PD-L1 expression in tumor-infiltrating lymphocytes (TILs) as an independent predictor of prognosis in patients with pN0 bladder cancer undergoing radical cystectomy

ObjectivesCheckpoint inhibitors have led to a paradigm shift in urothelial carcinoma (UC) treatment. However, the relationship between PD-L1 expression status and oncological outcomes in UC patients remains uncertain. Here, we investigated the prognostic value of PD-L1 expression status in patients with UC of the bladder (UCB) who underwent radical cystectomy (RC).Materials and methodsWe retrospectively analyzed pathological specimens from 97 UCB patients treated with RC from 1990 to 2015 at Kitasato University Hospital. Immunohistochemical staining using SP263 was performed to evaluate PD-L1 expression in tumor cells (TCs) and tumor-infiltrating lymphocytes (TILs). Kaplan-Meier plots and proportional Cox hazard ratios were examined to assess the relationship between PD-L1 expression and clinicopathological parameters and survival outcomes.ResultsOf the 97 specimens, 19.5% contained PD-L1-positive TCs, and 35.0% contained PD-L1-positive TILs. Regarding clinicopathological factors, PD-L1-positive TCs and TILs were significantly associated with high-grade tumors (TCs, P = 0.01; TILs, P = 0.003). Kaplan-Meier analyses showed that PD-L1-positive TCs were not correlated with survival rates. However, PD-L1-positive TILs were significantly associated with better recurrence-free survival (RFS; P = 0.03) and better cancer-specific survival (CSS; P = 0.02). Univariate analysis, but not multivariate analysis, CSS indicated that PD-L1-positive TILs were significant predictors of patient prognoses. Multivariate analysis showed that PD-L1-positive TILs independently predicted CSS in patients without lymph node metastasis (pN0).ConclusionPositive PD-L1 expression is associated with high-grade tumors. PD-L1-positive TILs are independent predictors of favorable survival outcomes in surgically resected UCB patients at stage pN0.     

Comparison of the prognosis of primary vs. progressive muscle invasive bladder cancer after radical cystectomy: Results from a large multicenter study

PurposeTo assess whether progressive and primary muscle invasive bladder cancer (MIBC) have different prognosis after radical cystectomy or not. To date only a few data are available on this topic with conflicting results. Further studies on large cohort are needed to clarify these outcomes that may influence bladder cancer management for these patients.Material and methodsA multicentre retrospective study was conducted on patient treated for MIBC at 5 centres between 2005 and 2015 by radical cystectomy. Patients’ outcomes were compared between patients with primary MIBC vs. progressive MIBC subsequent to a history of non-muscle invasive bladder cancer (NMIBC).ResultsA total of 1197 patients were included. Median (IQ) age was 65 (58–72) years and median follow-up was 65 months. Baseline characteristics were similar between the groups as well as the Tumour pT stage, N status and positive surgical margins. Patients with progressive MIBC had worse overall survival (OS) (hazard ratio [HR] 1.36, [95%CI 1.10–1.76]; P = 0.004), cancer specific survival (CSS) (HR 1.41 [1.13–1.78]; P = 0.002), and recurrence-free survival (RFS) (HR 1.21 [1.01–1.49]; P = 0.05). Pathological stage ≥pT3, positive surgical margins, and positive lymph nodes status (pN+) were also found as predictors of OS, CSS, and RFS.ConclusionsOur results suggest that patient having a progressive BC have a worse prognosis in terms of OS, PFS, and CSS than patient with primary disease. These 2 groups may require different management and patients with high risk NMIBC should be assessed properly to avoid progression and be offered early cystectomy.     

Diffusive Ki67 and vimentin are associated with worse recurrence-free survival of upper tract urothelial carcinoma: A retrospective cohort study from bench to bedside

ObjectivesThis study aimed to determine the prognostic values of Ki67 and vimentin in upper tract urothelial carcinoma (UTUC) after extirpative surgery.Methods and materialsBetween 2014 and 2019, patients diagnosed with UTUC and receiving radical nephroureterectomy were included retrospectively. Nuclear MIB-1 clones and cytoplasmic VIM 3B4 clones were used to assess Ki67 and vimentin levels, respectively. A unified reading protocol was applied, and the expression level was read by a single pathologist. Receiver operating characteristic curves were utilized to determine the best threshold for Ki67 and vimentin regarding recurrence, and this level was set as the diffusive level. The outcome of recurrence-free survival (RFS) was analyzed via a Cox regression model with univariable and multivariable approaches. Survival outcomes were analyzed via Kaplan–Meier (KM) curves.ResultsA total of 247 patients were included, and the mean follow-up was 29.90 ± 6.80 months. Diffusive thresholds were 17.5% for both Ki67 and vimentin. Under multivariable Cox regression, diffusive Ki67 (hazard ratio: 4.20 [2.39–7.37], P < 0.001) and diffusive vimentin (hazard ratio: 5.34 [3.10–9.22], P < 0.001) were significant prognostic indicators of worse RFS. Diffusive Ki67 was accompanied by diffusive vimentin (chi square with Yates’ correction, P = 0.015), and vice versa. In the KM curve, there was no difference between diffusive Ki67/nondiffusive vimentin and nondiffusive Ki67/diffusive vimentin (log-rank test, P = 0.073). Significant differences (log-rank test, P < 0.001) were seen in different combinations of diffusive Ki67/vimentin (Mean RFS: 19.76 [18.56–20.96] months), only one diffusive in Ki67 or vimentin (Mean RFS: 22.94 [21.88–24.00] months), and nondiffusive Ki67/vimentin (Mean RFS: 32.96 [32.43–33.50] months).ConclusionsDiffusive Ki67 and vimentin were related to each other, and they exerted equivalent and synergic effects on predicting worse RFS in UTUC.     

Locoregional recurrence after cystectomy in muscle invasive bladder cancer: Implications for adjuvant radiotherapy

PurposeWe report the patterns of locoregional recurrence (LRR) in muscle invasive bladder cancer (MIBC), and propose a risk stratification to predict LRR for optimizing the indication for adjuvant radiotherapy.Materials and MethodsThe study included patients of urothelial MIBC who underwent radical cystectomy with standard perioperative chemotherapy between 2013 and 2019. Recurrences were classified into local and/or cystectomy bed, regional, systemic, or mixed. For risk stratification modelling, T stage (T2, T3, T4), N stage (N0, N1/2, N3) and lymphovascular invasion (LVI positive or negative) were given differential weightage for each patient. The cohort was divided into low risk (LR), intermediate risk (IR) and high risk (HR) groups based on the cumulative score.ResultsOf the 317 patients screened, 188 were eligible for the study. Seventy patients (37.2%) received neoadjuvant chemotherapy (NACT) while 128 patients (68.1%) had T3/4 disease and 66 patients (35.1%) had N+ disease. Of the 55 patients (29%) who had a recurrence, 31 (16%) patients had a component of LRR (4% cystectomy bed, 11.5% regional 0.5% locoregional). The median time to LRR was 8.2 (IQR 3.3–18.8) months. The LR, IR and HR groups for LRR based on T, N and LVI had a cumulative incidence of 7.1%, 21.6%, and 35% LRR, respectively. The HR group was defined as T3, N3, LVI positive; T4 N1/2, LVI positive; and T4, N3, any LVI. The odds ratio for LRR was 3.37 (95% CI 1.16–9.73, P = 0.02) and 5.27 (95% CI 1.87–14.84, P = 0.002) for IR and HR respectively, with LR as reference.ConclusionLRR is a significant problem post radical cystectomy with a cumulative incidence of 35% in the HR group. The proposed risk stratification model in our study can guide in tailoring adjuvant radiotherapy in MIBC.     

Accuracy and prognostic value of variant histology and lymphovascular invasion at transurethral resection of bladder

Objectives

To evaluate the concordance rate of lymphovascular invasion (LVI) and variant histology (VH) of transurethral resection (TUR) with radical cystectomy (RC) specimens. Furthermore, to evaluate the value of LVI and VH at TUR for predicting non-organ confined (NOC) disease, lymph node metastasis, and survival outcomes.

Patients and methods

Two hundred and sixty-eight patients who underwent TUR and subsequent RC were reviewed. Logistic regression analyses were performed to evaluate the association of LVI and VH with NOC and lymph node metastasis at RC. Cox regression analyses were used to estimate recurrence-free survival (RFS) and cancer-specific survival (CSS).

Results

LVI and VH were detected in 13.8 and 11.2% of TUR specimens, and in 30.2 and 25.4% of RC specimens, respectively. The concordance rate between LVI and VH at TUR and subsequent RC was 69.8 and 83.6%, respectively. They were both associated with adverse pathological features such as lymph node metastasis and advanced stage. TUR LVI and VH were both independently associated with lymph node metastasis and TUR VH was independently associated with NOC. On univariable Cox regression analyses, TUR LVI was associated with RFS and CSS while TUR VH was only associated with RFS. Only TUR LVI was independently associated with RFS.

Conclusion

Detection of LVI is missed in a third of TUR specimens while VH seems more accurately identified. TUR LVI and VH are associated with more advanced disease and LVI predicts disease recurrence. Assessment and reporting of LVI and VH on TUR specimen are important for risk stratification and decision-making.

     

肿瘤标志物和Ki67在结直肠癌中的表达及预后因素分析

目的 探讨术前血清肿瘤标志物与术后Ki67联合检测对结直肠癌病人预后评估的价值.方法 收集2012年1 月至2014年6月在武汉大学人民医院胃肠外科就诊的结直肠癌病人的临床病理资料和随访资料.癌胚抗原(CEA)＞5 μg/L定义为阳性,癌抗原(CA)19-9＞35 kU/L定义为阳性.Ki67 LI大于其对应截断值定义...     

核增殖抗原表达基因Ki67与人肺癌临床病理生理特征及其预后的关系

目的：研究细胞增殖状态与肺癌临床病理生理特征和预后的关系,探讨Ki67对临床诊断和预后判断的价值。方法：应用免疫组织化学法检测166例肺癌组织标本和37例肺良性病变组织中Ki67的表达水平。结果：（1）肺癌组织中Ki67指数显著高于肺良性病变组织（P＜0．01）,而癌旁组织与良性病变组织相比判别无显著性意义;（2）肺癌组织中Ki67表达水平增强与肺癌组织学类型,细胞分化程度有关（P＜0．05）,而与患者PTNM分期,淋巴结转移程度,吸烟与否以及患者的性别,年龄无明显关系;（3）Ki67高表达组肺癌患者的术后生存时间显著你芋低表达组（P＜0．01）,按PTNM分期分层后这种差别仍然存在（P＜05）,结论：Ki67能较好地反映肺癌细胞的增殖状态,并对临床诊断和预后判断有一定价值。     

Elaboración de un índice pronóstico inmunonutricional en pacientes con cáncer de vejiga músculo-infiltrante candidatos a cistectomía radical

IntroductionMuscle-infiltrating bladder tumor (MIBT) has a recurrence-free survival (RFS) of 50% at 5 years. Although neoadjuvant chemotherapy (NCT) has increased it by 8%, which group of patients benefits the most from this treatment remains unclear.ObjectiveEvaluate the prognostic value of immune-nutritional status in patients with MIBT who are candidates for cystectomy, and to develop a score that allows identifying patients with a worse prognosis (pT3-4 and/or pN0-1).Material and methodsA retrospective analysis was carried out on 284 patients with MIBT treated with radical cystectomy. Preoperative laboratory tests were analyzed and immune-nutritional indices were calculated. The Kaplan–Meier method was used to calculate the PFS. Cox regression was used for multivariate analysis.ResultsUnivariate analysis showed a statistically significant relationship with leukocyte/lymphocyte index (p = 0.0001), neutrophil/lymphocyte index (p = 0.02), prognostic nutritional index (p = 0.002), and platelet/lymphocyte ratio (p = 0.002). In multivariate analysis, the leukocyte/lymphocyte ratio (p = 0.002) and PNI (p = 0.04) behaved as independent prognostic factors of decreased RFS. Based on these, a prognostic score was developed to classify patients into 3 prognostic groups. Eighty percent of patients with pT3-4 and/or pN0-1 tumors were in the intermediate–poor prognostic groups.ConclusionThe implementation of a precystectomy immune-nutritional score in clinical practice would help in the selection of a group of patients with a more unfavorable pathologic stage and worse PFS. We believe that these patients could benefit more from a NACT.     

High Ki67 expression is a risk marker of invasive relapse for classical lobular carcinoma in situ patients

BackgroundThe clinical management of lobular carcinoma in situ lesions remains challenging. Our aim was to evaluate the risk of relapse for lobular carcinoma in situ (LCIS) patients, diagnosed on mammography performed for microcalcifications and according to proliferation assessed by Ki67 staining.MethodsA series of 47 patient's files with LCIS and followed in our institution were retrospectively selected. All patients underwent lumpectomy without radiation therapy. The expression of E-cadherin, estrogen receptor (ER), progesterone receptor (PR), EGFR and Ki67 were determined. Four different classes were then defined with the following criteria: ER+ and Ki67 ≤ 10%; ER+, Ki67 > 10%; ER?; ER-PR? and EGFR+.ResultsPatient's mean age was 51.3 yrs. The majority of the lesions were classical LCIS (97%). All cases were E-cadherin either negative (71%) or weak and incomplete (29%). Among the 44 evaluable cases, 34 cases were ER or PR positive with KI67 ≤ 10% (79%), 9 cases ER positive with KI67 > 10% (21%), 1 case was ER and PR negative and expressed EGFR. At five years, all patients were alive, 1/34 ER positive and Ki67 low experienced a relapse contrasting with 3 out of 9 ER positive and Ki67 high (3 invasive carcinomas including 2 ductal and 1 lobular) (p = 0.0054).ConclusionIn this retrospective study, we observed a higher risk of relapse associated with a high proliferative activity of classical LCIS. If confirmed in larger series, this observation suggests that radiation therapy or hormonotherapy could be discussed for patients with Ki67 high classical LCIS in order to decrease their risk of relapse.     

Radical cystectomy for urothelial carcinoma of the bladder without neoadjuvant or adjuvant therapy: long-term results in 1100 patients

Background

The optimal treatment strategy for muscle-invasive bladder cancer (BCa) remains controversial.

Objective

Better define the long-term outcomes of radical cystectomy (RC) alone for BCa and determine the impact of pathologic downstaging after transurethral resection in a large and homogeneous single-center series.

Design, setting, and participants

A cohort of 1100 patients undergoing RC with pelvic lymph node dissection (PLND) without neoadjuvant therapy for urothelial carcinoma of the bladder between January 1, 1986, and December 2009 was evaluated. Patients with other than metastases to the pelvic lymph nodes were excluded. Median age was 65 yr. Clinical course, pathologic characteristics, and long-term outcomes were evaluated. Follow-up was obtained until December 2009 with a median of 38 mo and a completeness of 96.5%.

Intervention

RC with PLND; urinary diversion with ileal neobladder whenever possible.

Measurements

Primary end points were disease-specific survival (DSS), recurrence-free survival (RFS), and overall survival (OS) according to the tumor stage of the RC specimen versus the maximum tumor stage. The log-rank test was used to compare subgroups.

Results and limitations

The 30-d (90-d) mortality rate was 3.2% (5.2%). The 10-yr OS, DSS, and RFS rates were 44.3%, 66.8%, and 65.5%, respectively. Based on the tumor stage of the RC specimen, the 10-yr DSS rate was pT0/a/is/1 pN0: 90.5%, pT2a/b pN0: 66.8%, pT3a/b pN0: 59.7%, pT4a/b pN0: 36.6%, and pTall pN+: 16.7%. Downstaging by transurethral resection of the prostate was observed in 382 patients. Patients with maximum tumor stage pT2a/b pN0 had distinctly better 10-yr DSS rates than those with pT2a/b pN0 in the RC specimen: pT2a pN0: 92.2% versus 73.8%; pT2b: 75.0% versus 62.0%. A total of 49% female and 80% male patients received an ileal neobladder.

Conclusions

This contemporary and homogeneous single-center series found acceptable OS, DFS, and RFS for patients undergoing RC. Pathologic downstaging had a significant impact on survival.     

A systematic review and meta-analysis of lymphovascular invasion in patients treated with radical cystectomy for bladder cancer

Purpose

Lymphovascular invasion (LVI) is an important step in bladder cancer cell dissemination. We aimed to perform a systematic review and meta-analysis of the literature to assess the prognostic value of LVI in radical cystectomy (RC) specimens.

Predictive value of lymphangiogenesis and proliferation markers on mRNA level in urothelial carcinoma of the bladder after radical cystectomy

Objective

To evaluate the mRNA expression of lymphangiogenesis and proliferation markers and to examine its association with histopathological characteristics and clinical outcome in patients with urothelial carcinoma of the bladder (UCB) after radical cystectomy (RC).

High IL-22RA1 gene expression is associated with poor outcome in muscle invasive bladder cancer

BackgroundThe cell surface interleukin 22 (IL-22) receptor complex is mainly expressed in epithelial and tissue cells like pancreatitis cells. Recent studies described that IL-22R was overexpressed in malignant diseases and was associated with a poor overall survival (OS). The role of IL-22RA1 gene expression in muscle invasive bladder cancer (MIBC) has not been investigated, yet.ObjectivesThe aim of this study was to analyze the role of IL-22RA1 gene expression in patients with MIBC.MethodsIn a cohort of 114 patients with MIBC who underwent radical cystectomy, IL-22RA1 gene expression was analyzed with qRT-PCR and correlated with clinical parameters. Furthermore, Kaplan-Meier and Cox regression analysis were performed. For validation, an in silico dataset (TCGA 2017, n=407) was reanalyzed.ResultsIL-22RA1 gene expression was independent of clinicopathological parameters like age (P=0.2681), T stage (P=0.2130), nodal status (P=0.3238) and lymph vascular invasion (LVI, P=0.5860) in patients with MIBC. A high expression of IL-22RA1 was associated with a shorter OS (P=0.0040) and disease-specific survival (P=0.0385). Furthermore, a shorter disease-free survival (DFS) was also associated with a high expression of IL-22RA1 (P=0.0102). In the multivariable analysis, IL-22RA1 expression was an independent prognostic predictors regarding OS (P=0.0096, HR=0.48). In the TCGA cohort, IL-22RA1 expression was independent regarding to OS and DFS.ConclusionA high IL-22RA1 gene expression was associated with worse outcome. Furthermore, IL-22RA1 represented an independent predictor regarding OS in our cohort and therefore might be used for risk stratification in patients with MIBC.     

Muscle-invasive bladder cancer developing after nephroureterectomy for upper urinary tract urothelial carcinoma

ObjectivesTo evaluate the risk factors and prognosis of muscle-invasive bladder cancer (MIBC) developing after nephroureterectomy for upper urinary tract urothelial cell carcinoma (UUT-UC).Materials and methodsWe reviewed the medical records of 422 patients who underwent nephroureterectomy for UUT-UC between 1990 and 2010, and identified 173 (40.9%) with intravesical recurrence and 28 (6.6%) with MIBC. We evaluated the clinicopathologic features, risk factors, and cancer-specific survival (CSS) using the Kaplan-Meier method and the Cox proportional hazards regression models.ResultsThe median intervals from nephroureterectomy to intravesical recurrence and the development of MIBC were 8 and 17 months, respectively. On multivariate analysis, the pathologic stage (≥pT3 vs. Ta/T1, HR 5.03, P = 0.001) and ureteral tumor location (HR 2.79, P = 0.011) were independent risk factors for the development of MIBC, whereas a history of previous or concomitant bladder tumor was the only significant risk factor for intravesical recurrence. The probability of developing MIBC 5 years after nephroureterectomy was 12.6% in patients with 1 risk factor and 20.6% in patients with both risk factors. Patients with MIBC had significantly worse CSS than those without MIBC (P = 0.004), whereas CSS rates were similar in patients with and without intravesical recurrence (P = 0.593). However, stratification analysis for matching pathology revealed that CSS rates were not significantly different in patients with pT2 or higher stage of UUT-UC.ConclusionsApproximately 5% of the patients developed MIBC after nephroureterectomy with a median interval of 17 months. Patients with advanced pathologic stage (≥pT3) and a ureteral tumor location are at increased risk of developing MIBC after nephroureterectomy.     

Prognostic Role of Lymphovascular Invasion in Patients with Urothelial Carcinoma of the Upper Urinary Tract: An International Validation Study

Background

Lymphovascular invasion (LVI) identified following pathologic slide review has been shown to be an independent predictor of recurrence-free survival (RFS) and cancer-specific survival (CSS) in a multicenter series of patients undergoing radical nephroureterectomy (RNU) for upper urinary tract urothelial carcinoma (UTUC). However, the validity of LVI in everyday practice, where pathologic re-review of all slides is uncommon, has not been assessed.

Objective

Our aim was to evaluate the prognostic role of LVI in an international cohort of patients treated with RNU for UTUC without pathologic slide review.

Design, setting, and participants

Data from 762 patients treated with RNU for UTUC without neoadjuvant chemotherapy were collected at nine centers located in Europe, Asia, and Canada.

Measurements

We evaluated patients’ characteristics, RFS, and CSS.

Results and limitations

LVI was present in 148 patients (19.4%). At a median follow-up of 34 mo, 23.5% of the patients developed disease recurrence and 19.8% died of UTUC. The 5-yr RFS and CSS rates were 79.3% and 82.1%, respectively, in the absence of LVI compared with 45.1% and 45.8%, respectively, in the presence of LVI (p values <0.0001). On multivariable Cox regression analyses, LVI was an independent predictor of RFS (hazard ratio [HR]: 3.3; p = 0.005) and CSS (HR: 5.9; p < 0.0001). Similarly, among patients with pN0/Nx disease, LVI was an independent predictor of RFS (HR: 2.1; p = 0.001) and CSS (HR: 2.3; p < 0.0001).

Conclusions

In a large multicenter series of patients treated with RNU for UTUC and for which no pathologic slide review was performed, LVI was present in approximately 20% and was an independent predictor of both RFS and CSS. LVI status should always be included in the pathologic report of RNU specimens, and patients with LVI should be considered for adjuvant therapy studies.     

The potential role of bcl-2, bax, and Ki67 expression in thymus of patients with myasthenia gravis, and their correlation with clinicopathologic parameters.

OBJECTIVE: The aim of this study was to evaluate bcl-2, bax (apoptotic-oncoproteins), and Ki67 (cell proliferation-marker) expression in thymus of patients with myasthenia gravis (MG) and to determine the potential correlation with clinicopathologic parameters. METHODS: The study was done on 38 patients (16 males, 22 females; mean age 38+/-10 years) with MG who underwent modified maximal thymectomy (MMT). Clinical staging (Osserman classification) included stage I in three, IIA in 19, IIB in 13 and III in three. Microscopic examination of thymus showed thymic hyperplasia in 19, atrophy in eight, thymoma in nine and thymic carcinoma in two. On paraffin sections, the streptavidin-biotin technique, using antibodies to bcl-2, bax, and Ki67, was employed, and in situ hybridization with digoxigenin-labeled probes to bcl-2 and bax was performed. In addition, the apoptotic body index (ABI) was assessed via the TUNEL method. Staining results were correlated with clinicopathologic parameters. RESULTS: Bcl-2 expression was higher in hyperplasia and thymoma cases, compared to thymic carcinomas (P<0.001). Higher expression in carcinomas, compared to hyperplasia and thymomas, was observed for bax (P<0.001), Ki67 (P<0.001) and ABI (P<0.001). Statistical analysis demonstrated: (A) positive correlation of bax+ cells with MG stage (P<0.001), ABI and %Ki67+ cells with MG stage (P<0.001, respectively), %Ki67+ and %bax+ cells with ABI (P<0.05); and (B) reverse correlation between %bcl-2+ cells and MG stage (P<0.05). CONCLUSIONS: In patients with MG who underwent MMT, bcl-2, bax, and Ki67 expression correlates positively or reversibly with the microscopic findings of thymus. Increased apoptosis and proliferation accompany advanced disease stage and possible worse prognosis.     

Poliovirus receptor CD155 is up-regulated in muscle-invasive bladder cancer and predicts poor prognosis

ObjectiveTo investigate the expression pattern of CD155 and evaluate the prognostic value of CD155 in muscle-invasive bladder cancer (MIBC).Patients and methodsImmunohistochemical staining of CD155 and survival analysis were conducted on 228 nonmetastatic MIBC patients underwent radical cystectomy in cohorts from Fudan University Shanghai Cancer Center and Zhongshan Hospital. Association of CD155 gene expression with tumor stage and survival were analyzed in TCGA and GSE13507 dataset.ResultsCD155 was significantly up-regulated in MIBC compared to matched normal urothelium and majorly stained on the membrane of tumor cells. In Fudan MIBC cohort, CD155 high expression was significantly correlated with shorter recurrence-free survival (HR = 2.13, P < 0.001) and overall survival (HR = 2.49, P < 0.001). CD155 expression, T stage, and lymph node status were independent factors for predicting survival in multivariate analysis. In TCGA dataset, CD155 high expression was independently associated with shorter overall survival (HR = 1.74, P = 0.001) beyond age, T stage, and lymph node status. Further, explorative analysis in Fudan MIBC cohort showed that adjuvant chemotherapy was associated with longer recurrence-free survival and overall survival in stage III and IV disease with CD155-high tumors.ConclusionsThese findings suggest that CD155 is a robust prognostic factor and may help predict the benefit of adjuvant chemotherapy in MIBC.     

Impact of chronic kidney disease on oncological outcomes in patients with high-risk non-muscle-invasive bladder cancer who underwent adjuvant bacillus Calmette-Guérin therapy

ObjectivesTo investigate the impact of chronic kidney disease (CKD) on oncological outcomes in patients with high-risk non-muscle invasive bladder cancer (NMIBC) who underwent adjuvant induction bacillus Calmette-Guérin (BCG) therapy after transurethral resection of bladder tumor (TURBT).Materials and MethodsWe conducted a multi-institutional retrospective study assessing 209 patients with high-risk NMIBC who underwent TURBT and subsequent adjuvant induction BCG therapy from December 1998 to April 2019. Patients were divided into 2 groups: those with preoperative estimated glomerular filtration rate (eGFR) ≥ 60 ml/min/1.73 m² (non-CKD group), and those with eGFR < 60 ml/min/1.73 m² (CKD group). Primary endpoints were intravesical recurrence-free survival (RFS) and muscle-invasive bladder cancer (MIBC)-free survival. Background-adjusted multivariate analyses with the inverse probability of treatment weighting (IPTW) method using the propensity score were performed to evaluate the impact of CKD on intravesical RFS, MIBC-free survival, metastasis-free survival, cancer-specific survival, and overall survival. Moreover, multivariable analyses were performed to assess the impact of CKD on intravesical recurrence and MIBC progression, adjusting for the competing risk of death using the Fine-Gray competing risk regression model.ResultsMedian age and follow-up period after TURBT were 72 years and 45 months, respectively. Of 209 patients, 71 (34%) were diagnosed with CKD before TURBT. Background-adjusted multivariate analyses with the IPTW method indicated that CKD was significantly associated with shorter intravesical RFS, MIBC-free survival, metastasis-free survival, cancer-specific survival, and overall survival. In the Fine-Gray competing risk regression model, CKD showed significantly higher probabilities of intravesical recurrence and MIBC progression, with an adjusted subdistribution hazard ratio of 1.886 (95% confidence interval 1.069–3.330, P = 0.028) and 3.740 (95% confidence interval 1.060–13.20, P = 0.040), respectively.ConclusionsCKD presents a risk factor of poor oncological outcomes in patients with high-risk NMIBC who underwent adjuvant induction BCG therapy after TURBT.     

Intermediate-term survival of robot-assisted versus open radical cystectomy for muscle-invasive and high-risk non-muscle invasive bladder cancer in The Netherlands

BackgroundRadical cystectomy with pelvic lymph node dissection is the recommended treatment in non-metastatic muscle-invasive bladder cancer (MIBC). In randomised trials, robot-assisted radical cystectomy (RARC) showed non-inferior short-term oncological outcomes compared with open radical cystectomy (ORC). Data on intermediate and long-term oncological outcomes of RARC are limited.ObjectiveTo assess the intermediate-term overall survival (OS) and recurrence-free survival (RFS) of patients with MIBC and high-risk non-MIBC (NMIBC) who underwent ORC versus RARC in clinical practice.Methods and materialsA nationwide retrospective study in 19 Dutch hospitals including patients with MIBC and high-risk NMIBC treated by ORC (n = 1086) or RARC (n = 386) between January 1, 2012 and December 31, 2015. Primary and secondary outcome measures were median OS and RFS, respectively. Survival outcomes were estimated using Kaplan-Meier curves. A multivariable Cox regression model was developed to adjust for possible confounders and to assess prognostic factors for survival including clinical variables, clinical and pathological disease stage, neoadjuvant therapy and surgical margin status.ResultsThe median follow-up was 5.1 years (95% confidence interval ([95%CI] 5.0–5.2). The median OS after ORC was 5.0 years (95%CI 4.3–5.6) versus 5.8 years after RARC (95%CI 5.1–6.5). The median RFS was 3.8 years (95%CI 3.1–4.5) after ORC versus 5.0 years after RARC (95%CI 3.9–6.0). After multivariable adjustment, the hazard ratio for OS was 1.00 (95%CI 0.84–1.20) and for RFS 1.08 (95%CI 0.91–1.27) of ORC versus RARC. Patients who underwent ORC were older, had higher preoperative serum creatinine levels and more advanced clinical and pathological disease stage.ConclusionORC and RARC resulted in similar intermediate-term OS and RFS in a cohort of almost 1500 MIBC and high-risk NMIBC.