3563 - Prognostic Predictive Role of Short-Term Efficacy Indicators in Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer

Purpose/Objective(s): For locally advanced rectal cancer (LARC), the total neoadjuvant therapy (TNT) strategy has demonstrated a superior complete response (CR) rate and enhanced survival outcomes when compared to neoadjuvant concurrent chemoradiotherapy (CRT) alone. Here, we compared the predictive effects of different short-term efficacy indicators on prognosis based on the TNT strategy.

Materials/Methods: The STELLAR trial was a multicenter, open-label, randomized phase III study which compared short-course radiotherapy (5 Gy × 5) followed by 4 cycles of CAPOX (TNT group) to preoperatively concurrent chemoradiotherapy. Patients treated with TNT group and underwent surgery were evaluated. NAR score, pathologic complete response (pCR), and pathologic lymph node status (ypN) were included in univariate and multivariate analyses. The predictive ability of the predictive factors was quantitatively evaluated by constructing receiver operating characteristic (ROC) curves and using the area under the curve (AUC) value.

Results: 235 patients total were enrolled in this study. Median age was 55.0 years (range: 47.0 - 62.0). Among them, 70.2% were male, 14.5% had an ECOG score of 1, 62.4% had low - rectal cancer, 81.7% had a clinical T-stage of T3, and 87.7% had a clinical stage of N1-2. Patients with low and medium NAR scores exhibited higher 5-year disease free survival (DFS) rates and 5-year overall survival (OS) rates compared to those with high NAR scores (DFS: 81.0% vs. 63.0% vs. 47.4%; OS: 86.9% vs. 82.6% vs. 69.6%). Univariate analysis revealed that pCR, NAR score < 8, and ypN0 were associated with improved DFS (hazard ratio [HR] 0.19 [95% confidence interval (CI) 0.07 - 0.51], P = 0.001; HR 0.23 [95% CI 0.12 - 0.47], P < 0.001; HR 0.41 [95% CI 0.27 - 0.63], P < 0.001) and better OS (HR 0.34 [95% CI 0.12 - 0.95], P = 0.039; HR 0.41 [95% CI 0.19 - 0.90], P = 0.025; HR 0.50 [95% CI 0.30 - 0.84], P = 0.009). Multivariate analysis demonstrated that a low NAR score had a significant influence on DFS (HR 0.26 [95% CI 0.13 - 0.53], P < 0.001) and OS (HR 0.44 [95% CI 0.20 - 0.96], P = 0.038). The AUC values for predicting DFS by NAR score, pCR, and ypN were 0.701, 0.621, and 0.402, while the AUC values for predicting OS were 0.638, 0.584, and 0.436.

Conclusion: Under the total neoadjuvant therapy (TNT) strategy, the NAR score serves as a crucial indicator of the efficacy of neoadjuvant therapy for locally advanced rectal cancer (LARC) and exhibits the most potent predictive ability for disease-free survival (DFS). 5y-LCR: 5-year local control rate, 5y-DMFS: 5-year distant metastasis-free survival, NAR= [5pN-3(cT-pT)+12]2/9.61. NCT02533271.