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Purpose <p>Total neoadjuvant therapy (TNT) has emerged as alternative to conventional chemoradiotherapy (CRT) for locally advanced rectal cancer (LARC), with recent phase III trials showing improved treatment compliance and pathological response rates. However, concerns remain regarding long-term loco-regional control and distant metastasis outcomes. This retrospective study evaluates real-world outcomes of LARC patients treated with CRT or TNT at tertiary cancer centre.</p> Method <p>This retrospective study included 196 LARC patients treated between 2019 and 2022. Patients received either TNT (<i>n</i>=109) or CRT (<i>n</i>=87). CRT consisted of neoadjuvant long-course chemoradiotherapy followed by surgery and adjuvant CAPOX, while TNT included various sequences of short- or long-course radiotherapy with neoadjuvant CAPOX. Among the initial cohort, 100 patients underwent surgery and final analysis was performed in 90 patients. Surgical outcomes, pathological complete response (pCR), disease-free survival (DFS) and overall survival (OS) were analyzed using Kaplan-Meier and Cox regression models.</p> Results <p>Among 90 analyzed patients (TNT: 48, CRT: 42), TNT associated with higher R0 resection (97.9% vs. 88.1%, <i>p</i>=0.030) but similar pCR (16.7% vs. 21.4%, <i>p</i>=0.565). However, TNT showed inferior 2-year DFS (38.5% vs. 78.3%) and 3-year OS (54.9% vs. 78%). On multivariable analysis, TNT independently predicted recurrence (HR=4.38, <i>p</i>=0.001) and mortality (HR=2.45, <i>p</i>=0.036), likely due to higher baseline disease burden and treatment heterogeneity.</p> Conclusion <p>In this retrospective real-world cohort, TNT improved R0 resection rates but inferior survival benefit over CRT. These findings likely influenced by baseline stage imbalance, selection bias, treatment heterogeneity, and high attrition rates. Larger prospective studies with standardized protocols are required to validate these findings.</p>

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Real-World Treatment Outcomes in Locally Advanced Rectal Cancer: Assessing Total Neoadjuvant Therapy and Chemoradiation

  • 期刊论文

  • 发表日期：

    2026年7月28日

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  • Jyotiman Nath,
  • Joydeep Nath,
  • Yanpothung Yanthan,
  • Giridharan S,
  • Partha S. Roy,
  • Gaurav Das,
  • Anupam Sarma,
  • Ratnadeep Sharma

摘要

Purpose

Total neoadjuvant therapy (TNT) has emerged as alternative to conventional chemoradiotherapy (CRT) for locally advanced rectal cancer (LARC), with recent phase III trials showing improved treatment compliance and pathological response rates. However, concerns remain regarding long-term loco-regional control and distant metastasis outcomes. This retrospective study evaluates real-world outcomes of LARC patients treated with CRT or TNT at tertiary cancer centre.

Method

This retrospective study included 196 LARC patients treated between 2019 and 2022. Patients received either TNT (n=109) or CRT (n=87). CRT consisted of neoadjuvant long-course chemoradiotherapy followed by surgery and adjuvant CAPOX, while TNT included various sequences of short- or long-course radiotherapy with neoadjuvant CAPOX. Among the initial cohort, 100 patients underwent surgery and final analysis was performed in 90 patients. Surgical outcomes, pathological complete response (pCR), disease-free survival (DFS) and overall survival (OS) were analyzed using Kaplan-Meier and Cox regression models.

Results

Among 90 analyzed patients (TNT: 48, CRT: 42), TNT associated with higher R0 resection (97.9% vs. 88.1%, p=0.030) but similar pCR (16.7% vs. 21.4%, p=0.565). However, TNT showed inferior 2-year DFS (38.5% vs. 78.3%) and 3-year OS (54.9% vs. 78%). On multivariable analysis, TNT independently predicted recurrence (HR=4.38, p=0.001) and mortality (HR=2.45, p=0.036), likely due to higher baseline disease burden and treatment heterogeneity.

Conclusion

In this retrospective real-world cohort, TNT improved R0 resection rates but inferior survival benefit over CRT. These findings likely influenced by baseline stage imbalance, selection bias, treatment heterogeneity, and high attrition rates. Larger prospective studies with standardized protocols are required to validate these findings.