Predictors of Nodal Disease in Rectal Cancer Patients with Complete Mucosal Response to Neoadjuvant Therapy

Abstract

Background Some patients with locally advanced rectal cancer (LARC) achieve complete mucosal response following neoadjuvant therapy (NAT) and may be candidates for watch and wait strategy. This study aimed to identify predictors of nodal disease in patients with LARC who had a complete mucosal response to NAT. Methods This case–control study included patients with LARC who were treated with NAT in the National Cancer Database between 2004 and 2019. Patients with complete mucosal response, defined as pathologic T0, were identified and classified according to the status of the pathologic N stage into complete response (pT0, pN0) and complete mucosal response with positive nodal disease (pT0, pN +). The two groups were compared regarding baseline demographics and tumor characteristics to determine the predictors of nodal disease after NAT. Results A total of 5529 patients (59.7% male) with a mean age of 59.6 ± 12.2 years had a complete mucosal response following NAT. Nodal disease was detected in 443 (8%) patients with a complete mucosal response. Independent predictors of nodal disease were clinical N + stage (OR: 1.87, p < 0.001), mucinous histology (OR: 3.8, p = 0.003), and lymphovascular invasion (OR = 4.01, p < 0.001). The clinical T stage was inversely related to the risk of nodal disease. Conclusions Despite having a complete mucosal response following NAT, 8% of patients had nodal disease. Clinical evidence of nodal involvement on preoperative assessment, mucinous tumor histology, and lymphovascular invasion predicted nodal disease after NAT. These findings should be considered when making a decision on watch and wait strategy in patients with clinical complete response.

Non-operative management of rectal cancer: Highlighting the controversies

“…Furthermore, another hurdle related to the inaccurate assessment of clinical response is the potential of missing residual nodal disease even with a complete mucosal response. A large database analysis found that 8% of patients with complete mucosal response had positive lymph nodes on pathologic assessment after surgery[ 12 ]. These patients with residual nodal disease may not have been detected using imaging which has a low sensitivity in detecting nodal involvement in rectal cancer[ 13 ].…”