Lung Cancer Role of Surgery. Ricardo M. Terra Associate Professor of Thoracic Surgery University of Sao Paulo Medical School

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2 Lung Cancer Role of Surgery Ricardo M. Terra Associate Professor of Thoracic Surgery University of Sao Paulo Medical School

3 Disclosure Scientific Consultant/Advisory Board: Johnson&Johnson Educational grants: Medtronic Pfizer

4 General Objectives Surgery for Lung Cancer Local treatment Tissue for pathology Margins Surgical staging

5 Outline Role of of surgery in Lung Cancer: Stage 1 and 2 Stage 3 Technical aspects Type of resection Lymphadenectomy Minimally invasive surgery

6 Stage 1 and 2

7 California Cancer Registry patients Stage I 1432 no treatment Chest Jul;132(1):193-9.

8 Operated X not treated Chest Jul;132(1):193-9.

9 Therapeutic Alternatives Surgery Lobectomy Segmentectomy Stereotaxic Radiotherapy Percutaneous Ablation

10 Guidelines Resection is the gold-standard treatment ACCP, 2013 ESMO, 2013

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12 Lung Cancer Stage in Brazil (Sao Paulo Registry) Registro Hospitalar de Câncer do Estado de São Paulo 2000 a 2010 (n=20850) FOSP, 2015

13 Lung Cancer Stage in Brazil (Sao Paulo Registry) Registro Hospitalar de Câncer do Estado de São Paulo 2000 a 2010 (n=20850) 45% underwent surgery FOSP, 2015

14 Access to diagnostic resources n= 461 respostas (cirurgia torácica, pneumologia, radiologia) Access to Healthcare Resources in the Private and Public Systems % of Respondents 100% 80% 60% 40% 20% Easily available Somewhat difficult, requires some effort Moderately difficult, requires moderate effort Very difficult, requires a lot of effort Available but far away Available but very expensive for patient 0% Not Available CT PET-CT Bronchoscopy CT guided biopsy VATS biopsy PRIVATE Pathology report CT PET-CT Bronchoscopy CT guided biopsy VATS biopsy PUBLIC Pathology report JTD,2018

15 European Journal of Cardio-Thoracic Surgery 47 (2015) e19 e24, 2014

16 Stage 3 (N2)

17 N2 Disease Imprecise term Heterogeneous population

18 pn1 /N2 Stations 8th Revision N1a vs N1b vs N2a1 vs N2a2 vs N2b Comparisons Adjusted for Histology (adeno vs others), Sex, Age 60+, and Region. (Cox PH regression on R0 cases) P comparison HR Pathologic - R0 Location and Number of Pos Stations N1-N2 R0 100% N1b vs N1a N2a1 (skip) vs N1b N2a2 vs N2a1 (skip) N2b vs N2a2 N2a2 vs N1b 80% 60% 40% 20% 0% N1 N1 N2 N2 N2 0 Single Multiple Single Single+N1 Multiple N2 Ev ents / N 415 / / / / / 711 MST 60 Month NR 59% % % % % 2 4 YEARS AFTER RESECTION 6 Pathologic - any R Location and Number of Pos Stations N1-N2 Any R 80% 40% 20% 0% 0 Single Multiple Single Single+N1 Multiple N2 Ev ents / N 438 / / / / / 796 MST 60 Month NR 58% % % % % 2 4 YEARS AFTER RESECTION N1 Single = N1a N1 Multiple = N1b N Si gle N skip ets = N a N2 Single N2 + N1 = N2a2 N2 Multiple N2 = N2b N1b vs N1a N2a1 (skip) vs N1b N2a2 vs N2a1 (skip) N2b vs N2a2 N2a2 vs N1b 60% N1 N1 N2 N2 N N1a vs N1b vs N2a1 vs N2a2 vs N2b Comparisons Adjusted for Histology (adeno vs others), Sex, Age 60+, R0 Resection, and Region. (Cox PH regression on All cases) P comparison HR 100% Asamura H et al. J Thorac Oncol. 2015

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20 ESMO 2013

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22 2009

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24 Pneumonectomy Lobectomy

25 SD: Stable disease OR: objective response

26 Technical Aspects Type of Resection

27 Lobectomy is the gold-standard Segmentectomy (preferred) or wedge resection in patients with: Poor pulmonary reserve or major comorbidity Peripheral nodule < 2cm and: AIS histology >50% ground-glass appearance Long doubling time >400 days

28 Why Lobectomy? Lobectomy Segmentectomy Wedge resection

29 Clinical trial: 247 patients: T1 N0 Lung Cancer (intraoperative staging) Two Arms: Lobectomy Sublobar resection Outcomes: Local Recurrence Disease-free survival Ann Thorac Surg 1995;60:

30 Event Limited Resection No. of Rate (per Patients person/y) No. of Patients Lobectomy Rate (per person/y) p Value Recurrence (excluding second primary) b Recurrence (including second primary) b Locoregional recurrence d c Nonlocal recurrence d (NS) c Death (with cancer) b Death (all causes) b Ann Thorac Surg 1995;60:

31 Conclusion Sublobar resection is associated with a higher rate of local recurrence Lobectomy is the gold-standard Ann Thorac Surg 1995;60:

32 Enrollment: late 1980s, early 1990s CT Scan Staging methods Ann Thorac Surg 1995;60:

33 New challenges Small nodules Elderly patients Ground-glass opacities Is lobectomy really necessary?

34 Small nodules

35 N=2090 (688 sublobar resection) Propensity matched scores

36 4 Japanese Institutions Retrospective Stage IA (excluded R1/2 e multiple tumors) GGO predominance (>50%)

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38 3-year

39 Retrospective Stage IA Orginal set: 800 (lobectomy) 392 (sublobar)

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41 Clinical trial ACOSOGZ4032

42 Segmentectomy vs. Wedge resection

43 Technical Aspects Lymphadenectomy

44 No difference in complication rate

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46 Randomized clinical trial Linfadenectomy X Sampling Resectable TNMc I-IIIA N= 471 Resected Ly : SND: 9.45 MLS: 3.63

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48 Technical Aspects Minimally Invasive Surgery

49 Less invasive procedure

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56 28771 cases, matching with Propensity-scores

57 European Journal of Cardiothoracic Surgery, 2018

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59 Dexterity and lymph node dissection

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62 Lung lobectomy in lung cancer patients VATS vs. Robotics: Randomized study Ricardo Mingarini Terra, Pedro Henrique Xavier Nabuco de Araujo, Leticia Leone Lauricella, Alberto Jorge Monteiro Del Vega, Paulo Manuel Pego-Fernandes, Fabio Biscegli Jatene Serviço de Cirurgia Torácica do Instituto do Câncer do Estado de São Paulo - ICESP Disciplina de Cirurgia Torácica - Departamento de Cardiopneumologia Faculdade de Medicina da USP

63 Thank you! Ricardo M. Terra