The Phenomenon of "Therapeutic" Nodal Yield at Cystectomy for Bladder Cancer: Do Not Discount the Will Rogers Effect

While multiple mechanisms have been hypothesized to explain the therapeutic effect of lymph node (LN) yield in patients with urothelial cell carcinoma (UCC) undergoing radical cystectomy (RC), the effect of stage migration, commonly known as the Will Rogers effect, is often discounted. We reviewed the National Cancer Database for patients with UCC undergoing RC with pathologically node-negative (pN0) disease from 2004 to 2016. We tested for an adjusted association between LN yield and overall survival using multivariable Cox proportional-hazard models. Median survival was estimated using the Kaplan-Meier method. We identified 19 939 patients with pN0 UCC treated with RC. After adjustment, patients in the highest quantile for LN yield (≥26 LNs) had a 34% lower risk of death in comparison to patients in the lowest quantile (≤5 LNs). As we increased the threshold for LN yield for dichotomization from >5 to >15 to >25 LNs, median survival increased from 83 to 95 to 103 mo. The pN0 group with higher LN yield appeared to live longer in this analysis owing to the mathematical artifact of how patients are indexed. Resection of a greater number of negative LNs will lead to higher fidelity for pN0 cohorts being evaluated, as the likelihood of contamination by pN+ cases that were missed will be lower.

A strategy to dissect a high number of lymph nodes in patients undergoing removal of their bladder for bladder cancer can be associated with side effects, and the benefit in terms of cancer control or survival remains uncertain. Urologists and their patients should engage in shared decision-making and consider the risks and benefits of more extensive lymph node dissection during surgery.