Refining patient selection for neoadjuvant chemotherapy before radical cystectomy

Abstract

Purpose: We evaluated the survival of patients with muscle invasive bladder cancer undergoing radical cystectomy without neoadjuvant chemotherapy to confirm the utility of existing clinical tools to identify low risk patients who could be treated with radical cystectomy alone and a high risk group most likely to benefit from neoadjuvant chemotherapy.

Materials and methods: We identified patients with muscle invasive bladder cancer who underwent radical cystectomy without neoadjuvant chemotherapy at our institution between 2000 and 2010. Patients were considered high risk based on the clinical presence of hydroureteronephrosis, cT3b-T4a disease, and/or histological evidence of lymphovascular invasion, micropapillary or neuroendocrine features on transurethral resection. We evaluated survival (disease specific, progression-free and overall) and rate of pathological up staging. An independent cohort of patients from another institution was used to confirm our findings.

Results: We identified 98 high risk and 199 low risk patients eligible for analysis. High risk patients exhibited decreased 5-year overall survival (47.0% vs 64.8%) and decreased disease specific (64.3% vs 83.5%) and progression-free (62.0% vs 84.1%) survival probabilities compared to low risk patients (p <0.001). Survival outcomes were confirmed in the validation subset. On final pathology 49.2% of low risk patients had disease up staged.

Conclusions: The 5-year disease specific survival of low risk patients was greater than 80%, supporting the distinction of high risk and low risk muscle invasive bladder cancer. The presence of high risk features identifies patients with a poor prognosis who are most likely to benefit from neoadjuvant chemotherapy, while many of those with low risk disease can undergo surgery up front with good expectations and avoid chemotherapy associated toxicity.

Keywords: 3-D; 3-dimensional; BC; CSM; DSS; EUA; HR; LR; LVI; MDACC; MIBC; NAC; OS; PFS; RC; TUR; USC; University of Southern California; University of Texas M.D. Anderson Cancer Center; VH; bladder cancer; cause specific mortality; cystectomy; disease specific survival; examination under anesthesia; high risk; low risk; lymphovascular invasion; muscle invasive bladder cancer; neoadjuvant chemotherapy; neoadjuvant therapy; outcomes assessment; overall survival; progression-free survival; radical cystectomy; risk; transurethral resection; urinary bladder neoplasms; variant histology.

Figure 1

Survival of patients with MIBC who underwent radical cystectomy without NAC based on clinical high vs low risk (MDACC 2000 to 2010). A, Kaplan-Meier survival curve demonstrating overall survival. B, cumulative incidence of bladder cancer specific mortality, accounting for competing risk of nonbladder cancer death, and adjusted for age at surgery, gender, race, preoperative anemia, smoking history and year of surgery.

Figure 2

Survival of patients with MIBC who underwent radical cystectomy without NAC based on clinical high vs low risk and reclassification based on final pathology (MDACC 2000 to 2010). A, Kaplan-Meier analysis demonstrating overall survival. B, cumulative incidence of bladder cancer specific mortality, accounting for competing risk of nonbladder cancer death, and adjusted for age at surgery, gender, race, preoperative anemia, smoking history, history of intravesical therapy, margin status, total lymph nodes resected, adjuvant chemotherapy and year of surgery.

Figure 3

Survival of patients with MIBC who underwent radical cystectomy without NAC based on clinical high vs low risk (USC 1983 to 2008). A, Kaplan-Meier survival curve demonstrating overall survival. B, cumulative incidence of bladder cancer specific mortality, accounting for competing risk of noncancer death, and adjusted for age at surgery, gender, race, preoperative anemia, smoking history and year of surgery.

Figure 4

Neoadjuvant platform for clinical based staging and therapy for bladder cancer.