Name

William Allum

Upper GI Surgeon

Royal Marsden NHS Foundation Trust

London

UK

SURGERY FOR GASTRIC AND GE JUNCTION CANCER:

PRIMARY

PALLIATIVE

WHERE AND WHEN?

DISCLOSURE OF INTEREST

None

EMR D2 GASTRECTOMY

SN. WEDGE

N

H

P

Any surgeon can cure

No surgeoncan cure

Surgeon - dependent

EMR, endoscopic mucousal resection.

◆ SSURGERY

◆ Treatment of localised disease

• Stage Ia

• Stage Ib – III Resection and

lymphadenectomy

◆ Minimally invasive surgery

◆ Service provision

• Centralised

• Outcome

• Complications

◆Survivorship

T1 TUMOURS

• Protruding

• Superficial Elevated

• Superficial Flat

• Superficial Ulcerated

• Excavated

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ENDOSCOPIC RESECTION

• well / moderately well differentiated adenocarcinoma

• no lymphatic or venous invasion

• intramucosal cancer regardless of size without ulceration

• minute submucosal penetration (sm1) and <20mm

T Stage N1

T1a

m1 – m3

0%

T1b

sm1

0-8%

T1b

sm2-3

26-67%

SURGERY FOR EARLY GASTRIC CANCER

◆ T1 m D1 alpha (Stations 7 & 8)

◆ T1 sm D1 beta (D1 alpha + station 9 & 11p)

◆ Function preserving gastrectomy

LOCALLY ADVANCED GASTRIC CANCER

Mass

Ulcerative

Infiltrative, ulcerative

Infiltrative, diffuse

R0 RESECTION

◆ A surgical procedure in which there is no evidence of macroscopic residual tumour

in the tumour bed, lymph nodes and/or distant sites with microscopic negative

resection margins

Hermanek P, Wittekind C. Pathol Res Pract. 1994;190(2):115-123.

Indication and Division Lines for Distal Subtotal and Total Gastrectomy

Distal subtotalgastrectomy

Totalgastrectomy

Early cancer or well-circumscribed advanced cancer

Infiltrative advanced cancer

>2cm from cardia >5cm from cardia

When the proximal distance from the cardia is less than the required length, total gastrectomy is

indicated

<5cm

Total gastrectomy is always indicated in diffuse carcinoma (Borrmann type 4) regardless of its size

3cm

4d 4sb

1

2

4sa

63

57

8a 11p11d 10

12a9

D1

D1+

D2

Total Gastrectomy and Lymph Node Dissection

Japanese Gastric Cancer Association, 2011 Gastric Cancer 14: 113-23.

Distal Gastrectomy and Lymph Node Dissection

D1

D1+

D2

4d4sb

1

63

57

8a 11p12a9

Japanese Gastric Cancer Association, 2011 Gastric Cancer 14: 113-23.

Japanese RulesEnd Results of Surgical Resection

Years

Cu

mu

lati

ve S

urv

ival

Rat

e, %

Absolute curative78.7±1.7%; n=2706

0

40

60

80

100

0 1 2 3 4 5

20

Relative curative39.6±3.7%; n=823

Relative non-curative16.5±4.8%; n=281

Absolute non-curative1.4±0.9%; n=923

Maruyama 1981. Jpn J Surg 11: 127-45

14

ITALIAN D1 vs D2 TRIAL

D1 D2

Operative Mortality 3.0% 2.2%

5 year Survival 66.5% 64.2%

pT1 (p=0.015) 98% 83%

pT2-4

N+ (p=0.055)

38% 59%

DUTCH D1 VS D2 TRIAL UK MRC D1 VS D2 TRIAL

EUROPEAN GUIDELINES SURGERY

GUIDELINE GASTRIC RESECTION LYMPHADENECTOMY

SIGN (2006) R0 (proximal, distal circumferential

margins)

D2 > 25 lymph nodes

German S3 (2011) R0 (proximal, distal circumferential

margins)

5cm intestinal

8cm diffuse

D2 > 25 lymph nodes

> 16 nodes for TNM

No pancreatectomy / splenectomy

UK (2011) R0 D2 for stage II & III – if fit

> 15 nodes for TNM

St Gallen (2019) cT1 diffuse – resect

R0

D2 – without pancreatectomy or

splenectomy

ESMO (2016) T1a

T1b - III

D1 alpha / beta

D2

LYMPH NODE HARVEST

15 NODES 25 + NODES NODES EXAMINED

MAGIC 53% 19% NK

ST03 82% 49% 24 (0-96)

CRITICS 72.8% 87.5% (D1+) 20 (0-72)

Cunningham et al NEJM 2006; 355:11Allum et al BJS 2019; 106: 1204Claassen et al Ann Surg 2018; 268:1008

OESOPHAGO-GASTRIC JUNCTIONAL ADENOCARCINOMA

EORTC Consensus

St Gallen 2012 / 2018

◆ Type I – Oesophago-gastrectomy

◆ Type II – Oesophago-gastrectomy or

– Extended Total Gastrectomy

◆ Type I & II – Mediastinal Lymphadenectomy

– 2 field

◆ Type III - Extended Total Gastrectomy

TYPE II DEFINITION

◆ Centre of tumour 2cm above or below gastro-oesophageal junction

◆ Defining the centre is NOT easy

◆ endoscopy

◆ imaging

◆ Decisions based only on the centre ? Too simplistic

Aim of Surgery for Junctional Cancer

◆ Minimum 15 lymph nodes

◆ R0 resection

◆ Longitudinal margin

◆ Circumferential margin

Survival by Number examined in N0 DiseaseBollschweiller et al 2006

Bollschweiler et al 2006

Survival by Nodal Volume

Bollschweiler et al 2006

Risk of Systemic Disease and Number of Nodes InvolvedPeyre et al 2008

Peyre et al 2008 Ann Surg 248: 979-985

Aim of Surgery for Junctional Cancer

◆ Minimum 15 lymph nodes

◆ R0 resection

◆ Longitudinal margin

◆ Circumferential margin

PROXIMAL MARGIN ACCORDING TO SURGERY

Total Gastrectomy

(n= 77)

2.0cm (0.1 – 6.5cm)

Oesophago-gastrectomy

(n=199)

5.5cm (0.3 – 16.0cm)

Resection Margin and Survival

Barbour et al. Ann Surg 246: 1-8

Circumferential resection margin (CRM) size correlates with

overall survival

Prospective database, single institution study, N = 229

▪ CRM size is a significant prognostic factor for overall survival

▪ 40.6% of patients in this study had a CRM <1mm

▪ Post operative chemoradiation did not alter survival in patients with CRM <1mm

▪ BUT smaller CRM may just reflect a larger tumour

Kaplan-Meier curves of OS by margin size:

Time (years)

Pro

bab

ility

of

surv

ival

--- >2.0mm--- 1.0-1.9mm--- <1mm--- 0mm

CRM nMedian Survival

(95% CI)

Positive 45 1.2 yrs (0.9-1.4)

<1mm 48 1.9 yrs (1.4-3.2)

1.0-1.9mm 31 3.5 yrs (2.0–no upper CI)

≥ 2.0mm 105 Not reached

Landau et al., ESMO 2010 (Abstract 711PD)

CRM IN NEOADJUVANT TRIALS

CS S CF ECX CXRT S

OEO2 25% 28%

OEO5 41% 33%

CROSS 8% 30%

Radical Surgery – 13% - 2/62

ESMO GUIDELINES

OESOPHAGEAL AND GASTRIC CANCER

◆ Treatment of localised disease

• Endoscopic resection

• T1b N1 resection

• Stage Ib – III Resection and lymphadenectomy

◆ Minimally invasive surgery

◆ Service provision

• Centralised

• Outcome

• Complications

◆ Survivorship

Radical open vs minimally invasive

Minimally Invasive

Hybrid

Total

Robot assisted

SURGICAL APPROACH

Haverkamp et al 2019

MINIMALLY INVASIVE OESOPHAGECTOMY

TIME TRIAL

MIE Open

Number 3 stage 38 37

ILOG 17 15

Overall Complications 36% 64%

Mortality 30 day 2% 0%

Pulmonary Infections 12% 34%

Anastomotic Leak 13% 8%

Length of Stay 11 days 14 days

Straatman et alAnn Surg 2017; 266:232-6

FR = No Evidence of Residual Disease – all CROSS style neoadjuvant treatment

TIME TrialSurvival

MINIMALLY INVASIVE OESOPHAGECTOMY

MIRO TRIAL

Hybrid Open ILOG

Number 103 104

Overall Complications 36% 64%

Mortality 30 day 1% 2%

60 day 4% 6%

Pulmonary 18% 30%

Cardiac 12% 14%

Anastomotic Leak 11% 7%

Conduit necrosis 2% 3%

Mariette et alNEJM 2019; 380:152-62

MIRO TrialOverall Survival

Robot-assisted Minimally Invasive Thoracolaparoscopic Esophagectomy(RAMIE) Versus Open Transthoracic Esophagectomy for Resectable Esophageal Cancer

A Randomized Controlled Trial

RAMIE OPEN 3-STAGE

Number 54 55

ACA 76% 78%

SCC 24% 22%

Lower 1/3 48% 53%

OGJ 41% 33%

Neoadjuvant CXRT 79% 80%

Stage III 63% 54%

Van der Sluis et al Ann Surg 2019 269:621-30

Robot-assisted Minimally Invasive Thoracolaparoscopic Esophagectomy Versus Open Transthoracic Esophagectomy for Resectable Esophageal Cancer

RAMIE OPEN 3-STAGE

Complications

>C-D II

63% 80%

Pulmonary 32% 58%

Cardiac 22% 47%

Leak 22% 22%

Conduit Necrosis 2% 4%

Anastomotic stenosis 52% 47%

Mortality 30% 2% 0%

90% 9% 2%

INCURABLE DISEASE

PALLIATIVE INTENT

◆ Quality of life vs Quantity of life

◆ Patient Wishes

◆ Resection vs Chemotherapy ?

◆ Subtotal vs Total Gastrectomy ?

PALLIATIVE RESECTION

◆ Dutch D1 vs D2 trial

◆ 295 / 996 (29%) incurable

◆ T+ macroscopically irresectable

◆ H+ liver metastasis

◆ P+ peritoneal metastasis

◆ N4+ distant lymph nodes Hartgrink et al Br J Surg 2002, 89:1438

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Dutch Gastric Cancer Trial (D1 – D2)

Palliative Resection

Patients 996palliative resections 285 (26%)

Hartgrink Br J Surg 2002Years since surgery

Sur

viva

l pro

babi

lity

0.0

0.2

0.4

0.6

0.8

1.0

0 6 12 18 24 30 36

no resection

resection

P = 0.033

Numbers at risk: no resection: 33 10 2 1

resection: 73 31 11 5

Survival benefit of

Surgery:

patients < 70 and 1 metastatic siteH+ liver metastasisP+ peritoneal metastasisN4+ distant lymph nodes

PALLIATIVE SURGERY SELECTION

◆ ASA I & II

◆ Non – R0 resection

◆ Single site solid organ metastasis

◆ Localised peritoneal disease without signet ring cancer

(Robb et al 2012)

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Lancet Oncology 2016

!!

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23 trials including 870 patients

Median survival 22 months

5-y-surv. all 23,9 %

synchronous 22,6 %

metachronous 30,0 %

Yoshida, Kodera et al Gastric Cancer 2016

OLIGOMETASTATIC DISEASE

ESMO GUIDELINES

OESOPHAGEAL AND GASTRIC CANCER

◆ Treatment of localised disease

• Endoscopic resection

• T1b N1 resection

• Stage Ib – III Resection and lymphadenectomy

◆ Minimally invasive surgery

◆ Service provision

• Centralised

• Outcome

• Complications

◆ Survivorship

49

ECCO ESSENTIAL REQUIREMENTS FOR QUALITY CANCER CARE

• define the criteria to provide an optimal level of care.

• define organisational criteria on delivery of optimal care to each patient,

• establish Quality Performance Indicators to measure the efficacy of clinical guidelines

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Hospital volume over time

Oesophageal and Gastric Resection

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HR according to hospital volume

Adjusted for sex, age, deprivation, co-morbidity score, type of cancer and resection quintile

0.7

0.8

0.9

1.0

1.1

1.2

Haz

ard

Rat

io

<20 20-39 40-59 60-79 80+

Volume

Surgeon Outcome 2012-2014

54

USE SAME NOMENCLATURE

Benchmarking Complications Associated with Esophagectomy

2015 – 2016

24 Centres worldwide

2704 patients undergoing oesophagectomy

56.2% in distal oesophagus

Neoadjuvant treatmentChemoXRT 1192 (46.1%)Chemotherapy 763 (29.5%)

Open procedure 52.1%Minimally Invasive 47.9% Low et al Ann Surg 2019; 269: 291-8

ESMO GUIDELINES

OESOPHAGEAL AND GASTRIC CANCER

◆ Treatment of localised disease

• Endoscopic resection

• T1b N1 resection

• Stage Ib – III Resection and lymphadenectomy

◆ Minimally invasive surgery

◆ Service provision

• Centralised

• Outcome

• Complications

◆ Survivorship

Arnold et al Lancet Oncology 2019

5 year survival

IMPROVED SURVIVAL RMH EXPERIENCE

Fontana et al Gastric Cancer 2016; 19:1114-24

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Patient Priorities?

Outcomes reported in

trials

do not reflect

priorities of patients.

Thank you for your attention