Effect of Neoadjuvant Radiation Dose and Schedule on Nodal Count and Its Prognostic Impact in Stage II-III Rectal Cancer

It is unknown how neoadjuvant treatment schedule affects lymph node count (LNC) and lymph node ratio (LNR) and how these correlate with overall survival (OS) in rectal cancer (RC). Data were used from the Belgian PROCARE rectal cancer registry on RC patients treated with surgery alone, short-term radiotherapy with immediate surgery (SRT), or chemoradiation with deferred surgery (CRT). The effect of neoadjuvant therapy on LNC was examined using Poisson log-linear analysis. The association of LNC and LNR with overall survival (OS) was studied using Cox proportional hazards models. Data from 4037 patients were available. Compared with surgery alone, LNC was reduced by 12.3 % after SRT and by 31.3 % after CRT (p < 0.001). In patients with surgery alone, the probability of finding node-positive disease increased with LNC, while after SRT and CRT no increase was noted for more than 12 and 18 examined nodes, respectively. Per node examined, we found a decrease in hazard of death of 2.7 % after surgery alone and 1.5 % after SRT, but no effect after CRT. In stage III patients, the LNR but not (y)pN stage was significantly correlated with OS regardless of neoadjuvant therapy. Specifically, a LNR > 0.4 was associated with a significantly worse outcome. Nodal counts are reduced in a schedule-dependent manner by neoadjuvant treatment in RC. After chemoradiation, the LNC does not confer any prognostic information. A LNR of > 0.4 is associated with a significantly worse outcome in stage III disease, regardless of neoadjuvant therapy type.