Endobronchial metastases from renal cell carcinoma: A late manifestation of the disease with an increasing incidence
Article first published online: 3 SEP 2012
© 2012 BJU INTERNATIONAL
Volume 110, Issue 10, pages 1407–1408, November 2012
How to Cite
Khattak, M. A., Fisher, R. A., Pickering, L. M., Gore, M. E. and Larkin, J. M. (2012), Endobronchial metastases from renal cell carcinoma: A late manifestation of the disease with an increasing incidence. BJU International, 110: 1407–1408. doi: 10.1111/j.1464-410X.2012.11442.x
- Issue published online: 29 OCT 2012
- Article first published online: 3 SEP 2012
- Accepted for publication 20 June 2012
mammalian target of rapamycin
vascular endothelial growth factor.
Endobronchial metastases (EBM) from non-pulmonary solid tumours are uncommon, occurring in only 2–5% of patients [1–3]. RCC is amongst the most common tumours (besides breast and colorectal cancer) to metastasise to the lungs [1,3,4] and there are individual case reports of EBM from advanced RCC [5–7]. Our anecdotal experience over the last 5 years is that EBM from RCC are not rare in patients undergoing systemic therapy in the second and subsequent line setting. Furthermore, EBM present a highly challenging clinical problem; they typically remain undiagnosed until the patient develops symptoms related to mechanical obstruction of the airways. The development of infective and bleeding complications from EBM can significantly add to the patient symptom burden, in what is now a relatively chronic disease .
Thus, we undertook a retrospective review of the electronic records of patients treated at the Royal Marsden Hospital with everolimus for advanced RCC between May 2009 and December 2011. The mammalian target of rapamycin (mTOR) inhibitor, everolimus is a standard systemic therapy after failure of anti-vascular endothelial growth factor (anti-VEGF) treatments . In all, 64 patients were identified and most of them received two or more lines of systemic therapy: one line of systemic therapy eight (12.5%), two lines of systemic therapy 39 (61%) and three or more lines of systemic therapy 17 (27.5%). Of these 64 patients, six (9%) with histologically confirmed EBM from RCC were identified. Their clinical characteristics are summarised below.
The patient cohort comprised four men and two women, ranging in age between 53 and 65 years. Everolimus was second-line therapy in four patients, first-line clinical trial therapy in one patient, and third-line therapy in one patient. Five of the six patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 2 at the time of diagnosis of EBM and one patient had a performance status of 3. All patients had multiple sites of metastatic disease, with a combination of liver, brain, bone, adrenal or nodal disease. At the time of diagnosis of EBM, the overall tumour burden was stable according to RECIST criteria in four patients and was progressing in the remaining two patients. Five patients had clear cell histology, ranging from grade 2 to 4 and primary tumour stage T2 to T3, and the primary tumour pathology was unknown in one patient. The median time from onset of metastatic disease to diagnosis of EBM was 26.6 months. All patients presented with at least one symptom of bronchial obstruction, including dyspnoea, lower respiratory tract infection, haemoptysis and chest pain and were investigated with bronchoscopy. Four patients underwent debulking therapy at the time of bronchoscopy with symptomatic relief; three of these patients also had metallic stents inserted. An additional patient had a metallic stent inserted without debulking therapy. Of the five patients who received bronchoscopic intervention, two required subsequent bronchoscopy due to symptomatic deterioration, one at 3 weeks and one at 4 months after the initial bronchoscopic procedure. The time from initial bronchoscopy to death ranged from 1 to 13.3 months. The sixth patient was treated with radiotherapy (40 Gy in five fractions to the right chest and mediastinum) with initial clinical improvement but suffered disease progression and death 10 months later. The median survival time from diagnosis of EBM to death was 5.8 months. No patient was offered further systemic therapy after the diagnosis of EBM.
EBM is clearly a difficult clinical problem. In this single-centre experience, EBM was a late diagnosis as part of multisite disease and was associated with poor survival. All patients in this small retrospective series underwent local treatment, either with Nd : YAG laser, endoluminal stent insertion, debulking or palliative radiotherapy. Although this resulted in symptomatic improvement in all, the duration of clinical benefit was in general short. There were no obvious clinicopathological variables that predicted for the development of EBM.
The management of EBM in the context of metastatic RCC remains unstandardised. However, the management approach for EBM in general is determined by characteristics of the primary tumour, the anatomical location of lesions, evidence of other metastatic sites and performance status . Interventional bronchoscopy with laser resection and/or stent placement has been established as a palliative treatment for malignant obstructive trancheobronchial disease [10,11]. It is possible that improved palliation could be achieved by earlier diagnosis of EBM, by adequate debulking of relatively low volume EBM followed by stenting. If this is the case, clinicians must be alert to the early warning signs of bronchial obstruction, noting that in practice this is difficult because symptoms related to treatment toxicity, such as everolimus-induced pneumonitis, may overlap with those of EBM.
Although systemic therapy appeared to impact little upon the clinical outcomes seen in this series, delaying the onset of EBM is preferable to attempting to palliate a mechanical obstruction once established. Achieving this aim requires further improvements in the systemic management of metastatic RCC, to delay the development of resistant disease. Most importantly, clinical trials which include routine assessment of tumour tissue, including metastatic sites, at important time points may identify molecular markers predictive of resistance to therapy, and may also distinguish those cohorts of patients at risk of developing particular complications such as EBM. In the meantime, oncologists faced with this very difficult clinical problem require careful guidance from a multidisciplinary team, which includes a respiratory physician, in the management of the individual patient. Our experience in RCC in the targeted era of treatment shows that EBM is not rare, with an incidence of ≈10%. This is in contrast to the incidence reported in older literature, and may reflect the fact that patients treated with anti-VEGF and mTOR treatments have a significantly improved life expectancy compared with historical cohorts.
CONFLICT OF INTEREST
Consultant or advisory role: James M. Larkin, Pfizer, Bayer, GlaxoSmithKline, Novartis; Lisa M. Pickering, Pfizer, Novartis; Martin E. Gore, Pfizer, Bayer, GlaxoSmithKline, Novartis, Roche.
Stock ownership: None.
Honoraria: James M. Larkin, Pfizer, Bayer, GlaxoSmithKline, Novartis; Lisa M. Pickering, Pfizer, Novartis, GlaxoSmithKline; Martin E. Gore, Pfizer, Bayer, GlaxoSmithKline, Novartis, Roche.
Research funding: James M. Larkin, Pfizer, Bayer, Novartis; Lisa M. Pickering, Pfizer.