PMB definition guideline for metastatic (including ... › files › PMB Definition Project... ·...

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PMB definition guideline for metastatic (including advanced) stage gastric/ gastro-oesophageal junction

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cancer

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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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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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Abbreviations

5FU Fluorouracil

AJCC American Joint Committee on Cancer

CMS Council for Medical Schemes

CT Computed tomographic

DTPs Diagnosis treatment pairs

ESD Endoscopic submucosal dissection

EUS Endoscopic ultrasound

GEJ Gastro-oesophageal junction

PMB Prescribed minimum benefit

RT Radiotherapy

TNM Tumour, node, metastasis

UICC Union for International Cancer Control

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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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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 pre-

therapy 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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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

assessment

Consultations with

primary care practitioner, gastroenterologist, oncologist,

surgeon

2 consultations per

speciality

Imaging:

Radiology

CT chest with contrast 1

CT abdomen, pelvis with contrast 1

Chest x-ray 1

Pathology

Full blood count 1

Liver function test 1

Renal function 1

Imagining:

Procedures

Gastroscopy 1

Contrast meal 1

Endoscopic ultrasound 1

Diagnostic Laparoscopy 1

Histology

assessment

Histology/ cytology 1

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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 meta-

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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

subsequent lines

Epirubicin

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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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



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

diagnosis

3-10 years post

diagnosis

Recurrent work up – only

if there is suspicion of

disease recurrence

Frequency per year

Clinical assessment Consultations Depends on the treatment

intervention

Every 6 months for

the first 2 years

Once per annum

Imaging :Radiology CT chest 2 1 1 √

CT abdomen,

pelvis

2 1 1 √

Chest x-ray 2 1 1 √

Pathology

Full blood

count

6 2 1 √

Imaging : Procedures

Liver function

test

6 2 1 √

Renal function 6 0 0 √

Gastroscopy 2 1 1 √

Contrast meal 0 0 0 √

Diagnostic

laparoscopy

0 0 0 √

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PMB definition guideline for metastatic (including advanced) stage gastric/ gastro-oesophageal junction cancer

Endoscopic

ultrasound

0 0 0 √

Histology assessment Histology/

cytology

0 0 0 √

This guideline will be due for update on 31 December 2018

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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 Association-

Oncology, E1-E25.

http://globocan.iarc.fr/

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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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