Restaging after Induction Therapy 3A – B Disease

1. Restaging after Induction Therapy 3A – B Disease • Shaf Keshavjee MD MSc FRCSC FACS • Surgeon-in-Chief, University Health Network • James Wallace McCutcheon Chair in Surgery • Professor, Division of Thoracic Surgery and Institute of Biomaterials and Biomedical Engineering • University of Toronto 2012 Lung Cancer Summit – Focus on Thoracic Surgery: Lung Cancer Boston, MA, 16 November 2012

2. Presenter Disclosure Shaf Keshavjee MD No Relationships to Disclose

3. Considerations in Re-Staging after Induction Therapy • High oncologic risk patients  can progress during induction  must re-stage fully • Plan treatment and re-staging strategy at the outset • CT Chest and abdomen • MRI Head • PET scan • Invasive staging: EBUS-TBNA or mediastinoscopy? • Induction therapy • Re-staging • Re-do invasive staging: EBUS - FNA or mediastinoscopy?

4. Re-Staging the Mediastinum

5. Mediastinal Staging • Clinical staging can markedly differ from pathologic staging • 24% clinically overstaged • 20% clinically understaged • 190 cN2 patients: 38% pN0 / pN1, 6% pN3 • 119 cN2 patients: 14% with pN2 • Need pathologic evaluation in all patients thought to be a surgical candidate before thoracotomy Bülzebruck et al, Cancer 1992; 70: 1102 Watanabe et al, Ann ThoracSurg 1991; 51: 253 Am J RespirCrit Care Med 1997; 156: 320 Cerfolio et al Ann ThoracSurg 2005; 80: 1207 De Leyn et al, Eur J CardiothoracSurg 2007; 32: 1

6. Cervical Mediastinoscopy (First Time) • “Gold Standard”- Sensitivity 80%, Specificity 100% • FN rate: 10% • Downside • Invasive • Non-operable candidates may have to undergo surgical staging • Operable candidates may need a re-do mediastinoscopy Yasufuku K, Keshavjee S. Clinical Pulmonary Medicine. 2010; 17(5): 223-231

7. EBUS-TBNA • Access to all LN stations accessible by Med as well as N1 nodes • Minimally invasive modality • Sensitivity 85-96% • First time EBUS does not significantly affect 2nd time EBUS FNA or mediastinoscopy

8. EBUS-TBNA – Yieldvs. CT and PET10 studies (n=817) • EBUS-TBNA Systematic Review and Meta-analysis • Sensitivity = 0.88 (95%CI, 0.79-0.94), Specificity = 1.00 (95%CI, 0.92-1.00) • Results compare favorably with published results for PET and CT Adams et al. Thorax; 2009; 64: 757-62

9. Lung Cancer Staging (EBUS vs. Med) • Prospective cross-over trial (Ernst et al) • n=66, prevalence of malignancy 89% • Disagreement in the yield for #7 (24%; p=0.011). • Prospective controlled study (Yasufuku et al) • n=153, operable patients • No difference between EBUS and Med Ernst et al. J Thorac Oncol. 2008; 3: 577-82 Yasufuku et al. J Thorac Cardiovasc Surg. 2011 142: 1393-1400

10. Re-Staging Mediastinoscopy or EBUS -FNAHow will you use the information? Rule out N3 disease What about persistent disease? What about single station vs. Multi-Station involvement? Complete Pathological Response vs. Partial?

11. Lung Cancer Re-staging (EBUS) • EBUS-TBNA following neo-adjuvant chemotherapy • * All cases confirmed by thoracotomy • ** EBUS –ve cases confirmed by TEMLA (Transcervical bilateral extended mediastinal lymphadenectomy • TEMLA results suggest -ve EBUS may not require surgical restaging Herth et al. JCO. 2008; 26: 3346-50 Szlubowski et al. Eur J Cardiothorac Surg. 2009

12. Lung Cancer Re-staging (Mediastinoscopy) Eur J Cardiothorac Surg. 2010 Apr;37(4):776-80

13. Risk of Re-Do Mediastinoscopy • Scar tissue  from previous mediastinoscopy or chemo/RT • Risks  Bleeding, recurrent nerve, incomplete assessment • Higher false negative rate

14. Performance of Mediastinal Restaging Tests Candela and Detterbeck, J ThoracOncol 2010 5(3):389.

15. Staging and Post Induction Re-Staging Algorithm Surgery

16. Summary • Surgery for 3A-B disease • Staging and treatment must be carefully planned • Conventional imaging staging: CT, PET • Invasive Staging: EBUS-FNA, Mediastinoscopy • Optimal combination: • Initial: CT, PET, EBUS-FNA • Induction chemoradiation • Restaging: CT, PET response, Mediastinoscopy • Don’t forget systemic re-staging!