Dr. Sergi Call Caja Thoracic Surgery Service

Dr. Sergi Call Caja Thoracic Surgery Service

Introduction 1. Use of Lymphadenectomy in Lung Metastasectomy? 2. Incidence of lymph node metastases (LNM)? 3. What is the Impact on Survival?

Introduction LN Assessment in Lung Metastasectomy LN Assessment of ESTS members 2008

Introduction LN Assessment of ESTS members Internullo E, Cassivi SD, Van Raemdonck D, Friedel G, Treasure T. Pulmonary metastasectomy: a survey of current practice amongst members of the European Society of Thoracic Surgeons. J Thorac Oncol. 2008;3:1257 66

Introduction LN Assessment of ESTS members Internullo E, Cassivi SD, Van Raemdonck D, Friedel G, Treasure T. Pulmonary metastasectomy: a survey of current practice amongst members of the European Society of Thoracic Surgeons. J Thorac Oncol. 2008;3:1257 66

Introduction LN Assessment in Lung Metastasectomy Intraoperative LN assessment is not routinely performed Only suspicious LN are removed or biopsed

Introduction Incidence of LNM 1997 Incidence LNM: 5% (239) Histology: Epithelial Mets (43%) Sarcomas (42%) Germ-cell tumors (7%) Melanomas (6%) Limitations: 18 centers (9 countries) Heterogeneous work-up No routine LN assessment

Introduction Incidence of LNM 2006

Introduction Incidence of LNM in CRC 2010 12% - 32% 1307 patients No randomized trials 11 relevant prospective & retrospective studies SND or Sampling was performed

Introduction Incidence of LNM in Lung Metastasectomy 5% - 37.5% Cell type of Primary Tumor Intraoperative LN Assessment Preoperative workup

Introduction Impact on Survival 2007 20 series = 1684 pts. Heterogenity in LN assessment Not reported Performed selectively o Enlarged LN, PET + SND / sampling / minor 5-y Survival LNM No LNM 0% - 33.5% 38.7% - 71%

Introduction Impact on Survival 2013 Systematic review & Meta-Analisis Series between 2000-2011 Surgical series of LM from CRC >40 patients 1. Short DFI 2. Elevated CEA 3. Multiple M1 4. LNM

Introduction LNM (Hilar & Mediastinal) HR= 1.65 (95% CI 1.38-2) Gonzalez M, Poncet A, Combescure C, Robert J, Ris HB, Gervaz P. Risk Factors for Survival after Lung Metastasectomy in Colorectal Cancer Patients: A Systematic Review and Meta-Analysis. Ann Surg Oncol. Springer-Verlag; 2012 Oct 28;20(2):572 9.

GECMP-CCR-SEPAR Largest series of Lung Mets from CRC Prospective Study N= 543 patients (from 32 Hospitals) 2008-10: Data collection 2013: follow-up was completed

GECMP-CCR: LYMPHADENECTOMY 2015 Objective 1. Incidence of LNM in the Spanish Registry 2. Survival depending on (p) nodal status

GECMP-CCR: LYMPHADENECTOMY Methods 1. Study Design: Prospective, observational and multicenter 2. Period of recruitment: 2008-2010 3. Follow-up until March 2013 4. Patients N=522 (from 32 Hospitals) Inclusion criteria: o 1st Metastasectomy: March 2008 - March 2010 o Macroscopically complete resection fo all Mets o Histological confirmation of Lung Met from CRC Exclusion criteria: Surgery without radical intent Call S, Rami-Porta R, Embun R, Casas L, Rivas JJ, Molins L, Belda J. Impact of inappropriate lymphadenectomy on lung metastasectomy for patients with metastatic colorectal. Surg Today 2015.

GECMP-CCR: LYMPHADENECTOMY Call S, Rami-Porta R, Embun R, Casas L, Rivas JJ, Molins L, Belda J. Impact of inappropriate lymphadenectomy on lung metastasectomy for patients with metastatic colorectal. Surg Today 2015.

GECMP-CCR: LYMPHADENECTOMY Methods: Patients Characteristics (n=522) I II III IV Primary Tumor Stage 40 (7.7%) 141 (27%) 198 (38%) 135 (26%) Disease-free interval <12 months 181 (34.7%) >12 months 338 (64.8%) Lung Metastases Induction Therapy Synchronous Metachronous 77 (14.8%) 445 (85.2%) No Yes 111 (21.3%) 411 (78.7%) Number of Lung Mets Laterality of Lung Mets Unilateral 429 (82.2%) Bilateral 82 (15.7%) 1 2-3 >3 343 (65.7.%) 137 (26.2%) 42 (8.1%) Adjuvant chemotherapy Yes 206 (39.5%) No 316 (60.5%) Call S, Rami-Porta R, Embun R, Casas L, Rivas JJ, Molins L, Belda J. Impact of inappropriate lymphadenectomy on lung metastasectomy for patients with metastatic colorectal. Surg Today 2015.

GECMP-CCR: LYMPHADENECTOMY Methods: Definitions Lymphadenectomies were defined according to the GCCB-SEPAR (p) LN status (p) Absence of LNM Uncertain LN status (ulns) Sampling or SND Minor Lymphadenectomy Grupo Cooperativo de Carcinoma Broncogénico de la Sociedad Española de Neumología y Cirugía Torácica GCCB-S. Estadificación ganglionar intraoperatoria en la cirugía del carcinoma broncogénico. Documento de consenso. Arch Bronconeumol. 2001;37:495 503.

GECMP-CCR: LYMPHADENECTOMY Results of lymph node assessment Type of Lymphadenectomy SND 50 (20%) Nothing 272 (52%) LN Assessment Sampling 87 (34.8%) 250 (48%) Minor 113 (45.2%) Call S, Rami-Porta R, Embun R, Casas L, Rivas JJ, Molins L, Belda J. Impact of inappropriate lymphadenectomy on lung metastasectomy for patients with metastatic colorectal. Surg Today 2015.

GECMP-CCR: LYMPHADENECTOMY Results: LN Status N= 522 Lymphadenectomy N= 137 Uncertain lymph node assessment N= 385 SND Sampling N= 50 N= 87 * * Absence LNM= 43 Absence LNM= 76 Hilar LNM= 1 Hilar LNM= 3 Mediastinal LNM= 5 Mediastinal LNM= 7 Minor N= 113 Hilar LNM= 3 Mediastinal LNM= 6 ulns= 104 Without Lymphadenectomy N= 272 * ulns= 270 Absence LNM = 119 (22.8%) Hilar LNM = 4 (0.8%) Mediastinal LNM = 12 (2.3%) ulns= 374 (72%) Hilar LNM= 3 (0.6%) Mediastinal LNM= 6 (1.1%) * Four cases were considered missing due to implausible data

GECMP-CCR: LYMPHADENECTOMY Results: LN Status N= 522 Lymphadenectomy N= 137 Uncertain lymph node assessment N= 385 SND 1349 LNs were removed Sampling N= 50 N= 87 Median of 4 (1-41, SD 5.5) LN per patient * * Absence LNM= 43 Hilar LNM= 1 Mediastinal LNM= 5 Absence LNM = 119 (22.8%) Hilar LNM = 4 (0.8%) Absence LNM= 76 LNM Hilar LNM= 3 = 25 (5%) Mediastinal LNM= 7 Mediastinal LNM = 12 (2.3%) Minor N= 113 Hilar LNM= 3 Mediastinal LNM= 6 ulns= 104 Absence of LNM= 119 (23%) ulns= 374 (72%) ulns= 374 (72%) Without Lymphadenectomy N= 272 * ulns= 270 Hilar LNM= 3 (0.6%) Mediastinal LNM= 6 (1.1%)

GECMP-CCR: LYMPHADENECTOMY Results: Survival according on (p) LN status p=0.006 Whole Series Median S= 55 m 3-y 5-y LNM 50.5% 95% CI 29-71 24.8% 95% CI 3-46 3-y 5-y LNM ulns ulns 69% 95% CI 64-74 44% 95% CI 35-53 Absence LNM 3-y 5-y Absence LNM 73.5% 95% CI 65-82 58.3% 95%CI 41-75 Call S, Rami-Porta R, Embun R, Casas L, Rivas JJ, Molins L, Belda J. Impact of inappropriate lymphadenectomy on lung metastasectomy for patients with metastatic colorectal. Surg Today 2015.

GECMP-CCR: LYMPHADENECTOMY Results: Survival according on (p) LNM p=0.001 Mediastinal LNM 3-y 5-y 40.6% 16.3% 95% CI 15-65 95% CI 0-36 HR (Mediastinal LNM) = 3.3 (1.7-6.4) p < 0.0001 3-y 5-y Hilar LNM 71.4% 95% CI 38-100 ------ Mediastinal LNM Hilar LNM Absence LNM HR (Hilar LNM) = 1.45 (0.44-4.74) p = 0.538 3-y 5-y Absence LNM 73.5% 95% CI 65-82 58.3% 95%CI 41-75 Call S, Rami-Porta R, Embun R, Casas L, Rivas JJ, Molins L, Belda J. Impact of inappropriate lymphadenectomy on lung metastasectomy for patients with metastatic colorectal. Surg Today 2015.

In the Literature SUMMARY LN assessment in Lung metastasectomy is an uncommon practice The incidence of LNM ranges from 4.5% to 37.5% Cell type of primary tumor Variation in preoperative workup Type of LN Assessment performed Incidence of LNM in Lung Mets from CRC: 12%-32% LNM in Lung Mets from CRC is a significant independent negative prognostic factor for survival after metastasectomy

In the Spanish Registry SUMMARY LN assessment is also an uncommon practice Incidence of LNM: 5% (whole series) / 10% (when LNA) LNM remains a significant negative prognostic factor Patients with suboptimal LNA= 374 (72%) Coded as uncertain LN status (ulns) Worse Survival than the group without LNM Probably, missed LNMs can impair survival because of the misclassification of risk

CONCLUSION Awaiting a future randomized trial that can answer which is the precise impact of surgery in lung metastases from CRC Lymphadenectomy should be performed in clinical practice and promoted in future studies for: Accurate staging To determine the individual prognosis To decide the optimal adjuvant treatments

Coordinators: Juan J. Rivas (Miguel Servet University Hospital, Zaragoza) Laureano Molins (Sagrat Cor University Hospital, Barcelona) Secretary: Raul Embún (Miguel Servet University Hospital, Zaragoza) Local heads and Departments: Francisco Rivas (H.U. de Bellvitge, Hospitalet de Llobregat, Barcelona) Raul Embún (H.U. Miguel Servet, Zaragoza) Jorge Hernández (H.U. Sagrat Cor, Barcelona) Félix Heras (H.G.U. de Valladolid) Javier de la Cruz (H.U. Virgen del Rocío, Sevilla) Matilde Rubio (H.U. Josep Trueta, Girona) Esther Fernández (H.U. Germans Trias i Pujol, Badalona, Barcelona) Miguel Carbajo (H.U. Marqués de Valdecilla, Santander) Rafael Peñalver (H.U. Gregorio Marañón, Madrid) Jose Ramón Jarabo (H.C. San Carlos, Madrid) Diego González-Rivas (C.H.U. de A Coruña) Sergio Bolufer (H.G.U. de Alicante) Carlos Pagés (H.G.U. Carlos Haya, Málaga) Sergi Call (H.U. Mutua Terrassa, Barcelona) David Smith (H. Italiano, Buenos Aires, Argentina) Richard Wins (H.C.U. de Valencia) Antonio Arnau (H.G.U. de Valencia) Andrés Arroyo (H.U. Virgen de la Arrixaca, Murcia) Ma Carmen Marrón (H.U. 12 de Octubre, Madrid) Akiko Tamura (Clínica U. de Navarra, Pamplona) Montse Blanco (C.H.U. de Vigo, Pontevedra) Beatriz de Olaiz (H.U. de Getafe, Madrid) Gemma Muñoz (H.U. Ramón y Cajal, Madrid) Jose M. García Prim (H.C.U. de Santiago de Compostela, A Coruña) Carlos Rombola (H.G.U de Albacete) Santiago García Barajas (H.U. Infanta Cristina, Badajoz) Alberto Rodríguez (H.U. del Mar, Barcelona) Jorge Freixinet (H.U. Dr. Negrín, Las Palmas) Javier Ruiz (H.U. Virgen de las Nieves, Granada) Guillermo Carriquiry (H. Maciel, Universidad de la República, Montevideo, Uruguay) Moisés Rosenberg (Instituto Oncológico Alexander Fleming, Buenos Aires, Argentina) Leyre Malet Nuria Pajuelo Laura Casas

Thank you very much for your attention!