Risk factors of postoperative recurrence and potential candidate of adjuvant radiotherapy in lung adenosquamous carcinoma

BACKGROUND: Adenosquamous carcinoma (ASC) is a rare and aggressive histologic subtype of non-small cell lung cancer (NSCLC). Little is known about the prognostic significance of routine immunohistochemical (IHC) markers and clinical value of adjuvant radiotherapy in completely resected lung ASC. METHODS: Consecutive patients with pathologically confirmed lung ASC receiving curative resection from January 2007 to December 2017 at our center were retrospectively reviewed. The prognostic significance of 14 routine IHC markers and potential candidate of adjuvant radiotherapy were investigated. RESULTS: With a median follow up of 35 (range, 3.0–138) months, 95 out of the 176 enrolled patients had disease recurrence. The 1-, 3- and 5-year cumulative rate of recurrence was 25.8%, 55.8% and 63.1%, respectively. Using the Cox proportional hazard regression model, T stage, N stage, lymphovascular invasion (LVI), expression of CEA, expression of p53, but not EGFR mutations or expression of the other 12 IHC markers (CK20, CK5/6, PE10, ERCC1, Napsin A, RRM1, Ki67, CK7, P63, EGFR, HER2, TTF1), were significantly associated with postoperative recurrence. N stage, expression of CEA and LVI were identified as independent prognosticators of overall recurrence. Using competing risk methodology and distant recurrence chosen as a competing risk, T stage and N stage were identified as significant risk factors of loco-regional recurrence. Moreover, adjuvant radiotherapy significantly improved disease-free survival (DFS) (P=0.002) and was associated with non-significant longer overall survival (OS) (P=0.078) among 95 patients with either pathological T3–4 or N(+) disease (collectively defined as pT(3–4)/N(+) disease). CONCLUSIONS: This study provides the proof of concept for using routine IHC markers, along with common clinic-pathological parameters, in predicting postoperative recurrence and identifying potential candidate for adjuvant radiotherapy in completely resected lung ASC.