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Effective Date: 08/01/2011 |
Title: Liver Neoplasms Treatment
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Revision Date: 07/01/2019
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Document: BI301:00
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CPT Code(s): 47370-47371, 47380-47382, 75894, 75896, 77750, 77778, 79101, 79445, S2095
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Public Statement
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Effective Date:
a)
This policy
will apply to all services performed on or after the above revision date which
will become the new effective date.
b)
For all
services referred to in this policy that were performed before the revision
date, contact customer service for the rules that would apply.
1)
Some non
surgical treatment of liver cancers and metastases require pre-authorization.
2)
Several
different forms of treatment are used to treat liver tumors that are not
possible to treat with surgery.
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Medical Statement
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All of the following
procedures require pre-authorization with a diagnosis of liver cancer (C22.0 –
C22.9, C78.7):
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Percutaneous Ethanol
Injection
Percutaneous ethanol
injection (PEI) is considered medically necessary for the treatment of
hepatocellular cancers (HCC) without extrahepatic spread.
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Chemoembolization
Chemoembolization (CE,
TACE) is considered medically necessary for any of the following:
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For symptomatic
treatment of functional neuroendocrine cancers (i.e., carcinoid tumors
and pancreatic endocrine tumors) involving the liver. For carcinoid
tumors, TACE is considered medically necessary only in persons who have
failed systemic therapy with octreotide to control carcinoid syndrome
(e.g., debilitating flushing, wheezing and diarrhea); or
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For unresectable,
primary HCC; or
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As a bridge to
transplant in patients with hepatocellular cancer where the intent is to
prevent further tumor growth and to maintain a patient’s candidacy for
liver transplant when all of the following patient characteristics
apply:
·
A single tumor less than 5cm or no more than 3 tumors each less
than 3 cm in size, AND
·
Absence of extrahepatic disease or vascular invasion, AND
·
Child-Pugh score of either A or B. See
http://depts.washington.edu/uwhep/calculations/childspugh.htm
3.
Intra-hepatic Chemotherapy
Intra-hepatic
chemotherapy (infusion) is considered medically necessary for members with liver
metastases from colorectal cancer.
4.
Intra-hepatic Microspheres
Intra-hepatic
microspheres (e.g., TheraSphere, MDS Nordion Inc.; SIR-Spheres, Sirtex Medical
Inc., San Diego, CA) are considered medically necessary for any of the
following:
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For symptomatic
treatment of functional neuroendocrine cancers (i.e., carcinoid tumors
and pancreatic endocrine tumors) involving the liver. For carcinoid
tumors, intrahepatic microspheres are considered medically necessary
only in persons who have failed systemic therapy with octreotide to
control carcinoid syndrome (e.g., debilitating flushing, wheezing and
diarrhea);
or
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For unresectable,
primary HCC;
i.
Tumor volume is < 50% of the target liver volume
ii.
Child-Pugh grade A (no ascites, bilirubin < 2 mg/dL, albumin > 3.5
g/dL, prothrombin time < 4 seconds over control, INR < 1.7, no encephalopathy)
iii.
There are no extrahepatic metastases
iv.
ECOG performance status of 0 – 2 (Ambulatory and capable of all
self-care, but unable to carry out any work activities. Up and about more than
50% of waking hours.);
or
C.
For
unresectable liver tumors from primary colorectal cancer that has failed first
line and second line standard chemotherapy.
i.
There is minimal or no extra-hepatic disease
ii.
Tumor volume is 50% or less of total liver volume
iii.
Bilirubin is less than 3 mg/dL
iv.
ECOG
performance status of 0 – 2
Intra-hepatic
microspheres are considered experimental and investigational for other
indications.
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Cryosurgery, Microwave, Radiofrequency or Radiopharmaceutical (such as
yttrium-90) Ablation
Cryosurgery, microwave, or radiofrequency ablation is considered medically
necessary for:
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Isolated
colorectal cancer liver metastases or isolated hepatocellular cancer who
are not candidates for open surgical resection and who meet the
following criteria:
i.
Ablation is
being performed with curative not palliative intent.
ii.
Members
must either have hepatic metastases from a colorectal primary cancer or have a
hepatocellular cancer; and
iii.
Members
must have isolated liver disease. Members with nodal or extra-hepatic systemic
metastases are not considered candidates for these procedures; and
iv.
All tumors
in the liver, as determined by preoperative imaging, would be potentially
destroyed by cryotherapy, microwave, or radiofrequency ablation; and
v.
Because
open surgical resection is the preferred treatment, members must be unacceptable
open surgical candidates due to the location or extent of the liver disease or
due to co-morbid conditions such that the member is unable to tolerate an open
surgical resection; and
vi.
Liver
lesions must be 4 cm or less in diameter and occupy less than 50% of the liver
parenchyma. Lesions larger than this may not be adequately treated by either
procedure.
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Unresectable
neuroendocrine tumors metastatic to the liver.
Codes
Used In This BI:
47370 |
Laparoscopy, surgical, ablation of liver tumor, radiofrequency |
47371 |
cryosurgical |
47380 |
Ablation, open, of 1 or more liver tumors; radiofrequency |
47381 |
cryosurgical |
47382 |
Ablation 1 or more liver tumors, percutaneous |
75894 |
X-rays transcath therapy |
77750 |
Infuse radioactive materials |
77778 |
Apply
interstit radiat compl |
79101 |
Radiopharmaceutical therapy by IV admin |
79445 |
Radiopharmaceutical therapy by intra-arterial particulate admin |
S2095 |
Transcatheter occlusion or embolization for tumor destruction, using
yttrium-90 microspheres |
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Limits
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1.
Percutaneous ethanol injection (PEI) for other liver neoplasms is considered
experimental and investigational when criteria are not met. There is inadequate
information to document the effectiveness of PEI as an alternative to surgical
resection for the treatment of hepatic metastases.
2.
Combined
radiofrequency ablation and PEI is considered experimental and investigational
for the treatment of HCC.
3.
Chemoembolization is considered experimental and investigational for palliative
treatment of liver metastases from other non-neuroendocrine primaries (e.g.,
colon cancer, melanoma, or unknown primaries) because there is inadequate
evidence in the medical literature of the effectiveness of CE for these
indications.
4.
Intra-hepatic chemotherapy is considered experimental and investigational for
treatment of liver primaries or metastases from other primaries besides
colorectal cancer.
5.
“One-shot”
arterial chemotherapy for members with liver metastases from colorectal cancer
is considered experimental and investigational.
6.
Transarterially administered gene therapy is considered experimental and
investigational for primary and secondary liver malignancies.
7.
Drug-eluting beads trans-arterial chemoembolization are considered experimental
and investigational for primary and liver-dominant metastatic disease of the
liver.
8.
Cryosurgical, microwave, or radiofrequency ablation as a treatment of hepatic
metastases from non-colonic primary cancers is considered experimental and
investigational.
9.
Cryosurgical, microwave or radiofrequency ablation as a palliative treatment of
either hepatic metastases from colorectal cancer or hepatocellular cancer is
also considered experimental and investigational.
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Background
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Chemoembolization (CE)
involves the periodic injection of chemotherapy mixed with embolic material into
selected branches of the hepatic arteries feeding liver tumors. CE has been
successfully used as a palliative treatment of symptoms associated with
functioning neuroendocrine tumors involving the liver. The most common such
tumor is the carcinoid tumor whose hormone production is associated with the
carcinoid syndrome, characterized by debilitating flushing, wheezing, and
diarrhea. Pancreatic endocrine tumors that produce gastrin, insulin or other
pancreatic hormones are unusual types of neuroendocrine tumors. Pancreatic
endocrine (i.e., islet cell) tumors must be distinguished from the more common
pancreatic epithelial tumors that arise from the exocrine portion of the
pancreas.
The prognosis for
patients with unresectable hepatocellular carcinoma (HCC) tumors is extremely
poor. Even in the case of small nodular lesions detected by US screening,
patients receiving no treatment showed a mean 3-year survival rate of 12%.
Among non-surgical options, percutaneous ethanol injection (PEI) can be
considered the treatment of choice for patients with small HCC tumors.
Transcatheter arterial chemoembolization (TACE), most frequently performed by
intra-arterially injecting an infusion of antineoplastic agents mixed with
iodized oil (Lipiodol), has been extensively used in the treatment of large HCC
tumors. However, although massive tumor necrosis can be demonstrated in most
cases, a complete necrosis of the tumor has rarely been achieved with TACE,
since residual tumor can be found in a non-negligible number of the treated
lesions.
TACE
was found mostly effective in nodules less than 4 cm in diameter, with a thick
tumor capsule. In fact, small, encapsulated HCC are almost completely fed by
hepatic arterial blood and therefore highly responsive to hepatic arterial
embolization. On the contrary, in unencapsulated tumors or in tumors showing
extracapsular invasion of neoplastic cells, TACE often fails to induce complete
necrosis since tumor cells, either unimpeded by the absence of a capsule or
spreading across the capsule itself, invade the adjacent liver parenchyma, thus
obtaining additional blood supply from the sinusoidal portal system.
Large HCC lesions can be
more effectively treated with combined TACE and PEI. In fact, alcohol diffusion
is easier after the occurrence of the necrotic changes produced by TACE, thus
allowing the intranodular injection of larger amounts of ethanol. Moreover,
after arterial embolization, the normal wash-out of the injected ethanol is more
difficult in the tumorous area, resulting in longer retention of the substance.
The combination of TACE and PEI seems to be a highly effective treatment for
large HCC also in the instances when daughter nodules are associated with a main
tumor. The presence of the capsule significantly enhances the chances of
success and should be considered an important requirement when selecting
patients to be submitted to TACE and PEI.
According to available
literature, chemoembolization (TACE) may be indicated for symptomatic treatment
of functional neuroendocrine cancers (i.e., carcinoid tumors and pancreatic
endocrine tumors) involving the liver, in persons with adequate hepatic function
(bilirubin less than 2 mg/dl, absence of ascites; no portal vein occlusion;
and tumor involvement of less than 65 % of liver). For carcinoid tumors, TACE
is indicated only in persons who have failed systemic therapy with octreotide to
control carcinoid syndrome (e.g., debilitating flushing, wheezing, and
diarrhea). The safety and effectiveness of more than 4 TACE procedures is
unknown.
Percutaneous ethanol
injection has been shown to be effective only in primary hepatocellular
carcinoma with a limited number (fewer than 4) of small foci (less than 5 cm in
diameter) and with no evidence of extrahepatic metastasis. According to the
medical literature, PEI is not suitable for persons with coagulopathy or
ascites.
In a randomized
controlled study, Brunello and colleagues (2008) compared PEI and RFA for the
treatment of early HCC. A total of 139 cirrhotic patients in Child-Pugh classes
A/B with 1-3 nodes of HCC (diameter 15 to 30 mm), for a total of 177 lesions
were included in this study. Patients were randomized to receive RFA (n = 70)
or PEI (n = 69). The primary end-point was complete response (CR) 1 year after
the percutaneous ablation of all HCC nodes identified at baseline. Secondary
end-points were: early (30 to 50 days) CR, complications, survival, and costs.
In an intention-to-treat analysis, 1-year CR was achieved in 46/70 (65.7 %) and
in 25/69 (36.2 %) patients treated by RFA and PEI, respectively (p = 0.0005).
For lesions greater than 20 mm in diameter, there was a larger CR rate in the
RFA-treated subjects (68.1 % versus 26.3 %). An early CR was obtained in 67/70
(95.7 %) patients treated by RFA compared with 42/64 (65.6 %) patients treated
by PEI (p = 0.0001). Complications occurred in 10 and 12 patients treated by
RFA and PEI, respectively. The overall survival rate was not significantly
different in the RFA versus PEI arm (adjusted hazard ratio = 0.88, 95 % CI: 0.50
to 1.53). There was an incremental health-care cost of 8286 Euro for each
additional patient successfully treated by RFA. The authors concluded that the
1-year CR rate after percutaneous treatment of early HCC was significantly
better with RFA than with PEI, but did not provide a clear survival advantage in
cirrhotic patients.
Hepatic arterial infusion
(HAI) of chemotherapy involves the use of an implanted subcutaneous pump to
deliver continuous chemotherapy into the hepatic artery. Controlled trials have
shown that this therapy is associated with higher tumor response rates and this
approach is considered a potentially curative treatment of patients with
colorectal cancer (CRC) with isolated liver metastases. Other applications of
intra-hepatic chemotherapy are unproven.
In a review on recent
advances in transarterial therapy of primary and secondary liver malignancies,
Kalva and colleagues (2008) stated that transarterially administered gene
therapy holds promise but is still in the early stages of investigation.
The liver is the most
common site of distant metastasis from colorectal cancer. About one-fourth of
patients with liver metastases from colorectal cancer has no other sites of
metastasis and can be treated with regional therapies directed toward their
liver tumors. Based on a preponderance of uncontrolled studies for hepatic
metastatic colorectal carcinoma, surgical resection offers the only potential
for cure of selected patients with completely resected disease, with 5-year
survival rates of 25% to 46%; however, the majority of patients with primary or
metastatic malignancies confined to the liver are not candidates for resection
because of tumor size, location, or multifocality or inadequate functional
hepatic reserve. For the treatment of patients with non-resectable liver
metastases, alternative local ablative therapeutic modalities have been
developed. For most patients with spread of metastatic colorectal cancer beyond
the liver, systemic chemotherapy rather than regional therapy is a more
appropriate option.
Cryotherapy is an
effective and precise technique for inducing tumor necrosis, but it is currently
performed via laparotomy. Recent results suggest that ultrasound-guided
radiofrequency thermal ablation may be an effective, minimally invasive
technique for treating malignant hepatic tumors. Both interventional therapeutic
techniques have been shown to result in a remarkable local tumor control rate
with improved survival results for patients with liver metastases from
colorectal cancer.
The National Institute
for Clinical Excellence (NICE, 2004) guidance on radiofrequency ablation (RFA)
for the treatment of colorectal metastases to the liver stated that: "Current
evidence on the safety of radiofrequency ablation of colorectal metastases in
the liver appears adequate. However, the evidence of its effect on survival is
not yet adequate to support the use of this procedure without special
arrangements for consent and for audit or research". In patients who are not
eligible for traditional surgery, RFA can be used to destroy liver tumors.
However, existing evidence does not conclusively support the effectiveness of
RFA in improving patient survival.
Jungraithmayr, et al.
(2005) stated that local ablative procedures such as cryosurgery and
thermo-ablation are increasingly employed as a supplement to liver resection for
the treatment of primary and secondary liver tumors. However, it is still
unclear whether the survival time can be extended through local ablative
procedures. In this prospective study (n = 19), these investigators reported
operative actions, complications and long-term follow-up of patients with
malignant liver tumors undergoing cryotherapy. Subjects underwent cryotherapy
due to a non-resectable malignant liver tumor (17 subjects with metastases of a
colon carcinoma, and 2 subjects with a hepatocellular carcinoma). A total of 12
patients (63.2%) received cryotherapy only, and 7 patients (36.8%) received a
combination of resection and cryotherapy. The median follow-up period was 23
months. The 30-day mortality was 0 %, and the rate of major complications was
21%. After one year, 27.3% of the patients were still recurrence-free. The
recurrence rate for all tumors treated was 58.8%. The median survival time for
all patients was 21 months. The 1- and 3-year survival rates were 62.5% and
15.8%, respectively. The authors concluded that the mortality for cryotherapy
is low, but there is a high rate of complications and long-term tumor control is
insufficient. If local ablative procedures of hepatic lesions are to be
performed, not laparotomy but percutaneous, percutaneous thermoablation should
be discussed as an alternative therapeutic measure.
Microwave energy can also
be used to destroy liver neoplasms. Microwave ablation destroys tumor cells by
heat, resulting in localized areas of necrosis and tissue destruction. Guidance
from the National Institute for Health and Clinical Excellence (NICE, 2006)
concluded that there is sufficient evidence of the safety and effectiveness of
microwave ablation of hepatocellular carcinoma. This conclusion was based upon
the results of nonrandomized controlled studies of microwave ablation of
hepatocellular carcinoma that found similar outcomes to liver resection
(Midorikawa, et al., 2005), percutaneous ethanol injection (Seki, et al., 1999),
and radiofrequency ablation (Lu, et al., 2005). However, NICE (2007) found
insufficient evidence of the safety and effectiveness of microwave ablation of
colorectal cancer metastatic to the liver and other liver metastases. One small
randomized controlled clinical trial (n = 30) found similar overall and disease
free survival with liver resection and microwave ablation of liver metastases
(Shibata, et al., 2000). Other uncontrolled case series reported similar results
with microwave ablation of liver metastases (Liang, et al., 2003; Morikawa, et
al., 2002).
Guidelines on
neuroendocrine tumors from the National Comprehensive Cancer Network (NCCN,
2009) state that, for unresectable liver metastases from carcinoid tumors and
islet cell tumors, locally ablative therapy is recommended.
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Reference
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Poon RT, Tso WK, Pang RW, et al. A phase I/II
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Martin RC, Robbins K, Tomalty D, et al.
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Tokh M, Nugent FW, Molgaard C, et al.
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Ablation
-
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Shibata T, Iimuro Y, Yamamoto Y, et al. Small
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Liang P, Dong B, Yu X, et al. Prognostic
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National Comprehensive Cancer Network (NCCN).
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Kornprat P, Jarnagin WR, DeMatteo RP, et al.
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treatment of hepatic metastasis from colorectal cancer. Arch Surg. 2007;
142(11):1087-1092.
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Siperstein AE, Berber E, Ballem N, Parikh RT.
Survival after radiofrequency ablation of colorectal liver metastases:
10-year experience. Ann Surg. 2007; 246(4):559-565; discussion 565-567.
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Al-asfoor A, Fedorowicz Z, Lodge M. Resection
versus no intervention or other surgical interventions for colorectal cancer
liver metastases. Cochrane Database Syst Rev. 2008 :( 2):CD006039.
-
Brunello F, Veltri A, Carucci P, et al.
Radiofrequency ablation versus ethanol injection for early hepatocellular
carcinoma: A randomized controlled trial. Scand J Gastroenterol. 2008;
43(6):727-735.
-
Garrean S, Hering J, Saied A, et al.
Radiofrequency ablation of primary and metastatic liver tumors: A critical
review of the literature. Am J Surg. 2008; 195(4):508-520.
-
Lau WY, Lai EC. The current role of
radiofrequency ablation in the management of hepatocellular carcinoma: A
systematic review. Ann Surg. 2009; 249(1):20-25.
-
National Comprehensive Cancer Network (NCCN).
Neuroendocrine tumors. NCCN Clinical Practice Guidelines in Oncology
v.2.2009. Fort Washington, PA: NCCN; 2009.
-
Stang A, Fischbach R, Teichmann W, et al. A
systematic review on the clinical benefit and role of radiofrequency
ablation as treatment of colorectal liver metastases. Eur J Cancer. 2009;
45(10):1748-1756.
-
Wong SL, Mangu PB, Choti MA, et al. American
Society of Clinical Oncology 2009 clinical evidence review on radiofrequency
ablation of hepatic metastases from colorectal cancer. J Clin Oncol. 2010;
28(3):493-508.
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Application to Products
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This policy applies to all health plans and
products administered by QualChoice, both those insured by QualChoice and those
that are self-funded by the sponsoring employer, unless there is indication in
this policy otherwise or a stated exclusion in your medical plan booklet.
Consult the individual plan sponsor Summary Plan Description (SPD) for
self-insured plans or the specific Evidence of Coverage (EOC) or Certificate of
Coverage (COC) for those plans or products insured by QualChoice. In the event
of a discrepancy between this policy and a self-insured customer’s SPD or the
specific QualChoice EOC or COC, the SPD, EOC, or COC, as applicable, will
prevail. State and federal mandates will be followed as they apply.
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Changes: QualChoice reserves the right to alter, amend, change or supplement benefit interpretations as needed.
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