Michele Piazzolla

Thoracic surgery has progressively moved from open thoracotomy to video-assisted and robot-assisted approaches, reducing access-related trauma while changing the technical environment in which pulmonary resections are performed and taught. This narrative review examines the clinical evolution of open, video-assisted thoracic surgery (VATS), and robot-assisted thoracic surgery (RATS), with particular attention to the evidence supporting their perioperative and oncological outcomes, the learning curves associated with minimally invasive surgery, and the role of simulation-based training. Randomized trials now provide robust evidence that VATS improve postoperative recovery compared with thoracotomy in appropriately selected patients with predominantly early-stage non-small cell lung cancer, without compromising long-term oncological outcomes. Randomized comparisons between RATS and VATS support RATS as an oncologically acceptable minimally invasive alternative and suggest advantages in selected technical endpoints, particularly blood loss and lymph node retrieval, but do not demonstrate consistent superiority in major clinical or survival outcomes. Learning curves vary according to previous experience, case complexity, supervision, institutional volume, and the endpoint used to define competence, making fixed case-number thresholds an incomplete measure of proficiency. Simulation can improve selected technical skills and provide objective performance assessment, although evidence becomes progressively less robust when moving from simulator performance to operating room transfer and patient-level outcomes. Surgical approach, therefore, should be interpreted within a broader framework that includes patient and tumour characteristics, oncological quality, surgical expertise, institutional resources, and structured training.

Non-small cell lung cancer (NSCLC) accounts for approximately 85% of lung cancers, and surgical resection is the gold-standard treatment for resectable disease. Minimally invasive surgery (MIS), which includes video-assisted thoracoscopic surgery (VATS) and robotic-assisted thoracoscopic surgery (RATS), has emerged as an alternative option to thoracotomy, with the aim of minimizing perioperative morbidity without compromising oncological efficacy. This narrative review evaluates long-term oncological outcomes (overall survival (OS), disease-free survival (DFS) and recurrence-free survival (RFS)) in patients with NSCLC at different stages who underwent MIS. Retrospective and prospective studies, as well as meta-analyses, are included. VATS has shown comparable and, in many cases, superior oncological outcomes compared to open surgery, with more evident benefits in the early stages of the disease. Although mainly in retrospective studies, RATS has demonstrated efficacy in terms of oncological outcomes comparable to open surgery, even in advanced stages or complex resections. With regard to the direct comparison between VATS and RATS, the two MIS techniques have shown similar OS rates, albeit some prospective data and meta-analyses suggest a potential DFS advantage for RATS. MIS is a safe and effective surgical approach in terms of oncological outcomes for resectable NSCLC; nevertheless, it will be necessary to await the results of further randomized studies currently ongoing to better define the long-term benefits of each technique.

Background/Objectives: As one of the intensely studied epigenetic modifications, DNA methylation plays a key role in tumours, including lung cancer. Hypermethylation in tumour suppressor genes or hypomethylation in oncogenes is an important event in tumorigenesis. Minimally invasive detection of aberrant DNA methylation by liquid biopsy could provide invaluable biomarkers for lung cancer screening, early diagnosis, prognosis, and treatment, also providing a useful tool to monitor response to targeted therapies and immunotherapies. Methods: Here, we discuss the current state-of-the-art cfDNA methylation analysis of NSCLC patients, examine the unique features and limitations of detection methods in a clinical context, and highlight the last research findings in the context of main biological and immunological therapies in lung cancer. Thus, the main goal of this review is to provide a critical overview of the most important published studies that report cfDNA methylation as prognostic biomarker for resistance to target therapies and immunotherapies in lung cancer. Results and Conclusions: DNA methylation-based biomarkers show promise for lung cancer detection and management. In particular, ctDNA methylation has been shown to play an important role in detecting resistance to tyrosine kinase inhibitors and immunotherapies. Nonetheless, DNA methylation biomarkers still lack large-scale validation, actually precluding their rapid implementation in clinical practice.

Background/Objectives: The identification of driver mutations in NSCLC such as those in the EGFR and KRAS genes has revolutionized the understanding and management of many lung cancer patients and has opened up a new scenario in the early disease stages in terms of therapeutic options (EGFR) and prognosis (KRAS). Data on prevalence rates and disease stage distributions of EGFR and KRAS mutations in surgically resected NSCLC are growing, but in Southern Italy, estimation is limited, since upfront EGFR testing in early-stage adenocarcinoma has been only recently introduced according to the current guidelines in clinical practice, whereas KRAS screening is usually uninvestigated in resected NSCLC. In this real-life study of a single institution in the Apulia Region, we provide an overview of the epidemiological distribution of EGFR and KRAS mutations in patients in Southern Italy with resected NSCLC, highlighting their prevalence, clinical significance, and correlation with demographic and pathological factors. A literature review was also performed to compare our findings with the most recent available data from the screening of Italian cohorts of advanced and surgically resected NSCLC patients. Methods: Data from 149 patients coming from Southern Italy with surgically resected NSCLC were retrospectively collected over a period of 16 years. EGFR and KRAS mutation screenings were performed and correlated with clinical and pathological data. Results: In total, 24 out of 149 NSCLC (16%) patients harbored an EGFR mutation. Exon 19 deletions and missense p.L858R mutations of the EGFR gene have quite similar frequencies (46%) and were more observed in never smokers (p < 0.001) and female (p < 0.001) patients with the adenocarcinoma histotype. KRAS gene mutations were detected in 31.5% of cases, with missense p.G12C (32%), p.G12V (28%), and p.G12D (17%) mutations as the most frequent ones. Neither EGFR nor KRAS mutational status were found to impact overall survival (OS) in our study cohort. Conclusions: Our findings improve the understanding of lung cancer genetics in a small and homogeneous area of Southern Italy and guide future research. The EGFR and KRAS mutations in NSCLC resected patients from Southern Italy showed a global similar incidence compared to other recently described Italian cohorts of advanced and early-stage NSCLC, with a higher frequency of exon19 EGFR deletions. No prognostic impact was observed for both EGFR and KRAS status, but additional investigations on a larger cohort are needed.