Managing Early-Stage NSCLC Post Neoadjuvant Therapy in Patients Who Are Not Surgery Candidates

Patients who receive neoadjuvant therapy with intention for surgical resection occasionally become unable to proceed to surgery due to disease progression, medical complications, or personal preference, occurring in approximately 15% to 20% of cases historically. When patients cannot proceed to planned surgery, their health care teams must rapidly pivot to alternative treatment strategies through multidisciplinary consultation, considering the patient’s response to induction therapy, reasons for surgical ineligibility, and individual goals of care. Treatment options may include definitive chemoradiation, continuation of systemic therapy alone, or hypofractionated radiation depending on the clinical circumstances.

Health care providers increasingly recognize that resectability should ideally be determined before starting neoadjuvant therapy rather than being reassessed after treatment completion. Patients benefit from up-front multidisciplinary evaluation that clearly distinguishes between resectability (anatomic and pathologic factors) and operability (patient’s ability to tolerate surgery) before committing to a neoadjuvant treatment pathway. Some patients unfortunately receive conflicting information about surgical plans, being told that resectability will be determined after completing induction therapy, which can lead to disappointment and suboptimal treatment sequencing.

The management of patients who cannot proceed to surgery after neoadjuvant therapy requires individualized decision-making based on their response to treatment and current clinical status. For patients who achieved excellent responses but became medically inoperable, hypofractionated radiation without chemotherapy may provide definitive local treatment while minimizing additional toxicity. Patients who experienced disease progression during neoadjuvant therapy may benefit from chemoradiation approaches, though careful tissue analysis should be considered to evaluate for histologic transformation or identify previously undetected molecular alterations that could guide targeted therapy approaches.