Occult Nodal Metastases in Patients Down-Staged to Nonmuscle Invasive Disease Following Neoadjuvant Chemotherapy

Objectives To evaluate the risk of occult nodal metastasis in patients with muscle invasive bladder cancer who exhibit a complete or partial clinical response to neoadjuvant chemotherapy (NAC) and assess a potential role for “bladder sparing” management given that the gold standard treatment, radical cystectomy (RC), is associated with high morbidity. Methods We queried the National Cancer Database for bladder cancer from 2004 to 2013 including patients with cT2-4aN0M0 bladder cancer who underwent multiagent NAC followed by RC and pelvic lymphadenectomy and excluding patients with nonurothelial predominant histology and those undergoing partial cystectomy. Student's t test was used to evaluate patients’ demographics, presence of co-morbid conditions, and pathologic findings, notably the presence of lymphovascular invasion and variant histology. Results We identified 17,917 patients who underwent RC. Of these, 14.9% (n = 2673) received NAC before RC. About 13.1% and 14.5% of patients had complete (ypT0) and partial (ypTa, Tis, and T1) pathologic response, respectively. These 14.7% of cT2, 9.0% of cT3, and 6.9% of cT4 patients exhibited pT0 status on final pathology. And 4.9% of complete and 5.4% of partial responders demonstrated occult nodal metastases. Age, sex, ethnicity, the presence of co-morbidities, LVI, and variant histology were not significantly associated with occult nodal metastasis. Conclusion While bladder preservation may be a viable option in patients who are carefully selected and closely followed after NAC, patients undergoing NAC may be at risk of occult disease outside of the bladder despite an otherwise clinical complete response diagnosed with cross-sectional imaging, cystoscopy, TURBT, and cytology.