Search Results (13,475)

Non-small cell lung cancer (NSCLC) represents most lung cancer diagnoses worldwide and remains a leading cause of cancer-related mortality. The advent of precision oncology has transformed the therapeutic landscape of NSCLC through the identification of druggable genetic alterations, enabling the use of targeted therapies with significant clinical benefit. However, the reported prevalence of these alterations varies widely across studies and populations, raising important questions about the underlying determinants of such discrepancies. In this context, molecular epidemiology provides a framework to understand the distribution of genomic alterations and their interplay with demographic, clinical, and methodological factors. This narrative review examines the spectrum of druggable genetic alterations in NSCLC and critically analyzes the sources of variability in their reported frequencies. We discuss geographic and ethnic differences, particularly between East Asian, European, and North American populations, as well as the influence of smoking status, environmental exposures, histologic subtypes, and sex-related factors. Furthermore, we explore how disease stage and sample type source may contribute to heterogeneity in molecular profiles. A substantial focus is placed on methodological sources of discrepancy, including differences in molecular testing platforms, analytical sensitivity and limits of detection, tissue versus liquid biopsy approaches, tumor heterogeneity, and gene panel design. Finally, emerging trends in the field, such as the use of ultra-large genomic datasets, real-world evidence, multi-omics integration, and artificial intelligence, alongside ongoing efforts toward standardization of molecular testing, are discussed. Full article

Adjuvant and perioperative immune checkpoint inhibitors (ICIs) have created a growing population of patients who relapse after prior programmed death-1 or programmed death-ligand 1 blockade, yet these patients were underrepresented in many trials that established metastatic standards. We performed a structured narrative review of PubMed/MEDLINE, ClinicalTrials.gov, reference lists, and international oncology guideline repositories through 15 August 2026. Eligible reports addressed recurrence patterns or treatment after curative-intent ICI in melanoma, non-small-cell lung cancer (NSCLC), renal cell carcinoma (RCC), urothelial carcinoma, or triple-negative breast cancer (TNBC); landmark metastatic studies were included only when direct evidence was unavailable and are labeled as extrapolation. Timing was standardized as on-treatment recurrence, early off-treatment recurrence (after the last ICI dose through 12 months), and late recurrence (>12 months). Shorter disease-free interval is consistently prognostic, but treatment-by-timing interactions are rarely available; timing should not be described as a validated pan-tumor predictive biomarker. Direct post-adjuvant evidence supports switching away from anti-PD-1 monotherapy for melanoma recurring on treatment, while selected late relapses may retain sensitivity. In RCC, retrospective post-adjuvant data support VEGF-targeted options, whereas CONTACT-03 and TiNivo-2 discourage routine ICI-TKI rechallenge specifically after prior ICI-treated metastatic RCC. Evidence in NSCLC, urothelial carcinoma, and TNBC is largely indirect. IMpassion132 was not an ICI-rechallenge trial, and only a small minority of ASCENT-04 participants had prior perioperative ICI. Treatment should integrate tumor-specific biology, actionable alterations, recurrence distribution, prior toxicity, comorbidity, access, and patient preference. Prospective trials dedicated to post-adjuvant ICI recurrence are needed. Full article

Background: Immunotherapy and targeted therapy have gained ground over conventional chemotherapy in treating various cancers. While pulmonary toxicity associated with these agents is rare, it represents a significant factor in both mortality and morbidity and may influence the overall success of cancer treatment. This case series report adds to the emerging evidence of cancer therapy-induced pneumonitis features and corticotherapy outcomes. Patients and methods: This single-center, retrospective case series analyzed 12 consecutive cases of patients undergoing immunotherapy (four receiving nivolumab, four receiving pembrolizumab) or targeted therapy (three receiving obinutuzumab, one receiving abemaciclib) for cancer (seven with lung cancer, three with non-Hodgkin lymphoma, one with breast cancer, one with renal cancer) who developed pneumonitis during their follow-up. Results: The interval from oncological treatment initiation to pneumonitis onset ranged from 6 to 48 months (median = 18.5), and in four patients it occurred after discontinuation of oncologic therapy. In most patients, the diagnosis was established with high probability based only on the clinical presentation, radiologic pattern, and concomitant oncologic therapy. Bronchoscopy with bronchoalveolar lavage analysis was performed in eight of the 12 patients, particularly when onset followed treatment discontinuation. The main symptom was dyspnea (10/12 cases), and three of 12 patients had respiratory failure (SpO₂ ≤ 88%). The CTCAE severity grades were: one mild, seven moderate, three severe, and one life-threatening. The CT scan showed different patterns (7 OP, 4 NSIP-like, and 1 HP). Eleven patients received oral methylprednisolone (0.40 to 0.82 mg/kg) for 5 to 16 weeks. Two patients continued oncologic treatment, and six discontinued. Pneumonitis improved or resolved in 11 of the 12 patients; one patient deteriorated after reintroduction of immunotherapy and subsequently died from cancer-related complications. Conclusions: Immunotherapy- and targeted therapy-induced pneumonitis can express various features and severities, and prompt recognition and diagnosis based on clinical, radiologic and contextual elements are mandatory. In this small, heterogeneous series the individualized corticosteroid regimens used were followed by favorable outcomes. Our observations suggest that, in selected clinically improving patients, follow-up may rely only on clinical assessment and chest X-ray, and extensive tests may be reserved for non-responsive cases. Full article

Surgical resection is the main curative option for non-small-cell lung cancer. Pulmonary resections have historically been performed through a highly morbid open thoracotomy. Minimally invasive approaches to pulmonary resection have revolutionized the field with reduced perioperative morbidity, including less postoperative pain, length-of-stay, and complications, while potentially enhancing oncologic outcomes. In its current generation, robotically performed video-assisted thoracoscopic surgery (R-VATS) offers numerous advantages over traditional VATS and is increasingly becoming the standard of care. In this review, we highlight the technical and clinical advantages of R-VATS compared to VATS and traditional thoracotomy. We reflect on emerging advancements in the utilization of the minimally invasive platform for single-anesthetic marking and resection of pulmonary nodules, the integration of artificial intelligence and radiomics to augment preoperative planning, and the expanding role of single-incision robotic surgery. Lastly, we discuss the financial considerations of implementing a robotic thoracic platform and identify opportunities to optimize costs. Full article

Background/Objective: An analysis of microRNA (miRNA) expression signatures in lung adenocarcinoma (LUAD) harboring EGFR mutations revealed that multiple miRNAs, including miR-126-3p, were suppressed in cancer tissues. This study focused on miR-126-3p and aimed to identify therapeutic target genes regulated by miR-126-3p in LUAD harboring EGFR mutations and evaluate their potential for combination therapy with EGFR tyrosine kinase inhibitors. Methods: The antitumor function of miR-126-3p was analyzed by the ectopic expression of miR-126-3p into LUAD cells with EGFR mutation. The target genes of miR-126-3p were identified through an analysis of the TargetScan, Genecodis 4 and TCGA databases. The Chou–Talalay method was used to determine the potential synergistic effects of selected drug combinations. Results: The expression of miR-126-3p attenuated the malignant transformation of LUAD cells through targeting the “EGFR tyrosine kinase inhibitor resistance pathway”. We focused on AKT2 among the genes involved in this pathway. Capivasertib was recently approved as the first inhibitor of oncogenic AKT signaling. Therefore, we investigated the effect of combination therapy comprising osimertinib and capivasertib on LUAD cell viability. Combination therapy synergistically reduced cell viability in both PC9 and H1975 cells, with combination index values of 0.61 and 0.14, respectively, at Fa = 0.5. Conclusions: Our miRNA-based analysis is an excellent strategy for identifying therapeutic targets that enhance the effects of EGFR inhibitors on LUAD. Full article

Background: Lung cancer remains the leading cause of cancer-related mortality, with non-small cell lung cancer (NSCLC) accounting for approximately 85% of cases. Over the past decade, immune checkpoint inhibitors have become a core component of first-line treatment for advanced-stage NSCLC lacking driver mutations. Programmed death-ligand 1 (PD-L1) expression is currently used as the standard biomarker, yet its predictive value remains limited, and in most immunotherapy trials, treatment efficacy has been observed independently of PD-L1 expression status. Enhancer of zeste homolog 2 (EZH2), an epigenetic regulator, promotes immune escape by suppressing antigen presentation and impairing CD8+ T-cell function, thereby generating an immune-cold tumor microenvironment, positioning it as a promising candidate biomarker. Methods: We retrospectively analyzed 102 NSCLC patients treated with immunotherapy at a single center between 2018 and 2024. EZH2 expression was assessed by immunohistochemistry. A cohort-derived 25% threshold was used for the primary exploratory analysis, and the analyses were repeated using a 50% threshold as a sensitivity analysis. Patients were classified as EZH2-high (45.1%) and EZH2-low (54.9%) at the 25% threshold. Results: At the 25% threshold, objective response rate (ORR) was 53.6% in the EZH2-low group and 45.7% in the EZH2-high group (Fisher’s exact p = 0.551), while disease control rate (DCR) was 64.3% and 60.9%, respectively (p = 0.837). Median overall survival (OS) was 37 versus 27 months (log-rank p = 0.323), and median progression-free survival (PFS) was 15 versus 12 months (p = 0.387). No significant correlation was found between EZH2 and PD-L1 expression (r = 0.167, p = 0.138). In treatment-line-adjusted Cox models, EZH2 expression was not associated with OS (hazard ratio (HR) 0.953, 95% confidence interval (CI) 0.533–1.704; p = 0.870) or PFS (HR 0.996, 95% CI 0.573–1.733; p = 0.989), whereas squamous histology was an independent predictor of survival. Results remained non-significant at the 50% threshold. Early progression was uncommon and did not differ significantly by EZH2 status overall or within PD-L1 strata. Conclusions: In this real-world cohort, EZH2 expression was not independently associated with response, early progression, OS, or PFS, and showed no correlation with PD-L1. These exploratory findings do not support the clinical use of EZH2 as a biomarker at this stage; prospective, multicenter studies using predefined thresholds and standardized immunohistochemical methods are needed to clarify its potential role as a marker complementary to PD-L1. Full article

Background: The sequential use of anti-programmed cell death (ligand)-1 [PD-(L)1] immune-checkpoint inhibitors (ICIs) followed by targeted tyrosine-kinase inhibitors (TKIs) for advanced non-small cell lung cancer (NSCLC) with oncogenic alterations raises questions about tolerance and efficacy. Recent study results suggested an increased risk of adverse events (AEs) with this sequence. Methods: Multicenter retrospective study on advanced NSCLC patients treated with ICIs followed by targeted therapies between 2015 and 2021. The primary endpoint was the rate of grade 3–5 adverse events (AEs). Main secondary endpoints were progression-free survival (PFS), time-to-treatment failure and overall survival (OS). Results: The analysis included 109 patients (most with EGFR, 30.3%; BRAF, 17.4%; MET exon-14, 17.4%; ALK, 10.1%; and RET, 6.4% gene alterations); 28/109, which is 25.7% of the patients, experienced grade 3/4 AEs and 4/109 (3.7%) experienced grade 5 AEs, leading to the definitive cessation of targeted therapy treatment in 14/32 (44%) of cases; higher grade 3–5 rates were observed with the dabrafenib–trametinib combination (12/16, 75%), capmatinib (4/8, 50%) and crizotinib (8/16, 50%). A last ICI-administration-to-targeted therapy-start interval of <90 days appeared to be associated with grade ≥ 3 AEs (32/82, 39% vs. 0/27 p = 0.001). In these sequential strategies, effectiveness of targeted therapies, in this second-line or later setting, appears to be lower than that in the published historical data. Conclusion: According to this analysis, sequential ICI–targeted therapy use for advanced NSCLC appeared to be associated with more grade 3–5 AEs. Full article

Background and Objectives: Non-small cell lung cancer (NSCLC) comprises biologically distinct histologic subtypes, including lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). We evaluated whether the prognostic association of cyclin-dependent kinase-like 2 (CDKL2) differs by histology. Materials and Methods: TCGA CDKL2 expression was linked to harmonized clinical data. The primary analysis used a pooled multivariable Cox model with continuous standardized CDKL2 expression, histology, and a CDKL2 × histology interaction, adjusted for age, sex, pathologic stage, and smoking. Additional analyses assessed model assumptions, tumor purity, tumor-versus-normal expression, KEGG pathways, the tumor microenvironment, and single-cell RNA sequencing. External evaluation used GSE30219. Results: The primary TCGA cohort included 943 patients (471 LUAD, 472 LUSC; 375 deaths). Higher CDKL2 expression was associated with lower mortality in LUAD (HR per 1 pooled SD = 0.721, 95% CI 0.603–0.862, p < 0.001) but higher mortality in LUSC (HR = 1.237, 95% CI 1.011–1.515, p = 0.039), with a significant interaction (HR = 1.717, p < 0.001) persisting after tumor-purity adjustment. CDKL2-low tumors were enriched for cell-cycle, DNA-replication, proteasome, and DNA-repair programs. Single-cell analyses showed predominant epithelial detection and greater malignant-cell CDKL2 detection in LUAD. In GSE30219, the favorable LUAD association was supported in a median-split-adjusted analysis of 207073_at (HR = 0.473, 95% CI 0.250–0.897, p = 0.022), whereas the corresponding continuous estimate was directionally favorable but nonsignificant; 236331_at was nonsignificant in both models; neither probe supported the adverse LUSC association or histology interaction. Conclusions: Higher CDKL2 expression showed a favorable prognostic association in LUAD, with consistent TCGA sensitivity analyses and limited but suggestive independent-cohort support. The adverse LUSC association remains preliminary, and CDKL2 should be regarded as a candidate prognostically associated marker rather than an established clinical biomarker. Full article

Lung cancer is currently the most frequently diagnosed malignancy worldwide, accounting for approximately 12.4% of all cancers and, despite major advances in molecularly targeted therapies and immunotherapy, represents the leading cause of cancer-related mortality, In recent years, antibody–drug conjugates (ADCs) have emerged as a novel therapeutic strategy, combining the specificity of monoclonal antibodies with the potent cytotoxic activity of highly active payloads to selectively target tumor cells while limiting systemic toxicity. This narrative review summarizes the current role of ADCs in lung cancer, with particular focus on their structural components, mechanisms of action, and the biological features that determine treatment efficacy. We discuss the rationale for targeting established and emerging antigens in non-small cell and small cell lung cancer, including HER2, TROP2, c-MET, HER3, CEACAM5, DLL3, and other promising targets currently under clinical investigation. The principal mechanisms of primary and acquired resistance are also reviewed, including antigen modulation, altered intracellular trafficking, lysosomal dysfunction, drug efflux, tumor microenvironment-mediated immune suppression, and intratumor heterogeneity. In addition, we provide an overview of the safety profile of ADCs, highlighting the most clinically relevant adverse events and their underlying biological mechanisms. We also examine the evolving landscape of predictive biomarkers beyond antigen expression, including genomic, transcriptomic, proteomic, and liquid biopsy-based approaches, together with emerging spatial and single-cell technologies that may improve patient selection. Finally, we discuss future directions in the field, including novel payloads, next-generation linker technologies, bispecific ADCs, combination strategies, and personalized ADC development. Overall, ADCs are rapidly reshaping the therapeutic landscape of lung cancer. Continued optimization of drug design, biomarker-driven patient selection, and a deeper understanding of resistance mechanisms will be essential to fully realize their clinical potential. Full article

Background: NT-proBNP is a mechanistically grounded biomarker of ventricular wall stress with established prognostic value in cardiac surgery, but its perioperative role in lung cancer resection remains incompletely characterised. Pulmonary resection imposes unique haemodynamic stressors—including one-lung ventilation-induced right ventricular afterload increase, permanent pulmonary vascular bed reduction, and ischaemia–reperfusion injury—that create a distinct biological context for natriuretic peptide elevation not represented in general surgical cohorts. Methods: A narrative review of the literature was conducted through systematic searches of PubMed, EMBASE/MEDLINE, and the Cochrane Library (January 2000–June 2026), supplemented by manual reference screening. Approximately 135 articles were included in the final synthesis. Results: Perioperative NT-proBNP elevation predicts postoperative atrial fibrillation, major adverse cardiovascular events, and long-term survival after lung resection, with effect sizes substantially exceeding those reported in general surgical populations. The PRESAGE trial established that NT-proBNP-guided prophylaxis reduces postoperative atrial fibrillation from 40% to 6% in high-risk patients. No thoracic surgery-specific NT-proBNP threshold has been prospectively validated in a multicentre setting, and approximately half the evidence base derives from BNP rather than NT-proBNP assays, precluding direct threshold synthesis. Surgical approach—particularly robot-assisted thoracoscopy—modulates postoperative biomarker elevation through OLV duration rather than inflammatory burden alone. The combination of NT-proBNP with high-sensitivity troponin identifies a dual-elevation subgroup with a MACE rate of 18.4%. Conclusions: NT-proBNP measurement is clinically actionable in thoracic surgery but requires assay-standardised, multicentre validation of population-specific thresholds stratified by resection extent and surgical approach. A dual biomarker strategy combining NT-proBNP with high-sensitivity troponin represents the most evidence-based perioperative risk stratification framework currently available. Full article

Background/Objectives: ALK tyrosine kinase inhibitors (TKIs) have improved outcomes in patients with metastatic ALK-rearranged non-small cell lung cancer (NSCLC). However, real-world data on long-term outcomes, prognostic factors, and treatment sequencing remain limited. This study aimed to evaluate treatment outcomes, prognostic factors, and lorlatinib efficacy in different treatment settings. Methods: We retrospectively analyzed 83 patients with metastatic ALK-rearranged NSCLC treated with ALK TKIs at a tertiary oncology center. Survival outcomes, prognostic factors, treatment sequences, and adverse events were analyzed using Kaplan–Meier and Cox regression methods. Results: The median follow-up duration was 69.4 months, and the median overall survival (OS) was 73.9 months (95% CI, 58.51–89.32). Median OS was 84.8 months with first-line alectinib and 63.6 months with crizotinib. Median progression-free survival (PFS) durations were 47.5, 23.0, and 14.9 months for alectinib, brigatinib, and crizotinib, respectively. ECOG performance status, histological subtype (adenocarcinoma vs. non-adenocarcinoma), and PD-L1 expression were significant prognostic factors. First-line lorlatinib demonstrated durable disease control, with median PFS not reached and a 24-month PFS rate of 80%. Later-line lorlatinib showed continued activity, with median PFS-2 and PFS-3 of 12.2 and 6.1 months, respectively. Treatment-related adverse events were generally manageable. Conclusions: This real-world study provides long-term outcomes and prognostic insights in metastatic ALK-rearranged NSCLC. ECOG performance status, histological subtype, and PD-L1 expression were independent prognostic factors for OS. First-line lorlatinib findings suggest durable disease control but remain preliminary and require confirmation with longer follow-up. Full article

Background: Although high PD-L1 expression correlates with improved outcomes to immune checkpoint inhibitor (ICI), it remains an imperfect predictive biomarker. DNA damage response (DDR) pathway alterations are closely associated with antitumor immunity, shaping tumor immunogenicity and the immune microenvironment. This study evaluates the distribution and clinical impact of DDR alterations in advanced Non-small cell lung cancer (NSCLC) with Programmed death-ligand 1 (PD-L1) ≥ 50%, providing insights for personalized treatment selection and response prediction. Experimental Design: Patients with advanced NSCLC and PD-L1 expression ≥ 50% who received first-line ICI-based therapy were retrospectively enrolled. Tumor tissue samples underwent targeted next-generation sequencing using a comprehensive cancer panel, with a predefined 35-gene DDR panel used to identify and classify pathogenic or likely pathogenic DDR alterations. The associations between genomic DDR alteration status, clinicopathologic characteristics, cytokine profiles, and immunotherapy outcomes were evaluated. Results: Among 121 patients, 72 (59.5%) were classified as DDR-positive and 49 (40.5%) as DDR-negative based on genomic DDR alterations. DDR-positive patients exhibited a higher burden of DDR alterations and TMB, and DDR-positive status remained independently associated with improved outcomes after adjustment for clinical factors and TMB. DDR-positive patients had higher DCB rates and IL-2 levels, whereas TNF-α and IL-6 levels were elevated in DDR-negative patients. DDR-positive status was associated with longer PFS than DDR-negative status (median, 12.7 vs. 8.9 months), with the benefit of chemo-immunotherapy mainly observed in DDR-positive patients. Conclusions: Genomic DDR alterations are associated with distinct immune profiles and may represent a potential biomarker for immunotherapy stratification. DDR-positive patients may derive greater benefit from chemo-immunotherapy, supporting further prospective investigation. Full article

Background: The leading cause of cancer-related deaths globally is lung cancer, and the P2X7 receptor (P2X7R) is a promising therapeutic target due to its role in the disease progression. Methods: A deep learning-based molecular generation framework that integrates a fragment-based drug method with Relational Graph Convolutional Networks (RGCNs) and a Wasserstein Generative Adversarial Network (WGAN) was employed. Known P2X7R targeting drugs were fragmented to construct a fragment library, which was used to generate new candidate molecules. The generated molecules from the model were evaluated for chemical validity, novelty, Lipinski’s Rule of Five compliance, quantitative estimate of drug-likeness (QED), lipophilicity (LogP), similarity using the Tanimoto coefficient, and binding affinity through molecular docking. Results: The model generated 4498 chemically valid molecules, including 968 unique and 384 novel molecules. Approximately 97% satisfied standard drug-likeness criteria, with QED values predominantly above 0.6 and LogP values within acceptable pharmacokinetic ranges. The novel molecules demonstrated an improved docking score against P2X7R compared to the seed molecules. Conclusions: Despite training on 5000 SMILES due to limited computational resources, the model achieved high validity, strong molecular diversity, and drug-like physicochemical properties, demonstrating the feasibility of a scalable, target-specific AI pipeline for lung cancer drug discovery using fragment-based molecular generation, RGCN and WGAN. Nevertheless, the biological activity of the generated molecules remains experimentally unvalidated, and the findings are based solely on computational analyses. Full article

Cannabidiol (CBD), the principal non-psychoactive phytocannabinoid of Cannabis sativa, exhibits diverse pharmacological activities through interactions with multiple molecular targets. Thus, breast, colorectal, and lung cancers arise from distinct molecular mechanisms. This study investigated the potential multi-target pharmacological mechanisms of CBD using an integrated approach combining network pharmacology and molecular docking. CBD-associated targets from three prediction platforms were intersected with disease-associated genes for each cancer type, yielding 143 overlapping targets that formed a significantly enriched protein–protein interaction network. Maximal Clique Centrality (MCC) analysis identified 10 hub proteins, including SRC, SIRT1, PTGS2 (COX-2), PPARG, NFKB1, MMP2, IGF1R, ESR2, ESR1, and EGFR, which represent key regulators of hormone signaling, inflammation, cell proliferation, and tumor progression. Molecular docking against these targets, benchmarked using each protein’s authentic co-crystallized ligand, predicted predominantly moderate binding affinities for CBD. Compared with the corresponding reference ligands, CBD generally exhibited lower predicted binding affinity, although comparable or slightly stronger scores were observed for PTGS2, ESR2, and EGFR. Independent validation using AutoDock Vina demonstrated overall agreement with the MOE docking results, supporting the robustness of the predicted binding profiles. Collectively, these findings suggest that CBD may exert its biological activity through coordinated modulation of multiple cancer-related signaling pathways rather than a single molecular target. By integrating pooled cancer-associated network pharmacology with co-crystallized ligand benchmarking, this study provides a computational framework for prioritizing biologically relevant CBD targets for future experimental validation. These findings should be regarded as hypothesis-generating rather than evidence of clinical efficacy. Full article

Objective: Subcostal uniportal robot-assisted thoracic surgery (URATS) using the da Vinci Single-Port (SP) system avoids intercostal placement of the main robotic access. This prespecified secondary analysis of a prospective trial characterized chronic postsurgical pain and health-related quality of life (HRQOL) as primary patient-reported outcomes after subcostal URATS for early-stage lung cancer, with mid-term oncological outcomes as an exploratory endpoint. Methods: Patients from the parent trial (NCT05535712) undergoing subcostal URATS were assessed at 3, 6, and 12 months by structured telephone interviews. Chronic postsurgical pain was defined by the ICD-11 criterion (Numerical Rating Scale [NRS] > 0 on any of four activity-specific items). Neuropathic features were assessed with the painDETECT Questionnaire (PDQ), and HRQOL with EORTC QLQ-C30 summary score and selected domains. Results: In 33 patients, chronic postsurgical pain declined from 33.3% at 3 months to 6.1% at 12 months (p = 0.004), was mild among symptomatic patients (median NRS 1), and showed no PDQ-defined neuropathic features. Two patients received a 7-day course of gabapentin at 3 months. Baseline HRQOL (median QLQ-C30 summary score 91.5) increased at all postoperative time points (p < 0.001). At a median 40-month follow-up, one patient had bilateral pulmonary recurrence at 13 months, all remained alive, and no delayed hernia or other access-related complication was identified. Conclusions: Subcostal URATS was feasible in this prospective cohort. Chronic postsurgical pain was mild and decreased over time, HRQOL remained well preserved, although data on mid-term oncological outcomes were preliminary. Full article