Oncological outcomes after a pathological complete response following total neoadjuvant therapy or chemoradiotherapy for high-risk locally advanced rectal cancer in the RAPIDO trial

Wouter H Zwart; Sofieke J D Temmink; Geke A P Hospers; Corrie A M Marijnen; Hein Putter; Iris D Nagtegaal; Lennart Blomqvist; Elma Meershoek-Klein Kranenbarg; Annet G H Roodvoets; Anna Martling; Cornelis J H van de Velde; Bengt Glimelius; Koen C M J Peeters; Boudewijn van Etten; Per J Nilsson; Collaborative investigators

doi:10.1016/j.ejca.2024.114044

Oncological outcomes after a pathological complete response following total neoadjuvant therapy or chemoradiotherapy for high-risk locally advanced rectal cancer in the RAPIDO trial

Eur J Cancer. 2024 Apr 7:204:114044. doi: 10.1016/j.ejca.2024.114044. Online ahead of print.

Authors

Wouter H Zwart¹, Sofieke J D Temmink², Geke A P Hospers³, Corrie A M Marijnen⁴, Hein Putter⁵, Iris D Nagtegaal⁶, Lennart Blomqvist⁷, Elma Meershoek-Klein Kranenbarg⁸, Annet G H Roodvoets⁸, Anna Martling², Cornelis J H van de Velde⁸, Bengt Glimelius⁹, Koen C M J Peeters⁸, Boudewijn van Etten¹⁰, Per J Nilsson²; Collaborative investigators

Affiliations

¹ University Medical Center Groningen, Department of Medical Oncology, Groningen, the Netherlands. Electronic address: w.h.zwart@umcg.nl.
² Karolinska Institutet, Department of Molecular Medicine and Surgery, Stockholm, Sweden.
³ University Medical Center Groningen, Department of Medical Oncology, Groningen, the Netherlands.
⁴ Netherlands Cancer Institute, Department of Radiation Oncology, Amsterdam, the Netherlands; Leiden University Medical Center, Department of Radiation Oncology, Leiden, the Netherlands.
⁵ Leiden University Medical Center, Department of Biomedical Data Sciences, Leiden, the Netherlands.
⁶ Radboud University Medical Centre, Department of Pathology, Nijmegen, the Netherlands.
⁷ Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
⁸ Leiden University Medical Center, Department of Surgery, Leiden, the Netherlands.
⁹ Uppsala University, Department of Immunology, Genetics and Pathology, Uppsala, Sweden.
¹⁰ University Medical Center Groningen, Department of Surgery, Groningen, the Netherlands.

PMID: 38636289
DOI: 10.1016/j.ejca.2024.114044

Abstract

Background: A pathological complete response (pCR) following chemoradiation (CRT) or short-course radiotherapy (scRT) leads to a favourable prognosis in patients with rectal cancer. Total neo-adjuvant therapy (TNT) doubles the pCR rate, but it is unknown whether oncological outcomes remain favourable and whether the same characteristics are associated with pCR as after CRT.

Methods: Comparison between patients with pCR in the RAPIDO trial in the experimental [EXP] (scRT, chemotherapy, surgery, as TNT) and standard-of-care treatment [STD] (CRT, surgery, postoperative chemotherapy depending on hospital policy) groups. Primary and secondary outcomes were time-to-recurrence (TTR), overall survival (OS) and association between patient, tumour, and treatment characteristics and pCR.

Results: Among patients with a resection within six months after preoperative treatment, 120/423 (28%) [EXP] and 57/398 (14%) [STD] achieved a pCR. Following pCR, 5-year cumulative TTR and OS rates in the EXP and STD arms were 8% vs. 7% (hazard ratio 1.04, 95%CI 0.32-3.38) and 94% vs. 93% (hazard ratio 1.41, 95%CI 0.51-3.92), respectively. Besides the EXP treatment (odds ratio 2.70, 95%CI 1.83-3.97), pre-treatment carcinoembryonic antigen (CEA) <5, pre-treatment tumour size <40 mm and cT2 were associated with pCR. Distance from the anal verge was the only characteristic with a statistically significant difference in association with pCR between the EXP and STD treatment (P_interaction=0.042). pCR rates did not increase with prolonged treatment time.

Conclusions: The doubled pCR rate of TNT compared to CRT results in similar oncological outcomes. Characteristics associated with pCR are the EXP treatment, normal CEA, and small tumour size.

Keywords: Chemoradiation; Chemoradiotherapy; Complete response; Locally advanced rectal cancer; Pathological complete remission; Pathological complete response; RAPIDO trial; Total neoadjuvant therapy.