While lobectomy or pneumonectomy may be the surgical treatment of choice for most NSCLC tumors in younger, fit patients, a limited resection may be an ideal choice in certain settings. In my previous post I discussed the data supporting a limited resection in older patients, who are likely to have competing health risks that may make it less critical to pursue the most aggressive surgical strategy. Another situation in which a sub-lobar resection may be particularly appealing is when the tumor is quite small and/or has characteristics suggestive of an indolent natural history. In such cases, a lobectomy may be more surgery than is required. There are trials now asking the question of whether patients with the most favorable features based on size or histology (microscopic characteristics) may do as well or better with limited resections than the standard lobectomy or pneumonectomy.
One of the first issues is in identifying the right population for which special management should be considered. Stage IA is defined as a tumor less than 3 cm that does not involve the pleura (the lining around the lung) and is not too close to important structures in the middle of the chest, and this is the stage with the best prognosis after treatment of NSCLC. However, even within that group, several recent studies have shown that survival is particularly favorable for patients with tumors that are 2 cm or smaller. For example, Gajra and colleagues from Syracuse (abstract here) found that among their 246 consecutive patients with stage IA NSCLC tumors, survival was significantly better for those with tumors of 1.5 cm or less vs. those with larger tumors of 1.6 - 3.0 cm (5 year overall survival 85.5% vs. 78.6%, respectively). Very similar results were demonstrated in a series from NYC by Port and colleagues (abstract here), who analyzed results from 244 patients with stage IA NSCLC and found that the 5-year overall survival was 77% for those with tumors 2 cm or less, compared with 60% for those with larger tumors from 2.1 to 3.0 cm. Additional work from the group in NYC (abstract here) also showed that patients with tumors 2 cm or smaller had involvement of hilar lymph nodes half as often as the patients with larger stage IA tumors.
One study from more than a decade ago, by Warren and colleagues (abstract here), showed that the five-year survival of patients with tumors 2 cm or less were not significantly different if they underwent a segmentectomy compared to a lobectomy. However, it has been primarily more recently work that has established some momentum for sublobar resections in smaller tumors, especially work out of Japan, where the focus has been on small tumors with bronchioloalveolar carcinoma (BAC) histology.
Bronchioloalveolar carcinoma (BAC) tumors have been particularly identified as potentially demonstrating an indolent natural history and favorable survival, as I indicated in a previous post. In a retrospective review from Massachusetts General Hospital, the investigators compared survival among 33 patients with stage I BAC tumors to the survival of 105 other patients with stage I non-BAC adenocarcinomas (abstract here). They reported that the 5-year survival was 20% higher in the BAC patients:
Much of the leading work on sublobar resections in BAC has emerged out of Japan, where BAC is especially common. Such studies have demonstrated that peripheral (toward the outer edges of the lung) adenocarcinomas less than 2 cm have relatively low rates of lymph node involvement, especially BAC (abstract here). Several recent small prospective trials out of Japan (abstracts here and here) have performed limited resection on small BAC tumors and seen no evidence of recurrences and 100% survival in the first 2-3 years of follow-up. Other, larger trials directly comparing sub-lobar resection to lobectomy are currently being conducted in Japan.
In the US, the Cancer and Leukemia Group B (CALGB) is running a propsective phase III trial randomizing patients with small (2 cm or less in diameter), peripheral NSCLC tumors to lobectomy vs. wedge resection or segmentectomy. Patients will undergo a mediastinoscopy to confirm no evidence of involvement of any accessible lymph nodes and will then be randomized intra-operatively to one type of surgery or the other (so before going to the operating room, people will need to know they could receive either type of surgery). Other cancer cooperative groups are joining this important trial, so it will be running throughout North America, and it will plan to accrue up to nearly 1300 patients, looking for significant differences in the rate of NSCLC recurrence by the type of surgery performed. The trial, led by Dr. Nasser Altorki from NYU, is known by the rather un-catchy name "CALGB 140503" and should become widely available soon.
Until then, the more extensive lobectomy or pneumonectomy surgeries remain the standard of care, but the study from CALGB and work emerging from Japan may lead us to refine that position.