Validation of Preoperative Risk Grouping of the Selection of Patients Most Likely to Benefit From Neoadjuvant Chemotherapy Before Radical Cystectomy

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Neoadjuvant chemotherapy (NAC) has been demonstrated to be effective in prospective randomized trials for cT2-cT4a N0 patients. However, this benefit was more evident in patients with clinical stage ≥ T3 disease. On the other hand, toxicity grade 3 and 4 were reported in 35% and 37% of patients who underwent NAC. Following these considerations, we validate here the preoperative risk model proposed by Culp et al as a fundamental tool in the preoperative prediction of patients who will benefit more from NAC administration.


The aim of this study was to validate the value of preoperative patient characteristics in prognosticating survival after radical cystectomy (RC) to guide treatment decisions regarding neoadjuvant systemic treatment.


We evaluated a single cohort of 449 consecutive patients treated with RC for bladder cancer. Patients treated with neoadjuvant therapy were excluded from the study cohort (n = 24). Patients were stratified based on preoperative characteristics into 2 risk groups. The high-risk group included patients harboring clinically non–organ-confined disease (≥ cT3), hydroureteronephrosis, lymphovascular invasion, or variant histology (micropapillary, neuroendocrine, sarcomatoid, or plasmacytoid variants on transurethral resection). The low-risk group included patients with cT2 disease without any of the aforementioned features. Survival expectancies after surgery were evaluated using competing risk and Kaplan-Meier analyses.


We identified 153 (44.6%) low-risk and 190 (55.4%) high-risk patients. The majority of high-risk patients had only 1 high-risk feature (n = 111; 58.4%); the most common high-risk feature was preoperative hydroureteronephrosis (n = 107; 56.3%). The majority of low-risk patients were upstaged at time of RC (n = 118; 70.6%), whereas a pathologic downstage occurred only in 27 high-risk patients (14.2%). Cancer-specific mortality-free rates at 5 years after RC were 77.4% versus 64.4% for low-risk versus high-risk patients, respectively.


We confirm that preoperative risk features can stratify patients with muscle-invasive bladder cancer into differential risk groups regarding survival. Decision-making regarding neoadjuvant systemic therapy administration is likely to be improved by integrating clinical stage, lymphovascular invasion, variant histology, and hydroureteronephrosis.

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