Long-term recurrence patterns in rectal cancer after neoadjuvant therapy: Insights from 25-years of real-world data.

Abstract

239 Background: The management of locally-advanced rectal cancer has significantly evolved over recent years with the adoption of total neoadjuvant therapy (TNT). However, a lot of uncertainty remains regarding the selection of the optimal TNT regimen for the individual patient. We aimed to assess recurrence patterns in rectal cancer to improve patient risk stratification and neoadjuvant treatment decision-making. Methods: We conducted a cohort study of 850 rectal cancer patients treated with neoadjuvant radio- and chemotherapy over a 25-year period at the Leuven University Hospitals. Results: After a median follow-up of 12 years, the 5-year overall survival (OS) and disease-free survival (DFS) were 86.8% and 75.5% respectively. Overall, 167 (19.6%) patients developed a recurrence of which 31 (3.6%) patients had a locoregional recurrence (LRR), while 158 (18.6%) patients developed distant metastases (DM), and 22 (2.6%) patients experienced both LRR and DM. At 5 years, recurrence-free survival (RFS) was 76.9% (95% CI: 74.1%-79.9%), distant metastasis-free survival (DMFS) was 77.8% (95% CI: 75.0%-80.7%) and locoregional recurrence-free survival (LRFS) was 85.1% (95% CI: 82.7%-87.7%). Independent predictors of distant recurrence included lymphovascular invasion (LVI) (p<0.001), perineural invasion (PNI) (p=0.004), positive circumferential resection margin (CRM) (p=0.046) and higher lymph node ratio (LN-ratio) (p<0.001), while tumor diameter (p=0.025) and LN-ratio (p=0.047) were independent predictors of LRR. In contrast, no clinical or treatment-related factors demonstrated a significant association with recurrence on multivariable analysis. Patients with an early recurrence had a worse OS than late recurring patients, while post-recurrence survival (PRS) was not significantly different between the two groups. Factors associated with early recurrence were higher ypN-stage, LVI, larger tumor diameter, number of examined lymph nodes and LN-ratio. Conclusions: This study underscores the high prognostic value of histopathological features and tumor response to neoadjuvant treatment in rectal cancer. Hence, there is a clear need for reliable predictive biomarkers that can predict tumor response to neoadjuvant therapy at baseline. Although early recurrence comes at the cost of a reduced OS, post-recurrence survival is similar between early and late recurrence patients.