Primary staging and restaging for non-small cell lung cancer

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1 Primary staging and restaging for non-small cell lung cancer Vincent Ninane, Brussel Didier Lardinois, Zurich First Winter Workshop on Multidisciplinary Approaches to Chest Tumors SAMO, Lucerne 19th-20th January 2007

2 Survival according to the stage 5-y overall survival: 15% (Mountain, Chest 1997)

3 Lymph node status predicts outcome (Naruke, Ann Thorac Surg 2001)

4 Mediastinal staging before Induction therapy Group Patients 5-year survival Minimal N2*; single Level Minimal N2*; multiple Level Clinical N2; single Level Clinical N2; multiple Level % 11% * LN < 1 cm on CT or neg. mediastinoscopy (Andre, J.Clin Oncol 2000) (Ichinose, J Thorac Cardiovasc Surg 2001) 8% 3% - multimodality therapy concept (induction therapy) - precise preoperative clinical nodal staging required for patient selection (toxicity, morbidity)

5 Mediastinal restaging after Induction therapy Accurate mediastinal restaging is necessary, since residual nodal tumor seems to be associated with a poor outcome preinduction postinduction

6 Second ESTS Workshop on preoperative mediastinal staging - primary staging - restaging after induction therapy - what is the optimal strategy for preoperative mediastinal staging? ESTS guidelines for preoperative lymph node staging for non-small cell lung cancer (P. De Leyn, D. Lardinois, P. Van Schil, R. Rami-Porta, B. Passlick, M. Zielinski, D. Waller, T. Lerut, W. Weder. In press Eur J cardiothorac Surg)

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8 (Re)staging - political, geographical aspect - economical, financial consideration the use of the different (re)staging techniques differs according to - the equipment available in the centres - the experience of the surgeons - properties of the tumor (size, the location of the mediastinal abnormality)

9 Primary staging - operability - inclusion in induction protocols -CT - mediastinoscopy - PET (-CT) - VATS - endoscopic techniques

10 Primary mediastinal staging Chest CT scan Standard examination Contrast medium Anatomical information Criteria for LN metastasis: LN > 1cm (1.5 cm) in its short axis

11 Large lymph nodes: always metastases? Metastases: 38% 61% 84% (Wilkinson et al, Cancer 1974) LN size does not predict malignancy

12 Lymph-node metastases occur also in small primary tumors Clinical tumor LN positive at stage* mediastinoscopy (%) ct1n0 9.5 ct2n ct3n ct4n *(LN <15 mm on CT scan) De Leyn, Eur J Cardiothorac Surg 1997 Wu, Ann Thorac Surg 2001 Passlick, Eur J Cardiothorac Surg 2002 Lardinois, Ann Thorac Surg 2003

13 Cervical (Video-) Mediastinoscopy

14 Cervical Mediastinoscopy 2R 4R 2L 4L 7 (Mountain CF, Chest 1997) Lymph-node levels routinely accessed by cervical mediastinoscopy Systematic biopsy of five lymph-node levels in routine

15 Sensitivity and Specificity of Cervical Mediastinoscopy (Toloza, Chest 2003)

16 Morbidity and mortality of cervical mediastinoscopy (Series > 1000 patients) n Mortality (%) Morbidity (%) Puhakka, Cybulsky, Hammoud, Total % 0.7%

17 Which stations should be examined to prove cn0? - no internationally accepted recommendation - in summary: exploration of the stations ATS 2R, 2L, 4R, 4L, 7 considered by many authors as adequate exploration of the stations ATS 4R, 4L, 7 might be accepted for routine practice

18 Video-Mediastinoscopy - Minimal complications - 100% specificity - Clarifies local resectability - Discriminates between nodal/extranodal disease Gold standard for nodal staging

19 PET SCAN CT scan N0 disease Scott, J Thorac Cardiovasc Surg 1996; Fischer, Lancet Oncol 2001; Pieterman, N Engl J Med 2000 Can PET reduce the need for mediastinoscopy? (Kernstine, Ann Thorac Surg 2003)

20 Accuracy for nodal staging in lung cancer Literature data Technique Pat. No Sensitivity Specificity NPV PPV CT scan Mediastinoscopy PET scan (Toloza, Chest 2003)

21 General consideration on clinical use of PET - Diabetes (glucose level) : reduced sensitivity - Actual resolution : 6-8 mm - Uptake of FDG in macrophages, neutrophils - Highly variable physiologic tracer accumulation (colon, small intestine) - Experience of nuclear physician!

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23 Anatomical location problem Integrated PET- CT

24 Incremental Value of Integrated PET/CT Imaging in Staging of Non-Small Cell Lung Cancer (NSCLC) Prospective blinded study to compare diagnostic accuracy of - integrated PET/CT - CT alone - PET alone - visual correlation of PET+CT (Lardinois et al, N Engl J Med 2003)

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26 Primary staging PET scan Integrated PET/CT (Lardinois et al, N Engl J Med 2003; De Leyn et al, Lung Cancer 2005)

27 T 2 or T 4 (mediastinal?)

28 M-Staging: Where is the lesion located? (Weder et al, Ann Thorac Surg 1998)

29 NSCLC investigated by PET (n=350) Isolated extrapulmonary lesions (n=72) Solitary metastasis 37 54% Lesion without relation to NSCLC 32 46% 2 nd primary tumor 6 19% benign lesion 26 81% (Lardinois et al, J Clin Oncol 2005)

30 PET SCAN Integrated PET/CT It is generally admitted that: - PET(/CT) cn0 thoracotomy - caution in central tumors, broncho-alveolar carcinoma, weak FDG-uptake in primary, enlarged LN on CT

31 PET-positive findings need cytological or histopathological confirmation of metastases (mediastinoscopy, VATS, endoscopic techniques)