Colorectal cancer is still one of the leading causes of cancer-related death globally. For decades, although the wide application of early screening and the innovation of diagnosis and therapies have made it possible for patients with CRC in early stage to receive proper and effective treatment, how to improve the survival of patients with advanced CRC remains a problem. This study aimed to collect clinical data generated in our clinical routines in the “real world” setting as much as possible and assessed whether local treatments for lung metastases could improve survival of CRC-PM patient.
Patients with CRC-PM who were submitted to local treatments combined with chemotherapy or chemotherapy alone for pulmonary metastases were included in our study. Our data showed that the 3-year overall survival rate of 119 patients was 51.2%, and the 5-year overall survival rate was 39.7%, which was consistent with the previous literature. Previous studies had mostly focused on the patients undergoing resection of the lung metastases and patients who did not receive lung metastasectomy were excluded. Although the clinical factors analyzed in each study were different, the roles of some predictors had been confirmed in many studies[9–12], including: the distribution and size of lung metastases, the status of pulmonary lymph nodes, the CEA level of lung lesions before surgery, and the existence of liver metastases, etc. [10, 11, 13–17]. Tomohiko et al retrospectively investigated 1030 patients who underwent resection of colorectal cancer with lung metastasis, they found that more than one lung metastases, maximum tumor diameter of 2 cm or more suggested that patients with CRC-PM a poor prognosis. Maniwa et al also pointed out that patients with 5 or more lung metastases had a poor prognosis, while unilateral or bilateral distribution and the size of metastases were not related to the survival of patients. However, heterogeneity of tumor sizes in multiple CRC-PM was an independent factor of the prognosis of the patients. The association of survival and other factors, like age, gender, ASA score, primary tumor staging, tumor-free interval was controversial in different studies[14, 20–23]. In the present study, univariate analysis indicated that the overall survival of CRC-PM patients with bilateral metastasis was lower than that of patients with unilateral lung metastasis, but there was no statistical difference in multivariate analysis. Our data showed that the distribution, size, and number of lung metastases were not independent factors for the prognosis of patients. As a kind of systemic disease, advanced colorectal cancer might not be represented by the characteristics of local lesions.
The liver is the most common site of distant metastasis of colorectal cancer. Hepatic metastasis must be considered when assessing the prognosis of patients with lung metastasis. Several reports supported that patients with CRC-PM, who had previously received radical surgical resection or other local interventions for liver metastasis, had an overall survival rate comparable to that of patients with sole lung metastases after lung metastasectomy[16, 24, 25]. A meta-analysis of 2,925 patients with colorectal cancer who underwent radical lung metastasectomy concluded that the history of liver metastases was not related to survival of CRC-PM patients . Our result also supported that the history of curable liver metastases had no effect on the prognosis of patients with lung metastases.
The 5-year overall survival rate of patients who received lung metastasis resection is 25–50% [11, 25, 27]. However, patients who submitted to local intervention on lung metastases had better clinical features than those who did not, like single lung metastases, unilateral pulmonary metastases, etc. Therefore, it is believed that selection bias might exaggerate the benefit of local treatments[28, 29]. In addition to surgical resection of lung metastases, treatment of lung lesions includes laser-induced hyperthermia, radiofrequency ablation, microwave ablation, and targeted radiotherapy. Although the effects of these therapies are not widely accepted, some researchers believe that they are valuable treatments providing good local control and could be efficient treatments for lung metastases[30, 31].
The role of pulmonary metastasectomy was investigated by comparing the clinical outcomes of patients with CRC-PM who received surgical resection of pulmonary metastases and who did not. Chang et al analyzed the prognostic factors of 105 patients with CRC-PM, although there were differences in baseline characteristics between patients who underwent pulmonary resection and who were given just chemotherapy and/or best supportive care, multivariate analysis showed that the prognosis was poor for those who did not undergo surgery. Meimarakis et al evaluated the prognostic factors of 171 CRC-PM patients who underwent resection for lung metastasis, and compared them with patients receiving standard chemotherapy from FIRE-1 study by matched-pair analysis. The results showed that the prognosis of the surgery group was better than that of the standard chemotherapy group .
In the present study, we tried to reduce the effects of bias on baseline characteristics between Group-LI and Group-Chem by propensity matching score analyses. Our results showed that the patients in the local intervention group had a better prognosis than the chemotherapy-only group, suggesting that although advanced colorectal cancer should be treated as systemic diseases, local intervention of the metastases may good for controlling tumors and improving the survival of patients. For these selected patients, aggressive intervention could improve the 3-years OS and PFS.
There were some limitations in our research. Firstly, molecular markers related to the prognosis of patients were not included in retrospective analysis because they were not routinely tested until the last few years. Secondly, the impact of mediastinal and hilar lymph node metastases was not discussed because it had not been adopted as a routinely procedure during surgical resection of lung metastases in our center. Furthermore, there could be selection bias due to small sample of patients from two institutions. Nevertheless, our research provides evidence suggesting that local treatments of pulmonary metastases could improve survival of CRC-PM patients.
A randomized controlled study carrying out in Europe called PulMiCC trial, which explores whether local treatment benefit survival of CRC-PM, by comparing the overall survival of patients who receive either surgery or continued active monitoring. This experiment is expected to provide strong evidence for resection of lung metastases.