Neoadjuvant Therapy for Rectal Cancer Affects Lymph Node Yield and Status Without Clear Implications on Outcome: The Case for Eliminating a Metric and Using Preoperative Staging to Guide Therapy

Abstract

Background Nodal status has long been considered pivotal to oncologic care, staging, and management. This has resulted in rudimentary metrics determined for adequate lymph node yield in colon and rectal cancers for accurate cancer staging. In the era of neoadjuvant treatment the implications of lymph node yield and status on patient outcomes remains unclear. Patient and Methods The study included 1,680 locally advanced rectal cancer patients from the National Comprehensive Cancer Network (NCCN) prospective oncology database stratified into 3 groups based on preoperative therapy received: No neoadjuvant therapy, neoadjuvant chemoradiation, neoadjuvant chemotherapy. Clinicopathologic characteristics and survival were compared between groups with univariate and multivariate analyses undertaken. Results The 3 groups’ clinicopathologic characteristics demonstrated statistically significant differences and heterogeneity between groups. The neoadjuvant chemoradiation group demonstrated the statistically lowest median lymph node yield (15) compared to 17 and 18 for no neoadjuvant, and neoadjuvant chemotherapy, respectively (p<0.0001). Neoadjuvant treatment did impact survival with chemoradiation demonstrating increased median overall survival of 42.7 compared to 37.3 and 26.6 months for neoadjuvant chemotherapy and no neoadjuvant therapy, respectively (p<0.0001). Patients with <12 lymph node yield had improved median overall survival of 43.3 months compared to 36.6 months in patients with ≥12 lymph nodes (p=0.009). Multivariate analysis demonstrated that neither node yield nor status were predictors for overall survival. Discussion This analysis reiterates that nodal yield in rectal cancer is multi-factorial with neoadjuvant therapy being a significant factor. Node yield and status were not significant predictors of overall survival. A nodal metric may not be clinically relevant in the era of neoadjuvant therapy and guidelines for perioperative therapy may need reconsideration.

The prognostic impact of neoadjuvant chemoradiotherapy on lymph node sampling in patients with locally advanced rectal cancer

“…The lower number of lymph nodes retrieved after NACRT from the patients included in our study compared with the number retrieved in patients who did not receive NACRT could indicate an improved response to treatment rather than inadequate surgical resection and/or pathologic examination. Moreover, fewer lymph nodes in a surgical sample could be used as a marker for favorable tumor behavior and, consequently, a good prognosis [ 3 – 5 , 19 , 20 , 22 , 24 ].…”

Comparison of efficacy and safety of preoperative Chemoradiotherapy in locally advanced upper and middle/lower rectal cancer

“…McCarthy et al analyzed 6 randomised controlled trials and found a reduction in local recurrence in the NACRT group in comparison to the preoperative RT group (OR = 0.56, 95%CI 0.42–0.75, P < 0.0001), yet the results for overall survival were (OR = 1.01 95%CI 0.85–1.20, P = 0.88) for these patients with T3–4, node positive (locally advanced) rectal cancer [ 26 ]. Abdel et al studied 1680 patients with locally advanced rectal cancer and found NACRT increased median overall survival of 42.7 compared to 37.3 and 26.6 months for neoadjuvant chemotherapy and no neoadjuvant therapy, respectively ( P < 0.0001) [ 27 ]. The evidence is growing that NACRT may alter prognosis for patients with rectal cancer.…”

Neoadjuvant chemoradiation and rectal cancer

“…The NACR group had the lowest lymph node counts, almost two to three lymph nodes less than the other two groups 22. Furthermore, the group with <12 lymph nodes demonstrated a median overall survival of 43.3 months in comparison with 36.6 months to the cohort with ≥12 lymph nodes (p=0.009) 21.…”

“…Abdel-Misih et al looked at lymph node counts in three cohorts of patients22: (1) those who did not receive any neoadjuvant therapy, (2) patients who received NACR and (3) a group treated by neoadjuvant chemotherapy only. The NACR group had the lowest lymph node counts, almost two to three lymph nodes less than the other two groups 22.…”