Lobectomy is the standard of care in resectable lung cancer and appears to offer the best chance of cure in early, nonmetastasized disease. However, the presence of comorbidities can put a significant number of patients into a surgically high-risk or medically inoperable status, requiring alternative methods of treatment.
For surgically high-risk patients, sublobar (segmental or wedge) resection instead of lobectomy has become standard, with recent studies reporting 2- and 5-year survival rates of 90% and 83%, respectively. For medically inoperable patients, conventional radiotherapy has been used as an alternative, but has led to disappointing 5-year survival rates ranging from 10% to 30% (J. Thorac. Cardiovasc. Surg. 2007;134:857-67).
More recently, stereotactic body radiation therapy (SBRT) and radiofrequency ablation (RFA) have been offered as alternatives for medically inoperable and even for high-risk surgical patients, based on early, encouraging results.
Dr. Arjun Pennathur of the University of Pittsburgh and his colleagues are among a growing group of researchers who are demonstrating the benefits of RFA and SBRT as either a curative approach for early-stage non–small cell lung cancer (NSCLC) or as a palliative approach to more advanced lung neoplasms. Dr. Pennathur’s group reported SBRT survival rates at 1 and 5 years of 81% and 60%, respectively. Other researchers reported SBRT 1-year survival rates of 90%-95%, with 2-year survival of 60%-75%, and 5-year survival of 20%-65%.
For RFA treatment, Dr. Pennathur reported 1-year survival of stage I NSCLC patients at 95% and 2-year survival at 68%, as noted in an article by Dr. Hiran C. Fernando and colleagues from Boston University (Ann. Thorac. Surg. 2010;89:S2123-7).
Recently reported results by Dr. Lijun Huang and colleagues for patients treated with RFA have shown 1-, 2-, 5-year survival rates of 80.1%, 45.8%, and 24.3% for patients with NSCLC and 50.6%, 30.1%, and 17.3%, respectively, for patients with a pulmonary metastasis tumor (Eur. J. Cardio-Thorac. Surg. 2010 July 20 [doi:10.1016/j.ejcts.2010.06.004]).
Dr. Huang of the Fourth Military Medical University in Xi’an, China, found that progression-free survival was directly related to tumor size. Local progression occurred in 27% of patients with tumors measuring less than 3 cm and in 27.5% of patients with tumors of 3-4 cm, a nonsignificant difference. However, 42% of patients with tumors larger than 4 cm had a local recurrence, which was a significant difference. Based upon their findings, they recommended that RFA not be used in patients with tumors larger than 4 cm.
Tumor size was also seen as a significant factor in prognosis by Dr. Pennathur’s group (Ann. Thorac. Surg. 2009;87:1030-9).
With nonoperative techniques, it is always a question as to whether recurrence was truly recurrence. “It must be acknowledged that local tumor progression seen in this series most likely represents incomplete tumor treatment,” stated Dr. Huang and colleagues.
This is a good example of how nonoperative techniques, despite their benefits, have the inherent risk of not treating the complete tumor and can miss occult nodal disease (which has been determined to have around a 7% incidence even with peripheral tumors of 1 cm or smaller). This leads to undertreatment, according to Dr. Hiran C. Fernando and colleagues from the University of Pittsburgh, who object to current trends to recommend SBRT for high-risk (but not surgically inoperable) patients and even for patients considered eligible for lobectomy (Ann. Thorac. Surg. 2010;89:S2123-7). “Nonoperative therapies such as RFA and SBRT should be reserved for medically inoperable patients,” they stated.
Compared with surgical approaches, there are other considerations with both SBRT and RFA. Both approaches leave a scar that can interfere with future imaging assessment, making serial imaging and long-term follow-up a requisite to differentiate scar from recurring tumor. For SBRT, “the optimal method of delivery has not been determined with respect to the system used, the dose, and the fractionation schedule,” according to Dr. Fernando and his colleagues, thereby making comparisons and determination of optimal treatment difficult.
There are other differences between an operative and nonoperative approach that may be even more important in the future, as tailored cancer therapies become more available. Sublobar resection, compared with SBRT or RFA, provides adequate tissue for molecular profiling and for chemoresistance and sensitivity testing of tumors, all of which may be helpful in directing adjuvant chemotherapy if indicated, Dr. Fernando said.
In addition, the results of sublobar resection can be greatly improved by close attention to the surgical margin and lymph node assessment, taking advantage of the benefits of adjuvant brachytherapy to improve the surgical margins. “With these approaches, local recurrence can be reduced from the 17.2% reported in [an earlier] lung cancer group study to 5% or less,” according to Dr. Fernando.