I. Technical Issues. Surgical Resection of Gastric Cancer. Surgical Resection of Gastric Cancer Evidence & Issues. French and Italian RCT Antral Ca

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1 Surgical Resection of Gastric Cancer Evidence & Issues Carol J. Swallow Department of Surgical Oncology Princess Margaret and Mount Sinai Hospitals University of Toronto Surgical Problems in Proximal GI Cancer Management BC Surgical Oncology Network Conference Devember 3, 5 Vancouver, BC Surgical Resection of Gastric Cancer I. Technical Issues - RCT - Other II. III. Quality of Surgery Adjuvant Treatment Case #1 5 year old healthy man years of dyspepsia OGD: antral tumour path: invasive adenoca I. Technical Issues French and Italian RCT Antral Ca TG vs STG: Longterm Survival I. Extent of Gastrectomy II. III. IV. Extent of Lymphadenectomy Lap vs. Open Margins V. Other overall survival at 5 years French n=169 Italian n=618 STG TG Ann Surg :16; Ann Surg :613 1

2 MRC RCT: D1 vs D Dissection Longterm Survival Dutch RCT: D1 vs D Dissection Longterm Survival Disease free survival Overall survival D1, n= D, n= All patients Node neg n=31 Node pos n=39 D1, n=38 D, n=331 Br J Cancer : 15 NEJM 1999; 34:98 Dutch RCT: D1 vs D Dissection Very Longterm Survival % alive at 11 years All N n=315 N1 n=51 median f/u time = 11 years p=.78 N n=97 D1, n=38 D, n=331 N3 n=48 J Clin Oncol 4; :69 MRC RCT: D1 vs D Dissection Postoperative M & M Rates postop complications (%) D1, n= D, n= Morbidity Mortality p<.4 The Lancet :995 Dutch RCT: D1 vs D Dissection Postoperative M & M Rates postop complications (%) D1, n=38 D, n=331 Morbidity Mortality p<.4 NEJM 1999; 34:98 Standard D Dissection: Japanese RCT & Italian multicentre phase II trial postop complications (%) 3 1 Morbidity IGCSG, n= total gastrex's 49 splenectomies GCSSG of JCOG, n=63 1 total gastrex's 98 spenectomies Mortality Br J Cancer 4; 9: 177 J Clin Oncol 4; : 767

3 Survival after Standard D Dissection overall 5 yr. survival (%) (191) Br J Cancer 4; 9: 177 Gastrointest Surg 1999; 3: 4 (466) (375) (446) IGCSG, phase II MSKCC, prosp DB Chile, prosp cohrt Seoul, method NS Dig Surg 1999; 16: 385 Int J Radiat Oncol Biol Phys 5; 63: 179 UK postcode trial: D1 vs modified D Dissection Postoperative M & M Rates postop complications (%) Morbidity D1, n=36 D, n=8 Mortality Br J Cancer 4; 9: 1888 UK postcode trial: D1 vs modified D Dissection Longterm Survival p=.4 All patients p=.1 Stage III D1, n=36 D, n=8 Br J Cancer 4; 9: 1888 Extent of Lymphadenectomy: Cochrane Review D more dangerous when spleen/panc resected surgeon inexperienced studies limited by learning curves, poor compliance contamination no PROVEN survival benefit MAY benefit T3+ Stage II & IIIa McCulloch et al,the Cochrane Collaboration, 5 Extent of Lymphadenectomy: Current State of Play Laparoscopic vs Open Gastrectomy: : RCT D: -not harmful in expert hands -more nodes = better staging -direct survival benefit unclear pending: -Italian RCT D1 vs D, 5 centres, n=16 -Japan RCT D vs D+, 4 centres, n=53 Degiulu, EJSO 4; 3: 33 Sano, J Clin Oncol 4; : 767 % with complication Mortality STG for distal cancer LAP, n=3 OPEN, n=9 Morbidity Huscher, Ann Surg 5; 41:3 3

4 Laparoscopic vs Open Gastrectomy: : RCT Laparoscopic vs Open Gastrectomy: : RCT # nodes resected, mean LAP, n=3 OPEN, n=9 STG for distal cancer Huscher, Ann Surg 5; 41: OS STG for distal cancer LAP, n=3 OPEN, n=9 DFS Huscher, Ann Surg 5; 41:3 R Status Determines Prognosis Positive Margins and Survival R R1 R n=138 n=193 n=93 Karpeh et al., MSKCC Overall Survival (%) n=47 p< Stage II & III Years Kim et al, J Gastrointest Surg 1999; 3:4 n=57 NEG MARGIN POS MARGIN Overall Survival (%) Frozen Section Analysis and Re-Excision of Positive Margins > 5 pos nodes 5 pos nodes p=.5 n= Years 5 RE-EXC'D 1 NOT RE-EXC'D 8 p=.3 6 n=13 4 n=17 n= Years 8% had T3N+ Kim et al, J Gastrointest Surg 1999; 3:4 TNM Staging of Gastric Cancer Stage 1 Stage A B Stage 3 A Stage 4 B T1; N T1; N1 T; N T1; N T; N1 T3; N T; N T3; N1 T4; N T3; N T4; N1, N, N3 T1, T, T3; N3 M1 AJCC, 4

5 National Cancer Data Base (USA) Report on Gastric Cancer (Dx( ) Gastric Cancer Surgical RCT Pot- Pourri Overall Survival (%) Cancer 1997; 8: Years after Diagnosis 1A, n=33 1B, n=318 II, n=367 IIIA, n=46 IIIB, n=33 IV, n=119 Au, Inst, Date Question n Answer Doglietto, Rome, ± NJT in TG 37 no diff 4 Inaba, Tokyo, 4 midline vs transv 54 less pain, pneumonia, SBO in transv Mochiki, Maebashi, 3 JI ± pouch 6 less caloric intake in pouch Hori, Chiba, 4 stapled vs HS 187 stapled faster by 11 min, gastroduod no other diff Fiori, Rome, 4 pall stent vs gastroent 18 shorter op time, time to food, hosp stay with stent Case #1: Pathology Report TNM Staging of Gastric Cancer: T Stage poorly differentiated adenocarcinoma tumour penetrates through muscularis propria into adjacent greater omentum,, but not through visceral peritoneum proximal and distal margins negative of 1 nodes positive WHAT STAGE IS THIS? T1 T T3 T4 Lamina propria, submucosa Muscularis propria, subserosa Penetrates serosa Adjacent structures TNM Staging of Gastric Cancer: N Stage N N1 N N3 no regional nodes involved 1 to 6 nodes 7 to 15 nodes > 15 nodes TNM Staging of Gastric Cancer Stage 1 Stage A B Stage 3 A Stage 4 B T1; N T1; N1 T; N T1; N T; N1 T3; N T; N T3; N1 T4; N T3; N T4; N1, N, N3 T1, T, T3; N3 M1 AJCC, 6 th edition 5

6 1997 AJCC, 5th Ed. N- No regional LN metastases N1- Metastasis in 1-6 regional LN N- Metastasis in 7-15 regional LN N3- Metastasis in > 15 regional LN it is suggested that at least 15 regional nodes be assessed... The Question of Quality: Outcomes of Resection for Gastric Cancer I II III IV postop mortality North America 7% Japan % 1993 The Question of Quality: What is the Secret of Japan? younger, less CV disease less obese stage migration to better N staging TECHNIQUE Significant Regional Variation in Staging and Survival of Gastric Cancer- An Analysis of the SEER Database Natalie G. Coburn, MD, MPH Carol J. Swallow, MD, PhD Calvin Law, MD, MPH Proc ASCO, 5 Defining the Study Population SEER Other Digestive Cancer N = 16,83 Gastric Surgery (Excludes wedge, bx, endoscopy) N=1,99 Invasive Disease N = 1,9 Gastric Malignancy N = 58, N=4,651 Lymph Node Assessment Done N = 11,713 Final Study Population N = 1,19 Adenocarcinoma Only N=49,18 Age 18+ N = 49,8 Non-M1 N = 1,19 Overall Results 1,19 cases Male: 64% Age Median: 7 years Mean: 68.3±1.5 years Median # of LN assessed: 9 Overall percentage of patients with Adequate LN assessment: 8.6% Improved to 3.7% (p<.5) 6

7 Odds of Adequate LN Assessment- Year of diagnosis Odds of Adequate LN Assessment- SEER Region Percentage of Patients with Adequate LN Assessment 6 5 Percentage % ALNA Year SEER Region Reference Group Factors Predictive of Survival- SEER Region Cox HR of Death Final Model (p<.5 for all) Cum Survival Region 9 P<.1 Survival Functions Hawaii Region Survival Tim e Total in M onths SEER 1 1 SEER Region Age (vs. 6-74) 18-59: HR=.8 >74: HR=1.4 Race Japanese: HR=.8 Other Asian: HR=.8 African-American, American, Islanders, Other: HR=NS Female Gender HR=.8 Marital Status HR=.9 T-Stage HR=1.4,., 3.4 Grade HR= NS, 1.4, 1.4 Radiation Neoadjuvant: HR=NS Adjuvant: HR=.9 Surgery Type (v. Distal) Total: HR=.8 Gastrectomy NOS: HR=1. En bloc: HR=1.1 >15 LN assessed HR=.86 Gastric Cancer Lymph Node Retrieval in the Province of Ontario and at a Tertiary Care Cancer Centre Anirban Gupta, Riad Haddad, Julinor Bacani, Catherine O Brien, Aaron Pollett, Steven Gallinger and Carol Swallow Departments of Surgical Oncology and Pathology, Mount Sinai and Princess Margaret Hospitals, University of Toronto Canadian Society of Surgical Oncology 1 th Annual Scientific Meeting, Montreal Friday, April 1, 5 Methods Inclusion Criteria Gastric cancer between Curative Resection attempt, no distant mets Surgical pathology report Exclusion Criteria biopsy only Mount Sinai Hospital (MSH) 18 patients Mount Sinai Hospital (Dept Pathology Database) Province of Ontario 91 patients across Ontario, age<56 (OCR Database)

8 Lymph Node Retrieval Type of Gastrectomy P=. P=.76 Proximal Subtotal Total MSH OCR # Nodes, mean Lymph Node Retrieval NS MSH OCR Percentage Adequate LNR NS < 15 LN =/> 15 LN # Lymph Nodes Retrieved Mount Sinai Hospital Trends in Adequacy of LNR The Question of Quality: What do Ontario surgeons strive for? % n=188 who perform gastric surgery # nodes desired mean = 11 median = 1 (-3) Year routine intraop frozen section proximal 53% distal 34% Helyer, O Brien, Swallow 5 unpub Case #1: Revised Pathology Report Intergroup-116 RCT of Postoperative Adjuvant Chemoradiation poorly differentiated adenocarcinoma tumour penetrates through muscularis propria into adjacent greater omentum,, but not through visceral peritoneum, T proximal and distal margins negative 4 of nodes positive, N1 NOW WHAT? Overall Survival p<.1 Disease-free Survival Control C-XRT NEJM 1 345:75 8

9 Extent of LND in Intergroup 116 % of patients 6 5 n= D D1 D D recommended in protocol LND assessed from surgical checklist Hundahl et al, Ann Surg Oncol ; 9: 78 D1 Dissection Level 1 nodes (perigastric( perigastric,, stations 1-6) right & left cardiac (1 & ) lesser & greater curve (3 & 4) supra- and infra- pyloric [5 & 6] omentum D Dissection Level 1 nodes (perigastric( perigastric,, stations 1-6) Level nodes (intermediate, stations 7-9) left gastric (7), common hepatic (8), celiac (9) stations 1 (splenic( hilum) ) and 11 (splenic( artery) nodes omental bursa, anterior leaf of mesocolon THE HOT QUESTION OF TODAY: What is the role of postoperative adjuvant chemoradiation with D dissection? 1 n=544 +CRT 8 surgery only 6 n=446 4 p=. Overall Survival (%) Years NB: observational study! Kim et al, Int J Radiation Oncol Biol Phys 5; 63: 179 THE HOT QUESTION OF TODAY: What is the role of postoperative adjuvant chemoradiation with D dissection? Intergroup-116 RCT of Postoperative Adjuvant Chemoradiation: M & M Korean Protocol: D 5 cycles 5-FU 5 and leucovorin 45 Gy RT concurrent from nd cycle n=91, median f/u 48 mos. in-field recurrence rate= 16% (1/3 of all recurrences) Br J Cancer 4; 91: 11 3% needed change in XRT plan 3% couldn t complete Rx 1% mortality in C-XRT C arm 9

10 PMH Protocol for Postoperative Adjuvant Chemoradiation CCO Updated Practice Guideline Eligibility Criteria: R resection < 5 cm into esophagus stage 1B - IV, no distant mets start -9 days post-op op after surgical resection, patients whose tumours have penetrated the MP or involve regional lymph nodes should be considered for adjuvant combined chemoradiotherapy December, Management of Resectable Gastric Cancer Summary Goals in the resection of localized disease R resection accurate staging STG > TG D1+ dissection adjuvant treatment stage 1B - IV 1