Interact CardioVasc Thorac Surg 2009;8:467-473. doi:10.1510/icvts.2008.195776
© 2009 European Association of Cardio-Thoracic Surgery
Best evidence topic - Thoracic oncologic |
Does surgery for primary non-small cell lung cancer and cerebral metastasis have any impact on survival?
Amit Modi,
Hunaid A. Vohra and
David F. Weeden*
Department of Thoracic Surgery, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, UK
Received 4 October 2008;
received in revised form 9 December 2008;
accepted 26 December 2008
*Corresponding author. Tel.: +44 2380 777222; fax: +44 2380 798508.
E-mail address: david.weeden{at}suht.swest.nhs.uk (D.F. Weeden).
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Abstract
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A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was whether surgical resection of non-small cell lung cancer (NSCLC) with cerebral metastasis prolongs survival. Altogether 153 relevant papers were identified using the below mentioned search, 11 papers represented the best evidence to answer the question. The author, date, journal, country of publication, study type, patient group studied, relevant outcomes, results and study weaknesses were tabulated. A vast majority of patients with synchronous presentation underwent cerebral metastasectomy prior to lung resection which led to a rapid regression of neurological symptoms. In these studies, the median survival for the curative intent groups (bifocal therapy±adjuvant treatment) ranged from 19 to 27 months (mean 23.12±3.3 months) and at 1, 2 and 5 years from 56% to 69% (mean=63.9±5.6%), 28% to 54% (mean=38.7±11%) and 11% to 24% (mean=18±5.7%), respectively. In comparison, the median and 1-year survival of the palliative groups were 7.1–12.9 months (mean=10.3±2.9 months) and 33–39.7% (mean=35.3±3.8%), respectively. We conclude that in the absence of mediastinal lymph node involvement, surgical resection of NSCLC with complete resection of the brain metastasis improves prognosis. Further, adenocarcinoma, low CEA levels at presentation, response to preoperative chemotherapy before focal treatment and a high Karnofsky performance score (KPS) may have a positive prognostic value.
Key Words: Cerebral metastasis; Metastatectomy; Lung cancer; Evidence-based medicine
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1. Introduction
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A best evidence topic was constructed according to a structured protocol. This protocol is fully described in the ICVTS [1].
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2. Clinical scenario
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A 60-year-old gentleman is treated for a single cerebral metastasis with surgical resection and whole brain radiotherapy. Histology of the specimen shows complete excision with tumour-free margins and confirmed metastatic non-small cell lung cancer (NSCLC). CT-scan reveals a 2-cm intra-parenchymal spiculated mass in the upper lobe of the left lung and small (<1 cm) left hilar lymphadenopathy. There is no evidence of intra-thoracic and distant metastases. Positron-emission tomography (PET) demonstrated positive 2-fluoro-deoxyglucose (FDG) uptake in the lung mass only. The patient's Karnofsky performance score (KPS) was 100 and the lung function tests are favourable for anatomical resection. You are concerned whether a lobectomy will improve prognosis, despite complete removal of cerebral metastasis. Therefore, you resolve to search the literature to find the evidence.
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3. Three-part question
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In [patients with brain metastasis from NSCLC], does [surgical resection of lung cancer] improve [prognosis]?
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4. Search strategy
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Medline 1950–November 2008 using the OVID interface.
(exp lung cancer/ OR lung cancer.mp.) AND (exp brain neoplasms/ OR cerebral metastas$.mp.) AND (exp thoracic surgery/ OR exp thoracic surgical procedures/ OR lobectomy.mp. OR pneumonectomy.mp.)
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5. Search outcome
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A total of 153 relevant papers were found and from these, 11 papers were selected as representing the best evidence on this topic (Table 1).
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6. Comments
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No randomised or prospective studies were found. Eleven retrospective clinical studies involving 1035 patients were found. The studies looked at the outcome with different clinical situations involving treatment of primary lung cancer and cerebral metastases.
Bonnette et al. [2], in a retrospective multi-centre study involving 103 patients, who underwent combined resection of synchronous brain metastases from NSCLC, concluded that, at least in patients with adenocarcinoma subtype where the tumour is small and without enlarged intra-thoracic lymph nodes on CT-scan or mediastinoscopy, proceeding with lung resection after complete resection of a single brain metastasis improves survival. Survival was 56% at one year, 11% at five years and the median survival was 12.4 months. Getman et al. [3] studied 32 patients in two groups to compare the survival of patients with isolated synchronous and metachronous brain metastases from NSCLC and concluded that once isolated brain metastases from NSCLC have developed, there is no survival benefit after combined surgery. However, these patients underwent heterogeneous procedures administered in a non-randomised fashion. Penel et al. [4] assessed data of 249 patients diagnosed with lung cancer and synchronous brain metastasis and concluded that absence of adrenal metastases, neurosurgical resection, brain irradiation and chemotherapy improved survival. However, the study included patients with small cell lung cancer, extra-cranial metastases and the treatment groups were extremely heterogeneous. Mussi et al. [5] reported in a retrospective study involving 45 patients with NSCLC and solitary brain metastasis, a median survival of 18 months and 19 months for synchronous and metachronous groups, respectively. However, the 5-year survival in the synchronous group was 6.6% compared to 19% in the metachronous group. They concluded that combined lung and brain surgery, N0 status and type of lung surgery were the only variables associated with longer survival. In the study by Iwasaki et al. [6], the 70 patients with brain metastasis from NSCLC were grouped into lung resection–cerebral metastectomy group (Group I) and lung resection without cerebral metastatectomy group (Group II). Group I had a 3-year survival of 21.9% compared to 6.6% for the group II (P<0.034). Further, adenocarcinoma, N0 status and normal CEA levels at presentation were predictors of improved survival on multivariate analysis.
An excellent study by Girard et al. [7] involving 51 patients with resection of synchronous brain metastases from NSCLC, demonstrated that two-year survival in the curative intent group and the palliative intent group was 42% and 5%, respectively. They further report that KPS >70, adenocarcinoma type, surgical resection of primary and response to preoperative chemotherapy before focal treatment significantly prolonged survival. Despite complex treatment groups, the paper proposed simple treatment algorithms based on its conclusion. Wro ski et al. [8] performed a study comprising of 231 patients who underwent resection of brain metastases from NSCLC. Lung resection group had a median survival of 27 months vs. 11 months for the adjuvant treatment group. The study also included patients with extra-cranial metastases and reported that en-bloc resection of primary tumour, female sex, supra-tentorial metastases, absent extra-cranial metastases and age <60 years were associated with increased survival. Moazami et al. [9] evaluated 91 patients with stage III NSCLC and metachronous brain metastases. Stage IIIA, lung resection, no extra-cranial metastases and either metastasectomy or stereotactic radiosurgery predicted best survival. In 65 patients operated for both primary lung cancer and brain metastasis simultaneously, Furák et al. [10] showed that the 5-year survival was 23%. However, the study also included small cell lung cancer. The disease-free interval exhibited no significant impact on the survival rate, rather the complaint-free status exhibited a significantly greater impact on the survival. Billing et al. [11] performed an excellent retrospective study of 28 patients who underwent surgical resection with complete clearance of both synchronous brain metastases and primary NSCLC. The study group had a median survival of 24 months with 1, 2 and 5-year survival being 64.3%, 54% and 21.4%, respectively. They demonstrated that nodal disease was associated with poor prognosis on multivariate analysis. Abrahams et al. [12] in their study comprising of 70 patients with NSCLC and brain metastases report that with aggressive treatment, KPS of 100 and metachronous tumours are associated with significantly better survival.
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7. Clinical bottom line
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Multiple studies investigated a wide variety of clinical situations involving treatment of primary lung cancer and cerebral metastases to clarify the efficacy of treatment and evaluate factors affecting long-term patient survival. The presence of any intra-thoracic lymph node involvement (N1 or N2) significantly affects 5-year survival adversely. We conclude that in the absence of mediastinal lymph node involvement, surgical resection of NSCLC with complete resection of the brain metastases improves prognosis with a median survival from 10 months to approximately 23 months. Furthermore, adenocarcinoma subtype, low CEA levels at presentation, positive response to induction chemotherapy and a high KPS have a positive prognostic value.
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References
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Abstract
1. Introduction