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Closing the evidence gap in older adults with extensive-stage small-cell lung cancer: a CGA-guided, risk-adapted
Nana Zhao1,2,3, Haoyu Lu1,2,3, Yaning Luo1,2,3
1First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China.
Abstract:
Therapeutic decision-making for older adults, operationally defined in this review as patients aged ⩾65 years, with extensive-stage small-cell lung cancer (ES-SCLC) remains clinically challenging, complicated by heterogeneous decline in physiological reserve, multiple comorbidities, and narrow therapeutic indices. Although chemoimmunotherapy has redefined the first-line standard of care, the selection bias inherent in pivotal registrational randomized controlled trials-which often exclude the oldest-old and frail patients-limits the generalizability of their efficacy and safety profiles within complex real-world populations. As the therapeutic armamentarium expands, emerging modalities such as small-molecule anti-angiogenic agents, hypofractionated or adaptive radiotherapy, and novel molecular therapies (e.g., lurbinectedin and delta-like ligand 3-targeting constructs) offer tailored therapeutic avenues for this demographic. However, a pronounced evidence gap persists regarding geriatric-specific toxicity and functional endpoints within the existing evidence hierarchy. Consequently, the integration of Comprehensive Geriatric Assessment (CGA) for functional status stratification is imperative to navigate current therapeutic bottlenecks. The objective of this narrative review is to summarize recent therapeutic advances in older adults with ES-SCLC, critically examine the limitations of current evidence, and propose a CGA-guided framework for risk-adapted clinical decision-making and holistic management.
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