A considerable amount of literature has been dedicated to oligometastasis, and the importance of LCT in this context has gradually been accepted [16,17,18,19,20,21]. However, various problems must be addressed before specific patients with oligometastatic NSCLC who are expected to benefit from LCT can be identified. Therefore, the present study used RPA to examine the effects and prognostic heterogeneity of LCT for oligometastatic NSCLC. Our results indicate that patients who smoked and had T3/4 oligometastatic NSCLC would not be expected to benefit from LCT. However, the EGFR status was the only molecular characteristic considered in this study. As 60 patients (13.8%) did not undergo the related test, we cannot definitively comment on the contributions of molecular features in this group of patients. Moreover, in clinical practice, patients with a history of smoking and a large lung tumor typically have squamous cell carcinoma or a tumor without driver gene mutations, which suggests the presence of an unknown molecular mechanism that should be examined in future studies.
As shown in Table 1, sex characteristics were slightly imbalanced between the two datasets (p = 0.045). However, after careful consideration, we chose to accept this slight imbalance for the following reasons: 1) the relevant factors that could be affected by gender, such as pathology, EGFR status, and smoking history, were completely balanced between the two groups; 2) gender was not a statistically significant factor in the Cox regression model; 3) we believed that the slight gender difference would be acceptable and the subsequent RPA model could be verified in the two datasets; and 4) we used simple randomization in this study, which is likely to lead to this type of issue.
At the 60th ASTRO annual meeting, Professor Gomez presented the final results of a phase 2 trial that compared LCT to standard maintenance treatment or observation alone for patients with oligometastatic NSCLC. During a median follow-up period of 38.8 months (range: 28.3–61.4 months), the median OS was significantly longer in the LCT group than in the control group (41.2 months [95% CI: 18.9 months–not reached] vs. 17.0 months [10.1–39.8 months]; p = 0.017) . Interestingly, in our study, patients in Group IV had a median OS of 11.1 months, similar to that in the control group. Conversely, Group I had a median OS (42.8 months) similar to that in the LCT group. These preliminary results support our main conclusion that patients in our Group IV (smokers with T3/4 disease) may not benefit from LCT.
The present study excluded patients with pleural, pericardial, and meningeal metastasis because these metastases could not be counted separately. Moreover, evidence suggests that pleural or meningeal metastases are disease entities with unique biological behaviors. For example, Zhong et al. reported that patients with intrathoracic disseminated pT4-M1a pleural metastases had a favorable prognosis . In addition, several studies have indicated that limited surgery might be a good choice for the pleural dissemination of lung cancer [20, 24, 25]. However, meningeal metastasis, and especially leptomeningeal metastasis, is a different disease entity with a poor prognosis. Few studies have investigated the comprehensive profile of meningeal metastasis, for which no treatment strategies have been established. Li et al. recently reported that leptomeningeal metastasis was much more common in patients with EGFR-mutant NSCLC, who responded relatively well to EGFR-TKIs . Therefore, we believe that our exclusion of patients with pleural, pericardial, and meningeal metastasis was reasonable.
The present study had two major limitations. First, a retrospective design is associated with a risk of selection bias. The selection of LCT for oligometastatic patients may have been an additional source of bias. Second, censoring the data may have confounded the results of our analyses. Moreover, we intended to base the RPA tree on the most obvious prognostic differences, which could have introduced some degree of ambiguity in the categorical variables. Nevertheless, we believe that our findings may enable clinical oncologists to better select LCT for patients with oligometastatic NSCLC. We have launched a phase II study to further explore the role of LCT for oligometastatic NSCLC after first-line systemic treatment; this study commenced in 2018 (Chinese Thoracic Oncology Group, CTONG 1602).