martin-benson - Royal Marsden Hospital

The Royal MarsdenOesophago-gastric cancer – patient ageNew diagnosis oesophagealmalignancy - 2003New diagnosis gastricmalignancy – 2003

The Royal MarsdenStaging• Prognosis• Triage to appropriate therapyStage 0 /IStage II /III*Stage III*/IVUnimodalMultimodalEndoscopy(EMR/ESD)SurgeryNeo-adjuvanttherapyAdvanced diseaseprotocolEndoscopic palliationSurgery

The Royal MarsdenOesophageal cancer - TNM stagingPrimary Tumour (T)TX Unable to assess primaryT0 No evidence primaryTis Carcinoma in situT1 Invasion lamina propria/submucosaT2 Invasion muscularis propriaT3 Invasion adventitiaT4 Invasion of adjacent structuresRegional Lymph Nodes (N)NX Unable to assessN0 No metastasisN1 Nodal metastasisDistant metastasis (M)MX Unable to assessM0 No metastasisLower oesophagusM1a Metastasis in coeliac nodesM1b Other distant metastasisMid oesophagusM1a Not applicableM1b Non-regional lymph node orother distant metastasisUpper oesophagusM1a Metastasis to cervical nodesM1b Other distant metastasisAmerican Joint Commission on Cancer 2002

The Royal MarsdenOesophageal cancer - stage classificationStage 0TisNOM0Stage IT1NOM0Stage IIAT2, T3NOM0Stage IIBT1,T2N1M0Stage IIIT3N1M0T4Any NM0Stage IVAny TAny NM1Stage IVAAny TAny NM1aStage IVBAny TAny NM1bAmerican Joint Commission on Cancer 2002

The Royal MarsdenOesophageal cancer – survival according tostage1.0Survival Rate0.80.60.40.2001 2 3 4 5YearsStageIStage IIAStage IIBStage IIIStage IVIizuka et al Chest 1989

The Royal MarsdenGastric cancer - stage classificationSTAGE OTisN0M0STAGE IAT1N0M0STAGE IBT1T2a/bN1N0M0M0STAGE IIT1T2a/bT3N2N1N0M0M0M0STAGE IIIAT2a/bT3T4N2N1N0M0M0M0STAGE IIIBT3N2M0STAGE IVT4T 1 – T3Any TN1 – N3N3Any NM0M0M1American Joint Commission on Cancer 2002

The Royal MarsdenGastric cancer – survival according to stage1.0Survival Rate0.80.60.4Stage IAStage IBStage II0.2Stage III00Stage IV1 2 3 4 5YearsShiu et al Hepatogastroenterol 1989

The Royal MarsdenStaging - multi-detector CTMulti-Detector CT (MDCT)• Cornerstone• Accessible• Identifies metastatic disease• Assessment of local stagingStaging Accuracies

The Royal MarsdenStaging - laparoscopy• Gastric and junctional (type II & III)carcinoma – high rate of spread toperitoneum• 25-35% have peritoneal metastasesdespite normal CT

The Royal MarsdenStaging - endoscopic ultrasound (EUS)MucosaMuscularismucosaSubmucosaMuscularispropriaAdventitia orserosa

The Royal MarsdenStaging - endoscopic ultrasound (EUS)TumourTumourT1T2Staging AccuraciesT StageN StageOesophageal Cancer 87% 83%Gastric Cancer 84% 81%T3 N1TumourLN

The Royal MarsdenStaging - endoscopic ultrasound (EUS)LNAoAo

The Royal MarsdenFDG-PETCompared to MDCTSimilar sensitivity:• Primary tumour• Regional nodal metastasisHigher sensitivity for:• ?non-regional nodal metastasis• non-nodal metastasisRankin et al Clin Radiol 1998Ransenen et al Am Surg Oncol 2003Turlakow J Nuclear Med 2003

The Royal MarsdenOccult Supraclavicularlymph nodes, detected on 18 FDG-PET/CT

The Royal MarsdenOesophago-gastric malignancy - symptoms• Progressive dysphagia• Progressive vomiting• Abdominal pain• Epigastric mass• Chronic gastro-intestinal blood loss• Iron deficiency anaemia• Progressive unintentional weight loss• (Abnormal barium meal)

The Royal MarsdenEndoscopy – early vs advanced diseaseEarly gastric cancer(EGC)Advanced gastriccancer• 10-20% all gastric cancers• 60-90% EGC present withdyspepsia

The Royal MarsdenDyspepsia - Endoscopic findings in patientspresenting with dyspepsiaGastric Ca(2%)Gastritis/duodenitis(20%)Normal(33%)n = 3667PUD(21%)GORD(24%)(Fischer et al ‘77, Beavis et al ‘79, Holdstock et al ‘79, Hallissey et al ‘90)

The Royal MarsdenDyspepsia - Discriminatory value ofsymptoms• Suspicion of organic disease increased by presence of certainsymptoms* GORD:Heartburn, positional component, relief with antacids(Horrocks and deDombal ‘78)• Unaided clinical diagnosis (in absence of alarm symptoms):limited value• * 50% active PUD missed by clinical diagnosis• * 33% organic causes incorrectly diagnosed as functional(Byzer ‘91)

The Royal MarsdenDyspepsia - New ‘at risk’ patient -‘OGD forall’?Utopia• Exclude EGC, gastric atrophy, intestinal metaplasia,dysplasia• Stage severity of GORD - Barrett’s (+/- dysplasia)• Ascertain presence of PUD• Rx & F/U based on definitive findings

The Royal MarsdenDyspepsia - New ‘at risk’ patient - ‘OGD forall’?UtopiaThe real world• Endoscopy access• Pt waiting lists• Cost concerns

The Royal MarsdenDyspepsia.....Rx strategy for ‘new’ patientDyspepsiaClinical assessment< 45 yrs & noalarm symptomsTest for H Pylori> >5545yrs or alarmsymptomsAntacid or PPIor H2 - blocker-ve+ve??OGD+veSymptomsEradication RxRx based on findings-veDischarge

The Royal MarsdenOpen gastroscopy – EGCEarly gastriccancer (EGC)• >40 years with dyspepsia• Increase incidence EGC (26% vs 1%)• Increase curative resection (63% vs20%)(Halissey et al BMJ 1990; Sue-Ling et al Gut 1992)

The Royal MarsdenOpen gastroscopy – Barrett’sColumnar-linedoesophagus (Barrett’s)• Risk developing adenoCa – OR 44• Small absolute increase individual risk(1 cancer per 1000pts pa)• 40% pts adenoCa – no reflux symptoms• CLO incidence – 5-15% symptomatic pts• Endoscopic screening – chronic symptoms,>50 years• Surveillance: adenoCa -1/100 pt years F/U• No RCT to support• Observational studies – increased number ofearly tumours and increased survival

The Royal MarsdenAre early cancers missed?Portsmouth Upper GI Cancer audit:200 patients (Gastric 82 + Oesophageal 118)16/200 (8%) - OGD within 3 yearsChowdhary & Bhandari; Gut 2008 Endoscopic miss rate: 30/305 (10%) oesophago-gastric cancers at 3yearsYalamarthi S, Endoscopy 2004Endoscopist experience - lack of awareness of early neoplastic lesionsEffect of anti-secretory agents

The Royal MarsdenEffect of anti-secretory therapy• Can heal EGC• Delay index gastroscopy• False negative

The Royal MarsdenDyspepsia.....NICE guidelines Rx strategy –‘uninvestigated’ dyspepsiaDyspepsia notneeding referralReview medicationLifestyle adviceNo response / relapseFull dose PPI 1/12No response / relapseRelapseTest & treatResponseResponseResponseLow dose prn RxResponseNo responseH2RA/prokinetic 1/12No responseReviewReturn to self-care

The Royal MarsdenDyspepsia.....NICE guidelines Rx strategy –‘uninvestigated’ dyspepsia• 15-25% patients with oesophago- gastric cancer free of alarmsymptoms• Less advanced disease with better 5 year survivalFransen et al Aliment Pharmacol Ther 2004; Bowrey et al Surg Endosc 2006• Use of alarm symptoms as referral criteria• Early cancers not detected• Symptoms overlooked until features of more advanceddisease have occurred

The Royal MarsdenSummary– Oesophago-gastric cancer is a common cancer in UK– Prognosis depends on stage at presentation– Improved overall survival dependent upon earlier diagnosisrather than better treatment techniques– ‘Alarm symptoms’ identify patients with advanced disease atpresentation– Identification early disease, reliant upon timely referral ofsymptomatic ‘at risk’ patients for gastroscopy, prior topragmatic anti-secretory therapy