Surgical strategies in esophageal cancer

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1 Gastro-Conference Berlin 2005 October 1-2, 2005 Surgical strategies in esophageal cancer J. Rüdiger Siewert Department of Surgery, Klinikum rechts der Isar Technische Universität München

2 Esophageal Cancer Rate per 1,000, Incidence (SEER Database ) Histology and esophageal cancer incidence ( ). Data from the National Cancer Institute s Surveillance. Epidemiology and End Results program with ageadjustment using the 2000 U.S. standard population. Solid line = adenocarcinoma; dashed line = squamous cell carcinoma; dotted line = not otherwise specified. Pohl and Welch, J Natl Cancer Inst 2005

3 Relative increase in the prevalence of adenocarcinoma 100% 90% 80% squamous cell carcinoma adenocarcinoma prevalence (%) 70% 60% 50% 40% 30% 20% 10% 30,9 37,5 47,2 52,3 0% TU München

4 Adenocarcinoma and Squamous Cell Cancer Affect Different Patient Populations Adenocarcinoma Squamous Cell Cancer Age 65 Reflux Adipositas Coronary Heart Disease Age 55 Alcohol Nicotine COPD Liver Zirrhosis Malnutrition Second Cancers Cooperation

5 Surgical epidemiology of patients with squamous cell cancer and with adenocancer of the esophagus Squamous cell cancer Adenocancer of the p of the esophagus esophagus Median age 53,4 years 62,6 years p<0,001 Male/female 7:1 8:1 n.s. Occupation (prevalence) Academics 20,8 % 52,9 % p<0,001 White collar worker 27,2 % 27,7 % Blue collar worker 52,2 % 20,2 % Alcohol abuse (prevalence) 69,7 % 42,3 % p<0,001 Nicotine abuse (prevalence) 69,3 % 51,9 % p<0,05 Malnutrition (prevalence) 24,1 % 1,9 % p<0,001 Pulmonary capacity 82,5 % 93,7 % p<0,05 (average FEV % compared to normal) Cardiovascular risk factors 19,5 % 34,8 % p<0,01 (prevalence) Impaired liver functioning 35,3 % 24,9 % p<0,05 (prevalence) TU München 03

6 Resected Adenocarcinoma and Squamous Cell Cancer Have a Different Prognosis (TU München , n=1285) 1,0 Multivariate Analysis,8,6 Adenocarcinoma, n=494,4 p<0.01,2 Squamous Cell Carcinoma, n=791 0,

7 Survival SCC / Barrett-Ca B-Ca Survival (%) pt1 SCC pt1 ADC Stage I SCC Stage I ADC SCC Time (months) pt1 SCC pt1 ADC Stage I SCC Stage I ADC C. Mariette...J.P. Triboulet, World J. Surg. 2005

8 Independent Prognostic Factors Histologic Tumor Type 1.0 Early Adenocarcinoma, n= Survival Probability Early Squamous Cell Cancer, n= Months

9 Early Esophageal Cancer Prevalence of Lymphatic Spread Squamous Cell Cancer Adeno- Carcinoma Total 41/133 (30.8%) 18/157 (11.5%) HGIEN / pt1a 2/26 (7.7%) 0/70 (0%) pt1b 39/107 (36.4%) 18/87 (20.7%)* *p<0.05 Stein/Sie Ann. Surg 2005

8%) Postop Mortality: 0/64 (0 %) Postop Morbidity: 10/64 (15.

10 AEG-Early Ca Limited Resection n=64 TU Munich Complete Tumor Resection (R0): 64/64 (100%) Complete Resection of Barrett Mucosa: 62/64 (96.8%) Postop Mortality: 0/64 (0 %) Postop Morbidity: 10/64 (15.6%) Surgical Revisions: 2/64 (3.1%) Median F/U: 43 Months - No Recurrences - No Deaths No Reflux: 58/64 (90.6%) Good Overall Functional Results: 56/64 (87.5%)

11 Early SCC of the Esophagus needs always subtotal esophagectomy and mediastinal LA (transthoracic approach)

12 Locally advanced Esophageal Cancer What are the relevant questions with therapeutical consequences in preop. Staging / Diagnostic today? R 0 -Resectability Distant metastases ( CT scan) ( PET-Scan) T-Category for therapeutical Stratification (T 1/2 T 3/4 ) Neoadj. Th.

13 PET Staging of Esophageal Cancer Distant LN Metastases Primary Tumor May identify distant lymph node metastases Increases Detection of Distant Solid Organ Metastases (+20%)

14 Esophageal Cancer - Surgical treatment - TU Munich n=1367 SCC B-Ca 59% 41% n=807 n=560 Primary Res. Neoadj. Th. Primary Res. Neoadj. Th. 54% 46% 66% n=435 n=372 n=370 n=190 34%

15 Esophagectomy 30 day Mortality - Morbidity TU Munich % ,2 28,1 29,6 29,6 15,6 18,1 27,9 22,4 20, ,4 1,1 0 2,4 1,3 0 1,1 1 0,9 1,6 Morbidity 30 day mortality Years

16 Barrett-Ca / SCC below Bifurcation Procedure of Choice Abdomino-right thoracic Resection Transthoracic Esophagectomy (Ivor-Lewis) High located intrathoracic Anastomosis Transabdominal Gastric Tube preparation Abdominal LA

17 Cumulative Overall Survival (%) Surgery Choice of Procedure Barrett-Ca Survival Hulscher et al. N. Engl. J Transthoracic esophagectomy Transhiatal esophagectomy 0 No. at risk Transhiatal esophagectomy Transthoracic esophagectomy Years

18 Advantages of Intrathoracic Anastomosis Anastomosis-Healing safer (in case of leakage - stent) swallowing function better more adequate LA N. Recurrence paralysis fewer

19 Locally advanced Esophageal - SCCa Location more frequent above the bifurcation R 0 -Res. from the anatomical point of view more difficult ( RCTx) Cervical Anastomosis more frequent necessary OP-Risk higher

20 Esophageal-Ca Multiple logistic regression analysis of the effects on operative death Adjusted odds ratio p Age (Years) < (0.52, 8.22) (0.36, 6.72) > (1.35, 17.55) FEV1 (% predicted) (0.44, 12.25) (1.20, 25.22) (1.01, 21.99) Position Upper third 4.23 (1.06, 16.86) Other 1 H. Abunasra et al. Brit. J. Surg. 2005

21 What s new in Neoadj. Therapy? with surgical consequences FDG-PET: Response evaluation after therapy with sufficient accuracy is possible FDG-PET: Good correlation between metabolic response and survival Stratification of responders and non-responders in different treatment concepts to improve prognosis and avoid postoperative morbidity individualized therapy

22 Early Response Evaluation - Barrett-Ca Before therapy After 14 days of chemotherapy (PLF)

Early Response Evaluation - using FDG-PET Change in metabolic activity during RCTx and CTx 14 12 10 10-30% 9-35% 8 8 7 N = 12 SUV 6 4 2

23 Early Response Evaluation - using FDG-PET Change in metabolic activity during RCTx and CTx % 9-35% N = 12 SUV Before therapy after 14days after 28days before surgery SUV Pre CTx 14 Days 100 Days Squamous Cell Carcinoma Adenocarcinoma

24 Barrett-Ca / Municon Trial Treatment flowchart Non-Responder Surgery d21 AEG ut3 Nx PET d0 CTx PET d14 Responder CTx 3 Months Surgery d120

25 Barrett-Ca (Municon Trial) Post-operative morbidity and mortality, R 0 -Resektionsrate Complications Hospital R0 mortality (30 day) Metabolic responder % (n=47) (36 %) (2%) 52% Metabolic % Non-responder (38 %) (%) n.s. s. (n=44) 47%

26 AEG Typ I n=511 1,0 TU München n=511,8 Primary resected pt1/2 n=219,6,4 Neoadj. ypt0-4 n=154 Responder / R0-Res.,2 Primary resected pt3/4 n=138 0,

27 SCC Postoperative Results Histopathol. Histopathol. Total Response Non- p-value Response < 10 % > 10 % 30-day 3,5 % 1,2 % 6 % 0.02 (n=11) (n=2) (n=9) Hospital 6,1 % 3,7 % 8,7 % 0.06 (n=19) (n=6) (n=13) R 0 n=152 n= % 63.8% <0.0001

28 Response Prediction / Neoadjuvant Therapy Consequences for Surgery - ONLY RESPONDERS have a benefit! - RESPONSE PREDICTION (?) Molecular marker? - Early Response evaluation is now possible. (!) There is a difference in SURGICAL RISK following RCTX or CTX (Immunosuppression following RCTx) Relevant for surgical consequences OPEN QUESTIONS: If second line Surgery Who are the candidates for surgery - Responders or Non-Responders?

29 Neoadjuvant Therapy: Candidates for Surgery? Responders! Residual tumor evaluation needs a surgical specimen (for histopathological examination) Histopathological Response independent Progn. Factor! Only (~10%) Complete Responders (residual tumor free) Low surgical risk in responders Very good prognosis! Non-Responders? High surgical risk Few R0 resections Also following Surgery bad prognosis

30 Esophageal-Ca / (SCC; T 3/4 ) Survival curves for nonresponders to chemoradiotherapy 100 NS (p=0.168) Survival Rate (%) 50 64% 20% 33% 20% Surgery (n=11) No-surgery (n=5) years after therapy Fujita, H. et al. World J. Surg short time improvement

31 Surgery for T 3/4 SCC-Esophageal-Ca following Neoadj. RCTx Postoperative complications Complication Esophagectomy (n=26) Recurrent nerve paralysis 13 (50%) Aspiration pneumonia 9 (35%) Tracheal ischemia 6 (23%) (ulcer, erosion) Pyothorax 6 (23%) Anastomotic leak 5(19%) Ileus 3 (12%) Severe arrhythmia 2 (8%) Pulmonary infarction 1 a (4%) MRSA enteritis 1 (4%) Brain abscess 1 a (4%) Morbidity 22 (85%) Mortality 2 (8%) Fujita, H. et al World J. Surg 2005

32 Strategies to overcome Esophageal Cancer 2005 ( Munich Experiences ) Separate concepts for adenocarcinoma and squamous cell carcinoma! Patient selection (staging; risk analysis) Standardisation of surgery Complication-management safety surgery in high risk patient to avoid p.op. mortality Neoadjuvant therapy and early response evaluation for locally advanced tumors Different strategy for Responder vs. Nonresponder Limited procedures for early cancer! High Volume Centers

33 TU Munich / Germany ( , n=1285) Surgery for Esophageal Cancer has Improved Markedly 1,0, n=511, n=432,4, n=342 0, Improved prognosis of resected esophageal cancer over a twenty year period at TU München Stein / Siewert: World J Surg 2004

Determining the Optimal Surgical Approach to Esophageal Cancer

Determining the Optimal Surgical Approach to Esophageal Cancer Amit Bhargava, MD Attending Thoracic Surgeon Department of Cardiovascular and Thoracic Surgery Open Esophagectomy versus Minimally Invasive