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455 Background: The POUT trial (CRUK/11/027; NCT01993979) previously reported (with median follow-up 30.3 months) that adjuvant chemotherapy improves disease free survival (DFS) for patients (pts) with histologically confirmed pT2-T4 N0-3 M0 UTUC. Here we present results of a pre-planned analysis updating the primary endpoint and reporting key secondary endpoints including overall survival. Methods: 261 pts with UTUC were enrolled following nephro-ureterectomy and randomised (1:1) to 4 cycles of gemcitabine-cisplatin (gemcitabine-carboplatin if GFR 30-49ml/min) or surveillance with subsequent chemotherapy if required. Pts had 6 monthly imaging and cystoscopy for 2 years, then annually to 5 years. Toxicity was assessed by CTCAE v4. Primary endpoint was DFS. Secondary endpoints included metastasis free survival (MFS), overall survival (OS), toxicity and patient reported quality of life (QoL). The trial closed to recruitment early on advice of the independent data monitoring committee due to evidence of efficacy. Time-to-event endpoints are analysed (intention-to-treat) by Cox proportional hazard models. Unadjusted and adjusted (by nodal status, planned chemotherapy type, microscopic margin status, pathological stage) hazard ratios (HR, < 1 favouring chemotherapy) are reported. Results: From May 2012 to Nov 2017, 261 pts were recruited (129 surveillance; 132 chemotherapy) at 56 UK centres. One participant withdrew consent for data usage and was excluded from analyses. Pts had median age 69 years (range 37-88), 28% pT2, 66% pT3; 91% pN0. To 09/09/2020, median follow up was 48.1 months (IQR: 36.0-60.1). The unadjusted/adjusted HR for DFS was 0.48 (95% CI: 0.33-0.71; p = 0.0003) / 0.50 (95%CI: 0.34-0.75; p = 0.001), and for MFS was 0.52 (95% CI: 0.35-0.77; p = 0.001) / 0.54 (95% CI: 0.36-0.81; p = 0.002). 93/260 (35.8%) pts have died (52/129 [40.3%] surveillance and 41/131 [31.3%] chemotherapy). Chemotherapy conferred a non-statistically significant 28% reduction in relative risk of death (HR = 0.72, 95% CI: 0.47-1.08; p = 0.11; adjusted HR = 0.79, 95% CI: 0.52-1.19; p = 0.26). 3 year OS was surveillance: 67% (95% CI: 58-74%; chemotherapy: 79% (71%-85%). There was no evidence of long-term toxicity associated with chemotherapy (Wilcoxon rank-sum test p-value for worst grade post-6 months = 0.32). Most common grade 2+ adverse events were hypertension (25/240 [10.4%]), lethargy (25/240 [10.4%]) and hearing loss (13/240 [5.4%]). There was no evidence of statistically or clinically relevant differences in QoL. 12 months after treatment (EORTC Q30 global health status mean difference 4.1 and 4.8 at 12 and 24 months respectively in favour of chemotherapy). Conclusions: With additional follow-up, the previously reported DFS benefit for chemotherapy was maintained with no detrimental long-term toxicity. No statistically significant improvement in OS was observed. Clinical trial information: NCT01993979.

Background: Accurate assessment of urine flow remains challenging in both inpatient and outpatient settings. We hypothesized we could derive an equation that would accurately estimate urine flow rate (eV) through derivation from other existing equations commonly used in nephrology clinical practice. Methods: The eV equation was derived using the Cockcroft-Gault and the measured creatinine clearance (CrCl = U Cr V/P Cr ) equations. Within the African American Study of Kidney Disease and Hypertension (AASK; n = 570) and COMBINE (n = 133) clinical trials, we identified participants with concordant estimated and measured creatinine excretion rates to define a subset with highly accurate 24-h urine collections, to assure a reliable gold standard. We then compared eV to measured 24-h urine flow rates in these trials. Results: In AASK, we found a high correlation between eV and measured urine flow rate (V; r = 0.91, p < 0.001); however, Bland-Altman plots showed that eV was 9.5 mL/h lower than V, on average. Thus, we added a correction factor to the eV equation and externally validated the new equation in COMBINE. eV and V were again highly correlated (r = 0.91, p < 0.001), and bias was improved (mean difference 5.3 mL/h). Overall, 80% of individuals had eV that was within 20% of V. Conclusions: A simple equation using urine creatinine, demographics, and body weight can accurately predict urine flow rate and may have clinical utility in situations where it is difficult to accurately measure the urine flow rate.

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