Surgery is the treatment of choice for selected patients with pulmonary metastases. In particular, patients who have a single metastases, prolonged disease free interval (>36 months), complete control of the primary tumor and no evidence of extrathoracic disease are good candidates for resection and surgery offers good results in these patients with metastatic disease (1
). In the medically inoperable or unresectable patients with pulmonary metastases, there are few effective options. Many of these patients, for instance patients with inoperable colorectal metastases are treated with chemotherapy and the long term survival is not encouraging (5
). RFA may offer an alternative in these patients.
The International Registry for lung metastases (IRLM) reported the results in 5206 patients, of which 4572 had complete resection (1
). The estimated 5 year survival after complete resection was 36% and the median survival was 35 months. In multivariate analysis, disease-free interval of more than 36 months, single metastases and germ cell primary were independent predictors of better outcome. Recurrences occurred in 53% of patients and the median time to recurrence was 10 months. Complete resection of all lesions was an important prognostic factor. When the metastases were resectable and when all factors were favorable the median survival was 61 months; when they were unresectable, the median survival was 14 months with an estimated 5 year overall survival of 5%.
Potential role of Radiofrequency Ablation in Pulmonary Metastases
With complete resection being an important predictor of outcome, RFA may be utilized in combination with surgical resection as a parenchymal-sparing approach or in lesions which are not resectable. In the current series, five patients had RFA as an adjunct to surgical resection as a parenchymal-sparing procedure. This may be applicable in patients who have peripheral lesions which can be resected; more central lesions can be treated with RFA during a thoracotomy with care taken to be away from the bronchus and pulmonary vessels. This use of RFA as an adjunct may be helpful in avoiding a lobectomy in some instances and may serve as a parenchymal-sparing procedure.
Further, the IRLM study showed that recurrences occurred in 53% of patients, and the median time to recurrence was 10 months. Many of these recurrences present in the ipsilateral chest even after open thoracotomy. The morbidity of a redo thoracotomy is higher and about 60% of patients may re-present with recurrent disease even after a redo thoracotomy (14
). RFA in particular under CT-guidance may offer an alternative in some of these patients particularly as a parenchymal-sparing procedure.
Rolle and colleagues also demonstrated the importance of complete resection in using the 1318 nm Nd: YAG laser (2
). The 5 year overall survival after complete resection was 40% and 7% after incomplete resection. The overall survival after complete resection of single, 10 or more, and more than 20 resected metastases was 55%, 28% and 26% respectively. These authors stressed the importance of complete resection even when multiple lesions were present as a very important determinant of survival. The recurrence rate was 60% and the median time to recurrence was 9 months. Among local pulmonary recurrences, only 32% underwent redo surgery.
Radiofrequency ablation may play a role in the treatment of re-recurrent metastases when the risks of redo surgery are high. Further redo-resection is associated with a high re-recurrence rate and may point to a more aggressive behavior of the primary tumor (14
). In these circumstances, RFA may be a reasonable choice particularly in patients who have had one or more previous resections to avoid the morbidity of redo thoracotomy. In this series about a third of patients had a previous resection, and RFA was used to treat re-recurrences.
Prognostic Factors associated with survival after treatment with RFA
In addition to complete resection other prognostic factors have been examined after surgical resection of pulmonary metastases (3
). Pfannschmidt and colleagues reported the results in 167 patients who underwent resection for colorectal metastases (3
). These investigators reported that single vs. multiple lesions, and lymph node involvement were among the significant factors, while disease free interval,, resection of hepatic metastases, age, and sex were not significant factors.
In the current study, we examined the prognostic factors associated with survival and progression. Size was a significant predictor of both overall survival and disease free survival. The median overall survival was 39.1 months when the lesion size was less than 3 cm vs. 7.9 months when the lesion was more than more than 3 cm. We did not find a significant association for covariates such as cell type of primary, disease-free interval, site of first metastases, and single vs. multiple lesions, and survival; however this may be a limitation of a small group of patients.
In summary, with a mean follow-up of 27 months, the median overall survival was 29.4 months with an estimated two year overall survival rate is 68%, and the median time to progression was 5.8 months. These results while not equivalent to the reported results of complete surgical resection are better than reported results when the metastases are not completely resectable. Further, in this series several patients had failed other therapies prior to RFA, including previous surgical resection. Thus this group of patients treated may represent a group with biologically more aggressive tumors.
Other investigators have reported the results of RFA in the treatment of primary and metastatic lung tumors (5
). Recently Yan and colleagues reported the results of RFA for the treatment of pulmonary metastases in 55 patients with colorectal neoplasm (5
). The median follow-up in this series was 24 months. The median survival in these patients was 33 months and the estimated 2 year survival was 64%. On multivariate analysis the only factor which was associated with survival and overall progression was size (>3 cm). Interestingly, we also found that the size of the largest lesion was a significant factor in both overall and PFS in patients treated with RFA.
Strengths and Limitations
This study has its strengths and limitations. One of the novel aspects of this study which is applicable to thoracic surgeons is the combination of surgical resection in conjunction with RFA as a parenchymal-sparing procedure. There is minimal data in the literature where the intermediate term results of a combination of RFA in conjunction with surgical resection have been presented. In addition, this study represents one of the longest follow-up period (mean 27 months) reported in the literature on RFA for the treatment of pulmonary metastases. Further, we have evaluated prognostic variables which are associated with progression and survival with size of the lesion being significantly associated. This information may lead to better patient selection and prospective studies with development of protocols for larger lesions such as RFA with stereotactic radiosurgery and/or adjuvant therapy in these patients.
The current study however has the limitations which are inherent to retrospective studies, such as selection bias. The patients treated in this study comprise a very heterogeneous group, encompassing patients with different primary tumors who had metastatic disease. Finally, longer follow-up is required for greater maturity of time-to-event data. There are several factors which merit further investigation. These include optimal patient selection, and the role of combination therapy or adjuvant therapy.
Our experience indicates RFA is safe in this group of patients with pulmonary metastases with reasonable results. Surgery remains the standard for resectable patients, but RFA offers an alternative option in selected patients with pulmonary metastases or may be used as a parenchymal-sparing approach in combination with surgical resection in selected patients. Thoracic surgeons should continue to evaluate new technology and add these techniques to their armamentarium in the treatment of lung neoplasm. Prospective studies are necessary, and are ongoing at our institution and others, to define the role of RFA in the treatment of metastatic lung neoplasm.