Expert Perspectives in Challenging Situations: Progression After Neoadjuvant Chemoimmunotherapy

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Managing patients who cannot proceed to surgery after neoadjuvant chemoimmunotherapy presents complex clinical challenges requiring careful multidisciplinary coordination and treatment adaptation. The recommended approach involves transitioning to definitive concurrent chemoradiation therapy, though this strategy is complicated by the substantial prior chemotherapy exposure and potential cumulative toxicity concerns. Medical oncologists typically employ reduced-intensity regimens, such as weekly carboplatin and paclitaxel, to minimize toxicity while maintaining therapeutic efficacy during concurrent radiation therapy.

Critical to successful management is distinguishing between true disease progression and immunotherapy-related inflammatory responses, which can mimic progression on imaging studies. This differentiation often requires additional diagnostic procedures including repeat bronchoscopy, mediastinoscopy, or tissue sampling to confirm actual disease progression vs immune-mediated changes. The distinction is crucial because patients with true progression have poor outcomes regardless of subsequent local therapy, whereas those with stable disease may benefit significantly from definitive chemoradiation approaches.

Emerging real-world data suggest that patients who achieve radiographic responses to neoadjuvant therapy but cannot undergo surgery due to medical or technical factors may achieve outcomes comparable to surgical patients when treated with subsequent chemoradiation. The substantial tumor shrinkage following neoadjuvant treatment often reduces radiation field sizes, making definitive radiation therapy more tolerable than traditional up-front chemoradiation approaches. This evolving understanding supports the development of adaptive treatment strategies that can salvage potentially curative outcomes even when initial surgical plans cannot be completed, representing an important evolution in treatment flexibility for challenging clinical scenarios.