Non-small cell lung cancer (NSCLC) accounts for nearly 85% of lung cancer cases and remains a leading cause of cancer-related mortality worldwide. Advances in molecular diagnostics and targeted therapies have transformed treatment paradigms, yet the integration of molecular testing into routine care for resected NSCLC specimens continues to face significant challenges. This review outlines the technical, clinical, and systemic barriers that limit the effectiveness of molecular testing. Key considerations include tissue quality, the limitations of formalin-fixed paraffin-embedded (FFPE) samples, and the comparative roles of conventional methods—such as immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and reverse transcription polymerase chain reaction (RT-PCR)—versus next-generation sequencing (NGS). We also discuss the prevalence and clinical relevance of common genomic alterations, including TP53, KRAS, EGFR, and ALK, as well as their impact on prognosis and treatment selection. Real-world obstacles such as accessibility, reimbursement, delays in testing, interdisciplinary coordination, and sample adequacy are critically examined. Emerging innovations—including multi-omics integration, spatial profiling, liquid biopsy, artificial intelligence, and novel targeted therapies—offer opportunities to overcome current limitations and improve patient outcomes. Finally, practical recommendations are proposed to optimize tissue handling, testing algorithms, and access to precision-guided therapies. By addressing these challenges, molecular testing in NSCLC can be more effectively leveraged to personalize treatment strategies and enhance survival outcomes.

Background: Non-small-cell lung cancer (NSCLC) is driven by distinct oncogenic alterations with important therapeutic and prognostic implications. Noninvasive biomarkers that predict molecular status in surgically resectable disease may aid in their management. We investigated the association of preoperative primary-tumor SUVmax on PET/CT, smoking history, and corrected serum calcium levels with driver oncogenic alterations and PD-L1 expression in surgically resected NSCLC. Methods: We retrospectively studied 170 patients with surgically resected NSCLC at a single tertiary center. Resected tumors were assessed for EGFR, KRAS, and BRAF mutations, ALK and ROS1 rearrangements, and PD-L1 expression. Associations between molecular status, PD-L1 expression, and clinicometabolic parameters were evaluated using univariate analyses and multivariable regression models. Results: A driver alteration was detected in 51.2% of tumors, and 30% of evaluable cases showed high PD-L1 expression (≥50%). Corrected serum calcium was positively correlated with SUVmax and emerged as the strongest independent predictor retained in the final linear regression model, with pack-years also contributing independently. Most molecular subgroups did not show significant differences in SUVmax. EGFR-mutated tumors showed a trend toward a lower SUVmax compared with EGFR wild-type tumors, although this did not reach statistical significance. Smoking history was not significantly associated with PD-L1 expression, and pack-years did not differ significantly across the molecular groups examined. Conclusions: In this cohort of surgically resected NSCLC, preoperative corrected serum calcium and smoking exposure were more closely associated with tumor metabolic activity than with specific molecular alterations. These findings suggest that simple clinical and biochemical parameters may provide complementary information, although their utility for discriminating individual molecular subgroups appears limited.

Refractory thoracic infections require targeted antimicrobial combinations, repeated drainage interventions and often staged surgical procedures of varying complexity grades. In necrotizing pneumonia cases, successful treatment is complete removal of destroyed non-functional parenchyma, pleural cavity debridement, and complete pathogen eradication based on culture-based sensitivity-driven antimicrobials. The latter proves challenging in pan-resistant microbial strains where both medical and surgical treatments demonstrate limited effectiveness. We describe a case of persistent thoracic sepsis due to pan-resistant Pseudomonas receiving sequentially thoracoscopic decortication, thoracotomy for lobectomy, and open thoracostomy as the last treatment option to prevent fatal sepsis in view of non-available antibiotics. The immediate source-control effect raised the question of the ideal timing for selecting an aggressive thoracoplastic procedure despite its deforming nature over any other treatment approach.

Background: Non-small cell lung cancer (NSCLC) is driven by distinct oncogenic al-terations with important therapeutic and prognostic implications. Noninvasive bi-omarkers that predict molecular status in surgically resectable disease may aid in their management. We investigated the association of preoperative primary-tumor SUVmax on PET/CT, smoking history, and corrected serum calcium levels with driver oncogenic alterations and PD-L1 expression in surgically resected NSCLC. Methods: We retrospectively studied 170 patients with surgically resected NSCLC at a single tertiary center. Resected tumors were assessed for EGFR, KRAS, and BRAF mu-tations, ALK and ROS1 rearrangements, and PD-L1 expression. Associations between molecular status, PD-L1 expression, and clinicometabolic parameters were evaluated using univariate analyses and multivariable regression models. Results: A driver alteration was detected in 51.2% of tumors, and 30% of evaluable cases showed high PD-L1 expression (≥50%). Corrected serum calcium was positively correlated with SUVmax and emerged as the strongest independent predictor retained in the final linear regression model, with pack-years also contributing independently. Most molecular subgroups did not show significant differences in SUVmax. EGFR-mutated tumors showed a trend toward lower SUVmax compared with EGFR wild-type tumors, although this did not reach statistical significance. Smoking history was not significantly associated with PD-L1 expression, and pack-years did not differ significantly across the molecular groups examined. Conclusions: In this cohort of surgically resected NSCLC, preoperative corrected se-rum calcium and smoking exposure were more closely associated with tumor meta-bolic activity than with specific molecular alterations. These findings suggest that simple clinical and biochemical parameters may provide complementary information, although their utility for discriminating individual molecular subgroups appears limited.

Non-small cell lung cancer (NSCLC) accounts for nearly 85% of lung cancer cases and remains a leading cause of cancer-related mortality worldwide. Advances in molecular diagnostics and targeted therapies have transformed treatment paradigms, yet the in-tegration of molecular testing into routine care for resected NSCLC specimens contin-ues to face significant challenges. This review outlines the technical, clinical, and sys-temic barriers that limit the effectiveness of molecular testing. Key considerations in-clude tissue quality, the limitations of formalin-fixed paraffin-embedded (FFPE) sam-ples, and the comparative roles of conventional methods—such as immunohistochem-istry (IHC), fluorescence in situ hybridization (FISH), and reverse transcription poly-merase chain reaction (RT-PCR)—versus next-generation sequencing (NGS). We also discuss the prevalence and clinical relevance of common genomic alterations, including TP53, KRAS, EGFR, and ALK, as well as their impact on prognosis and treatment se-lection. Real-world obstacles such as accessibility, reimbursement, delays in testing, interdisciplinary coordination, and sample adequacy are critically examined. Emerg-ing innovations—including multi-omics integration, spatial profiling, liquid biopsy, artificial intelligence, and novel targeted therapies—offer opportunities to overcome current limitations and improve patient outcomes. Finally, practical recommendations are proposed to optimize tissue handling, testing algorithms, and access to preci-sion-guided therapies. By addressing these challenges, molecular testing in NSCLC can be more effectively leveraged to personalize treatment strategies and enhance survival outcomes.