Oncological outcomes of standard versus prolonged time to surgery after neoadjuvant chemoradiotherapy for oesophageal cancer in the multicentre, randomised, controlled NeoRes II trial

K Nilsson; F Klevebro; B Sunde; I Rouvelas; M Lindblad; E Szabo; I Halldestam; U Smedh; B Wallner; J Johansson; G Johnsen; E K Aahlin; H-O Johannessen; G Alexandersson von Döbeln; G O Hjortland; N Wang; Y Shang; D Borg; A Quaas; I Bartella; C Bruns; W Schröder; M Nilsson

doi:10.1016/j.annonc.2023.08.010

Oncological outcomes of standard versus prolonged time to surgery after neoadjuvant chemoradiotherapy for oesophageal cancer in the multicentre, randomised, controlled NeoRes II trial

Ann Oncol. 2023 Nov;34(11):1015-1024. doi: 10.1016/j.annonc.2023.08.010. Epub 2023 Aug 30.

Authors

K Nilsson¹, F Klevebro¹, B Sunde¹, I Rouvelas¹, M Lindblad¹, E Szabo², I Halldestam³, U Smedh⁴, B Wallner⁵, J Johansson⁶, G Johnsen⁷, E K Aahlin⁸, H-O Johannessen⁹, G Alexandersson von Döbeln¹⁰, G O Hjortland¹¹, N Wang¹², Y Shang¹³, D Borg¹⁴, A Quaas¹⁵, I Bartella¹⁶, C Bruns¹⁶, W Schröder¹⁶, M Nilsson¹⁷

Affiliations

¹ Department of Upper Abdominal Diseases, Karolinska University Hospital, Stockholm; Division of Surgery and Oncology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm.
² Department of Surgery, Faculty of Medicine and Health, Örebro University Hospital, Örebro.
³ University Hospital of Linköping, Linköping.
⁴ Department of Surgery, Sahlgrenska University Hospital, Gothenburg.
⁵ Department of Surgical and Perioperative Sciences, Surgery, Umeå University, Umeå.
⁶ Department of Surgery, Skåne University Hospital, Lund, Sweden.
⁷ Department of Gastrointestinal Surgery, St. Olav's Hospital, Trondheim University Hospital, Trondheim.
⁸ Department of GI and HPB Surgery, University Hospital of Northern Norway, Tromsø.
⁹ Department of Gastrointestinal Surgery, Oslo University Hospital, Oslo, Norway.
¹⁰ Division of Surgery and Oncology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm; Medical Unit of Head, Neck, Lung and Skin Cancer, Karolinska University Hospital, Stockholm, Sweden.
¹¹ Department of Oncology, Oslo University Hospital, Oslo, Norway.
¹² Department of Clinical Pathology and Cancer Diagnostics, Karolinska University Hospital, Stockholm.
¹³ Department of Medicine Huddinge, Karolinska Institutet, Stockholm.
¹⁴ Department of Oncology, Skåne University Hospital, Lund, Sweden.
¹⁵ Institute of Pathology, University of Cologne, Cologne.
¹⁶ Department of General, Visceral, Cancer and Transplantation Surgery, University Hospital of Cologne, Cologne, Germany.
¹⁷ Department of Upper Abdominal Diseases, Karolinska University Hospital, Stockholm; Division of Surgery and Oncology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm. Electronic address: magnus.nilsson@ki.se.

PMID: 37657554
DOI: 10.1016/j.annonc.2023.08.010

Abstract

Background: The optimal time to surgery (TTS) after neoadjuvant chemoradiotherapy (nCRT) for oesophageal cancer is unknown and has traditionally been 4-6 weeks in clinical practice. Observational studies have suggested better outcomes, especially in terms of histological response, after prolonged delay of up to 3 months after nCRT. The NeoRes II trial is the first randomised trial to compare standard to prolonged TTS after nCRT for oesophageal cancer.

Patients and methods: Patients with resectable, locally advanced oesophageal cancer were randomly assigned to standard delay of surgery of 4-6 weeks or prolonged delay of 10-12 weeks after nCRT. The primary endpoint was complete histological response of the primary tumour in patients with adenocarcinoma (AC). Secondary endpoints included histological tumour response, resection margins, overall and progression-free survival in all patients and stratified by histologic type.

Results: Between February 2015 and March 2019, 249 patients from 10 participating centres in Sweden, Norway and Germany were randomised: 125 to standard and 124 to prolonged TTS. There was no significant difference in complete histological response between AC patients allocated to standard (21%) compared to prolonged (26%) TTS (P = 0.429). Tumour regression, resection margins and number of resected lymph nodes, total and metastatic, did not differ between the allocated interventions. The first quartile overall survival in patients allocated to standard TTS was 26.5 months compared to 14.2 months after prolonged TTS (P = 0.003) and the overall risk of death during follow-up was 35% higher after prolonged delay (hazard ratio 1.35, 95% confidence interval 0.94-1.95, P = 0.107).

Conclusion: Prolonged TTS did not improve histological complete response or other pathological endpoints, while there was a strong trend towards worse survival, suggesting caution in routinely delaying surgery for >6 weeks after nCRT.

Keywords: neoadjuvant chemoradiotherapy; oesophageal adenocarcinoma; oesophageal squamous cell carcinoma; prolonged time; standard time; surgery.

Publication types

Clinical Trial, Phase II
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Adenocarcinoma* / drug therapy
Adenocarcinoma* / surgery
Chemoradiotherapy
Esophageal Neoplasms* / drug therapy
Esophageal Neoplasms* / surgery
Humans
Margins of Excision
Neoadjuvant Therapy
Progression-Free Survival
Time-to-Treatment