First Report of Oncological Outcome and Prognostic Analysis in a First-Line Setting of Short Hydration Gemcitabine and Cisplatin Chemotherapy for Patients with Metastatic Urothelial Carcinoma.

OBJECTIVES: The aim of the study was to examine the effectiveness of a modified-short hydration gemcitabine and cisplatin (m-shGC) regimen for patients with metastatic urothelial carcinoma (mUC) and to assess the efficacy of a geriatric nutritional risk index (GNRI) with regard to prognosis. PATIENTS AND METHODS: From January 2016 to July 2020, 68 patients with mUC underwent first-line m-shGC therapy with 70 mg/m2 cisplatin and 1,000 mg/m2 gemcitabine (days 1, 8, and 15), with 2,050 mL fluid replaced on the first day of each 28-day cycle. Prior to the start of treatment, the serum neutrophil-to-lymphocyte ratio (NLR), and levels of albumin and C-reactive protein (CRP) in serum, as well as body heights and weights were measured. Patients were grouped according to GNRI <92 (low) or ≥92 (high). The analysis of data was done retrospectively. RESULTS: Median follow-up was found to be 12.9 (range 1.7-50.2) months and the objective response rate (ORR) was 54.4% after m-shGC treatment. The ORR was significantly different when high and low-GNRI groups were compared (ORR: 28.0 vs. 69.8% in low- vs. high-GNRI groups). Median overall survival (OS) was calculated as 8.6 (95% confidence interval [CI]: 5.4-21.3) and 34.5 (95% CI: 20.5-NA) months for low- and high-GNRI groups, respectively (p < 0.0001). Unlike for NLR and CRP, univariate and multivariate analyses revealed that low GNRI and visceral metastases were significant prognostic factors for short OS. CONCLUSIONS: First-line m-shGC showed a survival benefit for mUC, with GNRI a useful prognostic biomarker.

Pre-therapy serum albumin-to-globulin ratio in patients treated with neoadjuvant chemotherapy and radical nephroureterectomy for upper tract urothelial carcinoma.

PURPOSE: The accurate selection of patients who are most likely to benefit from neoadjuvant chemotherapy is an important challenge in oncology. Serum AGR has been found to be associated with oncological outcomes in various malignancies. We assessed the association of pre-therapy serum albumin-to-globulin ratio (AGR) with pathologic response and oncological outcomes in patients treated with neoadjuvant platin-based chemotherapy followed by radical nephroureterectomy (RNU) for clinically non-metastatic UTUC. METHODS: We retrospectively included all clinically non-metastatic patients from a multicentric database who had neoadjuvant platin-based chemotherapy and RNU for UTUC. After assessing the pretreatment AGR cut-off value, we found 1.42 to have the maximum Youden index value. The overall population was therefore divided into two AGR groups using this cut-off (low, < 1.42 vs high, ≥ 1.42). A logistic regression was performed to measure the association with pathologic response after NAC. Univariable and multivariable Cox regression analyses tested the association of AGR with OS and RFS. RESULTS: Of 172 patients, 58 (34%) patients had an AGR < 1.42. Median follow-up was 26 (IQR 11-56) months. In logistic regression, low AGR was not associated with pathologic response. On univariable analyses, pre-therapy serum AGR was neither associated with OS HR 1.15 (95% CI 0.77-1.74; p = 0.47) nor RFS HR 1.48 (95% CI 0.98-1.22; p = 0.06). These results remained true regardless of the response to NAC. CONCLUSION: Pre-therapy low serum AGR before NAC followed by RNU for clinically high-risk UTUC was not associated with pathological response or long-term oncological outcomes. Biomarkers that can complement clinical factors in UTUC are needed as clinical staging and risk stratification are still suboptimal leading to both over and under treatment despite the availability of effective therapies.

Prognostic significance of the albumin-to-globulin ratio for upper tract urothelial carcinoma.

BACKGROUND: Although the albumin-to-globulin ratio (AGR) is a promising biomarker for various malignancies, few studies have investigated its prognostic significance for upper tract urothelial carcinoma (UTUC). METHODS: This retrospective study conformed to the REporting recommendations for tumour MARKer prognostic studies (REMARK) guideline. We reviewed 179 patients with UTUC who underwent radical nephroureterectomy at our institution between 2008 and 2018. Associations of preoperative clinicopathological factors, including the AGR, with cancer-specific survival (CSS) and overall survival (OS) were assessed. The Cox proportional hazards model was used for univariate and multivariable analyses. AGR was dichotomized as < 1.25 and ≥ 1.25, according to the most discriminatory cutoff determined from the receiver operating characteristic curve analysis. RESULTS: During a median follow-up of 34 months after surgery, 37 patients died from UTUC and 13 died of other causes. The preoperative AGR significantly correlated with pathological T stage, pathological N stage, and adjuvant chemotherapy. Multivariate analyses demonstrated that a decreased (< 1.25) preoperative AGR was an independent poor prognostic factor for both CSS (hazard ratio [HR] = 2.81, P <  0.01) and OS (HR = 2.09, P <  0.05). CONCLUSIONS: Preoperative AGR < 1.25 might serve as a useful prognostic marker for patients with UTUC undergoing radical nephroureterectomy.

Serum Hepcidin and GDF-15 levels as prognostic markers in urothelial carcinoma of the upper urinary tract and renal cell carcinoma.

BACKGROUND: Cancer is a life-threatening disease that causes every fourth death. It is often hard to determine the time point of progression. Therefore, biomarkers for cancer entities that indicate disease progression or aggressiveness and thereby guide therapeutic decisions are required. Unfortunately, reliable biomarkers are rare. In this study, the potential of serum hepcidin and serum GDF-15 as biomarkers that correlate with patient's survival in the two entities upper urinary tract urothelial carcinomas (UUTUC) and renal cell carcinoma (RCC) were analyzed. METHODS: In this retrospective study n = 38 patients suffering from UUTUC, n = 94 patients suffering from RCC and n = 21 patients without infections or cancer, all hospitalized at the University Hospital Muenster, were included. Serum samples of patients were retrospectively analyzed. Serum hepcidin and GDF-15 levels were measured and correlated to aggressiveness and progression of the disease as well as patient's outcome. RESULTS: For both entities, UUTUC and RCC, serum hepcidin levels as well as serum GDF-15 levels were increased compared to sera of controls. High serum hepcidin and GDF-15 levels were associated with metastases and cancer relapse. Also, in both entities, the overall survival was decreased in patients with increased serum hepcidin and GDF-15 levels. Hence, high serum hepcidin and GDF-15 levels correlated with patient's outcome. CONCLUSION: To conclude, the data of this study show a correlation of high serum hepcidin and GDF-15 levels with aggressiveness and progression of the disease and demonstrate potential prognostic properties of serum hepcidin and GDF-15 levels. The data support the further assessment of serum hepcidin and GDF-15 as prognostic markers in RCC and UUTUC.

Is neutrophil-to-lymphocytes ratio a clinical relevant preoperative biomarker in upper tract urothelial carcinoma? A meta-analysis of 4385 patients.

BACKGROUND: Preoperative blood-based inflammatory biomarkers have been suggested to improve staging and prognostication in patients with upper-tract urothelial carcinoma (UTUC). Neutrophil-to-lymphocyte ratio (NLR) is the most studied blood-based biomarker. NLR is an indicator of systemic inflammation and has been shown to be associated with a poor prognosis in various malignancies. The aim of this study was to analyze the current evidence regarding the prognostic significance of preoperative NLR in patients undergoing radical nephroureterectomy (RNU) for UTUC to assess its prognostic potential. MATERIALS AND METHODS: A systematic search of Web of Science, Medline/PubMed and Cochrane library was performed on the 1st of October, 2017. Studies were deemed eligible if they compared patients with high NLR before surgical treatment for UTUC to patients with low NLR to determine its predictive value for survival using multivariable logistic regression analysis. We performed a formal meta-analysis for cancer-specific survival (CSS), recurrence-free survival (RFS) and overall survival (OS). RESULTS: Nine studies including a total of 4385 patients assessing the importance of NLR were included in this meta-analysis. The cut-off NLR varied in the eligible studies ranging from 2 to 3. Increased pretreatment NLR predicted OS (pooled HR 1.64 95% CI; 1.23-2.17), RFS (pooled HR 1.60 95% CI; 1.16-2.20) and CSS (pooled HR 1.73 95% CI; 1.23-2.44) in multivariable analyses. CONCLUSION: In this meta-analysis, preoperative blood-based NLR is associated with worse prognosis in patients who underwent RNU for UTUC. NLR could be used to improve clinical decision making regarding RNU vs. kidney-sparing surgery, extent of lymphadenectomy, perioperative systemic therapy and follow-up schedule.

Timing of blood transfusion and oncologic outcomes in patients treated with radical nephroureterectomy for upper tract urothelial carcinoma.

PURPOSE: To evaluate the impact of timing of blood transfusion in patients with upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU). METHODS: Outcomes of consecutive patients with UTUC treated with RNU were analyzed. Clinicopathologic factors were compared using Fisher's exact test or the Wilcoxon rank-sum test between patients who received any transfusion and no transfusion, and between patients receiving intraoperative transfusion only and patients receiving no transfusion. Cancer-specific and overall survival were estimated and multivariable analyses were performed to assess the impact of timing of transfusion on clinical outcomes. RESULTS: Among 402 patients included in this study, 71 (17.6%) patients received a transfusion at any point and 27 (6.7%) patients received an intraoperative blood transfusion. Transfusion at any time, patient comorbidity, high grade, advanced stage, positive surgical margins, low preoperative hemoglobin, longer operative duration, and increased blood loss were significantly associated with cancer-specific survival (DSS) on univariable analysis (HR 1.85, 95% CI 1.20-2.85, p < 0.005). In the multivariable analysis, transfusion at any point was not a prognostic factor (HR 1.00, 95% CI 0.60-1.68, p = 0.99). When examining intraoperatively transfusion only, transfusion was significantly associated with DSS (HR 1.91, 95% CI 1.01-3.59, p = 0.045) but no longer significant in multivariable analysis (HR 0.72, 95% CI 0.32-1.65, p = 0.440). CONCLUSIONS: Our study indicates that the administration of blood transfusion either intraoperatively or postoperatively is not associated with clinical or oncological outcomes in patients with upper tract urothelial carcinoma when adjusted for other factors in multivariable analysis. Further study is required.

Prognostic role of the preoperative serum albumin : globulin ratio after radical nephroureterectomy for upper tract urothelial carcinoma.

OBJECTIVES: To elucidate the effects of the preoperative albumin : globulin ratio on the survival of patients with upper tract urothelial carcinoma after radical nephroureterectomy. METHODS: We retrospectively reviewed 124 consecutive patients with upper tract urothelial carcinoma who underwent radical nephroureterectomy at Chiba Cancer Center, Chiba, Japan between 2002 and 2015. The albumin : globulin ratio was defined: albumin / (total protein - albumin). Associations between preoperative clinicopathological factors, including the albumin : globulin ratio, and recurrence-free survival, cancer-specific survival and overall survival were assessed. The log-rank test and Cox proportional hazards models were used for univariate and multivariable analyses, respectively. The study cohort was separated into two groups based on the optimal albumin : globulin ratio cut-off value determined using receiver operating characteristic curve analysis. RESULTS: The median survival time was 55 months (interquartile range 28-76 months), and 31 patients died during follow up. A low preoperative albumin : globulin ratio <1.40 was associated with tumor grade and surgical margin status. Kaplan-Meier analyses showed that a low albumin : globulin ratio was more significantly correlated with worse recurrence-free survival, cancer-specific survival and overall survival. Multivariate analyses showed that a low albumin : globulin ratio was an independent predictive factor associated with poor recurrence-free survival (hazard ratio 3.758; P = 0.0028), cancer-specific survival (hazard ratio 5.687; P = 0.0044) and overall survival (hazard ratio 3.124; P = 0.0030). CONCLUSIONS: A low albumin : globulin ratio is an independent predictive factor associated with poor prognosis in upper tract urothelial carcinoma patients treated with radical nephroureterectomy.

Promising role of preoperative neutrophil-to-lymphocyte ratio in patients treated with radical nephroureterectomy.

OBJECTIVE: Several retrospective studies with small cohorts reported neutrophil-to-lymphocyte ratio (NLR) as a prognostic marker in upper tract urothelial carcinoma (UTUC) following radical nephroureterectomy (RNU). We aimed at validating the predictive and prognostic role of NLR in a large multi-institutional cohort. METHODS: Preoperative NLR was assessed in a multi-institutional cohort of 2477 patients with UTUC treated with RNU. Altered NLR was defined by a ratio >2.7. Logistic regression analyses were performed to assess the association between NLR and lymph node metastasis, muscle-invasive and non-organ-confined disease. The association of altered NLR with recurrence-free survival (RFS) and cancer-specific survival (CSS) was evaluated using Cox proportional hazards regression models. RESULTS: Altered NLR was observed in 1428 (62.8 %) patients and associated with more advanced pathological tumor stage, lymph node metastasis, lymphovascular invasion, tumor necrosis and sessile tumor architecture. In a preoperative model that included age, gender, tumor location and architecture, NLR was an independent predictive factor for the presence of lymph node metastasis, muscle-invasive and non-organ-confined disease (p < 0.001). Within a median follow-up of 40 months (IQR 20-76 months), 548 (24.1 %) patients experienced disease recurrence and 453 patients (19.9 %) died from their cancer. Compared to patients with normal NLR, those with altered NLR had worse RFS (0.003) and CSS (p = 0.002). In multivariable analyses that adjusted for the effects of standard clinicopathologic features, altered NLR did not retain an independent value. In the subgroup of patients treated with lymphadenectomy in addition to RNU, NLR was independently associated with CSS (p = 0.03). CONCLUSION: In UTUC, preoperative NLR is associated with adverse clinicopathologic features and independently predicts features of biologically and clinically aggressive UTUC such as lymph node metastasis, muscle-invasive or non-organ-confined status. NLR may help better risk stratify patients with regard to lymphadenectomy and conservative therapy.

The neutrophil-to-lymphocyte ratio as a predictor of intravesical recurrence in patients with upper urinary tract urothelial carcinoma treated with radical nephroureterectomy.

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) is a marker of systemic inflammation associated with recurrence and poor prognosis in numerous cancer types. The aim of this study was to evaluate the use of the NLR as a biomarker for intravesical recurrence (IVR) in patients undergoing radical nephroureterectomy (RNU) for upper urinary tract urothelial carcinoma (UTUC) for the first time. METHODS: We retrospectively analyzed the records of 100 patients with UTUC who had undergone RNU between 1999 and 2015 at our institution. The association between the preoperative NLR and IVR were assessed using multivariate models. RESULTS: Among the 100 patients enrolled in the study, 33 developed IVR during a median follow-up of 34 months. The receiver operating characteristic analysis revealed that the optimum cut-off value for the preoperative NLR was >3.8. A high preoperative NLR (n = 21) was associated with a significantly increased risk of lymph node involvement (p = 0.036) and IVR (p = 0.034) compared with a low preoperative NLR (n = 79). IVR-free survival in patients with a high preoperative NLR was significantly worse than that of patients with a low preoperative NLR (p = 0.018). On multivariate analysis, the preoperative NLR [hazard ratio (HR) 2.49; p = 0.015] and tumor multifocality (HR 2.96; p = 0.024) were independent risk factors predictive of IVR. CONCLUSION: In our study population of patients with UTUC who had undergone RNU the preoperative NLR was associated with a significantly increased risk of IVR, suggesting that the NRL could be a useful biomarker for predicting IVR.

Validation of the pretreatment derived neutrophil-lymphocyte ratio as a prognostic factor in a European cohort of patients with upper tract urothelial carcinoma.

BACKGROUND: The value of a combined index of neutrophil and white cell counts, named derived neutrophil-lymphocyte ratio (dNLR), has recently been proposed as a prognosticator of survival in various cancer types. We investigated the prognostic role of the dNLR in a large European cohort of patients with upper tract urothelial carcinoma (UTUC). METHODS: Data from 171 non-metastatic UTUC patients, operated between 1990 and 2012 at a single tertiary academic centre, were evaluated retrospectively. Cancer-specific- (CSS) as well as overall survival (OS) were assessed using the Kaplan-Meier method. To evaluate the independent prognostic significance of the dNLR, multivariate proportional Cox-regression models were applied. Additionally, the influence of the dNLR on the predictive accuracy of the multivariate model was further determined by Harrell's concordance index (c-index). RESULTS: The median follow-up period was 31 months. An increased dNLR was statistically significantly associated with shorter CSS (log-rank P=0.004), as well as with shorter OS (log-rank P=0.002). Multivariate analysis identified dNLR as an independent predictor for CSS (hazard ratio, HR=1.16, 95% confidence interval, CI=1.01-1.35, P=0.045), as well as for OS (HR=1.21, 95% CI=1.09-1.34, P<0.001). The estimated c-index of the multivariate model for OS was 0.68 without dNLR and 0.73 when dNLR was added. CONCLUSIONS: Patients with a high pretreatment dNLR could be predicted to show subsequently higher cancer-specific- as well as overall mortality after surgery for UTUC compared with those with a low pretreatment dNLR. Thus, this combined index should be considered as a potential prognostic biomarker in future.

Validation of the preoperative plasma fibrinogen level as a prognostic factor in a European cohort of patients with localized upper tract urothelial carcinoma.

PURPOSE: Fibrinogen is thought to have a potentially significant role in the progression and metastatic spread of different human cancers. A recent study from Asia indicated that elevated preoperative plasma fibrinogen might be associated with a worse outcome in patients with surgically treated localized upper tract urothelial carcinoma. We validated the prognostic impact of this potential biomarker in a European cohort of patients with localized upper tract urothelial carcinoma. MATERIALS AND METHODS: We evaluated data on 167 patients with nonmetastatic upper tract urothelial carcinoma who underwent surgery between 1990 and 2012 at a single tertiary academic center. Patients were categorized using an optimal cutoff value of preoperative plasma fibrinogen. Patient cancer specific and overall survival was assessed using the Kaplan-Meier method. Univariate and multivariate Cox regression models were performed for each end point. The influence of fibrinogen on the predictive accuracy of the multivariate model was further determined by the Harrell c-index. RESULTS: Multivariate analysis identified increased preoperative plasma fibrinogen as an independent prognostic factor for cancer specific survival (HR 3.00, 95% CI 1.32-6.80, p = 0.008) and overall survival (HR 2.48, 95% CI 1.31-4.68, p = 0.005). The estimated c-index of the multivariate model for cancer specific survival was 0.72 without fibrinogen and 0.74 when fibrinogen was added. The risk model that we developed significantly differentiated between low, intermediate and high risk groups for cancer related death (p <0.001). CONCLUSIONS: Elevated fibrinogen seems to represent a negative prognostic factor for cancer specific and overall survival in patients with upper tract urothelial carcinoma. This parameter should be considered an additional prognostic factor for upper tract urothelial carcinoma in the future.

Subclassification of upper urinary tract urothelial carcinoma by the neutrophil-to-lymphocyte ratio (NLR) improves prediction of oncological outcome.

OBJECTIVE: To examine the potential role of the neutrophil-to-lymphocyte ratio (NLR) for subclassification of localised upper urinary tract urothelial carcinoma (UUT-UC). PATIENTS AND METHODS: From 2004 to 2010, 234 patients with localised UUT-UC underwent radical nephroureterectomy (RNU). NLRs were only obtained under afebrile conditions before RNU. Patients that underwent neoadjuvant or adjuvant chemotherapy were excluded. The prognostic impact of the NLR was assessed using the log-rank test and multivariate analyses. RESULTS: Only advanced pathological stage (>T2) and a NLR of >3 were independently associated with metastasis (P < 0.001 and P = 0.02, respectively) and cancer-specific mortality (P = 0.002 and P = 0.006, respectively). The use of a NLR of >3 further identified a poor prognostic group, especially in patients with T3 UUT-UC for metastasis-free survival and cancer-specific survival (log-rank test, both P < 0.001). CONCLUSIONS: For localised UUT-UC, pathological stage and preoperative NLR independently predict systemic recurrence and cancer-specific death after RNU. Using the NLR for subclassification of T3 UUT-UC seems to further identify a poor prognostic group and may help with clinical decisions about treatment intervention in clinical practice.

Preoperative serum C- reactive protein: a prognostic marker in patients with upper urinary tract urothelial carcinoma.

BACKGROUND: To analyse the prognostic significance of preoperative C-reactive protein (CRP) serum level in patients with upper urinary tract urothelial carcinoma (UUT-UC). METHODS: We evaluated 158 UUT-UC patients who had undergone surgery in the University Hospital of Hannover (MHH). 143 (89.4%) suffered from cancer in the renal pelvis, 13 (8.1%) patients presented with tumour located in the ureter. A preoperative CRP value was available for 115 patients. The mean (median) follow-up for these patients was 28.3 (15.1) months. RESULTS: The median (mean) CRP value of all evaluable patients was 10.0 (40.7) mg/l. The CRP-level, stratified into two subgroups (CRP ≤5 vs. >5 mg/l), correlated significantly with muscle invasive tumour stage (36.4 vs. 78.9%; p<0.001), the risk of presenting nodal disease (4.5 vs. 26.8%; p=0.002) and distant metastasis (2.3 vs. 16.9%; p<0.016). The Kaplan-Meier 5-year cancer specific survival (CSS) rates were 54.2 and 26.4% for patients with preoperative CRP levels ≤ and >5 mg/l, respectively (p<0.006). Next to age and the presence of metastasis, multivariate analysis also identified CRP as a continuous variable as an independent prognosticator for CSS. CONCLUSIONS: A high preoperative serum CRP level is associated with locally advanced and metastatic disease in patients with UUT-UC. Its routine use could allow better risk stratification and risk-adjusted follow-up of UUT-UC patients.

Prognostic value of plasma fibrinogen levels in patients with localized upper tract urothelial carcinoma.

UNLABELLED: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Upper tract urothelial carcinoma (UTUC) is relatively uncommon, accounting for only ~5% of urothelial malignancies and 10% of all renal tumours. Radical nephroureterectomy (RNU) with bladder cuff excision is the surgical standard of care for treating localized UTUC, but the prognosis for patients who undergo RNU remains poor. Evidence suggests that an interactive relationship exists between haemostatic factors and tumour biology. A number of procoagulant and fibrinolytic factors have been found to be overexpressed in tumours. One of these factors is plasma fibrinogen. Recent studies have shown that elevated pre-therapeutic plasma fibrinogen levels are associated with worse outcome in various malignancies; however, the prognostic value of plasma fibrinogen levels for UTUC has not yet been reported. To the best of our knowledge, this is the first paper to evaluate the prognostic impact of preoperative plasma fibrinogen levels in patients with localized UTUC treated surgically. We believe that the present results may assist in decision-making with respect to the need for lymph node dissection and neoadjuvant chemotherapy. OBJECTIVE: To investigate the prognostic value of plasma fibrinogen levels as a predictor of patient outcome in upper tract urothelial carcinoma (UTUC). PATIENTS AND METHODS: A total of 218 patients who underwent radical nephroureterectomy (RNU) for localized UTUC (pTa-4N0M0) were identified between 1995 and 2009. The association between preoperative plasma fibrinogen levels and clinicopathological variables was analysed. RESULTS: Forty-five patients experienced tumour recurrence, and 36 died from disease during the mean follow-up of 51 months. The mean (sd) preoperative plasma fibrinogen level was 362 (103) mg/dL. Kaplan-Meier curves showed that subsequent tumour recurrence was strongly predicted in patients with preoperative plasma fibrinogen levels ≥450 mg/dL, and similar results were observed for cancer-specific survival. On multivariate analysis we found that a preoperative plasma fibrinogen level of ≥450 mg/dL was an independent risk factor for subsequent tumour recurrence and cancer-specific survival. The 5-year recurrence-free survival rate was 56.9% in patients with plasma fibrinogen levels ≥450 mg/dL and 81.5% in patients with plasma fibrinogen levels <450 mg/dL (P < 0.001). The 5-year cancer-specific survival rate was 59.5% in patients with plasma fibrinogen levels of ≥450 mg/dL and 84.8% in patients with plasma fibrinogen levels <450 mg/dL (P < 0.001). On multivariate analysis, controlling for preoperative indicators, a preoperative plasma fibrinogen level of ≥450 mg/dL predicted worse pathological features, such as ≥pT3 disease and positive lymphovascular invasion, in surgical specimens. CONCLUSIONS: Preoperative elevated plasma fibrinogen level was an independent predictor for poor survival after RNU and for worse pathological features. Plasma fibrinogen levels may become a useful biomarker, particularly because of its low associated cost and easy accessibility.

[Ureteral metastasis of prostatic adenocarcinoma: case report and literature review]. / Métastase urétérale isolée d'un adénocarcinome prostatique: à propos d'un cas et revue de la littérature.

Ureteral metastases of prostatic adenocarcinoma are very rare. We report the case of a 66-year-old man with a right ureteral metastasis of prostate cancer. Only 10 cases have been reported in the literature these last 30 years. Most patients had a multimetastatic prostate cancer. Local treatment is not standardized. Hormonotherapy seems to be the most appropriate treatment in first intention.

N-glycan signature of serum immunoglobulins as a diagnostic biomarker of urothelial carcinomas.

Discriminating between urothelial carcinoma (UC), including bladder cancer (BCa) and upper urinary tract UC (UTUC), is often challenging. Thus, the current study evaluated the diagnostic performance of N-glycosylation signatures of immunoglobulins (Igs) for detecting UC, including BCa and UTUC. N-glycosylation signatures of Igs from serum samples of the training cohort, including 104 BCa, 68 UTUC, 10 urinary tract infection, and 5 cystitis cases, as well as 62 healthy volunteers, were measured retrospectively using automated capillary-electrophoresis-based N-glycomics. UTUC or BCa scores were then established through discriminant analysis using N-glycan signatures of Igs. Diagnostic performance was evaluated using the area under receiver operating characteristics curve (AUC) and decision curve analyses (DCA). Our result showed that BCa and UTUC scores for discriminating BCa (AUC: 0.977) and UTUC (AUC: 0.867), respectively, provided significantly better clinical performance compared to urine cytology, gross hematuria, or clinical T1 cases. DCA revealed that adding BCa and UTUC scores to gross hematuria status was the best combination for detecting UC and avoiding the need for more intervention without overlooking UC (risk threshold: 13%-93%). The UC nomogram based on the combination of gross hematuria, UTUC score, and BCa score could detect UC with an AUC of 0.891, indicating significantly better performance compared to gross hematuria status in the validation cohort (251 patients). The limitations of this study include its small sample size and retrospective nature. The UC nomogram based on gross hematuria and N-glycosylation signatures of Igs can be a promising approach for the diagnosis of UC.

Prognostic role of preoperative De Ritis ratio in upper tract urothelial carcinoma treated with nephroureterectomy.

PURPOSE: To validate the predictive and prognostic role of the De Ritis ratio in patients with upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy in a large multi-institutional cohort. MATERIALS AND METHODS: The preoperative De Ritis ratio was assessed in a multi-institutional cohort of 2,492 patients. An altered De Ritis ratio was defined as a ratio >1.35. Logistic regression analyses were performed to assess the association of the De Ritis ratio with advanced disease. The association of the De Ritis ratio with survival outcomes was evaluated using Cox proportional hazards regression models. RESULTS: An altered De Ritis ratio was observed in 985 (41.5%) patients; it was associated with a more advanced pathological features. In a preoperative model, the De Ritis ratio was an independent predictive factor for the presence of lymph node metastasis and muscle-invasive and nonorgan-confined disease (P < 0.05). Compared to patients with a normal De Ritis ratio, those with an altered De Ritis ratio had worse recurrence free (P <0.0001), cancer specific (P = 0.0003), and overall survival (P = 0.0014) in the Kaplan-Meier analyses. In the multivariable analyses that was adjusted for the effects of standard clinicopathologic features, the De Ritis ratio did not retain its independent prognostic value. CONCLUSIONS: In UTUC, the preoperative De Ritis ratio is associated with adverse clinicopathologic features and independently predicts features of biologically and clinically aggressive UTUC. Therefore, it might be useful to incorporate the De Ritis ratio into prognostic tools in selecting appropriate treatment strategies.

Prognostic value of preoperative blood-based biomarkers in upper tract urothelial carcinoma treated with nephroureterectomy: A systematic review and meta-analysis.

PURPOSE: This systematic review and meta-analysis assessed the prognostic value of preoperative blood-based biomarkers in patients with upper tract urothelial carcinoma (UTUC) treated with nephroureterectomy. METHODS: PUBMED, Web of Science, Cochrane Library, and Scopus databases were searched in June 2019 according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement. Studies were deemed eligible if they compared cancer-specific survival in UTUC patients with and without pretreatment laboratory abnormalities. Formal meta-analyses were performed for this outcome. RESULTS: The review identified 54 studies with 23,118 patients, of these, 52 studies with 22,513 patients were eligible for the meta-analysis. Several preoperative blood-based biomarkers were significantly associated with cancer-specific survival as follows: neutrophil-lymphocyte ratio (pooled hazard ratio [HR]: 1.66, 95% confidence interval [CI]: 1.34-2.06), C-reactive protein (pooled HR: 1.17, 95% CI: 1.07-1.29), platelet-lymphocyte ratio (pooled HR: 1.68, 95% CI: 1.30-2.17), white blood cell (pooled HR: 1.58, 95% CI: 1.02-2.46), De Ritis ratio (pooled HR: 2.40, 95% CI: 1.92-2.99), fibrinogen (pooled HR: 2.23, 95% CI: 1.86-2.68), albumin-globulin ratio (pooled HR: 3.00, 95% CI: 1.87-4.84), hemoglobin (pooled HR: 1.51, 95% CI: 1.22-1.87), and estimate glomerular filtration rate (pooled HR: 1.52, 95% CI: 1.19-1.94). The Cochrane's Q test and I2 test revealed significant heterogeneity for neutrophil-lymphocyte ratio, C-reactive protein, white blood cell, hemoglobin, and estimated glomerular filtration rate (P = 0.022; I2 = 50.7%, P = 0.000; I2 = 80.4%, P = 0.000; I2 = 88.3%, P = 0.010; I2 = 62.0%, P = 0.000; I2 = 83.9%, respectively). CONCLUSIONS: Several pretreatment laboratory abnormalities in patients with UTUC were associated with increased risks of cancer-specific mortality. Therefore, blood-based biomarkers may have the potential to serve as prognostic factors to assist patients and physicians in selecting appropriate treatment strategies for UTUC. However, considering the study limitations including heterogeneity and retrospective nature of the primary data, the conclusions should be interpreted with caution.

The pretreatment neutrophil-to-lymphocyte ratio is a novel biomarker for predicting clinical responses to pembrolizumab in platinum-resistant metastatic urothelial carcinoma patients.

PURPOSE: We investigated the relationship between pretreatment neutrophil-to-lymphocyte ratio (pre-NLR) levels just before the initiation of treatment with pembrolizumab and clinical outcomes in platinum-resistant metastatic urothelial carcinoma (UC) patients treated with pembrolizumab. METHODS: Our study population comprised 78 patients diagnosed with metastatic UC and treated with pembrolizumab after platinum-based chemotherapy at our institutions between December 2017 and April 2019. We examined the relationships between pre-NLR levels just before pembrolizumab treatment and clinical outcomes. A pre-NLR level of ≥3.35 was defined as elevated according to a calculation by a receiver-operating curve analysis. RESULTS: The high pre-NLR group consisted of 33 patients (42.3%). Overall, 29.5% of patients had a clinical response and the sum of the target lesion longest diameter was decreased in 18.8% of the high pre-NLR group, which was significantly lower than that in the low pre-NLR group (58.1%, P = 0.005). Six-month progression-free survival and cancer-specific survival rates for the high pre-NLR group were 9.1 and 58.0%, which were significantly lower than those for their counterpart (45.9 and 89.1%, P < 0.001 and P = 0.002, respectively). The pre-NLR level was an independent indicator of disease progression and cancer-specific death (P < 0.001 and P = 0.003). Furthermore, patients with a postpembrolizumab NLR level that had decreased ≥25% from the pre-NLR level had significantly lower disease progression and cancer-specific death rates than their counterparts (P = 0.01 and P = 0.022, respectively). CONCLUSIONS: Elevated pre-NLR may be a novel biomarker for identifying poor responders to pembrolizumab among platinum-resistant metastatic UC patients.