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Marmara University School of Medicine Dept of Thoracic Surgery
Role of Surgery in Combined Treatment at
Stage III
Asso.Prof.Hasan F.Batırel
Marmara University School of Medicine Dept of Thoracic Surgery
• Stage III disease
• Role of surgery in Stage III NSCLC
• Results of studies
• Current problems and solutions
• Conclusion
Marmara University School of Medicine Dept of Thoracic Surgery
Stage III Disease
• Stage III disease according to the 1997 system.
• IIIA ve IIIB
• Before 1997 different staging system and results in series (T3N0).
Marmara University School of Medicine Dept of Thoracic Surgery
Which Stages?
Stage IIIA – T3N1, T1-3N2Stage IIIB – T4N0
Stage IIIB – T1-4N3
Marmara University School of Medicine Dept of Thoracic Surgery
Evolution of Surgery
• 1982 Pearson – Cervical mediastinoscopy
• Poor survival in N2 + pations 9% 5 yr survival (Pearson – 1982), 16% (Naruke – 1988)
• So locoregional disease?
Marmara University School of Medicine Dept of Thoracic Surgery
Multimodal Treatments
• Starting multimodality trials
• 2 small series (60 pts each) by Roth and Rosell 1994.
• Surgery + Adj / Neoadj Chemo + Surgery + Adj
Marmara University School of Medicine Dept of Thoracic Surgery
The Type of Preoperative Treatment• Chemotherapy – CALGB 8935
Sugarbaker 1995.
• Chemoradiation – SWOG 8805 Albain 1995.
Marmara University School of Medicine Dept of Thoracic Surgery
No role for surgery?
• Albain 2005 – INT 0139/RTOG 9309
• Van Meerbeck 2007 – EORTC 08941
Marmara University School of Medicine Dept of Thoracic Surgery
Pearson ve Naruke
Pearson 1982
• N2+ diagnosed preop, 5 yr survival 9% (n=79).
• N2+ found during surgery, 5 yr survival %24 (n=62).
Naruke 1988
• Clinical N2 disease, 5 yr survival 16% (n=345)
Marmara University School of Medicine Dept of Thoracic Surgery
Roth and Rosell Studies
• 60 patients each
• T3N0 included in each series.
• Routine mediastinoscopy only in Roth study.
• Roth 36% vs 15% 5 yr survival.
• Rosell 17% vs 0% 5 yr survival.
Marmara University School of Medicine Dept of Thoracic Surgery
Survival advantage continues at 7-8 year follow-up.
Marmara University School of Medicine Dept of Thoracic Surgery
Type of Preoperative Treatment
• CALGB 8935 – Sugarbaker 1995, Neoadj Chemo + Surgery + Adj XRT Pathologic partial response 22%.
• SWOG 8805 – Albain 1995, Concurrent Neoadj CRT, Surgery, Pathologic complete response 21%, Lymph node clearance 59%.
• 3 year survival 23% ve 26%.
Marmara University School of Medicine Dept of Thoracic Surgery
SWOG 8805
• Even in the case of radiologically and clinical stable disease %25 pathologic complete response!!!
• One of the most important findings to show the weaknesses of radiologic re-staging following neoadjuvant treatment…
Marmara University School of Medicine Dept of Thoracic Surgery
Metaanalysis – Stage III
Neoadjuvant• Bergmans, Lung Cancer 2005.
Marmara University School of Medicine Dept of Thoracic Surgery
EORTC – 08941 – JNCI 2007• %90 partial response, %7 pathologic complete
response• %47 pneumonectomy
Marmara University School of Medicine Dept of Thoracic Surgery
Issues with EORTC and INT studies
• The number of accrual is insufficient to show small differences.
• The percent of pneumonectomies is very high in the EORTC study.
• Long-term results of Intergroup study will be clinically important.
Marmara University School of Medicine Dept of Thoracic Surgery
Pneumonectomy following Neoadjuvant Treatment
• Martin MSKCC 2001 Ann Thorac Surg - %11 (right side %26).
• Albain INT 0139 2005 JCO - %26 (right side %39).
• EORTC 08941 2007 JNCI - %7 (right side %5).
Marmara University School of Medicine Dept of Thoracic Surgery
Survival in Patients with Lymph
Node Downstaging
• CALGB 8935 – J Surg Oncol 2006. N0 patients 47.8, N2 patients 8.2 months.
• Van Schil – EJCTS 2006. N0 patients 41, N2 patients 7 ay. Remediastinoscopy recommended.
• Bueno – Ann Thorac Surg 2000. N0 patients 21.3, N2 patients 15.9 months. 5 year survival 36% vs 9%.
Marmara University School of Medicine Dept of Thoracic Surgery
Lymph Node and Primary Tumor Response
Marmara University School of Medicine Dept of Thoracic Surgery
Staging Following Neoadjuvant Treatment
• Remediastinoscopy,
VAMLA
• VATS
• Transbronchial USG
• PET
Marmara University School of Medicine Dept of Thoracic Surgery
Pathologic Complete/Partial Response
• PET during neoadjuvant treatment?
• Concurrent Chemotx + RT
• Evaluation of complete response – Surgical specimen
Marmara University School of Medicine Dept of Thoracic Surgery
• N2 Stage IIIA NSCLC Surgery following neoadjuvant treatment > Surgery alone.
• Persistence of N2 disease following neoadjuvant treatment – Surgery < Curative CRT
Lessons Learned During Evolution of Surgery – 1
Marmara University School of Medicine Dept of Thoracic Surgery
Lessons Learned During Evolution of Surgery– 2
• Pneumonectomy required following neoadjuvant tx - Surgery < Curative CRT
• Lymph node downstaging, resectable with lobectomy – Surgery offers excellent long term local control and survival when compared with other modalities.
Marmara University School of Medicine Dept of Thoracic Surgery
Conclusion
• The boundaries and role of surgery is becoming more apparent in Stage IIIA NSCLC.
• This patient group will probably be stratified to microscopic systemic and locally limited (not locally invasive) disease via molecular/pathologic markers.
• There is no doubt that surgery is the best treatment in locally limited disease.