24. Ärzte-Fortbildungskurs in Klinischer Onkologie 20.-22. Februar 2014, Kantonsspital St. Gallen Chirurgie beim oligo-metastatischen NSCLC Prof. Dr. med. Walter Weder Klinikdirektor Thoraxchirurgie, UniversitätsSpital Zürich
The problem Suddenly a solitary horseman appeared on the horizon, then another, then another in a few moments a whole crowd of horsemen swooped down upon him Leacock
48-year old female with NSCLC 012008
Oligometastatic NSCLC 012008 48-year old female with bilateral synchronous NSCLC and isolated brain metastasis Poorly differentiated NSCLC left upper lobe ypt2, ypn2, pm1 (BRA) Adenocarcinoma right upper lobe ypt2, ypno, Mx Craniotomy with extirpation of brain metastasis 3 cycles cisgem + 3 cycles carbogem Segmentectomy left upper lobe + mediastinal lymphadenectomy Lobectomy right upper lobe + mediastinal lymphadenectomy
Follow up PET-CT 042012
062012 Local recurrence apical segment right lower lobe segmentectomy + local radiotherapy (60gy) 022014 No evidence of disease
Metastatic NSCLC The standard of care for metastatic NSCLC is chemotherapy or supportive care, with surgery being reserved for palliation of symptoms; However, in selected patients with distant metastases, resection of their metastases and primary tumor may improve survival
Oligometastatic disease One or two sites of lung or extra thoracic metastases Patients with N3 lymph node metastases are excluded
Treatment principle for oligometastatic disease Effective treatment would require: Eradication of the primary site Imaging of all sites of metastatic disease Effective treatment of all sites of metastases Effective adjuvant systemic therapy to eradicate presumed but undetectable sites of micro metastatic disease
Oligometastatic sites Lung Brain Adrenal Other
Oligometastatic disease (lung) The presence of additional lung nodule(s) in a patient with NSCLC is not per se a contraindication to surgical treatment Different histology (15%): synchronous tumors Same histology (85%): Molecular analysis for clonality is crucial for definite differentiation between MPLC (multiple pulmonary lung cancer) and metastasis 5-yr survival: Satellite (50%), MPLC (35%), metastasis (25%)
Discrimination of multiple primary lung cancers from intrapulmonary metastasis based on the expression of four cancer-related proteins p53 p16 p27 C-erbB2 Ono et al, Cancer, 2009
Ipsilateral pulmonary metastasis T. Nakagawa et al., European J of Cardio-thoracic Surgery 2005
Ipsilateral pulmonary metastasis T. Nakagawa et al., European J of Cardio-thoracic Surgery 2005
Oligometastatic disease (lung) Oligometastatic disease (lung) Satellite (same lobe) 28% Ipsilateral 21% Contralateral 5-20%* 5-yr survival rates * extrapolation from non-homogeneous data (synchronous, metachronous, mets, second primaries)
Oligometastatic disease (lung) Recommendations Surgical treatment of oligometastatic disease to the lung is indicated Careful staging has to rule out disseminated metastatic disease Wedge resectionsegmentectomy of the metastasis is sufficient (or laser resection) In bilateral disease a staged approach is favoured (low mortality rate) With surgical therapy, survival rates are higher than with palliative chemotherapy
M1 - brain MST 2 6 months but 11 21% 5-year survival in selected patients surgically treated (radio-therapy)
M1 brain Lung cancer causes 80% of all brain mets Median survival 2 months with steroids 3-6 months with radiation Pat. who are considered for radical resection should undergo invasive mediastinal staging and extrathoracic imaging Following radical resection of both sites (brain + lung) whole brain radiation is recommended Shen, Chest 2007
M1 brain Mayo Clinic study 28 NSCLC pat resected with sync solit brain met 1 YSR 64% 2 YSR 54% 5 YSR 21% (with N0 35%) Billing, J Thorac Cardiovasc Surg 2001
M1 brain Korean retrospective case controlled study 16 pat gamma-knife radiosurgery + pulmonary resection 15 pat gamma-knife radiosurgery only 1 YSR 100% vs. 67% 2 YSR 87% vs. 23% 5 YSR 55% Yang, Cancer 2006
Single brain metastasis Billing et al. J Thorac Cardiovasc Surg 2001
Single brain metastasis influence of N-stage Billing et al. J Thorac Cardiovasc Surg 2001
Synchronous, oligometastatic NSCLS Fig. 1 Overall patient survival Collaud, Weder, Lung Cancer, 2012
Synchronous, oligometastatic NSCLS Fig. 2 Patient survival according to pt stages Collaud, Weder, Lung Cancer, 2012
Synchronous, oligometastatic NSCLS Fig. 3 Patient survival according to pn stages Collaud, Weder, Lung Cancer, 2012
Isolated Brain Metastasis Recommendations In patients with no other metastatic sites and a synchronous resectable N01 NSCLC, resection or radiosurgical ablation of an isolated brain metastasis should be done, followed by resection of the primary tumor. In patients with no other metastatic sites and a previously completely resected NSCLC (metachronous presentation), resection or radiosurgical ablation of an isolated brain metastasis should be undertaken. Detterbeck, Chest 2003; 123:244S-258S
Isolated Brain Metastasis Recommendations Following curative resection of an isolated brain metastasis, adjuvant whole brain radiotherapy is reasonable, although there is conflicting and insufficient data regarding a benefit with respect to survival or the rate of recurrent brain metastases. Following curative resection of an isolated brain metastasis (and resection of the primary tumor), adjuvant chemotherapy can be neither recommended nor recommended against because of insufficient data regarding this issue. Detterbeck, Chest 2003; 123:244S-258S
Adrenal metastases Recommendations Frequency of isolated adrenal metastasis : 1.6-6% 2-9% of healthy subjects present adrenal adenoma (PET pos) 5-year survival 10-23% in selected cases PETCT and MRI have low accuracy in diagnosing adrenal MTS TC (US)-guided FNAB or laparoscopy are indicated in case of suspected PET pos adrenal mass Detterbeck, Chest 2003; 123:244S-258S
Adrenal metastases Highly selected patients have been reported who have undergone resection of an adrenal metastasis from NSCLC with intent to cure. The overall 5-year survival for these patients has been 10 to 23%. Survival after resection of the primary and the adrenal metastasis appears to be good primarily in patients without nodal involvement (N0).
M1 adreanal French study 23 NSCLC pat resected with solitary adrenal met 5 YSR overall - 23% (38% when disease free interval > 6 months) Mercier, J Thoracic Cardiovasc Surgery 2005
Adrenal metastasis Synchronous versus metachronous metastases Tanvetyanon, T. et al. J ClinOncol; 26:1142-1147 2008 Copyright American Society of Clinical Oncology
Isolated Adrenal Metastasis Recommendations Patients with an isolated adrenal metastasis from NSCLC should be considered for a curative approach. Careful exclusion of other distant metastases should be carried out with imaging tests. Mediastinoscopy should be done to rule out N2 involvement prior to resection in patients with a synchronous isolated adrenal metastasis and resectable primary lung cancer. Detterbeck, Chest 2003; 123:244S-258S
Isolated Adrenal Metastasis Recommendations In patients with no other metastatic sites and a synchronous resectable N01 NSCLC, resection of an isolated adrenal metastasis should be performed (as well as resection of the primary tumor). In patients with no other metastatic sites and a previously completely resected NSCLC (metachronous presentation), resection of an isolated adrenal metastasis should be undertaken. Detterbeck, Chest 2003; 123:244S-258S
Influence of 1, 2 or 3 metastatic sites Oh et al., Cancer 2009
Other extrathoracic metastases Very few reports Excellent results in selected patients Sites: stomach, pancreas, extrathoracic lymphnodes, liver, skeletal muscle, bone The primary NSCLC needs to be completely resected Mets should be metachronous Complete and comprehensive staging is essential to rule out disseminated metastatic disease PET detection of occult Mets: 6-17% Detterbeck, Chest 2003; 123:244S-258S
Other extrathoracic metastases This case proves, in principle, that resection of solitary metastatic lesions in certain clinical conditions can be improved regardless of location.
Prognosis of surgically treated oligometastatic NSCLS M1 (adrenal) after curative resection 5-year survival: 10-23% M1 (cerebral) after resection 5-year survival: 8-21% Detterbeck, Lung Cancer Guidelines, Chest 2003
Treatment of oligometastatic NSCLC Stage IV NSCLC patients presenting with solitary metastases, if localized to brain, adrenals, or lung, can be treated with curative intent. In the case of solitary brain metastasis, surgical resection followed by WBRT or alternatively radiosurgery ± WBRT might be beneficial. Further options include surgical resection of the primary lung combined with systemic chemotherapy [II; B], or definitive chemoradiotherapy, preferred in the case of locally advanced primary, such as solitary station N2 disease [III; B]. ESMO Clinical Practice Guidelines, Peters, S. et al, Ann Oncol (2012)
Treatment of oligometastatic NSCLC In cases of solitary histological proven adrenal metastasis, prolonged survival after resection of the adrenal and the primary tumor has been suggested in selected patients [II; B]. Solitary lesions in the contralateral lung should, in most cases, be considered as synchronous secondary primary tumors and treated, if possible, with surgery and adjuvant chemotherapy (if indicated), definitive radiotherapy or chemoradiotherapy [II;A]. ESMO Clinical Practice Guidelines, Peters, S. et al, Ann Oncol (2012)