Further Thoughts on a Rare Entity
Further Thoughts on a Rare Entity
Although relatively uncommon, carcinoid tumors of the lung seem to be discussed at thoracic tumor board conferences more frequently than their incidence would suggest, likely reflecting the uncertainty many feel when faced with managing patients with this rare entity.
In this issue of ONCOLOGY, Drs. Mackley and Videtic have written a concise and thoughtful review categorizing these lesions, presenting aspects of natural history, and describing treatment approaches, with a focus on the role of radiotherapy (RT).
Distinct Pathologic Entities
The importance of correctly classifying these lesions into one of the four distinct pathologic entities can not be overemphasized, given the profound differences in behavior, and thus, management and prognosis.
It is estimated that 170,000 cases of lung cancer will be diagnosed in the United States in 2006, and of these, approximately 15% will be the small-cell type. Primary carcinoids of the lung make up about 2%, 10% of which are classified as atypical. The incidence of large-cell neuroendocrine carcinoma (LCNECs) is estimated at 3%, or 5,000 cases.
We agree that surgery remains the standard of care for primary pulmonary carcinoid. Emerging evidence suggests, however, that initial bronchoscopic therapy (BT) and close surveillance is a potential alternative to surgical resection for selected patients.
Dr. T.G. Sutedja (personal communication) has a series of 67 patients-52 typical carcinoids (TCs) and 15 atypical carcinoids (ACs)-treated in this fashion, now with long-term follow-up. Fifty percent were spared resection, including 5 of the patients with AC. Further, in those who ultimately required resection following BT, a delay of even up to 10 years did not lead to either more extensive resection or worse outcome. Only one patient (1.5%), who initially presented with metastatic AC, died of metastatic disease. Luckratz et al came to a similar conclusion in his series of 28 patients published earlier this year. Such studies suggest that BT with close surveillance is an underrecognized, tissue-sparing alternative management option.
Role of Radiotherapy
Given that radiotherapy is a local modality, understanding the patterns of failure is critical in determining whether there is in fact a potential benefit for radiotherapy in this spectrum of disease. Considering the rarity of carcinoid tumors, we are unlikely to ever have prospective randomized data. Estimates of local failure in TC in a number of series following resections have consistently been reported in the single digits, and we agree with Drs. Mackley and Videtic that there is no support in the literature for adjuvant RT in TC, even in those rare instances when N1 or N2 disease is documented. Indeed, this is the same conclusion reached in a previously published review coauthored by one of us.
The documented higher risk of locoregional recurrence, as well as the perception that higher-grade tumors are more sensitive to fractionated radiotherapy, suggests that there may be a benefit for adjuvant RT in AC with pathologic N2 disease. It is reasonable to treat LCNEC patients as one would other non-small-cell histologies, ie, stage I and II disease with resection and stage III with combined chemotherapy and radiation therapy, perhaps followed by resection. Completely resected patients with pathologically confirmed N2 disease should be considered for chemotherapy followed by mediastinal RT. Finally, patients with positive surgical margins and no evidence of distant disease are candidates for radiation therapy.