What is the clinical benefit of resection of primary disease after complete resection of metastatic disease?

From Cancer Guidelines Wiki

Introduction

Improvements in both structural and metabolic imaging in recent years mean that once undetectable metastases may now be identified. This is a ‘double edged sword’. Whilst clinicians may be encouraged to pursue an aggressive approach on the basis that widespread metastasis have not been identified (despite PET, MRI and high resolution CT scan), a more pessimistic view is that it is only the high sensitivity of the imaging that has detected a metastasis whilst it is still solitary and that this in turn represents the ‘tip of an oncological iceberg’ that would in past years have been detected only when protruding from the water and at multiple sites.

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Case series: Resection of primary disease after complete resection of metastatic disease

Multiple case reports and retrospective case series have reported long term survival in highly selected patients with brain, adrenal, small bowel, spleen, lymph node, skeletal muscle, and bone metastases with 5 year survival ranging from approximately 5% – 30% after resection of both primary and metastatic sites.

A recent systemic review of publications reporting patients with isolated metastasis to sites other than brain or adrenal accumulated 62 patients undergoing complete resection of metastatic site after definitive treatment of primary. The study found a clinically and statistically significant difference on multivariate analysis in survival with a hazard ratio of 8.2 (95%CI:2.1–32.5),p=0.003, for involvement of mediastinal lymph nodes. [1]

The only published prospective phase II study was reported by Downey et al[2] and details the treatment of a heterogenous group of 23 patients between 1992 and 1997 at a single US centre with a solitary, synchronous, resectable metastasis (including brain, adrenal, bone, lung, spleen and colon), a T 1-3, N 0-2 NSCLC and good performance status and adequate cardio-respiratory reserve to allow lung resection. Treatment included induction chemotherapy with mitomycin, vinblastine and cisplatin, followed by restaging, resection of all sites of disease and adjuvant vinblastine and cisplatin. In the case of a brain metastasis it was resected prior to induction chemotherapy and whole brain irradiation administered at the discretion of the treating neurosurgeon.

The median survival for all patients entered into the study was 11 months. Actual five-year survival from time of thoracotomy was 8%.

The author concludes that induction chemotherapy; surgical resection of primary and metastatic sites; and adjuvant chemotherapy is so poorly tolerated and commonly associated with disease progression as to preclude its recommendation. Further, that retrospective series reporting superior survival epitomise selection bias with only those selected for and completing resection of both sites of disease finding their way into institutional databases subsequently searched to report retrospective experience. This fact is imperative to appreciate when counseling an individual patient with an isolated metastasis considering embarking on an aggressive approach with curative intent, as even the fittest patients screened and accepted onto a phase II protocol have a 4 – 8% chance of long term disease free survival.

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Evidence summary and recommendations

Evidence summary Level References
In patients with isolated metastasis to sites other than brain or adrenal and mediastinal nodal involvement complete resection of metastatic site after definitive treatment of primary does not result in cure.

Last reviewed December 2015

IV [1]


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In highly selected patients with T1-3 N0-1 lung cancers with good performance status, adequate pulmonary reserve and solitary site of metastasis, it may be reasonable to consider resection of primary and metastatic sites.
Last reviewed December 2015


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It is advisable to consider only those patients who would require less than pneumonectomy and with T 1-3, N0-1 NSCLC for resection of primary and metastatic sites.
Last reviewed December 2015

References

  1. 1.0 1.1 Salah S, Tanvetyanon T, Abbasi S. Metastatectomy for extra-cranial extra-adrenal non-small cell lung cancer solitary metastases: systematic review and analysis of reported cases. Lung Cancer 2012 Jan;75(1):9-14 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21864934.
  2. Downey RJ, Ng KK, Kris MG, Bains MS, Miller VA, Heelan R, et al. A phase II trial of chemotherapy and surgery for non-small cell lung cancer patients with a synchronous solitary metastasis. Lung Cancer 2002 Nov;38(2):193-7 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/12399132.

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Appendices

Further resources

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