Neoadjuvant chemotherapy combined with intraoperative radiotherapy is effective to prevent recurrence in high-risk non-small cell lung cancer (NSCLC) patients.

Background: Basal cell hyperplasia (BCH) and squamous metaplasia (SM) in the small bronchi distant from the tumor is associated with a high risk of non-small cell lung cancer (NSCLC) recurrence. Here, we assessed whether neoadjuvant chemotherapy (NAC), intraoperative radiotherapy (IORT), or adjuvant chemotherapy (AC) is effective to prevent recurrence in NSCLC patients (n=171) with different premalignant lesions in the small bronchi.

Methods: BCH, SM, and dysplasia (D) were identified in the samples of lung tissue distant from the tumor. NSCLC patients were treated by surgery, different combinations of NAC and IORT, and AC.

Results: Based on the type of bronchial lesions, NSCLC patients were classified into four groups: BCHSMD (55.6%, 95/171), BCHSMD (26.3%; 45/171), BCHSMD (6.4%, 11/171), and BCHSMD (11.7%, 20/171). During 5 years, recurrent carcinoma was found in 13.4% (23/171) of patients and represented by metachronous metastases in the thoracic lymph nodes (82.6%, 19/23) and by a relapse in the bronchial stump (17.4%, 4/23). Recurrence was frequent in BCHSMD patients (87.0%, 20/23), rare in BCHSMD and BCHSMD patients (13.0%, 3/23), and absent in BCHSMD patients (0/23). The 5-year recurrence-free survival was also shorter in BCHSMD patients (HR 27.35; 95% CI: 6.31-118.48; P<0.0001). In the high-risk (BCHSMD) group, recurrence occurred mainly in cases without NAC and IORT (88.2%, 15/17) and was absent (0/15) when these therapies were combined. NAC- and IORT-negative patients also showed poor overall survival (HR 4.35; 95% CI: 1.96-9.66; P<0.0001) and tended to have decreased recurrence-free survival (P=0.075). Importantly, the recurrence rate was not different between AC-treated and AC-naïve BCHSMD patients.

Conclusions: The combination of NAC and IORT is an effective strategy to prevent recurrence in high-risk NSCLC patients.