By Ramsey Hachem, M.D.
Washington University School of Medicine Barnes-Jewish Hospital
Division of Pulmonary and Critical Care
May, 2009
In general, lung cancer has been widely regarded as an absolute contraindication to lung transplantation because of the unacceptable risk of recurrence after transplantation. However, bronchioloalveolar carcinoma (BAC), an uncommon type of lung cancer, has been the indication for transplantation in rare cases. Smoking is clearly an important risk factor for the development of BAC, but up to one third of patients with BAC never smoked. In addition, while the majority of patients with lung cancer are male, the gender distribution among patients with BAC is even. The clinical presentation of BAC is variable. Some cases present as a solitary pulmonary nodule, detected on a routine chest x-ray in the absence of symptoms. On the other hand, some cases present with cough, often productive of a large amount of thin sputum, shortness of breath, or fever, and the presence of respiratory symptoms usually reflects the extent of the disease. The radiographic presentation in these cases can mimic that of pneumonia, and the diagnosis of BAC is typically not considered until the symptoms or radiographic findings fail to resolve with appropriate antibiotics. Ultimately, the diagnosis is made with a biopsy procedure.
As in all cancers, the prognosis is directly related to the stage of disease. However, the prognosis for BAC is significantly better than other types of lung cancer at comparable stages, and surgical resection is the treatment of choice for patients with early stage disease. This is especially true when the cancer is limited to a small solitary pulmonary nodule. However, multifocal BAC is usually not amenable to surgical resection. Chemotherapy, alone or in combination with radiation therapy, is the treatment modality in such cases. In rare cases, the response to certain chemotherapy can be striking, but the prognosis for multifocal disease is typically poor. In addition, tumor progression results in worsening and disabling symptoms that may result in respiratory failure and death. Therefore, the option of transplantation was suggested as a possible treatment in the mid 1990s. Initially, it was hoped that complete pulmonary resection and transplantation might be curative in carefully selected patients who had no extra-pulmonary involvement.
Over the past 15 years, the number of transplants performed for BAC has been quite small for a number of reasons. First, BAC is a rare type of lung cancer, accounting for less than 5% of all cancers. In addition, those that have focal disease can be treated with surgical resection alone, while those with multifocal disease may have thoracic lymph node involvement or distant metastases that preclude transplantation. Lastly, there is considerable concern of recurrence after transplantation even among carefully selected patients with no obvious nodal disease or metastases. In 2004, the transplant program at the University of Toronto surveyed 67 lung transplant programs worldwide regarding their experiences with transplantation for BAC (1). Twenty-six patients with multifocal BAC underwent transplantation and were reported; among these, 4 died in the early post-operative period and 13 of the remaining 22 developed recurrent BAC an average of 1 year after the transplant. Nine of the 13 patients who had recurrent BAC died an average 22 months after the transplant, and the overall 5-year survival for the 26 patients was 39% (1). Other single-center reports have demonstrated similar findings.
There is a clear survival difference after transplantation between those transplanted for BAC and those transplanted for other indications. In addition, recurrent BAC is the most common cause of death and the main limitation to better long-term outcomes. Therefore, many centers have considered BAC as a contraindication to transplantation. Nonetheless, while the incidence of recurrence is high and the long-term survival is worse than for other indications, some programs have considered transplantation a palliative treatment for BAC and point out that some patients have had extended survival without recurrence after transplantation. Obviously, this remains controversial, but a better understanding of the cancer biology of BAC may identify those patients who are likely to benefit the most from transplantation.
Reference:
1. de Perrot M, Chernenko S, Waddell TK, et al. Role of lung transplantation in the treatment of bronchogenic carcinoma for patients with end-stage pulmonary disease. J Clin Oncol 2004; 22: 4351-6.