EP374 - Evaluation of Lymph Node Retrieval with Evolution of Neoadjuvant Rectal Cancer Therapy

Purpose/Background: A standard quality measure of definitive surgery for rectal cancer includes a harvest of at least 12 lymph nodes, as this has been associated with accurate staging and improved survival. There has been a paradigm shift in treatment for locally advanced rectal cancer from neoadjuvant chemoradiation (nCRT) to total neoadjuvant therapy (TNT) including both chemotherapy (NACT) and nCRT prior to surgery. While first described in 2012, TNT has quickly gained popularity and is now part of the NCCN guidelines. Few studies have shown nCRT alone may lead to a decreased lymph node count, but the additional effects of NACT as part of TNT have not been investigated. It is important to understand the anatomic effects of TNT on resulting lymph node yield to interpret pathologic results and adjust standard quality measures.

Methods/Interventions: The National Cancer Database (NCDB) was queried from 2004 to 2021. Inclusion criteria were patients aged >18 years old, diagnosed with invasive rectal cancer, and underwent non-emergent definitive surgery including total mesorectal excision (TME). Patients were divided into the following four groups: 1) surgery first (no neoadjuvant), 2) NACT, 3) nCRT, and 4) TNT. Chi squared test was used to study the primary endpoint of lymph node count. Logistic regression for 0-11 nodes vs 12 or more was considered with the demographic confounders.

Results/Outcomes: 151,687 patients met the inclusion criteria and were divided accordingly: 51,841 (34.2%) had no neoadjuvant therapy, 4,338 (2.9%) had NACT, 74,240 (48.9%) received nCRT, and 21,268 (14.0%) received TNT. Median age was 60 years old; 60.5% were male and 39.5% were female. The average clinical stage of the entire cohort was 14.1% Stage I, 22.3% Stage II, 31.8% Stage III, 6.5% Stage IV, and 25.3% unknown. There was a significant difference in treatment modality based on clinical staging (p <.0001), 31.9% of the surgery only group were Stage I; 44.4% of NACT were Stage IV. Within the nCRT group, 32.7% were Stage II and 44.4% were Stage III. The TNT group was comprised of 22.1% Stage II and 51.2% Stage III disease. 104,054 (68.6%) of the entire cohort had >12 lymph nodes; 23,321 (15.4%) had 7-11 lymph nodes; 24,312 (16.0%) had 0-6 lymph nodes. When further analyzed by the impact of neoadjuvant treatment, there was a significant difference in nodes retrieved (p <.0001). Those meeting the measure of >12 lymph nodes were: 73.2% surgery, 75.9% NACT, 64.3% nCRT, and 70.8% TNT. Compared to surgery first, all treatments were associated with significantly higher rates of suboptimal retrieval of lymph nodes. The adjusted odds ratios (AOR) for suboptimal retrieval of lymph nodes were: NACT had an AOR of 1.51 (95% CI: 1.39-1.63, p<.0001), nCRT AOR was 2.22 (2.15-2.29, p<.0001), and TNT had an AOR 2.25 (2.15-2.34, p<.0001) compared to surgery.

Conclusion/Discussion: Focus on TME over the last 2 decades has led to overall improvement of lymph node retrieval. While neoadjuvant therapies have evolved over this time, the quality standard of 12 lymph node retrieval has remained since its inception. This analysis illustrates that patients who receive neoadjuvant radiation (nCRT or TNT) were significantly more likely to have lower lymph node yields though NACT did not add to this phenomenon. This study also demonstrates only 73% of patients with upfront surgery achieved a yield of 12 nodes. Neoadjuvant treatment and other potential factors affecting lymph node yield should be considered when examining pathology specimens for quality measures.

Adjusted Odds Ratio of Lymph Node Retrieval Based on Neoadjuvant Treatment 
Adjusted odds ratios for substandard lymph node retrieval (0 to 11 lymph nodes) by treatment: surgery first (no neoadjuvant), chemotherapy only (NACT), chemoradiation only (nCRT), and total neoadjuvant therapy (TNT). Analysis controls for confounders of age, sex, race, analytic stage, diagnosis, year, and facility type.