To analyze the clinical features of LUAD transformed into SCC or SCLC and explore its possible molecular mechanism and treatment.

The clinical characteristics and genetic tests of 7 LUAD patients transformed into SCC or SCLC were retrospectively analyzed. The 7 patients were followed up by telephone, and the outcome and prognosis of the patients were recorded.

Before the transformation of the 7 LUAD patients, case 1 detected no driver gene, case 3 was ROS1 fusion, and the others were EGFR mutations; case 6 was accompanied by TP53 and BRCA1 mutations. After transformation, 5 cases were SCC and 2 cases were SCLC; case 1 detected ALK fusion, cases 3, 5 and 6 remained original mutations. The rest cases didn′t receive the genetic test after transformation. The median time of taking TKIs was 14 months (0-74 months). At initial diagnosis, SCC-Ag was higher than the upper limit of normal in 2 of the patients transformed into SCC; NSE was higher than the upper limit of normal in 1 of the patients transformed into SCLC. After transformation, SCC-Ag was higher than the upper limit of normal in 1 of the patients transformed into SCC; NSE was about 4.7 times higher than the initial level in 1 of the patients transformed into SCLC; Pro-GRP in 2 SCLC patients was about 16 times higher than the initial level. The median transformation time of 7 LUAD patients was 27 months (11-92 months), the median transformation time of SCC was 27 months, and SCLC was 11 months. All patients received chemotherapy-based comprehensive therapy after transformation. The ORR of first-line therapy was 100%, the DCR was 100%, and the median PFS of first-line therapy was 7 months. the median OS after transformation was 9 months. The median OS of SCLC and SCC after transformation was 9 months and 8 months, respectively; and the median PFS of first-line therapy was 7 months and 8 months, respectively. Gender, smoking, initial TKI treatment for more than 12 months, third-generation TKI treatment, and EGFR mutation had no significant effect on transformation time(P>0.05).

Pathological transformation is one of the important drug resistance mechanisms of LUAD. Elevated levels of SCC-Ag, NSE, Pro-GRP and TP53 mutation may be related to pathological transformation; first-line chemotherapy can still benefit after transformation.