assigned to hyperthermic intraperitoneal chemotherapy or no hyperthermic intraperitoneal chemotherapy after complete cytoreductive surgery. Therefore, cytoreductive surgery and hyperthermic intraperitoneal chemotherapy is considered investigational for this indication.

Peritoneal mesothelioma

The conventional treatment of peritoneal mesothelioma (diffuse malignant type) has resulted in a median survival of approximately 12 months. Although the data on the use of cytoreductive surgery and perioperative intraperitoneal chemotherapy consists of non-randomized case series without control groups, they have shown a significant prolongation of survival ranging from 29.5 to 92 months. Therefore, cytoreductive surgery and hyperthermic intraperitoneal chemotherapy may be considered medically necessary for this indication.

References:

  1.  
    1. Elias D, Honore C, Ciuchendea R et al. Peritoneal pseudomyxoma: results of a systematic policy of complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Br J Surg 2008; 95(9):1164-71.
    2. Baratti D, Kusamura S, Deraco M. Diffuse malignant peritoneal mesothelioma: systematic review of clinical management and biological research. J Surg Oncol 2011; 103(8):822-31.
    3. Glockzin G, Ghali N, Lang SA et al. Results of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal carcinomatosis from colorectal cancer. J Surg Oncol 2009; 100(4):306-10.
    4. Glehen O, Gilly FN, Boutitie F et al. Toward curative treatment of peritoneal carcinomatosis from nonovarian origin by cytoreductive surgery combined with perioperative intraperitoneal chemotherapy. Cancer 2010; 116(24):5608-18.
    5. Elias D, Gilly F, Quenet F et al. Pseudomyxoma peritonei: a French multicentric study of 301 patients treated with cytoreductive surgery and intraperitoneal chemotherapy. Eur J Surg Oncol 2010; 36(5):456-62.
    6. Vaira M, Cioppa T, de Marco G et al. Management of pseudomyxoma peritonei by cytoreduction + HIPEC (hyperthermic intraperitoneal chemotherapy): results analysis of a twelve-year experience. In Vivo 2009; 23(4):639-44.
    7. Chua TC, Yan TD, Smigielski ME et al. Long-term survival in patients with pseudomyxoma peritonei treated with cytoreductive surgery and perioperative intraperitoneal chemotherapy: 10 years of experience from a single institution. Ann Surg Oncol 2009; 16(7):1903-11.
    8. Yan TD, Black D, Savady R et al. A systematic review on the efficacy of cytoreductive surgery and perioperative intraperitoneal chemotherapy for pseudomyxoma peritonei. Ann Surg Oncol 2007; 14(2):484-92.
    9. Maggiori L, Elias D. Curative treatment of colorectal peritoneal carcinomatosis: current status and future trends. Eur J Surg Oncol 2010; 36(7):599-603.
    10. Rampone B, Schiavone B, Martino A et al. Current role of hyperthermic intraperitoneal chemotherapy in the treatment of peritoneal carcinomatosis from colorectal cancer. World J Gastroenterol 2010; 16(11):1299-302.
    11. Verwaal VJ, Bruin S, Boot H et al. 8-year follow-up of randomized trial: cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy in patients with peritoneal carcinomatosis of colorectal cancer. Ann Surg Oncol 2008; 5(9):2426-32.
    12. Verwaal VJ, van Ruth S, de Bree E et al. Randomized trial of cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy and palliative surgery in patients with peritoneal carcinomatosis of colorectal cancer. J Clin Oncol 2003; 21(20):3737-43.
    13. Mahteme H, Hansson J, Berglund A et al. Improved survival in patients with peritoneal metastases from colorectal cancer: a preliminary study. Br J Cancer 2004; 90(2):403-7.
    14. Elias D, Lefevre JH, Chevalier J et al. Complete cytoreductive surgery plus intraperitoneal chemohyperthermia with oxaliplatin for peritoneal carcinomatosis of colorectal origin. J Clin Oncol 2008; 27(5):681-5.
    15. Levine EA. The randomized trial of cytoreductive surgery with hyperthermic intraperitoneal chemoperfusion: what it does and does not tell us. Ann Surg Oncol 2008; 15(10):2633-5.
    16. Markman M. Intraperitoneal hyperthermic chemotherapy as treatment of peritoneal carcinomatosis of colorectal cancer. Letter to the editor. J Clin Oncol 2004; 22(8):1527.
    17. McQuellon RP, Loggie BW, Fleming RA et al. Quality of life after intraperitoneal hyperthermic chemotherapy (IPHC) for peritoneal carcinomatosis. Eur J Clin Oncol 2001; 27(1):65-73.
    18. van Leeuwen BL, Graf W, Pahlman L et al. Swedish experience with peritonectomy and HIPEC. HIPEC in peritoneal carcinomatosis. Ann Surg Oncol 2008; 15(3):745-53.
    19. Glehen O, Kwiatkowski F, Sugarbaker PH et al. Cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for the management of peritoneal carcinomatosis from colorectal cancer: a multi-institutional study. J Clin Oncol 2004; 22(16):3284-92.
    20. Yan TD, Deraco M, Baratti D et al. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for malignant peritoneal mesothelioma: multi-institutional experience. J Clin Oncol 2009; 27(36):6237-42.
    21. National Comprehensive Cancer Network (NCCN). Colon cancer. 2013. Available online at: http://www.nccn.org/professionals/physician_gls/PDF/colon.pdf. Last accessed September, 2012.
    22. Esquivel J, Sticca R, Sugarbaker P et al. Cytoreductive surgery hyperthermic, intraperitoneal chemotherapy in the management of peritoneal surface malignancies of colonic origin a consensus statement. Society of Surgical Oncology. Ann Surg Oncol 2007; 14(1):128-33.
  2.  

Codes

Number

Description

CPT 

 

See Policy Guidelines section 

ICD-9 

197.6 

Secondary malignant neoplasm of retroperitoneum and peritoneum 

ICD-9-CM Procedure     No specific code for cytoreductive surgery; coding would be based on what is excised.  
    99.85 Hyperthermia for treatment of cancer  
ICD-10-CM (effective 10/1/13) C78.6 Secondary malignant neoplasm of retroperitoneum and peritoneum  
ICD-10-PCS (effective 10/1/13)    No specific code for cytoreductive surgery; coding would be based on what is excised.  
    DWY38ZZ Radiation oncology, anatomic regions, other radiation, abdomen, hyperhthermia  
    DWY68ZZ Radiation oncology, anatomic regions, other radiation, pelvic region, hyperhthermia 

 


Index

Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy
Hyperthermic Intraperitoneal Chemotherapy
Intraperitoneal Hyperthermic Chemotherapy


Policy History

Date

Action

Reason

06/27/05

Add policy to Medicine section, Oncology subsection

New policy

04/17/07 Replace Policy  Policy updated with literature search through February 2007; no changes in policy statement. Reference numbers 6–9 added 
06/12/08 Replace policy
Policy updated with literature search, reference numbers 10 and 11 added. Policy statement unchanged.
06/11/09 Replace policy Policy updated with literature search, reference numbers 11 through 13 added. Policy statement unchanged
10/08/10 Replace policy Policy updated with literature search; Rationale and Background sections revised extensively. Policy statement added 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. The term, “pseudomyxoma peritonei” was added to the policy title. References 1-8, 10-12, and 17 added; reference 18 updated
10/04/11 Replace policy Policy updated with literature search. References 2, 4 and 20 added; references renumbered. Title changed to include peritoneal mesothelioma. 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.
10/11/12 Replace Policy Policy updated with literature search. No references added. No change to policy statements.