Treatment patterns and outcomes of locally advanced rectal cancer in a real-world scenario

Keywords

locally advanced rectal cancer - total neoadjuvant therapy - total mesorectal excision

Introduction: Rectal tumors have a higher local recurrence risk than colon tumors at similar stages. The standard treatment for locally advanced rectal cancer (LARC) is total neoadjuvant therapy (TNT), which includes chemotherapy (ChT) and radiotherapy followed by total mesorectal excision (TME). TNT reduces the risk of local and systemic recurrence. With various approved TNT regimens, treatment should be individualized. This study aims to evaluate the treatment patterns and outcomes of these patients.

Methods: We retrospectively analyzed patients with LARC treated from January 2020 to June 2024 in a national cancer network. Clinical features, oncologic treatments, and outcomes were reviewed from electronic records.

Results: We evaluated 192 patients, 72% with ECOG performance status 0, and 67% at stage III (30% stage IIIc). Tumor locations were 51% low rectal, 39% mid-rectal, and 9% high rectal. Overall, 92% received neoadjuvant therapy (the few patients who did not receive it had mainly – 93.8% – high or mid-rectal tumors); 73% received TNT, and 24% received chemoradiotherapy (CRT) alone. The TNT group had a higher proportion of stage III tumors than the CRT alone group (81.4% vs 56.2%, p = 0.004). The TNT regimen chosen were: 51.6% CRT followed by FOLFOX/CAPOX (OPRA regimen), 24.6% short-course radiotherapy and FOLFOX/CAPOX (RAPIDO regimen), 12% FOLFOX/CAPOX followed by CRT (OPRA regimen), and FOLFIRINOX followed by CRT (PRODIGE regimen) (8%). After neoadjuvant therapy, the pathologic complete response (pCR) was 25.0% with TNT and 11.7% with CRT alone (p = 0.137). Comparing the TNT types, the pCR rates were: 27.2% with RAPIDO regimen, 0% with PRODIGE regimen, and 29.7% with OPRA regimen (p = 0.315). At a median follow-up of 19 months, the 2-year disease-free survival (DFS) was 70.1%, with neoadjuvant CRT alone and 79.4% with TNT (HR 0.73, 95% CI 0.37–1.43). No significant difference was observed between the TNT regimens. 2-year DFS was 75.2% with RAPIDO, 80% with PRODIGE (PRODIGE vs. RAPIDO: HR 0.91, 95% CI 0.18–4.42), and 85.4% with OPRA (OPRA vs. RAPIDO: HR 0.63, 95% CI 0.23–1.70). Discussion: Most stage III patients with low rectal tumors received TNT in this cohort. No significant difference was observed according to TNT type. Treatment choices should be individualized and ideally determined in a tumor board.

Corresponding author: Marina Nishimuni (e-mail: [e-mail]).