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Background:  In the West, pre-treatment abnormal lateral lymph nodes (LLN+) in patients with a low locally advanced rectal cancer (AJCC Stage III), are treated with neoadjuvant (chemo)radiotherapy (nCRT), without a lateral lymph node dissection (LLND). It has been suggested, however, that LLN+ patients have higher local recurrence (LR) rates than similarly staged patients with abnormal mesorectal lymph nodes only (LLN−), but no comparative data exist. Therefore, we conducted this international multi-center study in the Netherlands and Australia of Stage III rectal cancer patients with either LLN+ or LLN− to compare oncological outcomes from both groups.   Materials and Methods:  Patients with Stage III low rectal cancer with (LLN+ group) or without (LLN− group) abnormal lateral lymph nodes on pre-treatment MRI were included. Patients underwent nCRT followed by rectal resection surgery with curative intent between 2009 and 2016 with a minimum follow-up of 2-years. No patient had a LLND. Propensity score matching corrected differences in baseline characteristics.   Results:  Two hundred twenty-three patients could be included: 125 in the LLN+ group and 98 in the LLN− group. Between groups, there were significant differences in cT-stage and in the rate of adjuvant chemotherapy administered. Propensity score matching resulted in 54 patients in each group, with equal baseline characteristics. The 5-year LR rate in the LLN+ group was 11 vs. 2% in the LLN− group ( P  = 0.06) and disease-free survival (DFS) was 64 vs. 76%, respectively ( P  = 0.09). Five-year overall survival was similar between groups (73 vs. 80%, respectively;  P  = 0.90).   Conclusions:  In Western patients with Stage III low rectal cancer, there is a trend toward worse LR rate and DFS rates in LLN+ patients compared to similarly staged LLN− patients. These results suggest that LLN+ patients may currently not be treated optimally with nCRT alone, and the addition of LLND requires further consideration.

Lateral Lymph Node Metastases in Locally Advanced Low Rectal Cancers May Not Be Treated Effectively With Neoadjuvant (Chemo)Radiotherapy Only