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