Factors influencing locoregional recurrence rates in locally advanced rectal cancer after total neoadjuvant treatment versus chemoradiotherapy in the RAPIDO trial.

Ilaria Prata, Max D Tanaka, Bengt Glimelius, Iris D Nagtegaal, Regina G H Beets-Tan, Lennart K Blomqvist, Alice M Couwenberg, Boudewijn van Etten, Geke A P Hospers, Elma Meershoek-Klein Kranenbarg, Koen C M J Peeters, Hein Putter, Annet G H Roodvoets, Cornelis J H van de Velde, Per J Nilsson, Corrie A M Marijnen

Journal: The British journal of surgery 2025;112(9):

PMID: 41020329

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Abstract

BACKGROUND

The RAPIDO trial compared total neoadjuvant treatment (TNT) with preoperative chemoradiotherapy (CRT), both followed by total mesorectal excision, in patients with locally advanced rectal cancer (LARC). A higher locoregional recurrence (LRR) rate was observed after TNT. This study investigates factors contributing to the difference in LRR observed.

METHOD

Patients with high-risk LARC received TNT (5 × 5 Gy followed by 6 × CAPOX or 9 × FOLFOX4) or CRT (25-28 × 1.8-2 Gy with concurrent capecitabine). Patients with a local R0 or R1 resection were included in this study. Sphincter-preserving surgery encompassed (low) anterior resection and Hartmann's procedure. The influence of baseline, surgical and pathological factors on LRR was evaluated.

RESULTS

Of 920 randomized patients, 849 (430 versus 419 in the TNT and CRT arms) were eligible. The cumulative incidence of LRR at 8 years was 10.8% after TNT and 5.8% after CRT (HR 1.91). Following sphincter preserving surgery, 12.1% (TNT) and 4.8% (CRT) developed LRR (HR 2.60), compared to 8.5% versus 7.5%, respectively, after abdominoperineal resection. Distal resection margin rates (DRM) of 10 mm or less after sphincter-preserving surgery were similar in both arms (TNT 17.5% versus CRT 22.1%). However, a higher cumulative incidence of LRR was observed with a DRM of 10 mm or less after TNT (25.4% versus 1.8%; HR 15.51). Other factors were similar between treatment arms with respect to LRR.

CONCLUSION

The difference in LRR between TNT and CRT mainly occurred in patients treated with sphincter-preserving surgery. Baseline information on the original tumour bed should be considered when determining the surgical approach after total neoadjuvant treatment.

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Address: GROW, School for Oncology and Reproduction, Maastricht University, Maastricht, The Netherlands.; Department of Surgery, Netherlands Cancer Institute, Amsterdam, The Netherlands.; Department of Surgery, Leiden University Medical Centre, Leiden, The Netherlands.; Department of Radiation Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands.; Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.; Department of Pathology, Radboud University Medical Centre, Nijmegen, The Netherlands.; GROW, School for Oncology and Reproduction, Maastricht University, Maastricht, The Netherlands.; Department of Radiology, Netherlands Cancer Institute, Amsterdam, The Netherlands.; Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark.; Department of Nuclear Medicine/Radiation Physics, Karolinska University Hospital, Stockholm, Sweden.; Department of Surgery, University Medical Centre Groningen, Groningen, The Netherlands.; Department of Medical Oncology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands.; Department of Surgery, Leiden University Medical Centre, Leiden, The Netherlands.; Department of Biomedical Data Sciences, Leiden University Medical Centre, Leiden, The Netherlands.; Department of Pelvic Cancer, Karolinska University Hospital, Stockholm, Sweden.; Department of Radiation Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands.; Department of Radiation Oncology, Leiden University Medical Centre, Leiden, The Netherlands.

DOI: 10.1093/bjs/znaf190

MeSH Terms: Humans, Rectal Neoplasms, Neoadjuvant Therapy, Neoplasm Recurrence, Local, Male, Female, Middle Aged, Aged, Chemoradiotherapy, Antineoplastic Combined Chemotherapy Protocols, Adult, Chemoradiotherapy, Adjuvant, Leucovorin, Capecitabine