Biological and clinical characteristics of non-small cell lung cancer non-specific subtype

Non-small cell lung cancer-not otherwise specified (NSCLC-NOS) is a rare subtype of NSCLC that cannot be classified specifically based on morphology and/or special staining. This study aimed to explore the clinical features, biological and pathological characteristics, treatment, and prognosis of NSCLC-NOS.

This retrospective study included NSCLC-NOS patients diagnosed and treated between 2010 and 2022. Clinical features, gene expression, first-line treatment, and prognosis were analyzed. Kaplan-Meier methods were calculated and log-rank tests and univariable and multivariable Cox regression analyses were performed to determine the relationship between prognostic factors and survival.

Of 105 NSCLC-NOS patients, most were male (92.4 %), smokers (78.1 %), with a median age of 64 years, and advanced stage (IIIc-IV, 72.4 %). Immunohistochemical analysis showed minimal expression of p40, NapsinA, and TTF-1, whereas cytokeratin (CK) was expressed in 100 % of cases. 20.5 % of 39 patients who underwent genetic testing had driver gene mutations, including EGFR, KRAS, and ROS1. Among 69 patients with complete treatment information, 58 received platinum-based chemotherapy, with paclitaxel being the most commonly used combination chemotherapy drug (n = 25), followed by pemetrexed (n = 21). The objective response rate (ORR) of paclitaxel was found to be higher compared to pemetrexed (83.3 % vs. 54.5 %, P = 0.296). Furthermore, the combination of paclitaxel with immunotherapy demonstrated superior benefits in comparison to pemetrexed (76.9 % vs. 50.0 %, P = 0.367). The median progression-free survival (PFS) for patients treated with monotherapy paclitaxel, the paclitaxel-immunotherapy combination, and the pemetrexed-immunotherapy combination were 6.6 months (95 % CI: 1.508-11.692; P = 0.017), 15.7 months (95 % CI: 14.071-17.329; P = 0.017), and 11.8 months (95 % CI: 10.279-13.321; P = 0.324), respectively. The median overall survival (OS) was 13.6 months. Anatomic location (P = 0.026) and immunotherapy use (P = 0.003) were associated with OS. Multivariate analysis confirmed that anatomical location and immunotherapy use were factors influencing the prognosis.

NSCLC-NOS is common in male smokers and often diagnosed at an advanced stage with low mutation rate. Paclitaxel with immunotherapy may have better benefits as a first-line treatment. Anatomic location and immunotherapy use are prognostic factors.