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Hyperthermic Intraperitoneal Chemotherapy for Select Intra-abdominal and Pelvic Malignancies
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Policy

MEDICALLY NECESSARY

PSEUDOMYXOMA PERITONEI (PMP) AND MALIGNANT PERITONEAL MESOTHELIOMA
Hyperthermic intraperitoneal chemotherapy (HIPEC) following cytoreductive surgery is considered medically necessary and, therefore, covered for pseudomyxoma peritonei (PMP), and diffuse malignant peritoneal mesothelioma.

PERITONEAL CARCINOMATOSIS OF​ EPITHELIAL OVARIAN OR FALLOPIAN TUBE ORIGIN AND PRIMARY PERITONEAL CANCER ​​
HIPEC following cytoreductive surgery is considered medically necessary and, therefore, covered in newly diagnosed epithelial ovarian, fallopian tube, or primary peritoneal cancer at the time of interval cytoreductive surgery when ALL of the following criteria are met:
  • The individual has stage III disease
  • The individual is not eligible for primary cytoreductive surgery, or surgery had been performed but was incomplete and individual will receive neoadjuvant chemotherapy and subsequent interval debulking surgery, and
  • It is expected that complete or optimal cytoreduction can be achieved at the time of the interval debulking surgery.
PERITONEAL CARCINOMATOSIS OF APPENDICEAL ORIGIN
HIPEC following cytoreductive surgery is considered medically necessary and, therefore, covered for peritoneal carcinomatosis of epithelial appendiceal origins (e.g., appendiceal adenocarcinomas, mucinous neoplasms, and goblet cell adenocarcinomas) if it is expected that complete or optimal cytoreduction can be achieved at time of the cytoreduction.​

PERITONEAL CARCINOMATOSIS OF GASTRIC ORIGIN
HIPEC following cytoreductive surgery is considered medically necessary and, therefore covered for peritoneal carcinomatosis of gastric origin when ALL of the following criteria are met:
  • Peritoneal cancer index (PCI) is ≤​10
  • No evidence of extraperitoneal metastasis
  • It is expected that complete cytoreduction can be achieved at time of the cytoreduction​
EXPERIMENTAL/INVESTIGATIONAL

All other uses, including but not limited to stage IIIC or IV ovarian cancer, peritoneal carcinomatosis from colorectal cancer, or peritoneal carcinomatosis from​ endometrial cancer for HIPEC following cytoreductive surgery are considered experimental/investigational and, therefore, not covered because their safety and/or effectiveness cannot be established by review of the available published peer-reviewed literature.

REQUIRED DOCUMENTATION

The individual's medical record must reflect the medical necessity for the care provided. These medical records may include, but are not limited to: records from the health care professional's office, hospital, nursing home, home health agencies, therapies, and test reports.

The Company may conduct reviews and audits of services to our members, regardless of the participation status of the provider. All documentation is to be available to the Company upon request. Failure to produce the requested information may result in a denial for the service.​

Guidelines

BENEFIT APPLICATION

Subject to the terms and conditions of the applicable benefit contract, hyperthermic intraperitoneal chemotherapy (HIPEC), in conjunction with cytoreductive surgery, is covered under the medical benefits of the Company’s products when the medical necessity criteria listed in this medical policy are met.

US FOOD AND DRUG ADMINISTRATION (FDA) STATUS

Mitomycin, carboplatin, and other drugs used for HIPEC have not been US 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” (e.g., Performer® HT perfusion system; RanD S.R.L., Medolla, Italy). None has received marketing approval or clearance to administer chemotherapy. The 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 (e.g., ThermaSolutions Inc., Minneapolis, MN; Belmont Instrument Corp., Billerica, MA).

OVARIAN CANCER STAGING

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

Eligibility for neoadjuvant chemotherapy and interval debulking surgery is based on a high perioperative risk profile (i.e., 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 (i.e., the individual has extensive disease that precludes upfront optimal cytoreduction) or surgery has been performed but was incomplete (i.e., after surgery, one or more residual tumors measuring >1 cm in diameter were present).

DEFINITION OF COMPLETE CYTOREDUCTION

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.

Description

CYTOREDUCTIVE SURGERY (CRS) AND HYPERTHERMIC INTRAPERITONEAL CHEMOTHERAPY (HIPEC)

Gastrointestinal, gynecological, and other malignancies often progress and spread through the peritoneal cavity, causing peritoneal carcinomatosis. Because of the limited benefit achieved with current treatment options, a procedure called hyperthermic intraperitoneal chemotherapy (HIPEC), also known as intraoperative hyperthermic peritoneal perfusion, has been introduced to treat peritoneal carcinomatosis. When performed, this procedure delivers heated chemotherapy intraperitoneally, immediately following the CRS (i.e., debulking or macroscopically removing all visible tumors).

Response to HIPEC treatment varies among individuals with peritoneal carcinomatosis due to factors such as the grade of the tumor, the presence of metastases, and the success of the CRS. Two methods have been used to estimate the stage of peritoneal carcinomatosis and to estimate the likelihood for complete cytoreduction surgery. These are the Gilly method and the Peritoneal Cancer Index (PCI). As described by Sugarbaker, the PCI is used in the decision-making process and is a clinical summary of both lesion size and extent of peritoneal surface malignancy.

The thoroughness of the CRS plays a significant role in treatment because of the limited 1- to 3-mm penetration of cytostatic drugs into the peritoneal tissue. The goal of HIPEC is to eliminate microscopic metastases that are too small to be identified and removed during CRS. The intra-abdominal lavage with heated chemotherapy usually takes 90 to 120 minutes and may utilize an open or closed technique. It is theorized that the chemotherapy lavage serves to wash from the peritoneum any cancer cells that may have been dislodged by the surgical removal of the primary tumor before the cells are fixed within scar tissue, and that the heated chemotherapy increases cytotoxicity and will enhance penetration of the chemotherapy agent into any residual tumor. Additionally, hyperthermia itself has a cytotoxic effect on tumor tissue.

Previous research reported significant morbidity and mortality associated with the procedure, particularly for individuals with advanced tumor distribution. Therefore, the extent of tumor distribution and the success of the CRS were identified as the most important factors for predicting prolonged survival and as fundamental criteria for selecting individuals for this procedure. The literature also reported that additional predictors of prognosis are location, stage, and histopathology (aggressiveness) of the primary cancer; the extent of peritoneal carcinomatosis; and the technical skills of the surgeon.

Due to the evolving complex aspects of HIPEC, such as the selection and optimal temperature of the chemotherapeutic agents, the length of time for the HIPEC perfusion and its associated morbidity and mortality, current research recommends that procedures are done in facilities with personnel experienced in the scientific, technical, and surgical aspects of peritoneal surface oncology.

In sum, CRS includes peritonectomy (i.e., peritoneal stripping) procedures and multivisceral resections, depending on the extent of intra-abdominal tumor dissemination. CRS may be followed intraoperatively 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 HIPEC. CRS and HIPEC have been proposed for a number of intra-abdominal and pelvic malignancies such as pseudomyxoma peritonei (PMP) and peritoneal carcinomatosis from colorectal, gastric, or endometrial cancer. CRS and HIPEC have a sizeable amount of ongoing and unpublished clinical trials for a number of indications for which peer-reviewed evidence supporting routine clinical usage for HIPEC may be lacking.

PSEUDOMYXOMA PERITONEI (PMP)

PMP is not a diagnosis, but rather a descriptive term used for the clinical presentation of extracellular mucin within the peritoneum with or without a malignancy. Disease classification should be based on the pathological characteristics of the primary tumor. Several case studies and a systematic review on the use of CRS and HIPEC have been published. Although no randomized trials or comparative studies have been published, data have shown consistent, long-term disease-free survival (DFS) and overall survival (OS) with the use of this technique. Procedure-related morbidity and mortality have decreased over time. Because the prevalence of PMP is very low, the conduct of high-quality trials is difficult. Therefore, the available and published peer-reviewed literature support the use of HIPEC for PMP with the presence of extracellular, intraperitoneal mucin.

PERITONEAL MESOTHELIOMA

The conventional treatment of peritoneal mesothelioma (diffuse malignant type) has resulted in a median survival of approximately 12 months. Although data on the use of CRS and HIPEC comprises nonrandomized case series without control groups, these have shown a significant prolongation of median survival ranging from 29.5 to 92 months. Procedure-related morbidity and mortality has remained relatively steady over time at approximately 35% and 5%, respectively. Because the prevalence of peritoneal mesothelioma is low, the conduct of high-quality trials is difficult. Therefore, the currently available peer-reviewed literature has demonstrated that the combination of CRS and HIPEC results in significant improvement in the prolongation of survival when compared to conventional treatment for diffuse malignant peritoneal mesothelioma (DMPM).

​PERITONEAL CARCINOMATOSIS OF COLORECTAL ORIGIN

For individuals who have peritoneal carcinomatosis of colorectal origin who receive CRS plus HIPEC, the evidence includes randomized controlled trial​s​ (RCT), systematic reviews, and a large number of observational studies. Relevant outcomes are OS, disease-specific survival, quality of life, and treatment-related mortality and morbidity. A meta-analysis of controlled studies found that CRS plus HIPEC, compared with traditional therapy without HIPEC, was associated with significantly higher survival rates and was not associated with significantly higher treatment-related morbidity rates (Huang et al., 2017). ​​A 2022 meta-analysis evaluated 10 trials (three RCTs) including 3200 participants concluded that CRS plus HIPEC improved OS compared with control (hazard ratio [HR], 0.53; 95% CI, 0.38–0.73; P<0.00001​). The limitation of this analysis was the high heterogeneity among trials (Li et al.). A 2021 RCT ​by Quénet et al. that compared CRS plus HIPEC to CRS alone found there no difference in OS; however, a limitation of this study is that HIPEC was administered for only 30 minutes (90–120 minutes of perfusion is recommended).​ Another RCT, in which the majority of participants had peritoneal carcinomatosis due to colorectal cancer and who were followed for at least 6 years, demonstrated improved survival in patients who received CRS plus HIPEC and systemic chemotherapy compared with patients who received systemic chemotherapy alone.​ However, procedure-related morbidity and mortality rates were relatively high, and systemic chemotherapy regimens did not use currently available biologic agents (Verwaal et al., 2008). Goéré ​et al. (2020) reported results from a phase III trial that randomly assigned ​individuals at high risk of developing peritoneal carcinomatosis of colorectal origin to surveillance or systematic second-look surgery plus HIPEC. Those randomly assigned to the HIPEC group had worse 3-year DFS compared to surveillance (44% vs. 53%)​. The evidence is insufficient to determine the effects of the technology on health outcomes.​

PERITONEAL CARCINOMATOSIS OF GASTRIC ORIGIN
​
For individuals who have peritoneal carcinomatosis of gastric origin who receive CRS plus HIPEC, the evidence includes two small RCTs, observational studies, and a systematic review​s. Relevant outcomes are OS, disease-specific survival, quality of life, and treatment-related mortality and morbidity. Stefano et al. (2024) published a meta-analysis of 16 RCTs comparing surgery plus HIPEC versus other palliative options that evaluated patients (N=1641) with peritoneal carcinomatosis of gastric origin.​ Overall survival was significantly increased in both preventive (HR, 0.56; 95% CI, 0.46–0.68; P<0.0001; I2=23.1%) and therapeutic (HR, 0.57; 95% CI, 0.35–0.93; P=0.023) settings by surgery plus HIPEC. The pooled 3-year mortality rate was 32% (95% CI, 20–47) for surgery plus HIPEC for prophylactic use compared to 55% (95% CI, 29–78) in the control group.​ A 2022 meta-analysis ​by Granieri et al.​ identified 12 RCTs comparing CRS plus HIPEC to standard care in both prophylactic and curative settings. Improved survival was reported for CRS plus HIPEC at 1-, 2-, and 3-year follow-up, but not at 5-year follow-up. A 2017 meta-analysis by Desiderio et al. identified two RCTs and 12 controlled nonrandomized studies comparing surgery plus HIPEC with standard surgical management in​ individuals who had peritoneal carcinomatosis due to gastric cancer. The meta-analysis found significantly better survival in the surgery plus HIPEC group at 1 year but not at 2 or 3 years. A 2021 phase II trial (N=20) by Badgwell et al. (2021) reported ​the 90-day morbidity and mortality rates were 70% and 0%, respectively.​ A median OS of 16.1 months was observed from the time of cytoreduction, gastrectomy, and HIPEC. The OS rates for 1, 2, and 3 years from the diagnosis of metastatic disease were 90%, 50%, and 28%, respectively.​ In a phase III trial, Rau et al. (2024) randomly assigned 105 patients with peritoneal metastasis from gastric cancer to either perioperative chemotherapy and CRS alone (n=53) or CRS plus HIPEC (n=52). There was no difference in median OS between the two groups; however, median PFS (7.1 vs. 3.5 months; P=0.0472) and other distant metastasis-free survival (10.2 vs. 9.2 months; P=0.0286) were improved with the addition of HIPEC. ​The evidence is insufficient to determine the effects of the technology on health outcomes.​​

PERITONEAL CARCINOMATOSIS OF ENDOMETRIAL ORIGIN

For individuals who have peritoneal carcinomatosis of endometrial origin who receive CRS plus HIPEC, the evidence includes cohort studies. Relevant outcomes are OS, disease-specific survival, quality of life, and treatment-related mortality and morbidity. Only uncontrolled studies with small sample sizes were available (Cornali ​et al., 2018; Abu-Zaid​ et al., 2014; Bakrin et al., 2010; Delotte et al., 2014; Gomes David et al., 2024); the largest study included 43 individuals (Navarro-Barrios et al., 2020). Randomized trials that compare CRS plus HIPEC with standard treatment (e.g., CRS alone or systemic chemotherapy alone) are needed. The evidence is insufficient to determine the effects of the technology on health outcomes.

PERITONEAL CARCINOMATOSIS OF​ EPITHELIAL OVARIAN ORIGIN 

NEWLY DIAGNOSED STAGE III OVARIAN CANCER
For individuals who have newly diagnosed stage III ovarian cancer who receive CRS plus HIPEC, the evidence includes an RCT. Relevant outcomes are OS, disease-specific survival, quality of life, and treatment-related mortality and morbidity. For patients with newly diagnosed stage III ovarian cancer who had received neoadjuvant chemotherapy, HIPEC increased the time to disease recurrence and reduced mortality. HIPEC did not increase serious adverse events compared with surgery alone. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

STAGE IIIC OR IV OVARIAN CANCER
For individuals who have recurrent stage IIIC or IV ovarian cancer who receive CRS plus HIPEC, the evidence includes an RCT​s and systematic reviews. Relevant outcomes are OS, disease-specific survival, quality of life, and treatment-related mortality and morbidity. For recurrent stage IIIC or IV disease (second-line setting), evidence from an RCT indicated that CRS plus HIPEC improved survival compared with CRS without HIPEC. However, interpretation of this study is limited because treatment groups in this RCT were unbalanced at baseline (variation in the completeness of cytoreduction), which has been shown to be associated with survival (Spiliotis et al​., 2015). Zivanovic et al. (2021) reported on a multicenter RCT of 117 women who had platinum-sensitive recurrent ovarian cancer. There was a median follow-up of 39.5 months, and the median PFS in the CRS plus HIPEC group versus the control group was 12.3 and 15.7 months, respectively (P=0.05). There was no reported significant difference in median OS between the two groups (P=0.31).​ The evidence is insufficient to determine the effects of the technology on health outcomes.

PERITONEAL CARCINOMATOSIS OF APPENDICEAL ORIGIN 

For individuals who have peritoneal carcinomatosis of appendiceal origin who receive CRS plus HIPEC, the evidence includes two RCTs and cohort studies. Relevant outcomes are OS, disease-specific survival, quality of life, and treatment-related mortality and morbidity. One of the RCTs (Verwaal et al., 2003) did not include the population of interest—the majority of participants had metastasis of colorectal origin, not appendiceal—and the other RCT did not address the relevant clinical outcomes of interest, rather it compared two different chemotherapy agents with each other (Levine et al., 2018)​; therefore, the following cohort studies represent the highest quality of evidence. McConnell et al. (2014) (N=756) reported on the several histological appendiceal subtypes known to metastasize to the peritoneal space. Individuals who had complete cytoreduction with low-grade appendiceal mucinous neoplasms, goblet cell adenocarcinomas, high-grade mucinous neoplasms, or nonmucinous neoplasms had DFS of 38.1, 15.9, 21.6, and 22.7 months, respectively. Sluiter et al.'s (2020) comparative observational study analyzed a propensity-matched goblet cell adenocarcinoma cohort (n=45) and found HIPEC surgery was associated with better median OS than surgery without HIPEC (39.0 vs. 12.0 months; P=0.017). A noncomparative, single-center retrospective cohort study by Zambrano-Vera et al. (2020) reported outcomes in 20 individuals with peritoneal carcinomatosis from appendiceal goblet cell carcinoma who successfully underwent CRS plus HIPEC. Complete cytoreduction was achieved in 75%. With a median follow-up time of 70 months, 1-, 3-, and 5-year OS rates were 100%, 75%, and 65%, respectively. Median OS was not reached at 5 years. Rates of 1-, 3-, and 5-year PFS were 94%, 67%, and 59%, respectively, with a median PFS of 97 months.​ Additionally, Jimenez et al. (2014) (N=202) reported median OS and median progression-free survival (PFS) for peritoneal carcinomatosis of low- and high-grade appendiceal mucinous neoplasms of 90 months and 40 months, respectively. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.​​

NATIONAL COMPREHENSIVE CANCER NETWORK (NCCN) GUIDELINES
  • ​National Comprehensive Cancer Network (NCCN) guidelines include the following relevant recommendations for colon cancer (v.1.2025): “The panel currently believes that complete cytoreductive surgery and/or intraperitoneal chemotherapy can be considered in experienced centers for selected patients with limited peritoneal metastases for whom R0 resection can be achieved. However, the significant morbidity and mortality associated with HIPEC, as well as the conflicting data on clinical efficacy, make this approach very controversial.” 
  • NCCN guidelines for appendiceal neoplasm (colon cancer v.1.2025)​ state, "Patients deemed possible surgical candidates should be evaluated at a high-volume center for candidacy for hyperthermic intraperitoneal chemotherapy (HIPEC). These candidates are suggested to receive chemotherapy up to 6 months, preferably in the neoadjuvant setting. Additional chemotherapy may be considered for patients who are not resectable at initial diagnosis with the possibility of converting to resectable disease.​"​
  • NCCN guidelines on​ ​rectal cancer (v.1.2025) do not discuss CRS plus HIPEC.​
  • NCCN guidelines on gastric cancer (v.​ 1.2025) state, "IC/HIPEC may be a therapeutic alternative for carefully selected patients with peritoneal carcinoma as only disease."​
  • NCCN guidelines​ for uterine neoplasms (v.3.2025​) do not discuss CRS plus HIPEC.
  • NCCN guidelines on ovarian cancer (v.1.2025) state that,​ "HIPEC with cisplatin (100 mg/m2 ) can be considered at the time of IDS for stage III disease. HIPEC can also be considered for suitable stage IV patients (category 2B) who have had a favorable response to neoadjuvant therapy both intraperitoneally and extraperitoneally, or in whom stage IV disease sites have completely resolved (e.g., resolution of malignant pleural effusion) or are now deemed resectable. Sodium thiosulfate may be administered at the start of perfusion, followed by a continuous infusion, to allow for renal protection during HIPEC."​ ​

References

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Alexander HR, Jr., Bartlett DL, Pingpank JF, et al. Treatment factors associated with long-term survival after cytoreductive ​surgery and regional chemotherapy for patients with malignant peritoneal mesothelioma. Surgery. 2013;153(6):779-786.

Badgwell B, Ikoma N, Murphy MB, et al. A phase II trial of cytoreduction, gastrectomy, and hyperthermic intraperitoneal perfusion with chemotherapy for patients with gastric cancer and carcinomatosis or positive cytology. Ann Surg Oncol 2021;28:258-264.​

Bakrin N, Cotte E, Sayag-Beaujard A, et al. Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for the treatment of recurrent endometrial carcinoma confined to the peritoneal cavity. Int J Gynecol Cancer. 2010;20(5):809-814. 

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National Comprehensive Cancer Network (NCCN). NCCN Clinical practice guidelines in oncology: ovarian cancer, fallopian tube cancer, primary peritoneal cancer. Version 1.2025. https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1453. Accessed March 17, 2025​.

Navarro-Barrios Á, Gil-Martínez J, Ramos-Bernardo I, et al. Intraperitoneal hyperthermic chemotherapy after cytoreduction in patients with peritoneal metastases from endometrial cancer. The next frontier? Surg Oncol. 2020;33:19-23. 

Quénet F, Elias D, Roca L, et al. Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy versus cytoreductive surgery alone for colorectal peritoneal metastases (PRODIGE 7): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2021;22(2):256-266. 

Rau B, Lang H, Koenigsrainer A, et al. Effect of Hyperthermic Intraperitoneal Chemotherapy on Cytoreductive Surgery in Gastric Cancer With Synchronous Peritoneal Metastases: The Phase III GASTRIPEC-I Trial. J Clin Oncol. 2024;42(2):146-156.

Robella M, Vaira M, Mellano A, et al. Treatment of diffuse malignant peritoneal mesothelioma (DMPM) by cytoreductive surgery and HIPEC. Minerva Chir. 2014;69(1):9-15. 

Rudloff U, Langan RC, Mullinax JE, et al. Impact of maximal cytoreductive surgery plus regional heated intraperitoneal chemotherapy (HIPEC) on outcome of patients with peritoneal carcinomatosis of gastric origin: results of the GYMSSA trial. J Surg Oncol. 2014;110(3):275-284. 

Sardi A, Jimenez WA, Nieroda C, et al. Repeated cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in peritoneal carcinomatosis from appendiceal cancer: analysis of survival outcomes. Eur J Surg Oncol. 2013;39(11):1207-1213. 

Seretis C, Youssef H. Quality of life after cytoreductive surgery and intraoperative hyperthermic intraperitoneal chemotherapy for peritoneal surface malignancies: A systematic review. Eur J Surg Oncol. 2014;40(12):1605-1613. 

Shan LL, Saxena A, Shan BL, et al. Quality of life after cytoreductive surgery and hyperthermic intra-peritoneal chemotherapy for peritoneal carcinomatosis: A systematic review and meta-analysis. Surg Oncol. 2014;23(4):199-210.

Sluiter NR, van der Bilt JD, Croll DMR, et al. Cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC) versus surgery without HIPEC for goblet-cell carcinoids and mixed adenoneuroendocrine carcinomas: propensity score-matched analysis of centers in the Netherlands and Belgium. Clin Colorectal Cancer. 2020;19(3):e87-e99. 

Spiliotis J, Halkia E, Lianos E, et al. Cytoreductive surgery and HIPEC in recurrent epithelial ovarian cancer: a prospective randomized phase III study. Ann Surg Oncol. 2015;22(5):1570-1575. 

Stefano M, Perrina D, Vallicelli C, et al. Prophylaxis and treatment of peritoneal carcinomatosis of gastric origin using hyperthermic intraperitoneal chemotherapy: a systematic review and meta-analysis of randomized trials. J Gastrointest Surg. Jul 2024; 28(7): 1185-1193.​

Vaira M, Cioppa T, G DEM, et al. Management of pseudomyxoma peritonei by cytoreduction+HIPEC (hyperthermic intraperitoneal chemotherapy): results analysis of a twelve-year experience. In Vivo. 2009;23(4):639-644. 

van Driel WJ, Koole SN, Sikorska K, et al. Hyperthermic intraperitoneal chemotherapy in ovarian cancer. N Engl J Med. 2018;378(3):230-240. 

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;15(9):2426-2432. 

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):3737-3743. 

Vogel JD, Eskicioglu C, Weiser MR, et al. The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the Treatment of Colon Cancer. Dis Colon Rectum. 2017;60(10):999-1017. 

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):484-492. 

Yan TD, Cao CQ, Munkholm-Larsen S. A pharmacological review on intraperitoneal chemotherapy for peritoneal malignancy. World J Gastrointest Oncol. 2010;2(2):109-116.

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):6237-6242. 

Yang XJ, Huang CQ, Suo T, et al. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy improves survival of patients with peritoneal carcinomatosis from gastric cancer: final results of a phase III randomized clinical trial. Ann Surg Oncol. 2011;18(6):1575-1581. 

Yonemura Y, Endou Y, Shinbo M, et al. Safety and efficacy of bidirectional chemotherapy for treatment of patients with peritoneal dissemination from gastric cancer: Selection for cytoreductive surgery. J Surg Oncol. 2009;100(4):311-316. 

Yonemura Y, Kawamura T, Bandou E, et al. Advances in the management of gastric cancer with peritoneal dissemination. Recent Results Cancer Res. 2007;169:157-164. 

​​​Zambrano-Vera K, Sardi A, Munoz-Zuluaga C, et al. Outcomes in Peritoneal Carcinomatosis from Appendiceal Goblet Cell Carcinoma Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (CRS/HIPEC). Ann Surg Oncol. 2020;27(1):179-187. 

Zivanovic O, Chi DS, Zhou Q, et al. Secondary Cytoreduction and Carboplatin Hyperthermic Intraperitoneal Chemotherapy for Platinum-Sensitive Recurrent Ovarian Cancer: An MSK Team Ovary Phase II Study. J Clin Oncol. 2021;39(23):2594-2604.

Coding

CPT Procedure Code Number(s)
96547, 96548​
ICD - 10 Procedure Code Number(s)
N/A
ICD - 10 Diagnosis Code Number(s)
​C45.1 Mesothelioma of peritoneum

C48.0 Malignant neoplasm of retroperitoneum

C48.1 Malignant neoplasm of specified parts of peritoneum

C48.2 Malignant neoplasm of peritoneum, unspecified

C48.8 Malignant neoplasm of overlapping sites of retroperitoneum and peritoneum

​C78.6 Secondary malignant neoplasm of retroperitoneum and peritoneum​
HCPCS Level II Code Number(s)
N/A
Revenue Code Number(s)
N/A


Coding and Billing Requirements

Policy History

Revisions From 11.00.13k:​
​​09/30/2026
​This policy has been reissued in accordance with the Company's annual review process.​
06/16/2025

This version of the policy will become effective 06/16/2025.


The medical necessity determination of the following indication has changed from experimental/investigational to medically necessary:​
  • Peritoneal carcinomatosis of gastric origin​
​The coverage header for Ovarian Cancer and Fallopian Tube Cancer has been expanded to specify peritoneal carcinomatosis of ovarian and fallopian tube origin. Primary peritoneal cancer was also added to the header.​

The following ICD-10 codes have been removed from this policy:
C18.1, ​C56.1​, C56.2, C56.3, C56.9, C57.00, C57.01, C57.02​

Revisions From 11.00.13j:​
02/26/2024​

This version of the policy will become effective 02/26/2024.

The following criterion has been added to this policy as medically necessary:

Peritoneal carcinomatosis of appendiceal origin

The following ICD-10 code has been added to this policy as medically necessary:

C18.1 Malignant neoplasm of appendix​

The following CPT codes have been deleted from this policy:

77620, 96446, 96549​

Revisions From 11.00.13i:
01/02/2024

This policy has been identified for the CPT code update effective 1/02/2024.​

The following CPT codes have be added to the policy:

96547 and 96548

The following CPT code has been revised in the policy:

96446​


Revisions From 11.00.13h:
​11/03/2021

This policy has been reissued in accordance with the Company's annual review process.
10/01/​2021

This policy has been identified for the ICD-10 CM code update effective 10/01/2021.​

The following ICD-10 CM code has be added to the policy :

C56.3 Malignant neoplasm of bilateral ovaries​

 Revisions From 11.00.13g:
03/25/2020This policy has been reissued in accordance with the Company's annual review process.
11/20/2019This policy has been reissued in accordance with the Company's annual review process.
01/21/2019This version of the policy is effective as of 01/21/2019.

Major update for this version includes the following:

Hyperthermic intraperitoneal chemotherapy (HIPEC) following cytoreductive surgery is considered medically necessary and, therefore, covered in newly diagnosed epithelial ovarian or fallopian tube cancer at the time of interval cytoreductive surgery when specific criteria, (described in this policy) are met.

Revisions From 11.00.13f:
09/12/2018The policy has been reviewed and reissued to communicate the Company’s continuing position on Hyperthermic Intraperitoneal Chemotherapy (HIPEC).

Effective 10/05/2017 this policy has been updated to the new policy template format.
6/16/2025
6/16/2025
9/30/2026
11.00.13
Medical Policy Bulletin
Commercial
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