760 Background: Neoadjuvant chemotherapy (NAC)-induced acute kidney injury (AKI) is one of the frequent complications in patients with muscle-invasive bladder cancer (MIBC) and we previously have reported the negative impact of NAC-induced AKI on oncological outcomes. However, its risk factors remain unclear. Methods: This multi-institutional retrospective study included 517 patients with MIBC who received 2–4 cycles of NAC followed by radical cystectomy. AKI was defined according to the KDIGO criteria. Patients were divided into two groups: patients who developed any stage AKI during NAC (AKI group) and patients who did not (non-AKI group). Multivariable logistic regression analysis was performed to identify the risk factors for NAC-induced AKI. The predictive abilities for AKI were evaluated using the area under the receiver operating characteristic (ROC) curve. Results: The median age was 69 years. Of the 517 patients, 188 (36%) received cisplatin-based regimens and 92 (18%) developed any stage AKI. Approximately 86% AKI were stage 1 AKI. eGFR in the AKI group was significantly lower than that in the non-AKI group ( P <0.001). The rate of AKI development in patients who received cisplatin-based regimens was significantly higher than that in patients who received carboplatin-based regimens ( P <0.001). In the multivariable analysis, hypertension, impaired renal function, and cisplatin-based regimen were independently and significantly associated with increased risk of AKI (Table). The optimal cutoff value of estimated glomerular filtration rate for AKI was 65.0 mL/min/1.73m 2 . ROC analysis showed that the area under the curve (AUC) of hypertension plus eGFR <65.0 mL/min/1.73m 2 plus cisplatin-based regimen was 0.748 (95% confidence interval: 0.697–0.799). Conclusions: Hypertension, impaired renal function, and cisplatin-based regimens were risk factors for NAC-induced AKI in patients with MIBC. Multivariable analysis for AKI development. Factor P value Odds ratio 95% CI Age Continuous 0.462 0.989 0.959–1.019 Hypertension Presence 0.016 1.894 1.128–3.179 eGFR Continuous <0.001 0.955 0.939–0.971 Cisplatin-based regimens Positive <0.001 6.530 3.725–11.45
873 Background: Platelet-to-lymphocyte ratio (PLR), a novel inflammatory marker, has been suggested to predict recurrence and mortality in several malignancies. Patients with muscle-invasive bladder cancer (MIBC) who achieved a pathological complete response (ypT0) to neoadjuvant chemotherapy (NAC) have a favorable prognosis. However, the risk factors for recurrence and mortality remain unclear. Methods: This multi-institutional retrospective study assessed 950 patients with MIBC who underwent radical cystectomy (RC). Of the 950 patients, 128 patients who achieved a pathological complete response (ypT0) to 2–4 cycles of NAC were included. Univariable and multivariable Cox proportional hazards regression analyses were performed to identify the risk factors for recurrence and mortality. Results: The median age and follow-up period were 69 years and 80 months, respectively. Of the 128 patients, 15 (12%) and 30 (23%) experienced recurrence and died from any cause, respectively. The most frequent recurrence site was lymph nodes (n = 11, 73%), followed by urothelium (n = 4, 27%). The 10-year recurrence-free survival (RFS) and 10-year overall survival (OS) rates were 85.9% and 73.1%, respectively. In the univariable and multivariable analyses, clinical lymph node involvement, neobladder reconstruction, and PLR were independently and significantly associated with RFS (Table). In the univariable and multivariable analyses, age and PLR were independently and significantly associated with OS. Conclusions: Recurrence was not a rare event in patients with MIBC who achieved ypT0. PLR may be a useful biomarker to assess recurrence and mortality risks. Multivariable analysis for RFS. Factor P value Hazard ratio 95% CI Clinical lymph node involvement Positive 0.021 3.732 1.219–11.42 Urinary diversion Neobladder 0.281 0.281 0.094–0.842 PLR Continuous 0.029 1.003 1.000–1.006
The presence of glycosylated isoforms of prostate-specific antigen (PSA) in prostate cancer (PC) cells is a potential marker of their aggressiveness. We characterized the origin of α2,3-sialylated prostate-specific antigen (S23PSA) by tissue-based sialylation-related gene expression and studied the performance of S23PSA density (S23PSAD) alone and in combination with multiparametric magnetic resonance imaging (MRI) for the detection of clinically significant prostate cancer in men with elevated PSA.Tissue-based quantification of S23PSA and sialyltransferase and sialidase gene expression was evaluated in 71 radical prostatectomy specimens. The diagnostic performance of S23PSAD was studied in 1099 men retrospectively enrolled in a multicenter systematic biopsy (SBx) cohort. We correlated the S23PSAD with Prostate Imaging Reporting and Data System (PI-RADS) scores in 98 men prospectively enrolled in a single-center MRI-targeted biopsy (MRI-TBx) cohort. The primary outcome was the PC-diagnostic performance of the S23PSAD, the secondary outcome was the avoidable biopsy rate of S23PSAD combined with DRE and total PSA (tPSA), and with or without PI-RADS.S23PSA was significantly higher in Gleason pattern 4 and 5 compared with benign prostate tissue. In the retrospective cohort, the performance of S23PSAD for detecting PC was superior to tPSA or PSA density (PSAD) (AUC: 0.7758 vs. 0.6360 and 0.7509, respectively). In the prospective cohort, S23PSAD was superior to tPSA, PSAD, and PI-RADS (AUC: 0.7725 vs. 0.5901, 0.7439 and 0.7305, respectively), and S23PSAD + PI-RADS + DRE + tPSA was superior to DRE + tPSA+PI-RADS with avoidance rate of MRI-TBx (13% vs. 1%) at 30% risk threshold.The diagnostic performance of S23PSAD was superior to conventional strategies but comparable to mpMRI.
BackgroundNeoadjuvant chemotherapy (NAC) use for patients with locally advanced upper tract urothelial carcinoma (UTUC) is debatable.ObjectiveTo investigate the efficacy and safety of platinum-based NAC for locally advanced UTUC.Design, settings, and participantsOf 233 consecutive patients who underwent radical nephroureterectomy, 55 patients received NAC (NAC group) and 138 patients did not (Ctrl group).Outcome measurements and statistical analysisThe two arms (Ctrl vs NAC) were matched using propensity scores to minimize selection bias. We retrospectively evaluated tumor response, post-therapy pathological downstaging, lymphovascular invasion, Ki67 status, and prognosis between pair-matched patients. Multivariate Cox regression analysis was performed for independent factors for prognosis.Results and limitationsWe selected 51 pair-matched patients in each group. The regimens in the NAC group included gemcitabine and carboplatin, and gemcitabine and cisplatin. The median response rate in the NAC group was 28%. NAC-related adverse events were tolerable. Pathological downstaging of the primary tumor was significantly higher in the NAC group than in the Ctrl group. The MIB1 index (immunostaining for Ki67) was significantly higher in the NAC group. NAC for locally advanced UTUC significantly prolonged progression-free, cancer-specific, and overall survival. Multivariate Cox regression analysis using an inverse probability of treatment weighting method showed that NAC was selected as an independent predictor for prolonged cancer-specific survival. Limitations are the retrospective design and the small sample size.ConclusionsPlatinum-based NAC for advanced UTUC potentially improves oncological outcomes. Further prospective studies are needed.Patient summaryPlatinum-based neoadjuvant chemotherapy for locally advanced upper tract urothelial carcinoma was safe and potentially improves oncological outcomes. A carboplatin-based regimen may be used as an alternative in patients with impaired renal function.
