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Objectives: To evaluate whether pathological downstaging (pDS) was more informative in predicting overall survival (OS) than pathological complete response (pCR) in patients treated with neoadjuvant chemotherapy (NAC) for upper tract urothelial carcinoma (UTUC). Patients and Methods: The National Cancer Database was queried for patients with high‐grade cN0M0 disease who had received NAC. pDS was defined as a decrease of at least one stage from cT to pT stage along with pN0, including pCR. A multivariable Cox model predicting OS was generated by fitting alternatively either pDS or pCR, and adjusted for potential confounders. The discrimination of the Cox models for predicting OS was evaluated using Harrell's C‐index. The analyses were repeated in patients diagnosed as having cT2–4N0M0 disease. Results: Among 264 patients meeting the inclusion criteria, 72 (27%) and 39 (15%) achieved pDS and pCR, respectively. On multivariable analysis, both pDS (hazard ratio [HR] 0.24, 95% confidence interval [CI] 0.13, 0.45; P < 0.001) and pCR (HR 0.37, 95% CI 0.18, 0.79; P = 0.01) were associated with OS. The model including pDS achieved better discrimination with respect to the model including pCR: C‐index 76.4 vs 72.7, respectively. In the 128 patients diagnosed with cT2–4 disease, both pDS (HR 0.19, 95% CI 0.09, 0.40; P < 0.001) and pCR (HR 0.31, 95% CI 0.11, 0.85; P = 0.023) were confirmed as predictors of OS. The model including pDS was confirmed to discriminate better than the model including pCR: C‐index 75 vs 68.9, respectively. Conclusion: The study showed that pDS after NAC for UTUC was more informative than pCR when predicting OS. These findings, although requiring prospective validation, can aid in the design of clinical trials seeking to refine the use of chemotherapy and other systemic therapies in this setting. [ABSTRACT FROM AUTHOR]

Purpose Level 1 evidence supports the use of neoadjuvant chemotherapy (NAC) for the treatment of muscle-invasive bladder cancer (MIBC), but observational data demonstrate that this approach is underused. A barrier to shared decision making is difficulty in predicting and communicating survival estimates after cystectomy with or without NAC. Methods We included patients with MIBC from the National Cancer Database treated with cystectomy. A state-transition model was constructed for calculating 5-year death risk using baseline patient-, tumor-, and facility-level variables. Internal-external cross-validation by geographic region was performed. The effect of NAC was integrated using a literature-derived hazard ratio. Bladder cancer-specific and other-cause mortality was estimated from all-cause mortality rates from US life tables. From the state-transition model, a Web-based tool was developed and pilot usability testing performed. Results A total of 9,824 patients with MIBC who underwent cystectomy were eligible for inclusion. Median overall survival was 39.6 months (95% CI, 37.4 to 42.4 months). Increasing age, higher clinical T stage, higher comorbidity index, and black race were associated with shorter survival. Private insurance, higher income, and cystectomy at a high-volume facility were associated with longer survival. The prediction model was well calibrated across geographic regions, with observed-to-predicted 5-year death risks ranging from 0.85 to 1.17. Absolute risk reductions with NAC varied from 8.6% to 10.1%. The Web-based tool allowed input of the predictor variables and a user-defined hazard ratio associated with the effect of NAC to generate individualized survival estimates. The tool demonstrated good usability with clinicians. Conclusion A Web-based tool was developed to individualize outcome prediction and communication in patients with MIBC treated with cystectomy with or without NAC to facilitate shared decision making. [ABSTRACT FROM AUTHOR]

Background Although radical cystectomy (RC) is a standard treatment for muscle-invasive bladder cancer (MIBC), for many patients the risks versus benefits of RC may favor other approaches. We sought to define the landscape of early postcystectomy mortality in the United States and identify patients at high risk using pretreatment variables. Methods We identified patients with MIBC (cT2-T4aN0M0) who underwent RC without perioperative chemotherapy within the National Cancer Database (2003–2012). Using multistate multivariable modeling, we calculated time spent in three health states: hospitalized, discharged, and death more than 90 days postcystectomy. Cross-validation was performed by geographic region. Time spent in each state was weighted by utility to determine 90-day quality-adjusted life days (QALDs). Results Among 7922 patients, 90-day mortality was 7.6% (8.0% for lower and 6.7% for higher volume hospitals). Increasing age, clinical T stage, Charlson Comorbidity Index, and lower volume were associated with higher 90-day mortality and were included in the model. Cross-validation revealed appropriate performance (C-statistics of 0.53–0.74; calibration slopes of 0.50–1.67). The model predicted 25% of patients had a 90-day mortality risk higher than 10%, and observed 90-day mortality in this group was 14.0% (95% CI = 12.5% to 15.6%). Mean quality-adjusted life days (QALDs) was 63 (range = 44–68). Conclusions RC is associated with relatively high early mortality risk. Pretreatment variables may identify patients at particularly high risk, which may inform clinical trial design, facilitate shared decision making, and enhance quality improvement initiatives. [ABSTRACT FROM AUTHOR]

Purpose: Achieving a pathologic complete response (pCR) with neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (MIBC) is associated with a favorable prognosis. Patients with pathologic residual disease (pRD) generally have poor outcomes. However, prognosis after radical cystectomy (RC) improves with ongoing survivorship. Our objective was to determine whether the difference in prognosis of patients with pCR and pRD changes over time.Materials and Methods: We queried the National Cancer Database for patients who received NAC and RC for localized MIBC (cT2-T4aN0M0) between 1998 and 2012. pCR was defined as ≤Tis disease. Kaplan-Meier analysis was used to estimate conditional survival to 5 years given survival to 1, 2, 3, and 4 years post-RC. Cox proportional hazard modeling was used to estimate the effect of pRD vs. pCR on overall survival.Results: The cohort comprised 1,553 patients (pCR: 314 and pRD: 1,239). With median follow-up 2.65 years (range 0.01-9.97), median survival was 2.5 years (95% confidence interval 2.2-2.9) and not reached for pRD and pCR, respectively. All patients had improved conditional survival with each additional year of survivorship. Patients with pCR had improved overall survival relative to those with pRD. The effect of pRD vs. pCR on conditional survival did not differ over time (P = 0.7).Conclusions: MIBC patients with pCR after NAC have improved conditional survival relative to those with pRD post-RC. This survival advantage does not significantly change over time. These findings may inform patient counseling, surveillance intensity, and novel adjuvant approaches for patients with pRD. [ABSTRACT FROM AUTHOR]