Adenocarcinoma of High-Grade Patterns Associated with Distinct Outcome of First-Line Chemotherapy or EGFR-TKIs in Patients of Relapsed Lung Cancer

PURPOSE: High-grade patterns (micropapillary/solid/complex gland) are associated with a higher recurrence rate and shorter disease-free survival. Thus far, it remains unclear whether the efficacy of first-line anticancer therapy is different from that of the other adenocarcinoma subgroups for patients with high-grade patterns. The study aimed to investigate the association between an adenocarcinoma with high-grade patterns with the outcomes of first-line treatment in patients with lung cancer. PATIENTS AND METHODS: Patients with a high-grade pattern adenocarcinoma (more than 20% of micropapillary/solid components/complex glandular patterns) were retrospectively analyzed between June 2015 and June 2017. Patients’ clinical characteristics and treatment outcomes were compared with those of the remaining control adenocarcinoma subgroups. RESULTS: In total, 239 patients with adenocarcinoma, including 115 (48.1%) high-grade patterns and 124 (51.9%) control groups, were enrolled. Patients’ clinical characteristics such as age, sex, smoking status, and stage were similar between the two groups. Among them, 108 patients received first-line chemotherapy, and 131 received epidermal growth factor receptor–tyrosine kinase inhibitors (EGFR-TKIs). In the chemotherapy group, adenocarcinoma of high-grade patterns had a significantly lower objective response rate (ORR; 15.6% vs 36.4%, P=0.045), shorter progression-free survival (PFS; median 4.1 vs 5.4 months, P=0.007) and overall survival (OS, median 19.6 vs 23.8 months, P=0.048) compared with the control group. As for these treated with EGFR-TKIs, a similar ORR (70.7% vs 72.1%, P=0.703), PFS (median 11.3 vs 13.9 months, P=0.065) and OS (median 34.1 vs 29.6%, p=0.575) were observed between these two groups. CONCLUSION: An adenocarcinoma with high-grade patterns is associated with inferior outcomes to first-line chemotherapy in relapsed lung cancer. Patients who received chemotherapy had a significantly shorter PFS and OS and lower ORR than control subjects, while there was no difference in the EGFR-TKI cohort. This study is the first to report the distribution of adenocarcinoma with high-grade patterns.