Integrated Molecular and Clinical Approaches to Pulmonary Large Cell Neuroendocrine Carcinoma

Large cell neuroendocrine carcinoma (LCNEC) of the lung is an aggressive tumor with substantial molecular heterogeneity. The clinical challenge is integrating evolving genomic insights with pragmatic treatment pathways to inform care today while building evidence for tomorrow.

Against this clinical backdrop, a primary driver of progress is the growing understanding of molecular heterogeneity within LCNEC. Distinct subtype classifications, represented by non-small cell lung cancer–like markers (such as KEAP1 and KRAS) or small cell lung cancer–like profiles (featuring RB1 and TP53), may inform therapy selection or clinical trial referral; however, validated targeted approaches in LCNEC remain limited, with agents such as KRAS G12C inhibitors and immunotherapy strategies being explored in selected cases.

This differentiation may inform therapy selection or clinical trial enrollment, as suggested by molecular profiling studies such as the Nature Communications report. Taken together, these insights may help translate genetic complexity into therapeutic opportunities.

Transitioning from the molecular canvas to the clinic, staging and select biomarkers (such as PD-L1) inform care, but in LCNEC treatment is often extrapolated from SCLC/NSCLC paradigms and PD-L1’s predictive value remains uncertain. Reports on PD-L1 expression in neuroendocrine lung tumors provide context, though LCNEC-specific prognostic implications remain uncertain, as reflected in analyses available through the Wiley Online Library.

Yet, while molecular insights and clinical markers frame the challenge, it is the integrated multidisciplinary approach that welds these aspects into comprehensive patient care. Multidisciplinary tumor boards coordinate input from oncology, pathology, radiology, and surgery to align on a plan tailored to each patient. The value of this framework is illustrated in broader oncology experience: integrated care models improve coordination and patient experience, and across oncology are associated with better outcomes; LCNEC-specific survival effects remain to be defined, as discussed in the International Journal of Integrated Care.

Patient scenarios further illuminate these complex interactions. For example, a patient with LCNEC harboring a KRAS G12C mutation may be referred to a clinical trial evaluating a KRAS G12C inhibitor after platinum-based chemotherapy, whereas a patient with an SCLC-like TP53/RB1 co-altered profile may receive platinum–etoposide with immunotherapy per extrapolated practice.

In real-world clinics, decisions often hinge on balancing disease tempo with the availability of trials and the patient’s goals. Molecular reports are reviewed alongside imaging, pathology, and performance status to prioritize options that are feasible and timely.

As evidence accumulates, cross-talk between thoracic oncology and neuroendocrine tumor programs can help refine care pathways for LCNEC. Shared datasets and prospective registries are particularly valuable to connect genomic subtypes with outcomes and treatment responses.

Current insights suggest future directions in personalized oncology, but prospective studies are needed to clarify benefits in LCNEC. Continued collaboration across research and clinical teams will be essential to translate subtype-aware strategies into routine care where they demonstrably improve patient-centered outcomes.

Key takeaways

• LCNEC management today relies on extrapolation from SCLC/NSCLC, with PD-L1’s predictive value uncertain in this disease.
• Molecular subtypes (NSCLC-like vs SCLC-like) may guide trial referral and selected therapies under investigation, but validated targeted options remain limited.
• Multidisciplinary care and coordinated pathways help align complex data to individualized plans while the evidence base grows.