Real-world effectiveness of total neoadjuvant therapy in locally advanced rectal cancer: a multicenter retrospective study

This study aims to evaluate the effectiveness and real-world applicability of total neoadjuvant therapy (TNT) in patients with locally advanced rectal cancer (LARC), focusing on pathological complete response (pCR) and disease-free survival (DFS) across different chemotherapy regimens. In this multicenter retrospective study, patients treated between January 2019 and January 2023, 437 patients with locally advanced rectal cancer who underwent total neoadjuvant therapy followed by surgery were analyzed. Standard fluoropyrimidine-based chemotherapy regimens (CAPOX, FOLFOX, or FOLFIRINOX) were used according to institutional practice, and long-course chemoradiotherapy constituted the predominant radiotherapy approach. Patients were grouped based on chemotherapy sequencing as induction, consolidation, or sandwich regimens. Outcomes were evaluated using multivariable logistic regression for pathological complete response and Kaplan–Meier analysis with Cox proportional-hazards modeling for disease-free survival. The median follow-up duration was 66 months. The overall pCR rate was 26.3% (n = 115). pCR rates did not differ significantly between induction, sandwich, and consolidation chemotherapy regimens. A longer interval (> 8 weeks) between radiotherapy and surgery was associated with a higher likelihood of achieving pCR. In contrast, cT4 disease and baseline CEA levels > 3 ng/mL were associated with lower pCR rates.The estimated 3-year disease-free survival (DFS) rate was 83.8%. Recurrence rates within 3 years were numerically higher in patients receiving induction and sandwich regimens compared with consolidation chemotherapy, although these differences did not reach statistical significance. In multivariable analysis, poor tumor regression grade, ypT4 stage, ypN + disease, and post-TNT CEA ≥ 3 ng/mL were independently associated with an increased risk of recurrence. TNT is effective and feasible in real-world settings, achieving pCR and DFS outcomes comparable to clinical trials. No statistically significant differences were observed in pCR or recurrence rates between induction, consolidation, and sandwich chemotherapy regimens. Prospective phase III trials are needed to compare DFS and OS outcomes across these treatment strategies.

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Journal
Discover Oncology
Published
2026-03-23
DOI
https://doi.org/10.1007/s12672-026-04842-3
Primary Topic
Colorectal Cancer Surgical Treatments
Type
article
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article

Real-world effectiveness of total neoadjuvant therapy in locally advanced rectal cancer: a multicenter retrospective study

Hacer Demir, Süleyman Alkan, Nilgün Özbek Okumuş, Nargız Majidova et al.
Discover Oncology
Colorectal Cancer Surgical Treatments
article

Real-world effectiveness of total neoadjuvant therapy in locally advanced rectal cancer: a multicenter retrospective study

Hacer Demir, Süleyman Alkan, Nilgün Özbek Okumuş, Nargız Majidova, Ali Murat Tatlı, M. Özcan Ersoy, Sabin Göktaş Aydın, Didem Çolpan Öksüz, Özgür Tanrıverdi, İlhan Hacıbekiroğlu, Mert Erciyestepe, Işıl Yıldız, O. Sutcuoglu, Necmettin Özdemir, Serhat Sekmek, Teoman Şakalar, Musa Barış Aykan, Oğuzhan Selvi, Ferit Aslan, Ömer Genç, Fahriye Tuğba Köş, Daisuke Kaya, Gözde Kavgacı, Serkan Menekşe, Gülhan Özkanlı, Elif Şahin, Elif Şenocak Taşçı, Fatih Karataş, İlknur Deliktaş Onur, Bahiddin Yılmaz, Şafak Yıldırım Dişli, Nilüfer Avcı, Gül Sema Yıldıran, Fariz Emrah Özkan, Murat Araz, Atike Pınar Erdoğan, O. Akdogan, Muhammet Ali Kaplan, A. Alkan, Ali İnal, Suayib Yalçın, Atilla Çiftçi, Engin Kut, Mehmet Sıddık Dilek, Emine Türkmen, Mutlu Doğan, Abdullah Sakin, Ali Kaan Güren, Ömer Dizdar, Hasibe Bilgi Gür
article en

Abstract

This study aims to evaluate the effectiveness and real-world applicability of total neoadjuvant therapy (TNT) in patients with locally advanced rectal cancer (LARC), focusing on pathological complete response (pCR) and disease-free survival (DFS) across different chemotherapy regimens. In this multicenter retrospective study, patients treated between January 2019 and January 2023, 437 patients with locally advanced rectal cancer who underwent total neoadjuvant therapy followed by surgery were analyzed. Standard fluoropyrimidine-based chemotherapy regimens (CAPOX, FOLFOX, or FOLFIRINOX) were used according to institutional practice, and long-course chemoradiotherapy constituted the predominant radiotherapy approach. Patients were grouped based on chemotherapy sequencing as induction, consolidation, or sandwich regimens. Outcomes were evaluated using multivariable logistic regression for pathological complete response and Kaplan–Meier analysis with Cox proportional-hazards modeling for disease-free survival. The median follow-up duration was 66 months. The overall pCR rate was 26.3% (n = 115). pCR rates did not differ significantly between induction, sandwich, and consolidation chemotherapy regimens. A longer interval (> 8 weeks) between radiotherapy and surgery was associated with a higher likelihood of achieving pCR. In contrast, cT4 disease and baseline CEA levels > 3 ng/mL were associated with lower pCR rates.The estimated 3-year disease-free survival (DFS) rate was 83.8%. Recurrence rates within 3 years were numerically higher in patients receiving induction and sandwich regimens compared with consolidation chemotherapy, although these differences did not reach statistical significance. In multivariable analysis, poor tumor regression grade, ypT4 stage, ypN + disease, and post-TNT CEA ≥ 3 ng/mL were independently associated with an increased risk of recurrence. TNT is effective and feasible in real-world settings, achieving pCR and DFS outcomes comparable to clinical trials. No statistically significant differences were observed in pCR or recurrence rates between induction, consolidation, and sandwich chemotherapy regimens. Prospective phase III trials are needed to compare DFS and OS outcomes across these treatment strategies.

Discover Oncology
Sakarya University (TR), Dicle University (TR), Manisa Celal Bayar University (TR), Karabük University (TR), Bursa Technical University (TR), Akdeniz University (TR), Ondokuz Mayıs University (TR), Kütahya Dumlupınar Üniversitesi (TR), Istanbul Medipol University (TR), Acıbadem University (TR), Gülhane Askerî Tıp Akademisi (TR), Eskişehir City Hospital (TR), Memorial Ankara Hospital (TR), Necmettin Erbakan University (TR), Ankara Onkoloji Eğitim ve Araştırma Hastanesi (TR), Istanbul University-Cerrahpaşa (TR), Istanbul Eye Hospital (TR), Kayser (Italy) (IT), Acıbadem Adana Hospital (TR), İstanbul Kanuni Sultan Süleyman Eğitim ve Araştırma Hastanesi (TR), Afyonkarahisar Sağlık Bilimleri Üniversitesi, Kahramanmaraş Sütçü İmam University (TR), Mersin Üniversitesi (TR), Kocaeli Üniversitesi (TR), Afyon Kocatepe University (TR), Hacettepe University (TR), Marmara University (TR), Muğla University (TR), Gazi University (TR)
Openalex Percentile: Top 11%
Colorectal Cancer Surgical Treatments
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