Recent years have seen substantial advances in lung cancer management, with therapeutic options expanding rapidly through the integration of targeted therapies, immunotherapies, antibody-drug conjugates, and novel, immune-engaging agents. Although outcomes have improved for selected patients with non-small cell lung cancer and small cell lung cancer, the increasing number of regimens has amplified clinical complexity, with persistent evidence gaps, limited head-to-head comparisons, and underrepresentation of key subgroups in trials. Emerging genomic tools and novel therapeutic modalities provide opportunities to further improve patient outcomes but also add to the challenges of clinical decision-making. To address these issues, a multidisciplinary panel of oncology experts, primarily based in the United States, convened to review current evidence gaps, controversies, and unmet needs in the management of lung cancer. Key areas were identified in treatment selection and sequencing as well as the management of high-risk subtypes, highlighting the need for prospective, head-to-head clinical trials. Findings from this panel will inform a 2026 follow-up conference in which a modified Delphi method will be used to develop formal consensus recommendations to provide actionable guidance for practicing clinicians.

The objective of this systematic review and meta-analysis was to evaluate the validity of progression-free survival (PFS) and the objective response rate (ORR) as surrogate end points for overall survival (OS) in randomized controlled trials (RCTs) of metastatic renal cell carcinoma. The MEDLINE, Embase, and Cochrane CENTRAL databases were searched from inception to June 10, 2025. Associations between treatment effects on OS, PFS, and ORR were assessed using Pearson correlation coefficients (r). Surrogate threshold effect (STE) analyses determined the minimum PFS hazard ratio (HR) or ORR odds ratio (OR) required to predict OS benefit. Subgroup analyses were conducted by treatment class, line of therapy, and histology. Sixty-two randomized controlled trials comprising 24,518 patients were included. PFS-OS demonstrated a moderate correlation (r = 0.52; 95% confidence interval [CI], 0.38-0.66), with an STE (HR, 0.92; 95% CI, 0.79-1.09). ORR-OS demonstrated a moderate correlation (r = -0.59; 95% CI, -0.72, -0.45), with an STE (OR, 1.40; 95% CI, 0.99-1.89). Subgroup estimates varied across treatment settings and were frequently imprecise, particularly for ORR and in smaller treatment-class subgroups; limited representation of non-clear cell renal cell carcinoma precluded reliable histology-specific conclusions. Overall, PFS and ORR had moderate trial-level associations with OS in metastatic renal cell carcinoma, but the overall analyses did not demonstrate sufficiently consistent surrogacy to reliably predict OS benefit. These findings should be interpreted cautiously given the substantial heterogeneity of the included trials. Surrogate validity appears to be context-dependent, supporting continued reliance on OS and the need for more robust surrogate end points.