Background: The advent of immunotherapy has significantly improved survival outcomes in advanced non-small cell lung cancer (NSCLC). In this evolving context, salvage surgery has emerged as a potential curative strategy, despite the risk of serious complications. This study aimed to evaluate the safety and efficacy of surgical resection following chemo-immunotherapy in patients with initially unresectable NSCLC. Methods: We retrospectively analyzed patients with stage III–IVB NSCLC who underwent salvage surgery at our institution between January 2019 and June 2024. All cases were initially deemed unresectable by a multidisciplinary tumor board. Perioperative complications, complete (R0) resection rate, major pathologic response (MPR), complete pathologic response (pCR), progression-free survival (PFS), and overall survival (OS) were analyzed. Results: Twenty-one patients (thirteen males, eight females; median age: 68 years [IQR: 9]) were included. Reasons for initial unresectability were metastatic disease (28.6%), N2 bulky disease (14.3%), local invasiveness (33.3%), or a combination of factors (23.7%). Chemo-immunotherapy was administered in 19 patients (90.5%), while 2 (9.5%) received immunotherapy alone, with a median of four treatment cycles (IQR: 1). Complete (R0) resection was achieved in all patients (100%). Anatomical resections were performed in 17 patients (81%), predominantly lobectomies (66.7%). There were no intraoperative or major postoperative complications, and 30-day mortality was zero. Median hospital stay was 7 days (IQR: 4). pCR and MPR were achieved in 33.3% and 14.3% of patients, respectively. After a median follow-up of 17 months (IQR: 19), the estimated 3-year PFS and OS were 50.9% and 66.3%, respectively. Recurrences included locoregional (4.8%), distant (14.3%), and combined (14.3%). Cox regression analysis identified stage III at diagnosis (OR: 0.292; 95% CI: 0.093–0.912; p = 0.034) and achieved pCR or MPR (OR: 0.113; 95% CI: 0.013–0.959; p = 0.046) as independent predictors of improved PFS. Conclusions: Salvage surgery after chemo-immunotherapy in initially unresectable NSCLC appears to be a safe and effective strategy in selected patients, offering favorable pathological responses and encouraging mid-term oncologic outcomes.

Introduction: DIPNECH is a rare and under-recognized pre-neoplastic condition, often incidentally found on surgical specimen. Aims: We sought to identify predictive factors for DIPNECH, focusing on clinico-pathological and radiological characteristics. Methods: Data of a single-center cohort of patients undergoing lung resection with DIPNECH diagnosis on surgical specimens were retrospectively analyzed. Pre-operative computed tomography (CT) images were reviewed to identify radiological-pathological correlation. Results: Among 2340 patients surgically treated from January 2016 to December 2023, twenty-six had incidental histological finding of DIPNECH (F/M: 22/4; 69.4±9.4 years; 30.8% never-smokers; 11.5% asthma; 50% cough). Surgery consisted of 38.4% lobectomies, 15.4% segmentectomies and 46.2% wedge resections. There were 30.8% benign lesions and 69.2% malignant: 13 carcinoids, 4 adenocarcinomas and 1 ovarian cancer metastasis. Pathologic exam revealed at least one tumorlet in 65.4% patients. Review of pre-operative chest-CT showed bilateral small nodules suggestive of DIPNECH in 80.8% patients and the incidental histologically found lesions were identified in 53.9%. The presence of ≥1 tumorlets in lung specimen was significantly associated with diffuse micronodules on CT-scan (OR 0.119, 95% CI: 0.018-0.785; p=0.027). Conclusions: Radiological finding of multiple small, scattered nodules associated with a dominant lung lesion may be predictive for DIPNECH. Incidental pre-cancerous lesions in patients with benign lung disease suggest the need for follow-up protocols, although further studies are needed to advance DIPNECH knowledge.