Risk and location of distant metastases in patients with locally advanced rectal cancer after total neoadjuvant treatment or chemoradiotherapy in the RAPIDO trial

• Published in: European journal of cancer (1990) Vol. 185; pp. 139 - 149
• Main Authors: Bahadoer, Renu R., Hospers, Geke A.P., Marijnen, Corrie A.M., Peeters, Koen C.M.J., Putter, Hein, Dijkstra, Esmée A., Kranenbarg, Elma Meershoek-Klein, Roodvoets, Annet G.H., van Etten, Boudewijn, Nilsson, Per J., Glimelius, Bengt, van de Velde, Cornelis J.H.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-05-2023
• Subjects: Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Chemoradiotherapy; Distant metastases; Humans; Medicin och hälsovetenskap; Metastatic pattern; Neoadjuvant Therapy; Neoplasm Recurrence, Local - pathology; Neoplasm Staging; Neoplasms, Second Primary - pathology; Rectal cancer; Rectal Neoplasms - pathology; Rectum - pathology; Total neoadjuvant therapy; Treatment Outcome; Rectal cancer; Distant metastases; Metastatic pattern; Total neoadjuvant therapy
• ISSN: 0959-8049; 1879-0852; 1879-0852
• DOI: 10.1016/j.ejca.2023.02.027

Although optimising rectal cancer treatment has reduced local recurrence rates, many patients develop distant metastases (DM). The current study investigated whether a total neoadjuvant treatment strategy influences the development, location, and timing of metastases in patients diagnosed with high-risk locally advanced rectal cancer included in the Rectal cancer And Pre-operative Induction therapy followed by Dedicated Operation (RAPIDO) trial.
Patients were randomly assigned to short-course radiotherapy followed by 18 weeks of CAPOX or FOLFOX4 before surgery (EXP), or long-course chemoradiotherapy with optional postoperative chemotherapy (SC-G). Assessments for metastatic disease were performed pre- and post-treatment, during surgery, and 6, 12, 24, 36, and 60 months postoperatively. From randomisation, differences in the occurrence of DM and first site of metastasis were evaluated.
In total, 462 patients were evaluated in the EXP and 450 patients in the SC-G groups. The cumulative probability of DM at 5 years after randomisation was 23% [95% CI 19–27] and 30% [95% CI 26–35] (HR 0.72 [95% CI 0.56–0.93]; P = 0.011) in the EXP and SC-G, respectively. The median time to DM was 1.4 (EXP) and 1.3 years (SC-G). After diagnosis of DM, median survival was 2.6 years [95% CI 2.0–3.1] in the EXP and 3.2 years [95% CI 2.3–4.1] in the SC-G groups (HR 1.39 [95% CI 1.01–1.92]; P = 0.04). First occurrence of DM was most often in the lungs (60/462 [13%] EXP and 55/450 [12%] SC-G) or the liver (40/462 [9%] EXP and 69/450 [15%] SC-G). A hospital policy of postoperative chemotherapy did not influence the development of DM.
Compared to long-course chemoradiotherapy, total neoadjuvant treatment with short-course radiotherapy and chemotherapy significantly decreased the occurrence of metastases, particularly liver metastases.
•With the experimental treatment, the risk of distant metastases is reduced.•The metastatic pattern of LARC changed after the RAPIDO total neoadjuvant schedule.•The experimental treatment caused a decrease in liver metastases.•This treatment did not change the timing of the diagnosis of DM.•Survival after DM was poorer in the experimental group.