In this study, we retrospectively investigated the clinicopathological characteristics and postoperative prognosis of 210 patients with p-stage IA lung adenocarcinoma, according to the 8th edition of the AJCC/UICC TNM classification. Univariate and multivariate analyses confirmed that micropapillary/solid pattern was independent predictor of RFS in patients with p-stage IA IADC after complete resection of lung cancer.
So far, a number of studies have been conducted on the survival and prognosis of patients with lung adenocarcinoma based on the 2011 IASLC/ATS/ERS classification and the 2015 WHO classification of lung adenocarcinoma. Most of these studies have reached the same conclusion that lung adenocarcinoma with micropapillary and solid predominant subtypes have poorer prognosis than other common subtypes[12, 13]. However, few studies have confirmed the prognosis predictive value of pathological subtypes in p-stage IA lung adenocarcinoma. Previous studies on the postoperative prognosis of early stage lung adenocarcinoma mainly focused on stage I or IB. Hung et al reported the prognosis predictive value of micropapillary/solid patterns in lung adenocarcinoma with tumor diameter ≤ 3 cm and lymph node negative. However, the study also included visceral pleural invasion, which is a known risk factor for poor prognosis in stage I lung adenocarcinoma. What is more, some studies investigated the prognosis in patients with clinical stage IA lung cancer. These studies included patients diagnosed as clinical stage IA before surgery but found pleural invasion and even lymph node metastasis after resection, which may lead to the decline of RFS and OS rates. There is another special type of stage IA lung adenocarcinoma, that is MIA, which has a good prognosis as AIS. The inclusion of MIA may affect the outcome of prognostic analysis, especially for stage IA1.Therefore, this study excluded cases with pleural invasion, lymph node metastasis and MIA, focusing on patients with p-stage IA IADC.
This study showed that micropapillary/solid pattern was related to the RFS of patients with p-stage IA IADC. In both of the univariate and multivariate survival analyses, the differences were statistically significant (P < 0.05), meaning that micropapillary/solid pattern was an independent risk factor for poor prognosis of p-stage IA IADC. Stage IA lung adenocarcinomas without micropapillary/solid pattern had a better prognosis after complete resection. In terms of the univariate analysis for main pathological subtype, patients without micropapillary/solid pattern have higher RFS rate (P < 0.01), meaning the predominant pathological subtype of lung adenocarcinoma was associated with prognosis. However, there was no significant difference in multivariate analysis (P > 0.05). It may be due to the small proportion of patients with micropapillary/solid predominant subtype in this study, which affected our judgment on the prognosis predictive value of predominant pathological subtype. Further studies with larger sample sizes are still needed to verify the validity.
In addition to pathological subtypes, this study showed that, LVI was another prognostic factor (P < 0.05) in univariate Kaplan-Meier survival analysis of RFS. In a study of 306 patients, Samejima et al found that LVI was a prognostic factor for p-stage IA1-2 lung adenocarcinoma. Patients with LVI had worse 5-year OS and 5-year RFS rates than those without LVI in stage IA1-2 lung adenocarcinoma. However, LVI could not be used to predict the prognosis of p-stage IA3 lung adenocarcinoma, which may be related to the low proportion of patients with stage IA3 included in that study. Therefore, LVI may also be an important factor for the prognosis of early-stage lung cancer.
In the univariate analysis, T stage was also associated with the prognosis of p-stage IA lung adenocarcinoma in this study. Patients with p-stage T1b had a worse prognosis than those with stage T1a (P < 0.05). However, there was no significant difference in 5-year RFS rates between stage T1c and T1a (P > 0.05), probably due to the small number of patients in p-stage T1c and few of them relapsed in our study. Secondly, segmentectomy is allowed for some early-stage lung cancers ≤ 2 cm according to preoperative assessment. Moreover, lobectomy was generally selected for tumor > 2 cm which may also lead to this result of p-stage T1c. In the multivariate analysis, there was no statistically significant difference among the 5-year RFS rates of stage T1a, T1b and T1c (P > 0.05). We believe that stage T1c IADC is more invasive than T1a and T1b IADC, but the prognosis is affected by multiple factors. Pathological T stage may not be an independent risk factor for recurrence of completely resected p-stage IA lung adenocarcinoma, but it needs to be further verified by more studies.
According to current guidelines, adjuvant chemotherapy is not recommended for p-stage IA lung adenocarcinoma after complete resection. However, Wang et al found that postoperative adjuvant chemotherapy was a favorable prognostic factor for p-stage IA IADC with micropapillary predominant subtype. Patients with p-stage IA micropapillary predominant adenocarcinoma could benefit from postoperative adjuvant chemotherapy. The use of adjuvant chemotherapy in this study was depended on surgeon’s preference and experience. We seldom recommended patients with p-stage IA lung adenocarcinoma to perform adjuvant chemotherapy after surgery. Therefore, the sample size of this study was too small to evaluate the effect of adjuvant chemotherapy on early-stage lung adenocarcinoma. Multicenter clinical trials are needed to illuminate the value of postoperative adjuvant chemotherapy or immunotherapy for completely resected stage IA lung adenocarcinoma with high-risk factors.
In this study, the 5-year OS rate was 94.5% and the 5-year RFS rate was 93.1%, which were higher than the data reported previously. The possible reasons included: 1) the mean age of patients in this study was young; 2) the proportion of lepidic and acinar predominant subtypes were high, and the number of patients with micropapillary/solid predominant was small. As a result, the number of patients with postoperative recurrence was small in our study, which may affect the result. What is more, there are several other limitations in this study. Firstly, as a retrospective study, patient selection bias and potential selection bias between surgical procedures were inevitable. Secondly, only patients with p-stage IA IADC were selected as subjects and the overall prognosis of them was good. Therefore, prospective randomized control studies are needed to confirm these findings in the future.