Prospective observational studies are essential in clinical research, mainly when randomized controlled trials (RCTs) are infeasible, unethical, or impractical. These studies involve the prospective collection of data from cohorts stratified by exposure status, allowing investigators to observe the natural progression of outcomes while preserving temporality. Their main strengths include measuring incidence, assessing multiple outcomes, and avoiding recall bias, thus offering valuable insights into real-world clinical practices. However, these studies also face inherent limitations, most notably the risk of confounding, the absence of randomization, extended duration, and high resource demands. Biases related to selection, performance, and attrition can compromise internal validity if not adequately addressed through rigorous design and statistical adjustment. Although generally favorable, ethical considerations must be carefully navigated, especially concerning data protection and informed consent. While causality cannot be established, prospective observational studies complement RCTs by reflecting effectiveness in typical clinical settings. This Pros & Cons review examines the structure, advantages, limitations, and methodological considerations of prospective observational studies, incorporating insights from contemporary medical literature and educational frameworks. It also underscores their continued relevance in evidence-based medicine.

e20068 Background: Neoadjuvant chemoimmunotherapy (CIT) improves pathologic complete response (pCR) rates in resectable non–small cell lung cancer (NSCLC), yet substantial variability persists across studies. Robust predictors of pCR are not well defined, limiting patient selection and translational application. We conducted a systematic review and meta-analysis to identify clinicopathologic and biologic factors associated with pCR and to assess gaps in current predictive approaches. Methods: MEDLINE, Embase, Web of Science, and Cochrane Library were searched for prospective trials and observational cohorts (2015–2025) reporting surgical resection after neoadjuvant CIT for resectable NSCLC and evaluating predictors of pCR. Candidate predictors included PD-L1 expression, clinical stage and nodal status, radiologic response (RECIST), metabolic response on FDG-PET, systemic inflammatory markers, circulating tumor DNA dynamics, tumor mutational burden, and radiomics features. Random-effects meta-analyses estimated pooled odds ratios (ORs) with 95% confidence intervals (CIs) for associations with pCR when ≥2 studies reported comparable data. Studies proposing multivariable prediction models were evaluated qualitatively using TRIPOD and PROBAST criteria. Results: A total of 14 studies including 1,842 patients were eligible (6 prospective trials, 8 observational cohorts). Higher PD-L1 expression was associated with increased odds of pCR (per 10% increase in TPS: OR 1.28, 95% CI 1.10–1.49, I²=58%). FDG-PET metabolic response (ΔSUVmax ≥50%) showed a strong association with pCR (OR 2.41, 95% CI 1.62–3.58, I²=42%) and outperformed size-based radiologic response. Absence of mediastinal nodal disease (cN0–1 vs cN2) was associated with higher pCR rates (OR 1.76, 95% CI 1.22–2.54, I²=36%). Data on tumor mutational burden, circulating tumor DNA clearance, systemic inflammatory markers, and radiomics were sparse and heterogeneous, precluding quantitative synthesis. Only a minority of studies reported multivariable analyses, and none included external validation, calibration assessment, or evaluation of clinical utility; no study met PROBAST criteria for low risk of bias. Conclusions: PD-L1 expression, metabolic response on FDG-PET, and baseline nodal status are the most reproducible factors associated with pCR after neoadjuvant CIT in resectable NSCLC. However, current evidence highlights a significant translational gap, with insufficient data and methodological rigor to support generalizable predictive models. Prospective studies integrating imaging and biologic variables with external validation are urgently needed to enable clinically actionable pCR prediction.

BACKGROUND:Robotic-assisted bronchoscopy with the ION™ Endoluminal System facilitates precise access to peripheral pulmonary lesions. However, procedural duration and diagnostic performance remain influenced by patient and lesion-specific factors. To investigate the impact of lesion diameter, radiological appearance, and presence of bronchial signs on procedural duration and diagnostic yield using conventional regression and gradient boosting machine learning models. METHODS:In this single-center retrospective cohort study, 189 ION™ Endoluminal System procedures (November 2024-June 2025) were analyzed. Procedural duration and diagnostic yield served as primary outcomes. Predictive modeling included multivariable regression and gradient boosting. Feature importance metrics were extracted. RESULTS:The median lesion diameter was 12.3 mm, with a "strict" diagnostic yield of 87.3%. Gradient boosting regression identified lesion diameter as the primary predictor of procedural time (89.2% importance; test MSE = 865.6). Diagnostic classification achieved an ROC-AUC of 0.68, with lesion diameter (85.8%) and bronchial sign (14.2%) as key predictors. CONCLUSIONS:Lesion diameter emerged as the most consistent predictor of procedural efficiency and was associated with diagnostic performance, albeit within the limitations of the dataset. Broader datasets are needed for external validation and generalizability.

BACKGROUND:Chondrosarcomas of the manubrium are exceedingly rare, accounting for approximately 20% of all primary bone malignancies, and present unique challenges in surgical management and reconstruction. Reliable reconstructive strategies for medial clavicular stabilization remain limited. CASE PRESENTATION:We report the first documented use of STRATOS bars for unilateral clavicular stabilization following manubrial chondrosarcoma resection. A 19-year-old woman with a poorly differentiated (G3) chondrosarcoma of the manubrium underwent neoadjuvant chemotherapy followed by en bloc resection of the manubrium, medial clavicle, and first rib. Reconstruction and clavicular stabilization were achieved using STRATOS, which is traditionally employed for chest-wall reconstruction. This represents a novel use of the device for medial clavicular stabilization after SCJ resection. At the 6-month follow-up, the patient remained disease-free, with preserved shoulder function and stable reconstruction. STRATOS provided stable fixation, preserved shoulder function, and an excellent cosmetic outcome. A brief review of the literature on sternal chondrosarcoma and reconstruction techniques is also presented. CONCLUSION:This unique application expands the reconstructive possibilities of modular titanium systems. It may offer a more reliable biomechanical alternative to traditional fixation methods in cases requiring stability of the shoulder girdle after SCJ resection. Further validation through biomechanical studies and larger case series is warranted.

BACKGROUND:The molecular concordance between primary lung adenocarcinoma and metastatic lesions remains incompletely characterized despite its direct implications for precision oncology and biopsy-driven therapeutic decision-making. This prospective monocentric paired-sample study evaluated genomic concordance between primary lung adenocarcinoma and synchronous thoracic metastatic lesions using targeted next-generation sequencing (NGS). METHODS:We identified 27 treatment-naïve patients with histologically confirmed lung adenocarcinoma who underwent paired molecular profiling of the primary tumor and a synchronous thoracic metastatic site (pleural or intrapulmonary). DNA and RNA were analyzed using validated institutional NGS platforms. Genomic alterations, including clinically actionable oncogenic drivers consistently covered by the sequencing panel used in each pair, were compared across matched samples. Concordance was assessed using exact binomial confidence intervals, Cohen's κ statistics, McNemar tests, and paired Wilcoxon signed-rank tests. RESULTS:Actionable driver alterations were identified in 17 of 27 patients (63.0%; 95% CI 42.4-80.6), including EGFR mutations (40.7%), KRAS alterations (18.5%), and one ALK gene rearrangement (3.7%). TP53 concurrent mutations were detected in 14 cases (51.9%). Across all 27 paired samples, driver-level concordance was 100% (95% CI 87.2-100), with perfect agreement for EGFR, KRAS, and ALK alterations (κ = 1.00). TP53 mutations showed high concordance (92.9%; κ = 0.85), while CNVs were concordant in 88.0% of evaluable pairs. Variant allele frequency (VAF) comparisons, adjusted for tumor cellularity, further supported the apparent clonal stability of driver alterations across paired samples. CONCLUSIONS:This study demonstrates very high molecular concordance between primary lung adenocarcinomas and their synchronous pleural or intrapulmonary metastases. The observed 100% concordance of actionable driver alterations across paired specimens supports the clinical reliability of thoracic metastatic biopsies for baseline molecular profiling in treatment-naïve disease. Although limited by sample size, these findings support the biological stability of actionable driver alterations during early thoracic metastatic dissemination.

BACKGROUND Thoracic trauma is a major cause of trauma-related morbidity and mortality, often resulting from blunt mechanisms. While advances in acute management have improved short-term outcomes, long-term results-particularly health-related quality of life (QoL) after chest wall surgery-remain poorly defined. Identifying factors influencing long-term QoL is essential to optimize patient care. AIM To investigate long-term QoL and identify clinical factors influencing outcomes. METHODS Forty-one consecutive patients underwent chest wall surgery for thoracic trauma between November 2016 and November 2024 at our Hospital. Data collected for this retrospective cohort study included demographics, trauma characteristics, surgical details, postoperative complications, hospital and intensive care unit stay, and long-term patient-reported outcomes [EuroQol 5-Dimension 3-Level Questionnaire (EQ-5D-3 L), Numerical Rating Scale (NRS) for pain, and dyspnea scores]. Univariable and multivariable linear regression analyses were performed to identify predictors of QoL and pain. RESULTS At a median follow-up of 14 months (range 1-72), the median EQ-5D-3 L score was 0.68 (range 0.027-1), with no significant correlation with follow-up duration (Spearman’s rho = -0.05, P = 0.78). Pain was the only independent predictor of lower QoL (β = -0.079 per NRS unit, P = 0.016). Age, male gender, and comorbidities showed non-significant negative trends with QoL. For pain, a greater number of comorbidities was significantly associated with lower pain scores (β = -0.810, P = 0.041), while male sex was non-significantly associated with less pain. Dyspnea and perioperative variables were not significantly related to either outcome. CONCLUSION Long-term QoL after chest wall surgery is lower than the general population; pain is the main determinant. Effective pain control and comorbidity management are essential for personalized postoperative care.

Objectives: Pulmonary metastasectomy is not a standardised procedure, with no consensus regarding the optimal extent of lung resection. This international multicentre study aimed at comparing short and long-term outcomes of anatomical versus non-anatomical pulmonary metastasectomy. Methods: Retrospective database including 1647 patients aged ≥18 years, who underwent curative intent pulmonary metastasectomy between January 2010 and December 2018 at 15 European centres. Patients who underwent pneumonectomy, previous metastasectomies, and/or suffered from extrapulmonary recurrence at the time of lung surgery were excluded. Primary endpoint was overall survival. Secondary endpoints were recurrence-free survival and 30-day morbidity. Differences between the two groups were analysed using 3:1 matching. Results: In the matched cohort, 324 patients underwent anatomical resection, and 830 patients underwent non-anatomical resection. Five-year overall survival was 62.0%. Averaged over the entire follow-up, there was no significant difference in overall survival between the two groups (HR = 1.122, 95% CI = 0.909-1.385, p = 0.283). In the early period following pulmonary metastasectomy, anatomical resections were associated with worse overall survival (HR = 1.549, 95% CI = 1.135-2.114, p = 0.006). The difference in any-site recurrence-free survival between the two groups was not significant (HR = 0.832, 95% CI = 0.690-1.002, p = 0.053). Locoregional recurrence-free survival was significantly longer after anatomical resection (HR = 0.651, 95% CI = 0.520-0.817, p < 0.001). Thirty-day morbidity was significantly higher after anatomical resection (22.2% versus 13.7% for non-anatomical resections, p = 0.001). Conclusions: In a highly selected cohort, non-anatomical resection showed comparable survival and lower morbidity compared to anatomical resections, supporting the surgical strategy of favouring limited resections whenever technically and oncologically feasible. Anatomical resections remain a valid option in selected cases with acceptable outcomes.

OBJECTIVES:This study aimed at identifying predictors of loco-regional recurrence in patients who underwent non-anatomical (wedge) resection(s) of lung metastases at 15 European centres. METHODS:Multicentre retrospective analysis of patients ≥18 years who underwent curative-intent wedge resection(s) of lung metastases (January 2010-December 2018). Exclusion criteria were: previous metastasectomy, non-curative intent, incomplete (R1/R2) resection, and lack of data concerning recurrence. Loco-regional recurrence was defined as any recurrence occurring in the lungs, hilar-mediastinal lymph nodes, and/or pleurae. Subset analyses were conducted on patients with a solitary metastasis. RESULTS:A total of 588 patients were included (56.1% adenocarcinoma). Five-year overall survival was 63.9% (95% CI = 60.43; 67.18). Five-year loco-regional recurrence rate was 47.7% (95% CI = 42.8; 52.4). Mean resection margin width was 6.8 mm (IQR = 2.0-10.0). 422 patients (71.8%) underwent a single wedge resection. In the total sample, univariable Cox regression showed that primary tumour site (P = .0003), primary tumour histology (P = .0027), resection margin width (P = .0060), log(margin-to-tumour size ratio) (P = .0022), and number of metastases (P < .0001) were significantly associated with loco-regional recurrence. In patients with a solitary metastasis, univariable analyses showed that primary tumour site (P = .0150), primary tumour histology (P = .0248), and log(margin-to-tumour size ratio) (P = .0355) were significantly associated with loco-regional recurrence. In multivariable analyses (solitary metastasis group), primary squamous-cell carcinoma histology was significantly associated with loco-regional recurrence (P = .0023). Resection margin width and log(margin-to-tumour size ratio) did not significantly affect loco-regional recurrence. CONCLUSIONS:Loco-regional recurrence after pulmonary metastasectomy seems to be correlated with primary tumour histology and the number of metastases. Further studies are needed to clarify the role of size-adjusted margin parameters in preventing recurrence.

BACKGROUND:In lung cancer, adequate treatment selection relies on accurate diagnosis and staging. Tissue sampling is generally indicated. This guideline explores the role of endosonography via the major airways (endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA)) and oesophagus (endoscopic transoesophageal ultrasound-guided fine-needle aspiration (EUS-FNA)). EUS-FNA can also be performed using an EBUS scope (EUS-B-FNA). METHODS:Task force members were selected from the European Respiratory Society, European Society of Gastrointestinal Endoscopy and European Society of Thoracic Surgeons. Members formulated 12 guideline questions. Systematic literature searches were performed in MEDLINE and Embase (final searches: April 2025). Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was applied for assessing the certainty of evidence and developing recommendations. RESULTS:In (suspected) non-small cell lung cancer, endosonography is recommended over mediastinoscopy for mediastinal nodal tissue staging. Systematic staging is suggested over targeted staging as the minimal standard. Ideally, combined EBUS-TBNA+EUS(-B)-FNA is performed instead of EBUS-TBNA alone. Add-on mediastinoscopy after a negative endosonography is not recommended. Endosonography is suggested over mediastinoscopy for restaging after induction therapy. EBUS-TBNA and EUS(-B)-FNA are recommended for centrally located tumours adjacent to the major airways/oesophagus. Both EUS-B-FNA and EUS-FNA are suggested for left adrenal gland analysis. It is suggested that competence is acquired in a simulation-based environment and ensured using valid assessment methods. 21G/22G TBNA needles are considered the standard; there is insufficient evidence to support the structural use of alternative needle sizes/types or cryobiopsy. EBUS-TBNA has a high suitability rate for programmed death-ligand 1 assessment. CONCLUSIONS:Endobronchial and oesophageal endosonography provide accurate and minimally invasive tests for the diagnosis and staging of lung cancer.

Background: The integration of neoadjuvant and perioperative chemo-immunotherapy (CT-IO) has significantly reshaped the treatment of resectable non-small-cell lung cancer (NSCLC), improving pathological response and survival outcomes. However, its impact on surgical management-particularly robotic-assisted thoracic surgery (RATS)-remains incompletely defined. This review provides a practical overview of current evidence and technical considerations for robotic lung resection following neoadjuvant chemo-immunotherapy. Methods: A narrative review of the literature was performed, focusing on phase III trials, meta-analyses, and surgical series reporting perioperative, oncological, and technical outcomes of minimally invasive-especially robotic-approaches after neoadjuvant or perioperative chemo-immunotherapy. Results: Randomized trials have established CT-IO as a standard treatment option for selected patients with resectable stage II-III NSCLC-although the specific standard varies according to stage, molecular and PD-L1 status, and regulatory approval-significantly improving pathological complete response and event-free survival. However, immune-related fibrosis, nodal scarring, and altered tissue planes increase surgical complexity and intra-postoperative complications. Available evidence, largely retrospective and derived from selected patient populations treated at experienced centers, suggest that RATS is feasible and safe, offering enhanced visualization and dexterity that may facilitate dissection in challenging post-induction settings. Vascular management and lymph node dissection remain critical technical aspects, and early conversion to open surgery, when required, should be regarded as an appropriate safety strategy rather than a complication. Conclusions: RATS after neoadjuvant chemo-immunotherapy appears feasible and promising in selected patients treated at experienced centers, but current evidence does not yet establish it as the preferred approach for all patients. Careful patient selection, adherence to oncological principles, and surgeon experience are essential. Prospective data are needed to define optimal surgical timing and standardize techniques.

Introduction and importance: Coexistence of malignant and granulomatous pulmonary lesions can represent a diagnostic and therapeutic challenge. Distinguishing between tumor recurrence, infectious, or iatrogenic conditions is crucial for guiding appropriate management. Case presentation: We report the case of a 69-year-old woman referred to our center for evaluation of a 6-mm solid nodule in the left lower lobe, incidentally discovered during a coronary computed tomography scan. Endobronchial ultrasound-guided transbronchial needle aspiration confirmed invasive adenocarcinoma, whereas granulomatous inflammation was identified exclusively in the postoperative surgical specimen. The postoperative course was uneventful, and the patient was discharged in good condition. Clinical discussion: This case highlights the importance of considering differential diagnoses when encountering granulomatous changes adjacent to malignant tumors. The overlap between iatrogenic, infectious, and tumor-related findings can complicate the diagnostic process. Our experience underscores the importance of histopathological confirmation to avoid misinterpretation, ensure adequate oncological treatment, and prevent overtreatment. Conclusion: Granulomatous lesions concomitant with lung cancer are rare but clinically relevant. Awareness of this possibility is essential for accurate diagnosis and optimal patient management.

Lung neuroendocrine tumors (NETs), including typical and atypical carcinoids, show heterogeneous outcomes. The existing nomograms are often complex and insufficiently validated, limiting their bedside use. A simple, reproducible model based on routine pathology is therefore needed. This study aimed to develop and internally validate the NET score, an interpretable, AI-assisted tool to estimate individualized mortality risk. In a retrospective cohort of resected pulmonary carcinoids, candidate predictors were screened using LASSO regression to reduce overfitting and identify key variables: nodal status, mitotic index (>2 per 2 mm2), necrosis, and Ki-67 (>5%). Selected variables were incorporated into a logistic regression model to generate a point-based score (0-8). The model estimates cumulative mortality risk across follow-up, not fixed-time survival. Internal validation included bootstrap and cross-validation to assess discrimination and calibration. The final model included LODDS > -0.5 (3 points), mitotic index >2 (2 points), necrosis (2 points), and Ki-67 (1 point). Discrimination was moderate (bootstrap-corrected AUC: 0.70). Risk groups were defined as low (0-2 points, ≤5%), intermediate (3-4 points, 8-12%), and high (≥5 points, ≥18%). Kaplan-Meier curves demonstrated progressive survival stratification across risk groups. The NET score is a practical and interpretable prognostic tool for lung NETs. It supports risk communication and clinical decision-making while maintaining transparency. External validation is required. Combining AI-based variable selection with a simple scoring system represents a pragmatic approach to prognostic modeling in rare thoracic malignancies.

In the original publication [...].

The number of long-term survivors after pancreatic cancer is increasing due to recent advances in diagnosis and multidisciplinary treatments. However, the effectiveness of pulmonary metastasectomy remains uninvestigated. This study aims to evaluate the oncological outcomes of pulmonary metastasectomy in pancreatic cancer and to identify potential prognostic factors affecting survival. Patients undergone pulmonary metastasectomy, with previous radical surgery on pancreatic cancer and no evidence of disease in other organs, were selected. Therefore, clinical data of 56 patients from 7 high-volume centers were retrospectively analyzed. Long-term oncological outcomes and prognostic factors were evaluated. Five- and 10-year OS from pancreatectomy were 76

Backgrounds/Objectives: Malignant pleural effusion (MPE) is a frequent complication of advanced cancer, and talc pleurodesis via video-assisted thoracoscopic surgery (VATS) represents a standard palliative treatment with high efficacy. However, evidence regarding synchronous bilateral pleurodesis in patients with bilateral MPE is limited. This study evaluates the feasibility, safety, and outcomes of a single-stage bilateral VATS talc pleurodesis approach. Materials and Methods: We retrospectively analyzed patients undergoing synchronous bilateral VATS talc poudrage between 2000 and 2025 at a single tertiary cancer center. Inclusion criteria included adult patients with bilateral MPE, expandable lungs, and suitability for surgery. Preoperative assessment involved imaging and multidisciplinary evaluation. Perioperative data, complications, mortality, and recurrence rates at 30 days and 3 months were collected. Survival and pleural effusion-free survival were estimated using the Kaplan-Meier method. Results: Thirty patients were included (median age 63.2 years). The most common primary tumors were breast (43%), lung (30%), and ovarian cancer (17%). Mean operative time was 78.6 min, with no intraoperative complications. Mean hospital stay was 6 days. Postoperative morbidity included atrial fibrillation (13%) and respiratory failure (6.6%), both managed conservatively. Thirty-day mortality was 3%. Pleural effusion recurrence occurred in 6.6% at 3 months and 10% at 7 months. Mean follow-up was 9.7 months. Conclusions: Synchronous bilateral VATS talc pleurodesis is a feasible and safe procedure in selected patients with bilateral MPE with acceptable morbidity. Further prospective studies are needed to confirm these findings and refine patient selection.

Pulmonary atypical carcinoid (AC) demonstrates a variable prognosis influenced by both tumor biology and anatomic staging. It remains unclear whether histopathologic markers such as mitotic count, necrosis, and Ki-67 more effectively predict overall survival (OS) than nodal involvement (pN). This study aims to determine whether OS after surgical resection of pulmonary AC is more strongly associated with pathologic markers or with nodal involvement, by directly comparing their prognostic performance within a single institutional cohort. We retrospectively analyzed 111 patients with resected AC and complete OS data, comparing prognostic performance between a biologic model (mitoses > 2 per 2 mm2, necrosis present, Ki-67 > 10