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PMB definition guideline for metastatic (including advanced) stage gastric/ gastro-oesophageal junction
cancer
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PMB definition guideline for metastatic (including advanced) stage gastric/ gastro-oesophageal junction
cancer
Disclaimer:
The metastatic stage gastric/ gastro-oesophageal junction (GEJ) cancer benefit definition has been
developed for the majority of standard patients. These benefits may not be sufficient for outlier patients.
Therefore Regulation 15(h) and 15(I) may be applied for patients who are inadequately managed by the
stated benefits. The benefit definition does not describe specific in-hospital management such as theatre,
anaesthetists, anaesthetist drugs and nursing care. However, these interventions form part of care and
are prescribed minimum benefits.
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PMB definition guideline for metastatic (including advanced) stage gastric/ gastro-oesophageal junction
cancer
Table of Contents
1. Introduction ............................................................................................................................................... 5
2. Scope and Purpose .................................................................................................................................. 5
3. Epidemiology ............................................................................................................................................ 6
4. Diagnosis and Staging Investigations ....................................................................................................... 6
5. Treatment for metastatic stage gastric / gastro-oesophageal junction cancer .......................................... 8
6. Follow Up Care ....................................................................................................................................... 10
7. References ............................................................................................................................................. 13
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PMB definition guideline for metastatic (including advanced) stage gastric/ gastro-oesophageal junction
cancer
Abbreviations
5FU
AJCC
CMS
CT
DTPs
ESD
EUS
GEJ
PMB
RT
TNM
UICC
Fluorouracil
American Joint Committee on Cancer
Council for Medical Schemes
Computed tomographic
Diagnosis treatment pairs
Endoscopic submucosal dissection
Endoscopic ultrasound
Gastro-oesophageal junction
Prescribed minimum benefit
Radiotherapy
Tumour, node, metastasis
Union for International Cancer Control
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PMB definition guideline for metastatic (including advanced) stage gastric/ gastro-oesophageal junction
cancer
1. Introduction
1.1.
The legislation governing the provision of the prescribed minimum benefits (PMBs) is contained in the
Regulations enacted under the Medical Schemes Act, 131 of 1998 (the Act). In respect of some of the
diagnosis treatment pairs (DTPs), medical scheme beneficiaries find it difficult to know their entitlements
in advance. In addition, medical schemes interpret these benefits differently, resulting in a lack of
uniformity of benefit entitlements.
1.2.
The benefit definition project is coordinated by the Council for Medical Schemes (CMS) and aims to define
the PMB package as well as to guide the interpretation of the PMB provisions by relevant stakeholders.
2. Scope and purpose
2.1.
This is a recommendation for the diagnosis, treatment and care of individuals with metastatic stage gastric
/ gastro-oesophageal junction (GEJ) cancer in any clinically appropriate setting as outlined in the Act.
2.2
The purpose is to improve clarity in respect of funding decisions by medical schemes, taking into
consideration evidence based medicine, affordability and in some instances cost-effectiveness.
Table 1: Possible ICD10 codes for identifying metastatic stage gastric/ GEJ cancer
ICD 10 code
WHO description
C16.1
Malignant neoplasm, fundus of stomach
C16.2
Malignant neoplasm, body of stomach
C16.3
Malignant neoplasm, pyloric antrum
C16.4
Malignant neoplasm, pylorus
C16.6
Malignant neoplasm, greater curvature of stomach, unspecified
C16.8
Malignant neoplasm, overlapping lesion of stomach
C16.9
Malignant neoplasm, stomach, unspecified
D00.2
Carcinoma in situ, stomach
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PMB definition guideline for metastatic (including advanced) stage gastric/ gastro-oesophageal junction
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3. Epidemiology and burden of Disease
3.1. Despite the marked decline of gastric cancers incidence over the past decades, approximately 990 000
people globally are diagnosed with gastric cancer (Ferlay,Shin, Bray, Forman, Mathers & Parkin, 2008)
and gastric cancer is reported to be the 4th most common incident cancer (Jemal, Center & DeSantis,
2010).
3.2. In Africa, gastric cancer is ranked twelfth most common cancer (Ferlay, Shin & Bray, 2010). Southern
Africa has an incidence rate of 11.9/100 000 (Parkin, Bray & Ferlay, 2005). In South Africa, gastric cancer
is the 7th most frequent cancer and is ranked the 9th leading cause of death amongst the cancers (Ferlay,
Autier & Boniol, 2007; Global Burden of Disease Cancer Collaboration, 2016).
3.3. In most countries, gastric cancer is reported to show a constant declining trend and part of the decline
may be due to the recognition of risk factors such as H. pylori and other dietary and environmental risks
(Lunet & Barros, 2003; Singh & Ghoshal, 2006). The mechanism by which H. pylori contributes to gastric
carcinogenesis is still largely unknown.
4. Diagnostic and staging investigations
4.1. Involvement of a multidisciplinary treatment planning before any treatment is essential.
4.2. The initial staging and risk assessment of a patient with a suspected gastric carcinoma should include
other than a physical examination, a full blood count and differential, liver and renal function tests,
endoscopy and contrast-enhanced computed tomography (CT) scan of the chest, abdomen and pelvis
(Edge, Byrd & Compton, 2010).
4.3. Accurate categorization of the tumour stage is important for prognostic assessment and decision making
of the stage-specific management, the American Joint Committee on Cancer (AJCC)/Union for
International Cancer Control (UICC) tumour, node, and metastasis (TNM) staging system should be used
as it represents the most important independent prognostic factor (Edge et al, 2010).
4.4. If staging scans are negative, a laparoscopic evaluation - with peritoneal washings for cytology, to rule
out peritoneal metastases is suggested prior to surgical resection.
4.5. Endoscopic ultrasound (EUS) is a useful staging tool in gastric cancer, specifically to determine pretherapy T and N stages so as to guide the sequence of therapy as well as enhance the information on
the extent of disease. It is also used preoperatively to assess the submucosal vasculature in order to
predict intraoperative bleeding during endoscopic therapy. Apart from the utility of EUS for diagnosing
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PMB definition guideline for metastatic (including advanced) stage gastric/ gastro-oesophageal junction
cancer
invasion depth, EUS can be used preoperatively to assess the submucosal vasculature in order to predict
intraoperative bleeding during endoscopic therapy (Guimbaud, Louvet, & Ries, 2014).
4.6. To overcome the limitations of contrast-enhanced imaging, diagnostic laparoscopy is recommended as
an additional staging tool to avoid nontherapeutic laparotomy. Staging laparoscopy can detect
radiographically occult peritoneal metastases and prevent futile laparotomy in patients with gastric
adenocarcinoma. This is evidenced by reports of up to 30% of patients with no preoperative evidence of
metastatic disease that harbor occult intra-abdominal metastases that cannot be detected
radiographically by modern imaging techniques (Baiocch Baiocchi, D’Ugo & Coit, 2016; D’Ugo, Biondi &
Tufo, 2013; Tey, Back, Shakespeare, Mukherjee, Lu, Lee, Wong, Leong & Zhu, 2007).
Table 2: Diagnosis and staging work up of metastatic stage gastric cancer
Description
Frequency
Clinical
Consultations with
2 consultations per
assessment
primary care practitioner, gastroenterologist, oncologist,
speciality
surgeon
Imaging:
Radiology
Pathology
Imagining:
Procedures
Histology
CT chest with contrast
1
CT abdomen, pelvis with contrast
1
Chest x-ray
1
Full blood count
1
Liver function test
1
Renal function
1
Gastroscopy
1
Contrast meal
1
Endoscopic ultrasound
1
Diagnostic Laparoscopy
1
Histology/ cytology
1
assessment
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PMB definition guideline for metastatic (including advanced) stage gastric/ gastro-oesophageal junction
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5. Treatment for metastatic stage gastric / gastro-oesophageal junction cancer
Involvement of a multidisciplinary strategy for the treatment of patients with newly diagnosed gastric cancer is
strongly recommended. Several factors such as the patient’s underlying comorbidities, performance status
and electrolyte imbalances are some of the factors that should be considered in the evaluation of such patients
for surgical treatment.
5.1. Surgical management
For metastatic gastric surgery alone whilst not providing any advantages, remains the central curative
intervention (Bouché, Raoul & Bonnetain, 2004). Recurrence of gastric cancer after undergoing surgical
treatment has been reported in approximately 45% of cases in Western countries and about 22% of cases
in Korea and Japan (Roviello, Marrelli & de Manzoni, 2003). Patients with locally advanced disease with
or without distant metastases can have significant local symptoms and surgical procedures such as wide
local excision, partial gastrectomy, total gastrectomy, simple laparotomy, gastrointestinal anastomosis,
and bypass are performed with palliative intent, with a goal of allowing oral intake of food and alleviating
pain.
The following surgical interventions of gastric cancer are PMB level of care:

gastrointestinal anastomosis

bypass

stent

PEJ / feeding jejunostomy
5.2. Chemotherapy
5.2.1. Although radical resection in gastric cancer is an integral part of treatment for curative intent, the
rates of local and distant failures are high following surgery alone and as such adjuvant or
perioperative regimens of chemo-radiotherapy or chemotherapy respectively are considered.
Patients therefore assessed to have inoperable metastatic stage IV disease should be considered
for systemic treatment (chemotherapy), which has shown improved survival and quality of life
compared with best supportive care alone (Wagner, Unverzagt & Grothe, 2010).
5.2.2. Although there is no standard international regimen that has been approved for palliative
chemotherapy in patients with advanced gastric cancer, fluoropyrimidine (5-FU, or capecitabine),
platinum (cisplatin or oxalipatin), taxane (docetaxel or paclitaxel) and epirubicin utilized alone or in
combination is considered the first line of therapy of advanced gastric cancer. However, a meta8|Page
PMB definition guideline for metastatic (including advanced) stage gastric/ gastro-oesophageal junction
cancer
analysis showed a trend toward improved survival with combination therapy (Guimbaud, Louvet &
Ries, 2014).
5.2.3. Platinum-based chemotherapy, in combinations such as epirubicin/cisplatin/5-FU or
docetaxel/cisplatin/5-FU, represents the current first-line regimen.
5.2.4. Second-line chemotherapy with a taxane (docetaxel, paclitaxel) as single agent or in combination
with paclitaxel is recommended for patients who are of performance status (PS) 0–1. In patients
of adequate PS, second-line treatment is associated with proven improvements in overall survival
(OS) and quality of life compared with best supportive care (Allum, Blazeby, & Griffin, 2011; Ford,
Marshall & Bridgewater, 2014; Kang, Lee & Lim, 2012).
Table 3: Chemotherapy options in metastatic stage gastric and GEJ cancer
Indication
Medicine details
Chemotherapy :First and
Epirubicin
subsequent lines
Cisplatin
Fluorouracil
Levofolinic acid
Capecitabine
Docetaxel
Paclitaxel
Oxaliplatin
5.3.
Radiotherapy
For patients with advanced gastric cancer, palliative radiation therapy is one of a number of therapeutic
options for control of local disease progression such as bleeding, nausea and pain. Palliative treatments
for advanced gastric cancer can be either local or systemic (Kim, Rana, Janjan, Das, Phan, Delclos,
Mansfield, Ajani, Crane & Krishnan, 2008). In patients with metastatic gastric cancer experiencing
severe anemia but are not able to undergo surgery, endoscopy, or intravascular embolization,
radiotherapy (RT) is used (Tey, Back, Shakespeare, Mukherjee, Lu, Lee, Wong, Leong & Zhu, 2007).
For all forms of palliative therapy, the overall prognosis of the patient must be taken into account to
avoid excessive morbidity and mortality.
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PMB definition guideline for metastatic (including advanced) stage gastric/ gastro-oesophageal junction
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Table 4: Radiation therapy in metastatic gastric cancer
Conventional Radiation therapy
Definitive Chemoradiation
-
25 – 28# over 5 weeks, TD 45 -50.4 Gy
Neo-adjuvant chemoradiation
-
23# over 5 weeks, TD 41.4 Gy (CROSS study – only included oesophageal or
esophagogastric-junction cancers)
-
25# over 5 weeks, TD 45 Gy
Adjuvant chemoradiation
25 – 28# over 5 weeks, TD 45 – 50.4 Gy
Palliative radiation
-
5# conventional single volume / multiple volumes
-
10# conventional single volume / multiple volumes
-
15# conventional single volume / multiple volumes
6. Follow Up Care
6.1. Regular follow-up may allow for investigation and treatment of symptoms, psychological support and
early detection of recurrence, though there is no evidence that it improves survival outcomes;
6.2. Table 5 provides guidance and recommendation for follow up for metastatic gastric cancer patients.
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PMB definition guideline for metastatic (including advanced) stage gastric/ gastro-oesophageal junction
cancer
Table 5: Frequency of interventions considered to be PMB level of care in metastatic stage gastric cancer during therapy and up to 10 years post diagnosis
Frequency during therapy
Up to 2 years post
3-10 years post
Recurrent work up – only
diagnosis
diagnosis
if there is suspicion of
disease recurrence
Frequency per year
Clinical assessment
Imaging :Radiology
Consultations
Depends on the treatment Every 6 months for Once per annum
intervention
the first 2 years
CT chest
2
1
1
√
CT abdomen,
2
1
1
√
Chest x-ray
2
1
1
√
Full blood
6
2
1
√
6
2
1
√
Renal function
6
0
0
√
Gastroscopy
2
1
1
√
Contrast meal
0
0
0
√
Diagnostic
0
0
0
√
pelvis
Pathology
count
Liver function
Imaging : Procedures
test
laparoscopy
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PMB definition guideline for metastatic (including advanced) stage gastric/ gastro-oesophageal junction cancer
Endoscopic
0
0
0
√
0
0
0
√
ultrasound
Histology assessment
Histology/
cytology
This guideline will be due for update on 31 December 2018
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PMB definition guideline for metastatic (including advanced) stage gastric/ gastro-oesophageal junction cancer
7. References
Allum, W.H., Blazeby, J.M. & Griffin S.M. 2011. Guidelines for the management of oesophageal and gastric
cancer. Gut: 60: 1449–1472.
Baiocchi, G.L., D’Ugo, D. & Coit, D. 2016. Follow-up after gastrectomy for cancer: the Charter Scaligero
Consensus Conference. Gastric Cancer, 19: 15–20.
Bouché, O., Raoul, J.L. & Bonnetain, F. 2004. Randomized multicenter phase II trial of a biweekly regimen of
fluorouracil and leucovorin (LV5FU2), LV5FU2 plus cisplatin, or LV5FU2 plus irinotecan in patients with
previously untreated metastatic gastric cancer: a Federation Francophone de Cancerologie Digestive Group
Study— FFCD 9803. Journal of Clinical Oncology; 22: 4319–4328.
D’Ugo, D., Biondi, A. & Tufo, A. 2013. Follow-up: the evidence. Digestive Surgery, 30: 159–168.
Edge, S.B., Byrd, D.R. & Compton, C.C. (eds). 2010. AJCC Cancer Staging Manual, 7th edition. New York, NY:
Springer.
Ferlay, J., Autier, P. & Boniol, M. 2007. Estimates of the cancer incidence and mortality in Europe in 2006.
Annals of Oncology: 18: 581-592.
Ferlay, J., Shin, H.R. & Bray, F. 2010. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008.
International Journal of Cancer, 127: 2893–917.
Ferlay, J., Shin, H.R., Bray, F., Forman, D., Mathers, C. & Parkin, D.M. 2008. GLOBOCAN v2.0, Cancer
Incidence and Mortality Worldwide: IARC Cancer Base No. 10 [Internet] Lyon, France: International Agency for
Research on Cancer. Available from: http://globocan.iarc.fr [Accessed 12 January 2017]
Ford, H.E., Marshall, A. & Bridgewater, J.A. 2014. Docetaxel versus active symptom control for refractory
oesophagogastric adenocarcinoma (COUGAR-02): an open label, phase 3 randomised controlled trial. Lancet
Oncology, 15: 78–86.
Global Burden of Disease Cancer Collaboration. 2016. Global, Regional, and National Cancer Incidence, Mortality,
Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life-years for 32 Cancer Groups, 1990 to
2015. A Systematic Analysis for the Global Burden of Disease Study. Journal of the American Medical AssociationOncology, E1-E25.
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PMB definition guideline for metastatic (including advanced) stage gastric/ gastro-oesophageal junction
cancer
Guimbaud, R., Louvet, C. & Ries, P. 2014. Prospective, randomized, multicenter, phase III study of fluorouracil,
leucovorin, and irinotecan versus epirubicin, cisplatin, and capecitabine in advanced gastric adenocarcinoma: A
French intergroup (Fédération Francophone de Cancérologie Digestive, Fédération Nationale des Centres de
Lutte Contre le Cancer, and Groupe Coopérateur Multidisciplinaire en Oncologie) Study. Journal of Clinical
Oncology, 32: 3520–3526.
Jemal, A., Center, M.M. & DeSantis, C. 2010. Ward EM. Global patterns of cancer incidence and mortality rates
and trends. Cancer Epidemiology Biomarkers & Prevention, 19:1893–907
Kang, J.H., Lee, S.I. & Lim, D.H. 2012. Salvage chemotherapy for pretreated gastric cancer: a randomized
phase III trial comparing chemotherapy plus best supportive care with best supportive care alone. Journal of
Clinical Oncology; 30: 1513–1518.
Kim, M.M., Rana,V., Janjan, N.A., Das, P., Phan, A.T., Delclos, M.E., Mansfield, P.F., Ajani, J.A., Crane, C.H. &
Krishnan, S. 2008. Clinical benefit of palliative radiation therapy in advanced gastric cancer. Acta Oncologica,
47:421–7.
Lunet, N., & Barros, H. 2003. Helicobacter pylori infection and gastric cancer: facing the enigmas. International
Journal of Cancer: 106: 953-960.
Myint, A.S. 2000. The role of radiotherapy in the palliative treatment of gastrointestinal cancer. European
Journal of Gastroenterology and Hepatology, 12:381–390.
Parkin, D.M., Bray, F. & Ferlay, J. 2005. Global cancer statistics, 2002. CA Cancer Journals of Clinicians: 55:
74-108.
Roviello, F., Marrelli, D. & de Manzoni, G. 2003. Prospective study of peritoneal recurrence after curative
surgery for gastric cancer. British Journal of Surgery, 90:1113–1119.
Singh, K. & Ghoshal, U.C. 2006. Causal role of Helicobacter pylori infection in gastric cancer: an Asian enigma.
World Journal of Gastroenterology: 12: 1346-1351.
Tey, J., Back, M.F., Shakespeare, T.P., Mukherjee, R.K., Lu, J.J., Lee, K.M., Wong, L.C., Leong, C.N. & Zhu, M.
2007. The role of palliative radiation therapy in symptomatic locally advanced gastric cancer. International journal
of radiation oncology, biology, physics, 67:385–8.
Wagner, A.D., Unverzagt, S. & Grothe, W. 2010. Chemotherapy for advanced gastric cancer. Cochrane
Database Syst Rev: (3):CD004064.
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PMB definition guideline for metastatic (including advanced) stage gastric/ gastro-oesophageal junction
cancer