Elsevier

Lung Cancer

Volume 75, Issue 1, January 2012, Pages 9-14
Lung Cancer

Review
Metastatectomy for extra-cranial extra-adrenal non-small cell lung cancer solitary metastases: Systematic review and analysis of reported cases

https://doi.org/10.1016/j.lungcan.2011.07.014Get rights and content

Abstract

Back ground

Although patients with stage IV non-small cell lung cancer (NSCLC) have a poor prognosis, a subset of patients with solitary brain or adrenal metastasis have more favorable outcome following surgical resection. Nevertheless, the outcome and predictive factors for survival following metastatectomy for patients with other metastatic sites are not well defined.

Methods

We performed a systematic review using PUBMED database for all articles which included patients with NSCLC and solitary metastasis to sites other than the adrenal gland or the brain who had undergone resection of their metastasis and definitive treatment of the primary lung cancer. Potential prognostic factors on survival including age, sex, histology, T and N stage of the primary tumor, synchronous vs. metachronous presentation, visceral vs. non-visceral metastasis and the use of perioperative chemotherapy were analyzed using multi-variable Cox proportional hazard model.

Results

62 cases were eligible for the analysis. The 5-year survival rate was 50% for the entire cohort. Mediastinal lymph node involvement was independently predictive of inferior outcome; 5-year survival rate 0% vs. 64% in favor of no involvement, p < 0.001. Similarly, patients with intra-thoracic stage III disease had an inferior outcome compared to patients with stage II and stage I disease: 5-year survival rate 0% vs. 77% and 63%, respectively, p < 0.001. Other factors have no effect on outcome.

Conclusion

Selected patients with distant metastatic NSCLC can achieve long term survival following metastatectomy and definitive treatment of the primary tumor. Mediastinal lymph node involvement is associated with poor prognosis.

Introduction

Metastatic non-small cell lung cancer (NSCLC) is an incurable disease. Although platinum-based chemotherapy is considered the mainstay of treatment, as it was shown to improve survival without compromising quality of life [1], [2], the survival benefit is only modest with the median survival of around 8–11 months [2].

A growing body of literature suggests that selected patients with solitary brain or adrenal metastasis from NSCLC can achieve a long term survival following metastatectomy if the primary lung cancer is also resectable. In several series, 5-year survival rates of 15–35% had been reported after resection of solitary brain metastasis [3], [4], [5], [6], [7]. Likewise, other studies had shown that resection of isolated adrenal gland metastasis can result in long term survival (up to 26% at 5 years, and a median survival of 11–31 months) [8], [9], [10], [11].

In these reports, predictive factors of survival following resection of solitary metastases to the brain or adrenal gland from NSCLC primary have been identified [4], [5], [6], [7], [8], [9], [10]. The prognostic factors of interest commonly included mode of presentation (synchronous vs. metachronous), histology and T and N stage of the primary tumor. However, for patients with other distant metastatic sites, very limited data are available.

Although many case reports suggested that there is a chance for long term survival after metastatectomy in cases of solitary extra cranial, extra adrenal metastases from NSCLC, it is difficult to derive a conclusion about which particular subset of patients are likely to benefit from such surgical intervention. This manner of presentation is rare and available literatures are mostly in the form of case reports or descriptive case series containing small number of patients [12], [13]. Furthermore, it is extremely difficult to conduct a prospective clinical trial to compare the outcome of chemotherapy vs. metastatectomy in these cases given the rarity of such presentation and existing strong practice preference among various clinicians.

In this article, we review reported cases in the literatures to summarize the survival outcomes as reported in the literatures and to analyze factors that may predict better outcome after surgery.

Section snippets

Search strategy

We undertook a search on the PUBMED database and National Library of Medicine (NLM Gateway) for publications relevant to NSCLC with solitary metastasis to sites other than the brain or the adrenal gland. The articles were retrieved for review if they described both the metastatectomy and the definitive therapy of the primary lung cancer. To maximize the inclusion of eligible articles, we used the search term: metastasis, solitary or isolated, lung cancer, surgery or resection, and/or

Search result and study characteristics

On the basis of our inclusion criteria, 51 articles including 75 patients were initially identified. Of these 75 patients, 13 patients were excluded for the following reasons (one patient had two reasons for exclusion): no follow up data (6 patients), unclear definitive treatment for the primary tumor (5 patients), other metastatic sites could not be ruled out (2 patients, one with bilateral nonspecific lung nodules and another with possible adrenal metastasis on positron emission tomography

Discussion

In order to interpret the results from this review, it is important to first understand that, without therapy, the median survival time for metastatic NSCLC is 3–4 months and up to 8–11 months with systemic chemotherapy alone [1], [2]. Indeed, lung cancer remains the most common cancer world wide and the leading cause of cancer-related deaths among males and females [1]. The prognosis of NSCLC is poor because metastasis develops early, and most patients present as advanced stage with metastasis

Conclusion

Patients with stage IV NSCLC who present with an isolated extra-cranial, extra-adrenal metastatic lesion, who are candidates for complete resection, especially if they have stage I or II intra-thoracic tumor, should be offered metastatectomy after complete and meticulous staging of the mediastinum and other distant sites. Because of the limitations of our analysis, we recommend further studies including larger number of patients.

Conflict of interest

None declared.

Acknowledgements

We thank all of the following for their assistance: The staff of the Moffitt Cancer Center Medical Library, Alice Haddadine from the medical library of King Hussein Cancer Center, and Mohannad Al-Shobaki, MD, fellow of medical oncology at King Hussein Cancer Center. We are also grateful to Tokujiro Yano, MD, FACS and Giorgio Ercolani, MD, for providing us with data about their reported cases.

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