Malignant features present in pre-treatment lateral pelvic lymph nodes in low rectal cancer predict distant metastases and survival, but not local recurrences

Abstract

Background: Pre-treatment enlarged lateral lymph nodes (LLNs) in patients with low rectal cancer predict local recurrences after neoadjuvant (chemo)radiotherapy (n(C)RT) followed by total mesorectal excision (TME). Not much is known what the impact on oncological outcomes is when malignant features are present in LLNs. Materials and Methods: An international multi-center cohort study at five tertiary referral centers in the Netherlands and Australia was conducted. All patients were diagnosed with low rectal cancer with or without LLNs on pre-treatment MRI and underwent n(C)RT followed by TME. LLNs were considered enlarged in case of a short-axis of ≥5mm on pre-treatment MRI. Malignant features in LLNs were defined as nodes with internal heterogeneity or border irregularity. Survival was estimated using the Kaplan-Meier method with the Mantel-Haenszel test. Three-year recurrences were evaluated with the Chi-square/Fisher's exact test. Results: A total of 213 patients were included. The majority was male (67.7%) with a median age of 64 years (range 20-89). Median pre-treatment LLN short-axis was 7mm (range 5-28), 52.2% of the LLNS had malignant features. After a median follow-up of 47 months, patients with enlarged LLNs (7-9mm and 10mm+) had a worse local recurrence-free survival (LRFS; p<0.0001), but similar distant metastatic-free (DMFS; p=0.30) and overall survival (OS; p=0.27) compared to patients with smaller LLNs (0-4 and 5-6mm). On the other hand, patients with malignant features in LLNs had a similar LRFS (p=0.20), but worse DMFS (p=0.004) and OS (p=0.006) compared to patients without malignant features in the LLNs. Similar patterns were seen upon three-year recurrence analysis (table). Conclusions: Malignant features present in LLNs on pre-treatment MRI are predictive for worse DMFS and OS, but not for local recurrences.