In the present study, moderate CKD was present in 3.6% of newly diagnosed lung cancer patients. A previous cohort study conducted in Taiwan reported an incidence of 1.7% for lung cancer coexisting with CKD . However, the previous study defined CKD on the basis of International Classification of Disease codes from health insurance data; thus, the incidence of moderate CKD was higher than that in our study, which defined CKD on the basis of the eGFR.
Lung cancer is histopathologically classified as NSCLC or SCLC. NSCLC accounts for more than 80–85% of lung cancers, of which almost 40% are adenocarcinomas and 25–30% are squamous cell carcinomas [14–16]. In the present study, the histological type of lung cancer was SCLC in 17% and NSCLC in 83% of the patients, similar to the general proportions based on lung cancer histology. Among the NSCLC patients, squamous cell carcinoma was the most common type (45%), followed by adenocarcinoma (41%). In a retrospective study of 671 patients who underwent pulmonary resection for NSCLC, Yamamoto et al.  reported that squamous cell carcinoma was more frequently diagnosed in CKD patients than in non-CKD patients (34.5% vs. 15.4%, respectively; p < 0.01). Cigarette smoking is a stronger risk factor for squamous cell carcinoma than for adenocarcinoma, and the proportion of smoking was higher in CKD patients than in non-CKD patients in the previous study.
In the present study, we analyzed the clinical course of lung cancer in moderate CKD patients and found that old age (≥ 75 years) and stage IV NSCLC were poor prognostic factors, whereas adenocarcinoma and stage 3 CKD were good prognostic factors. The older patients (≥ 75 years) had a 1.66-fold higher mortality rate than the younger patients. Mortality due to lung cancer generally peaks at 85 years, consistent with our results . As a result of subgroup analysis, although there was no difference in the stage of lung cancer, surgery (38.8%) was the most frequently preferred treatment option for patients aged < 75 years, whereas only supportive treatment (44.8%) was preferred for patients aged ≥ 75 years (p < 0.001).
In addition, stage IV NSCLC was an independent poor prognostic factor for lung cancer patients with coexistent CKD. In the present study, the 5-year survival rates for NSCLC were 34% for stage I patients, 0% for stage II patients, 9% for stage III patients, and 3% for stage IV patients. The 5-year survival rates were lower in the present study than in a previous study that reported 5-year survival rates of 68–92% for stage I NSCLC, 53–60% for stage II NSCLC, 13–36% for stage III NSCLC, and 0–10% for stage IV NSCLC . The subgroup analysis showed that 36% (65/181) of the patients had stage IV NSCLC at diagnosis and received palliative chemotherapy (49.2%) or supportive treatment (38.5%). In a large retrospective study of medical cost according to the treatment modality and disease stage, Cipriano et al.  reported that 13.9% of stage IV NSCLC patients did not receive anti-cancer treatment. Similarly, in the present study, anti-cancer treatment was not administered to a large proportion of stage IV NSCLC patients with CKD, which may explain the poor prognosis of these patients.
By contrast, adenocarcinoma pathology and stage 3 CKD were favorable prognostic factors in this study. EGFR mutations are the most common target driver mutations found in lung adenocarcinoma and are detected in 62% of the Asian population [23, 24]. In lung adenocarcinoma, the median OS was 14 months when treated with pemetrexed-platinum doublet chemotherapy, but the value increased to 39 months upon treatment with a third-generation EGFR tyrosine kinase inhibitor (TKI) [25–27]. In the present study, 61 patients were diagnosed with lung adenocarcinoma, of whom 16 had EGFR mutations and 15 were treated with EGFR-TKIs. The survival analysis, although not reached statistically significant, revealed a longer median OS in the EGFR-TKI treatment group compared to the non-EGFR-TKI treatment group (21.7 vs. 15.8 months; p = 0.593).
In addition, the mortality risk of patients with lung cancer was reduced by 43% in CKD stage 3 compared CKD 4 or 5 stages in this study. The rate of early diagnosis (i.e., at cancer stages I–IIIA) was highest in stage 5 CKD patients (40.9%) compared to stage 3 and 4 patients (37.6% and 40.5%, respectively), which may be explained by the frequent chest X-rays being performed on stage 5 CKD patients who are receiving hemodialysis. The proportions of patients who underwent surgical treatment in patients with resectable lung cancer stage I–IIIA were 63.6%, 47.1%, and 66.7% for stage 3–5 CKD, respectively (Supplementary Table 1). However, in stage I–IIIA lung cancer patients, the 5-year survival rates were 25.0% for stage 3 CKD, 5.9% for stage 4 CKD, and 22.2% for stage 5 CKD. Previous studies have reported 5-year survival rates of 28–43% after lung resection in hemodialysis patients with lung cancer, which was non-inferior to those among patients not receiving hemodialysis [28, 29]. In this study, the survival rate was highest among patients with stage 3 CKD, probably because they frequently received adjuvant chemotherapy after lung resection. Almost 84.6%, 15.4%, and 0.0% of patients with stage 3–5 CKD received adjuvant chemotherapy, respectively. In other words, the early diagnosis rate was higher in stage 5 CKD patients compared to stage 3 CKD patients, whereas the rate of surgery was similar. Nevertheless, the poor survival rate for stage 5 CKD patients was likely due to the low adjuvant chemotherapy rate. Although the study results are limited by the retrospective study design and relatively small sample size (n = 181), the clinical outcomes of lung cancer in patients with CKD were significantly influenced by factors related to renal function as well as lung cancer characteristics (old age, cancer stage, and pathological type). Additionally, despite patients with stage 3 CKD having a better lung cancer prognosis than stage 4 or 5 CKD patients, the former received more aggressive lung cancer treatment than patients with impending or definitive end-stage renal disease (i.e., stage 4 or 5 CKD, respectively).