Response-Adapted Benefit of Postoperative Adjuvant Therapy Following Neoadjuvant Treatment in Resectable NSCLC: A Single-Center Retrospective Cohort Study           

TL;DR

This study shows that lung cancer patients who respond well to pre-surgery treatment may not need more therapy after surgery, while those with poor responses benefit from additional immunotherapy.

Contribution

The study introduces a response-adapted approach to postoperative therapy in NSCLC based on pathological response to neoadjuvant treatment.

Findings

Patients with major pathological response (MPR) derived minimal benefit from postoperative immunotherapy.

Patients with poor pathological response (0–60%) had better survival outcomes with adjuvant immunotherapy.

Response-adapted therapy could spare good responders from unnecessary treatment while ensuring high-risk patients receive needed therapy.

Abstract

Treatment before surgery is effective for resectable non-small cell lung cancer, but it remains uncertain whether all patients require further treatment after surgery. This study aimed to determine if the necessity of postoperative therapy depends on how well the tumor responded to the initial treatment. The authors found that patients achieving a major pathological response derived minimal benefit from additional immunotherapy, whereas those with a poor response achieved significantly better survival outcomes with adjuvant immunotherapy. These findings suggest that postoperative treatment should be tailored based on pathological response rather than using a uniform approach. This research supports a personalized strategy that could spare good responders from unnecessary side effects and financial costs while ensuring that high-risk patients receive the intensive therapy required to prevent disease recurrence.

Background: Neoadjuvant immunochemotherapy improves pathological response in resectable non-small cell lung cancer (NSCLC), but the need and intensity of postoperative adjuvant therapy across different pathological response rate (PRR) strata remain uncertain. Methods: In this single-center retrospective cohort, 105 patients with resectable NSCLC received neoadjuvant platinum-based chemotherapy with or without PD-1/PD-L1 inhibitors followed by R0 resection. PRR was defined as 1—residual viable tumor fraction and categorized as 0–60%, 60–90%, and ≥90% (major pathological response, MPR). Postoperative strategies included no further therapy, chemotherapy alone, or immunotherapy ± chemotherapy. Event-free survival (EFS) was analyzed using Kaplan–Meier estimates, multivariable Cox models, and restricted cubic spline-based treatment × PRR interaction. Results: Deeper PRR was associated with lower ypT/ypN stage and improved EFS. In the PRR 0–60% subgroup, immunotherapy-containing adjuvant regimens were associated with better EFS, whereas chemotherapy alone did not outperform observation. In the PRR 60–90% and MPR strata, EFS curves for different postoperative strategies largely overlapped, and in MPR patients, hazard ratios were close to 1. Interaction modeling suggested that the absolute 3-year EFS benefit of immunochemotherapy peaked at intermediate PRR (≈60–80%) and diminished as PRR approached ≥90%. Conclusions: The robustness of these findings was further confirmed through a sensitivity analysis focusing on a homogeneous cohort of clinical stage II-III patients receiving adjuvant therapy. Among NSCLC patients treated with neoadjuvant systemic therapy, PRR is a strong prognostic marker and modulates the benefit of postoperative immunotherapy. These data support a response-adapted strategy, with adjuvant immunotherapy intensification in low-PRR patients and potential de-escalation or surveillance alone in MPR patients, warranting validation in prospective PRR-stratified trials.

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