3642 - A Nationwide Cohort Study using a Target Trial Framework of Post-Operative Radiotherapy for Stage III Non-Small Cell Lung Cancer: Is There Another Way to Go?

Purpose/Objective(s):

For long, researches had aimed to find the proper indication for post-operative radiotherapy (PORT) in surgically resected non-small lung cancer (NSCLC), balancing the toxicity and disease control. However, despite applying modern radiotherapy techniques, the Lung-ART and the PORT-C trial revealed no disease-free survival (DFS) advantage with PORT in pN2 NSCLC. In the report of long-term outcomes of the PORT-C trial, subgroup analysis indicated potential DFS benefits in individuals with visceral pleural invasion (VPI), or 1-3 positive lymph nodes (PLN). Trends or statistically significant inter-subgroup difference regarding the effect of PORT were also observed among these factors and the epidermal growth factor receptor (EGFR) mutation status. Thus, we aim to evaluate these possible predicting factors for PORT in resected pN2 NSCLC in a larger cohort from real-world data.

Materials/Methods:

The national wide cancer registry database from area with high prevalence of EGFR mutated NSCLC were screened for surgically resected pN2 stage III NSCLC. Patients receiving pre-operative radiotherapy, not receiving any adjuvant systemic therapy, or coded with persistent disease were excluded. Clinicopathological factors, treatment course, and survival outcomes were retrospectively collected. The primary outcome was DFS. The secondary outcomes included locoregional control (LC), distal metastasis (DM) and overall survival (OS). We have applied the Clone-Censor-Weighting analysis (CCW) and the landmark analysis to eliminate the impact of immortal time bias when evaluating the effect of PORT. Subgroup analysis was performed to evaluated possible predicting factors.

Results:

Between 2010 and 2019, 2,493 patients who met the inclusion criteria were analysed; 947 received PORT and 1,546 did not. About half of the cohort had received at least 4 cycles of platinum-base adjuvant chemotherapy within 1 year post-operatively. Despite PORT significantly improved LC (HR 0.68, p < 0.0001), it did not confer a DFS benefit (HR 1.02, p = 0.61). The lack of DFS benefit was observed across all subgroups, regardless of the VPI, PLN, EGFR, nor cycles of chemotherapy received. Moreover, PORT was associated with a modestly increased risk of distant metastasis (HR 1.14, p = 0.015), especially in adenocarcinoma or EGFR mutated subgroups. The median time-to-event was shorter for distal metastasis than that of locoregional recurrence.

Conclusion:

There was no robust predicting factor for PORT found at present. The lack of DFS advantage might be the result of high distal metastatic rate. In the era of adjuvant EGFR target therapy following surgery, the role of PORT might warrant further evaluation in EGFR-mutated NSCLC.