Lymph Node Involvement Tied to Worse Rectal Cancer Outcomes

TOPLINE: 
In patients with rectal cancer, having persistent lymph node metastases after neoadjuvant chemoradiotherapy is associated with worse overall survival outcomes and higher rates of recurrence and distant metastasis, a new analysis found.
METHODOLOGY:
Patients with locally advanced rectal cancer who have persistent lymph node metastasis after neoadjuvant therapy face a higher risk for recurrence. Despite advances in neoadjuvant approaches, patients still demonstrate poor long-term outcomes.
In the current cohort study, researchers evaluated how pretreatment clinicopathologic parameters and neoadjuvant treatment intensity may affect long-term outcomes. The study included 1888 eligible patients (median age, 62 years) with locally advanced rectal cancer (tumor stage 3-4 and/or clinically node positive) from three randomized trials conducted in Germany.
Patients received treatments of varying intensities — preoperative fluorouracil-based chemoradiotherapy (n = 1009), fluorouracil-based chemoradiotherapy plus oxaliplatin (n = 586), or total neoadjuvant treatment with fluorouracil-based chemoradiotherapy plus oxaliplatin with induction or consolidation FOLFOX (n = 293).
The median follow-up after curative resection was 54 months.
Following neoadjuvant therapy, lymph node metastases were observed in 552 patients (29%) — 174 (9%) of whom had more extensive lymph node involvement (ypN2). The remaining 1336 patients (71%) had no lymph node involvement. Patients with more extensive lymph node disease were significantly younger than those with less or no lymph node involvement (median of 59 vs 62 years).
TAKEAWAY:
After a median follow-up of 54 months, the 5-year cumulative incidences of locoregional and distant metastases were highest for patients with extensive lymph node involvement (19% and 72%, respectively) compared with those with no (3% and 20%, respectively) or low involvement (6% and 40%, respectively).
Similarly, the 5-year overall survival rate was also worst among patients with extensive involvement (43%) compared to those with no (86.1%) or low involvement (74%).
The percentage of patients with extensive lymph node involvement was lowest following total neoadjuvant treatment (6%) compared with fluorouracil-based chemoradiotherapy (11.3%) and chemoradiotherapy plus oxaliplatin (7.2%). But the intensity of neoadjuvant treatment did not significantly affect patients’ overall survival or recurrence outcomes.
Patients with more and less extensive lymph node involvement had higher carcinoembryonic antigen levels (5 ng/mL and 4.1 ng/mL, respectively) than those without lymph node involvement (2.8 ng/mL). Higher tumor stage and grades were also associated with lymph node metastases, though sex and tumor location were not.
IN PRACTICE:
“Persistent lymph node metastases unmask an aggressive phenotype of rectal cancer at high risk for treatment failure irrespective of intensity of neoadjuvant treatment,” the authors concluded. “Early initiation of recurrence-directed surgery, if feasible, is an important strategy in this group of patients with chemoradiotherapy and/or chemotherapy resistant disease.”
SOURCE:
The study, led by Markus Diefenhardt, MD, University Hospital, Frankfurt, Germany, was published online in JAMA Network Open.
LIMITATIONS:
The study’s limitations include its post hoc design. Slight differences in inclusion criteria across the three studies, and the mandatory use of MRI in all, could affect comparability. Additionally, the study might be underpowered to detect the effects of neoadjuvant treatment on the relationship between lymph node stage and long-term outcomes. 
DISCLOSURES:
The study was supported by grants from German Cancer Aid. Two authors reported receiving personal fees or honoraria from various sources.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
 
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