Prognostic Significance of ROR2 Expression in Patients with Urothelial Carcinoma

We investigated the association of receptor tyrosine kinase-like orphan receptor 2 (ROR2) expression with clinicopathological features and oncologic outcomes in large urothelial carcinoma (UC) of the upper tract (UTUC) and urinary bladder (UBUC) cohorts. Through transcriptomic profiling of a published dataset (GSE31684), ROR2 was discovered to be the most upregulated gene during UC progression, focusing on the JNK cascade (GO:0007254). Initially, the evaluation of ROR2 mRNA expression in 50 frozen UBUCs showed significantly upregulated levels in high-stage UC. Moreover, high ROR2 immunoexpression significantly correlated with high tumor stage, high tumor grade, lymph node metastasis, and vascular invasion (all p < 0.05). In multivariate analysis, after adjusting for standard clinicopathological features, ROR2 expression status was an independent prognosticator of cancer-specific survival and metastasis-free survival in UTUC and UBUC (all p < 0.01). In the subgroup analysis, it also significantly predicted bladder tumor recurrence in non-muscle invasive UBUC. Furthermore, the GO enrichment analysis showed that fatty acid, monocarboxylic acid, carboxylic acid metabolic processes, negative regulation of neutrophil migration, and negative regulation of granulocyte and neutrophil chemotaxis were significantly enriched by ROR2 dysregulation. In conclusion, high ROR2 immunoexpression was associated with aggressive pathological characteristics in UC and independently predicted worse prognosis, suggesting it could play roles in clinical risk stratification and therapy decisions.

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Impact of cachexia on oncologic outcomes of sarcopenic patients with upper tract urothelial carcinoma after radical nephroureterectomy

PLoS ONE ◽

10.1371/journal.pone.0250033 ◽

2021 ◽

Vol 16 (4) ◽

pp. e0250033

Author(s):

Hao-Wei Chen ◽

Yu-Chen Chen ◽

Li-Hwa Yang ◽

Ming-Chen Paul Shih ◽

Ching-Chia Li ◽

...

Keyword(s):

Urothelial Carcinoma ◽

Cox Regression ◽

Medical Center ◽

Prognostic Significance ◽

Tumor Grade ◽

Tumor Stage ◽

Oncologic Outcomes ◽

Radical Nephroureterectomy ◽

Cancer Specific Survival ◽

Poor Prognostic Factor

Objectives To investigate the prognostic significance of sarcopenic cachexia compared to sarcopenia without cachexia in the outcomes of upper urinary tract urothelial carcinoma (UTUC) patients treated with radical nephroureterectomy (RNU). Materials and methods Between 2011 and 2016, 163 patients with UTUC who received RNU at a tertiary medical center were included. Pre-operatively clinical data, history, and abdominal computer tomography scans were analyzed retrospectively. The diagnosis of sarcopenia was based on abdominal computed tomography data on the patient’s skeletal muscles. Outcomes of relapse-free, cancer-specific, and overall survival were analyzed by multivariate Cox regression. Results After adjusting for age, sex, pre-operatively estimated glomerular filtration rate, body mass index, underlying diseases, tumor grade, and tumor stage, cachexia was a significant poor prognostic factor for relapse-free survival (hazard ratio [HR]: 18.5, 95% confidence interval [CI]: 2.87–118, p = 0.002) and cancer-specific survival (HR: 26.6, 95% CI: 4.04–175, p = 0.001). In contrast, sarcopenia without cachexia was not a significant predictor of cancer outcomes. Conclusions To date, this is the first study to investigate the effect of cachexia among sarcopenic patients with UTUC treated with RNU. We identified the prognostic significance of cachexia on outcomes. Indeed, when UTUC is treated with RNU, we should evaluate not only sarcopenia status but also cachexia. The low survival rate among patients with UTUC complicated with cachexia deserves attention.

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Prognostic significance of platelet-to-lymphocyte ratio in urothelial carcinoma patients: a meta-analysis

Cancer Cell International ◽

10.1186/s12935-019-1032-6 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 2

Author(s):

Yuhai Bao ◽

Yin Wang ◽

Xiaodong Li ◽

Mingjun Pan ◽

Hongze Zhang ◽

...

Keyword(s):

Urothelial Carcinoma ◽

Meta Analysis ◽

Prognostic Significance ◽

Disease Free Survival ◽

Cochrane Library ◽

Prognostic Impact ◽

Platelet To Lymphocyte Ratio ◽

Cancer Specific Survival ◽

Free Survival ◽

Lymphocyte Ratio

Abstract Background The prognostic value of pre-treatment platelet-to-lymphocyte ratio (PLR) in patients with urothelial carcinoma (UC) remains controversial. Therefore, this meta-analysis aimed to identify the prognostic impact of PLR on UC. Methods The PubMed, Embase, Web of Science, and Cochrane Library databases were systematically searched. Hazard ratios (HRs) with 95% confidence intervals (CIs) were used to summarize the correlations between PLR and overall survival (OS), progression-free survival (PFS), disease-free survival (DFS), and cancer-specific survival (CSS). Odds ratios (ORs) with 95% CIs were used to measure the association between PLR and tumor clinicopathological factors. Results The meta-analysis included 15 studies published from 2015 to 2019 with a total of 5354 patients. Overall, a high PLR was correlated to poorer PFS (HR = 1.81, 95% CI 1.28–2.56, p = 0.001) and DFS (HR = 1.09, 95% CI 1.31–2.16, p < 0.001) but not poor OS (HR = 1.23, 95% CI 0.95–1.59, p = 0.124) or CSS (HR = 1.000, 95% CI 0.998–1.002, p = 0.919) in UC. In addition, an elevated PLR was correlated with patient age > 65 years (OR = 1.72, 95% CI 1.25–2.38, p = 0.001) and hypertension (OR = 1.48, 95% CI 1.01–2.18, p = 0.046). However, no significant association was observed between PLR and sex (OR = 0.79, 95% CI 0.56–1.14, p = 0.206) or diabetes (OR = 1.29, 95% CI 0.77–2.15, p = 0.333). Conclusions Our results demonstrated a significant correlation between elevated PLR and poor prognosis in UC. The prognostic role of PLR may help guide the management and prognostication of UC patients.

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PD-L1 expression in anogenital and oropharyngeal squamous cell carcinomas associated with different clinicopathological features, HPV status and prognosis: a meta-analysis

Bioscience Reports ◽

10.1042/bsr20203669 ◽

2021 ◽

Author(s):

Yuan Qin ◽

Jiaochen Luan ◽

Xiang Zhou ◽

Ying Li

Keyword(s):

Squamous Cell ◽

Meta Analysis ◽

Disease Free Survival ◽

Tumor Grade ◽

Clinicopathological Characteristics ◽

Squamous Cell Carcinomas ◽

Clinicopathological Features ◽

Advanced Age ◽

Cancer Specific Survival ◽

Hpv Status

Background: Little research has been done on clinicopathological characteristics and human papillomavirus (HPV) status of anogenital and oropharyngeal squamous cell carcinomas (SCC) with a strong expression of programmed death ligand 1 (PD-L1) in tumor cells. Therefore, we conducted this meta-analysis. Methods: We performed a comprehensive research in PubMed, Embase and Cochrane databases up to September 30th, 2020. The effect size was hazard ratio (HR) with 95% confidence interval (CI) for overall survival (OS), cancer specific survival (CSS), disease free survival (DFS). The pooled odds ratio (OR) with 95%CI were used to assess the association between PD-L1 expression and clinicopathological features along with HPV status. Results: A total of 2003 cases (944 anogenital and 1059 oropharynx SCC patients) were included. High PD-L1 expression in anogenital SCC cases were associated with advanced age (OR=1.63, 95%CI:1.04-2.58) and HPV negativity (OR=0.47,95%CI:0.31-0.71). Besides, PD-L1 positive anogenital SCC cases held a significant declined OS (HR=2.18, 95%CI:1.37-3.47) and CSS (HR=2.45, 95%CI:1.30-4.65). For oropharynx SCC, PD-L1 was more frequent in younger and HPV positive patients (OR=0.60, 95%CI:0.37-0.98; OR=3.01, 95%CI:1.78-5.09) and PD-L1 expression was relevant to better OS and DFS (HR=0.76, 95%CI:0.60-0.97; HR=0.50, 95%CI:0.33-0.75). Conclusions: The meta-analysis demonstrated that in anogenital SCC, PD-L1 positivity had to do with a worse outcome, which might attribute to advanced age, higher tumor grade, lymph node metastasis and HPV negativity, while in oropharynx cancer, PD-L1expression was related to better prognosis for the reason that PD-L1 was less frequent in the aged and negative HPV status.

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Prognostic significance of non-urothelial carcinoma of bladder: analysis of nationwide hospital-based cancer registry data in Japan

Japanese Journal of Clinical Oncology ◽

10.1093/jjco/hyaa072 ◽

2020 ◽

Vol 50 (9) ◽

pp. 1068-1075

Author(s):

Yoshiyuki Nagumo ◽

Koji Kawai ◽

Takahiro Kojima ◽

Masanobu Shiga ◽

Kosuke Kojo ◽

...

Keyword(s):

Urothelial Carcinoma ◽

Cancer Registry ◽

Prognostic Significance ◽

Stage I ◽

Registry Data ◽

Oncologic Outcomes ◽

Small Cell Neuroendocrine Carcinoma ◽

Cancer Registry Data ◽

Kaplan Meier ◽

Aggressive Surgical Approach

Abstract Objectives To identify the prognosis of pure non-urothelial carcinoma (non-UC) of bladder and to compare them with those of pure urothelial carcinoma (UC). Methods We used Japan’s nationwide hospital-based cancer registry data to extract histologically confirmed pure non-UC and UC cases of bladder diagnosed in 2008–2009. We estimated the 5-year overall survival (OS) by a Kaplan–Meier analysis. Results A total of 8094 patients with confirmed histological subtypes of bladder cancer were identified. The most common pure non-UC was squamous cell carcinoma (SQ, n = 192, 2.4%) followed by adenocarcinoma (AC, n = 138, 1.7%) and small cell neuroendocrine carcinoma (SmC, n = 54, 0.7%). The proportion of female patients (48%) was significantly higher in the SQ group compared with the pure UC group (P < 0.001). The 5-year OS rate of the non-UC patients was significantly worse than that of the UC patients (40 vs. 61%, P < 0.001). According to stages, the 5-year OS rates of the stage I and III non-UC patients were significantly worse than those of the UC patients (P = 0.001). Considering histologic subtypes and stages, the 5-year OS rates of the stage I SQ patients were worse than those of the AC and SmC patients (46, 68 and 64%, respectively). Conclusion The prognosis of pure non-UC was worse than that of pure UC, especially in the stage I and III non-UC patients. To improve these patients’ oncologic outcomes, a more aggressive surgical approach may be necessary in stage I patients with non-UC, especially in pure SQ.

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Prognostic significance of the albumin-to-globulin ratio for advanced urothelial carcinoma treated with pembrolizumab: a multicenter retrospective study

Scientific Reports ◽

10.1038/s41598-021-95061-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Satoru Taguchi ◽

Taketo Kawai ◽

Tohru Nakagawa ◽

Yu Nakamura ◽

Jun Kamei ◽

...

Keyword(s):

Urothelial Carcinoma ◽

Proportional Hazards Model ◽

Risk Model ◽

Characteristic Curve ◽

Performance Status ◽

Prognostic Significance ◽

Cox Proportional Hazards Model ◽

Cancer Specific Survival ◽

Advanced Urothelial Carcinoma ◽

Albumin To Globulin Ratio

AbstractAlthough the albumin-to-globulin ratio (AGR) is a promising biomarker, no study has investigated its prognostic significance for advanced urothelial carcinoma (UC). This study conformed to the REporting recommendations for tumor MARKer prognostic studies (REMARK) criteria. We retrospectively reviewed 176 patients with advanced UC treated with pembrolizumab between 2018 and 2020. We evaluated the associations between pretreatment clinicopathological variables, including the AGR and performance status (PS), with progression-free survival, cancer-specific survival, and overall survival. The Cox proportional hazards model was used for univariate and multivariable analyses. The AGR was dichotomized as < 0.95 and ≥ 0.95 based on receiver operating characteristic curve analysis. After excluding 26 cases with missing data from the total of 176 cases, 109 (73%) patients experienced disease progression, 75 (50%) died from UC, and 6 (4%) died of other causes (median survival = 12 months). Multivariate analyses identified PS ≥ 2 and pretreatment AGR < 0.95 as independent poor prognostic factors for all endpoints. Furthermore, a prognostic risk model incorporating these two variables achieved a relatively high concordance index for all endpoints. This is the first report to evaluate the significance of AGR in advanced UC. Pretreatment AGR < 0.95 may serve as a prognostic marker for advanced UC treated with pembrolizumab.

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The Influence of Tumor Size on Oncologic Outcomes for Patients with Upper Tract Urothelial Carcinoma after Radical Nephroureterectomy

BioMed Research International ◽

10.1155/2016/4368943 ◽

2016 ◽

Vol 2016 ◽

pp. 1-7 ◽

Cited By ~ 6

Author(s):

Xiaohong Su ◽

Dong Fang ◽

Xuesong Li ◽

Gengyan Xiong ◽

Lei Zhang ◽

...

Keyword(s):

Urothelial Carcinoma ◽

Tumor Size ◽

Univariate Analysis ◽

Upper Tract Urothelial Carcinoma ◽

Oncologic Outcomes ◽

Advanced Tumor Stage ◽

Clinicopathologic Characteristics ◽

Cancer Specific Survival ◽

Upper Tract ◽

Advanced Tumor

Previous studies have reached diverse conclusions about the influence of tumor size on the oncologic outcomes in patients with upper tract urothelial carcinoma (UTUC). In this study, we retrospectively analyzed the records of 687 patients and evaluated how tumor size affected the prognosis of patients with UTUC after surgery. Clinicopathologic characteristics and oncological outcomes were compared according to tumor size (≤3 cm versus >3 cm). During a median follow-up period of 65 months (range 3–144 months), 225 patients (32.8%) died from UTUC and 228 patients (33.2%) experienced intravesical recurrence (IVR). Patients with a larger tumor size tended to have a significantly higher percentage of being male (p=0.011), tobacco consumption (p=0.036), lack of preoperative ureteroscopy history (p=0.003), renal pelvic location (p<0.001), tumor necrosis (p=0.003), advanced tumor stage (p<0.001), higher tumor grade (p=0.003), and lymph node metastasis (p=0.018). Univariate analysis revealed that a tumor size >3 cm was significantly associated with worse cancer-specific survival (p=0.002) and IVR (p=0.011). However, the influence was not statistically significant after controlling for other factors in the multivariate analysis (hazard ratio [HR] 1.124, p=0.414 and HR 1.196, p=0.219). In conclusion, UTUC patients with a larger tumor present aggressive biological characteristics and tend to have a worse prognosis.

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Trends in management and outcomes in patients with upper tract urothelial carcinoma following radical nephrouretectomy at Memorial Sloan Kettering Cancer Center.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.6_suppl.469 ◽

2020 ◽

Vol 38 (6_suppl) ◽

pp. 469-469

Author(s):

Nathan Colin Wong ◽

Melissa Assel ◽

Andrew Tracey ◽

Ricardo Alvim ◽

Nima Almassi ◽

...

Keyword(s):

Lymph Node ◽

Urothelial Carcinoma ◽

Generalized Additive Models ◽

Additive Models ◽

Upper Tract Urothelial Carcinoma ◽

Oncologic Outcomes ◽

Cancer Center ◽

Cancer Specific Survival ◽

Upper Tract ◽

The Past

469 Background: Although there have been changes in the treatment paradigm of patients with upper tract urothelial carcinoma (UTUC) over the past 2 decades, there is limited data on the particular management strategies and associated outcomes. We evaluated surgical trends, perioperative management, and oncologic outcomes of patients who underwent radical nephroureterectomy (RNU) for UTUC at Memorial Sloan Kettering Cancer Center over a 24-year period. Methods: Between 1995 and 2018, we identified 760 patients with UTUC who underwent RNU. 15 had multiple RNU and we kept only the first procedure for analysis. Generalized additive models were fitted to examine the association between date of surgery and continuous while generalized additive models with a logit link were used to estimate categorical variables. As surgical approach was defined using three different categories (open, laparoscopic and robotic) a generalized additive multinomial model was used. Generalized additive cox proportional hazards models were used to estimate the association between surgery date and estimate 2-year cancer-specific survival. Results: The use of pre-operative diagnostic endoscopic biopsies also increased from 12% to 72% which coincides with an increased proportion high grade disease on final pathology from 55% to 91%. The rate of open RNU declined from 100% to 54% with a coinciding rise in the utilization of minimally invasive approaches. Laparoscopy peaked in 2008 and then was subsequently replaced by the robotic approach. Mean lymph node yield increased over the study interval with more retroperitoneal lymph node dissections performed. Utilization of neoadjuvant chemotherapy also increased over time with a current rate of 31%, coinciding with an increase in pT0 rate from only 2% to 9%.The 2-year cancer specific survival probability has improved from 76% to 87% over the study period. Conclusions: Several changes in treatment patterns for patients with UTUC over the past 2 decades appear to correspond with an improvement of oncologic outcomes. How these changes directly relate to each other requires further investigation.

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Prognostic Significance of the Albumin-to-globulin Ratio for Advanced Urothelial Carcinoma Treated with Pembrolizumab: A Multicenter Retrospective Study

10.21203/rs.3.rs-569029/v1 ◽

2021 ◽

Author(s):

Satoru Taguchi ◽

Taketo Kawai ◽

Tohru Nakagawa ◽

Yu Nakamura ◽

Jun Kamei ◽

...

Keyword(s):

Urothelial Carcinoma ◽

Proportional Hazards Model ◽

Risk Model ◽

Characteristic Curve ◽

Performance Status ◽

Prognostic Significance ◽

Cox Proportional Hazards Model ◽

Cancer Specific Survival ◽

Advanced Urothelial Carcinoma ◽

Albumin To Globulin Ratio

Abstract Although the albumin-to-globulin ratio (AGR) is a promising biomarker, no study has investigated its prognostic significance for advanced urothelial carcinoma (UC). This study conformed to the REporting recommendations for tumor MARKer prognostic studies (REMARK) criteria. We retrospectively reviewed 176 patients with advanced UC treated with pembrolizumab between 2018 and 2020. We evaluated the associations between pretreatment clinicopathological variables, including the AGR and performance status (PS), with progression-free survival, cancer-specific survival, and overall survival. The Cox proportional hazards model was used for univariate and multivariable analyses. The AGR was dichotomized as < 0.95 and ≥ 0.95 based on receiver operating characteristic curve analysis. After excluding 26 cases with missing data from the total of 176 cases, 109 (73%) patients experienced disease progression, 75 (50%) died from UC, and 6 (4%) died of other causes (median survival = 12 months). Multivariate analyses identified PS ≥ 2 and pretreatment AGR < 0.95 as independent poor prognostic factors for all endpoints. Furthermore, a prognostic risk model incorporating these two variables achieved a relatively high concordance index for all endpoints. This is the first report to evaluate the significance of AGR in advanced UC. Pretreatment AGR < 0.95 may serve as a prognostic marker for advanced UC treated with pembrolizumab.

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Prognostic Significance of Primary Tumor Location in Upper Tract Urothelial Carcinoma Treated with Nephroureterectomy: A Retrospective, Multi-Center Cohort Study in Taiwan

Journal of Clinical Medicine ◽

10.3390/jcm9123866 ◽

2020 ◽

Vol 9 (12) ◽

pp. 3866

Author(s):

Lian-Ching Yu ◽

Chao-Hsiang Chang ◽

Chi-Ping Huang ◽

Chao-Yuan Huang ◽

Jian-Hua Hong ◽

...

Keyword(s):

Urothelial Carcinoma ◽

Prognostic Significance ◽

Disease Free Survival ◽

Tumor Location ◽

Upper Tract Urothelial Carcinoma ◽

Cancer Specific Survival ◽

Free Survival ◽

Upper Tract ◽

Ureteral Tumor ◽

Worse Prognosis

We sought to examine the effect of tumor location on the prognosis of patients with upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU). This retrospective study came from the Taiwan UTUC Collaboration Group, which consisted of 2658 patients at 15 institutions in Taiwan from 1988 to 2019. Patients with kidney-sparing management, both renal pelvic and ureteral tumors, as well as patients lacking complete data were excluded; the remaining 1436 patients were divided into two groups: renal pelvic tumor (RPT) and ureteral tumor (UT), with 842 and 594 patients, respectively. RPT was associated with more aggressive pathological features, including higher pathological T stage (p < 0.001) and the presence of lymphovascular invasion (p = 0.002), whereas patients with UT often had synchronous bladder tumor (p < 0.001), and were more likely to bear multiple lesions (p = 0.001). Our multivariate analysis revealed that UT was a worse prognostic factor compared with RPT (overall survival: HR 1.408, 95% CI 1.121–1.767, p = 0.003; cancer-specific survival: HR 1.562, 95% CI 1.169–2.085, p = 0.003; disease-free survival: HR 1.363, 95% CI 1.095–1.697, p = 0.006; bladder-recurrence-free survival: HR 1.411, 95% CI 1.141–1.747, p = 0.002, respectively). Based on our findings, UT appeared to be more malignant and had a worse prognosis than RPT.

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Sarcomatoid variant urothelial carcinoma of the bladder: a systematic review and meta-analysis of the clinicopathological features and survival outcomes

Cancer Cell International ◽

10.1186/s12935-020-01626-9 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Liangyou Gu ◽

Qing Ai ◽

Qiang Cheng ◽

Xin Ma ◽

Baojun Wang ◽

...

Keyword(s):

Systematic Review ◽

Urothelial Carcinoma ◽

Meta Analysis ◽

Progression Free Survival ◽

Clinicopathological Features ◽

Cochrane Library ◽

Survival Outcomes ◽

Cancer Specific Survival ◽

Comprehensive Search ◽

Carcinoma Of The Bladder

Abstract Background A systematic review and meta-analysis was performed to compare the clinicopathological features and survival outcomes between sarcomatoid variant (SV)-urothelial carcinoma of the bladder (UCB) and conventional UCB (C-UCB). Methods A comprehensive search of PubMed, Embase, and Cochrane Library was performed. Endpoints included clinicopathological features and survival outcomes (overall survival [OS], cancer-specific survival [CSS], and progression-free survival [PFS]). The survival benefits of neoadjuvant chemotherapy (NAC) or adjuvant chemotherapy (AC) for SV-UCB also have been studied. Results A total of 8 observational studies were included. Patients with SV-UCB had a higher rate of ≥ stage pT3 (odds ratio [OR], 2.06; 95% confidence interval [CI], 1.64–2.59; p < 0.001) and a lower rate of concomitant carcinoma in situ (OR, 0.25; 95% CI, 0.09–0.72; p = 0.010). The other clinicopathological variables were similar between SV-UCB and C-UCB. With unadjusted data, patients with SV-UCB had a significant inferior OS (HR, 1.24; 95% CI, 1.07–1.44; p = 0.004) and CSS (HR, 2.08; 95% CI, 1.63–2.66; p < 0.001). However, after adjusted, SV-UCB had worse OS (HR, 1.41; 95% CI, 0.95–2.08; p = 0.090) and CSS (HR, 1.54; 95% CI, 0.95–2.52; p = 0.080) approaching the borderline of significance. For SV-UCB, NAC (HR, 0.73; 95% CI, 0.51–1.05; p = 0.090) and AC (HR, 0.88; 95% CI, 0.66–1.17; p = 0.370) seemed to have no benefit on OS. Conclusions Compared to C-UCB, SV-UCB was associated with more advanced disease and more inferior OS and CSS. NAC and AC had no survival benefit for SV-UCB.

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