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Four-Year Survival Outcomes of Personalized Total Neoadjuvant Therapy Versus Chemotherapy During the 'Wait Period'
Sergei Bedrikovetski1,2, Zachary Bunjo3,4, Ishraq Murshed3,4
1School of Medicine, College of Health, Adelaide University, Adelaide, SA, Australia. sergei.bedrikovetski@adelaide.edu.au.
Purpose:
Total Neoadjuvant Therapy (TNT) is increasingly replacing standard chemoradiotherapy (sCRT) for the treatment of locally advanced rectal cancer (LARC). Data on the use of personalized TNT (pTNT) regimens tailored to patient disease characteristics remain scarce. Accordingly, this study aimed to assess long-term outcomes of pTNT in patients with LARC.
Methods:
This was a secondary analysis of a multicentre retrospective cohort study. Patients treated with pTNT between 2019 and 2022 were compared to a historical cohort from the WAIT trial (2012-2014), which included extended chemotherapy during the interval period (xCRT) or sCRT followed by adjuvant chemotherapy. The main outcomes were 4-year disease-free survival (DFS) and overall survival (OS).
Results:
Forty patients treated with pTNT were matched with 49 patients from the WAIT trial (25 xCRT, 24 sCRT). All WAIT trial patients underwent surgery, whereas 27 (67.5%) pTNT patients underwent surgery and 13 (32.5%) were managed non-operatively. Median follow-up was 48 months. No significant differences were observed in 4-year DFS (pTNT 70% vs. xCRT 68% vs. sCRT 75%, P = 0.764) or OS (pTNT 82.5% vs. xCRT 80% vs. sCRT 83.3%, P = 0.907). Within the pTNT group, patients with an oCR had significantly higher OS compared to those without oCR (95.2% vs. 68.4%, P = 0.021).
Conclusion:
Our findings suggest that pTNT achieves comparable survival outcomes to xCRT and sCRT in patients with LARC, despite higher rates of non-operative management. These findings should be interpreted cautiously given the exploratory nature of the analysis and limited sample size. Larger studies with longer follow-up are required to validate these early data.
