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Hang Xu,1,2,&ast; Tianhai Lin,1,2,&ast; Jianzhong Ai,1,2,&ast; Jiapeng Zhang,1,2 Shiyu Zhang,1,2 Yifan Li,1,2 Xiaonan Zheng,1,2 Peng Zhang,1,2 Qiang Wei,1,2 Ping Tan,1,2 Lu Yang1,2 1Department of Urology, West China Hospital, Sichuan University, Sichuan, People’s Republic of China; 2Institute of Urology, West China Hospital, Sichuan University, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ping Tan; Lu Yang, Department of Urology, West China Hospital, Sichuan University, Sichuan, People’s Republic of China, Tel +86 18980606829 ; +86 15208212056, Email uro_tanping@163.com; wycleflue@scu.edu.cnPurpose: Previous studies have suggested that the preoperative lactate dehydrogenase-to-albumin ratio (LAR) is correlated with survival in several cancers except bladder cancer (BCa). This study aimed to determine the prognostic value of the LAR in patients with urothelial carcinoma of the bladder (UCB) after radical cystectomy (RC).Patients and Methods: A total of 595 UCB patients with RC in West China Hospital from December 2010 to May 2020 were enrolled. A receiver operating characteristic (ROC) curve was used to determine the optimal cutoff value of the LAR. Kaplan–Meier curves and Cox regression analyses were applied to evaluate the association of the LAR with overall survival (OS) and recurrence-free survival. Independent factors in multivariate analyses were selected to construct nomograms. Calibration curves, ROC curves, concordance index (C-index) and decision curve analyses were used to evaluate the performance of the nomograms.Results: The optimal cutoff value of the LAR was determined to be 3.8. Preoperative low LAR was associated with decreased OS (P < 0.001) and RFS (P < 0.001), especially in patients with ≥ pT2 disease. LAR was an independent factor for OS (hazard ratio [HR]: 1.719; P < 0.001) and RFS (HR: 1.429; P = 0.012). The addition of the LAR into nomograms could result in better prediction performance. The areas under the curves of the nomograms were 0.821 and 0.801 for the prediction of 3-year OS and RFS, respectively. The C-indexes of the nomograms were 0.760 and 0.741 for the prediction of OS and RFS, respectively.Conclusion: The preoperative LAR is a novel and reliable independent prognostic biomarker for survival in UCB after RC.Keywords: lactate dehydrogenase, albumin, lactate dehydrogenase to albumin ratio, bladder cancer, prognosis

Background Bladder cancer with Human Epidermal Growth Factor Receptor 2 (HER2) high expression is related to pathological malignancy and poor prognosis. The standard care for muscle-invasive urothelial bladder cancer (MIBC) is neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) with pelvic lymph node dissection. For HER2 positive MIBC, the efficacy of cisplatin- based NAC is unsatisfied, and adverse reactions are inevitable or even intolerable. New regimens with higher efficiency and lower toxicity are needed to be explored in the neoadjuvant setting for this population. Methods HOPE-03 is a multi-center, open-label, single-arm, phase Ib/II study, aiming to evaluate the safety and efficacy of RC48-ADC (Distamab Vedotin, DV), a humanized anti-HER2 antibody conjugated with monomethyl auristatin E, and tislelizumab (PD-1 antibody) as a novel neoadjuvant treatment combination in patients with HER2 positive locally advanced urothelial MIBC. Fifty-one patients with cT2-4bN0-3M0-1a pathological and imaging diagnosed HER2 positive (Immunohistochemistry status 3 + or 2 + or 1+) MIBC will be recruited. Of them, 6 patients are enrolled in the dose-escalation phase (3 patients in RC48-ADC 1.5kg/m2 group and 3 patients in 2.0mg/kg group), and 45 patients enter into phase II study (the expected recommended phase II dose for RC48-ADC is 2.0mg/kg). Patients without disease progression will receive radical cystectomy or bladder-sparing therapies as their will after neoadjuvant treatment. The primary endpoints are clinical complete remission rate (cCR, T0/Ta/Tis), pathological complete remission rate (pCR) and safety. The secondary endpoints are overall survival (OS), local recurrence free survival (LRFS), distant metastasis free survival (DMFS) and quality of life. Discussion HOPE-03 trial will give a description about the safety profile of RC-48 and tislelizumab combination in the neoadjuvant treatment of HER2 positive locally advanced urothelial MIBC, and the efficacy will be explored as well in this population.

There are unmet clinical needs for novel therapeutic targets and drugs for bladder cancer. Majority of previous work relied on limited bladder cancer cell lines, which could not well represent the tumor heterogeneity and pathology of this disease. Recently, it has been shown that cancer organoids can recapitulate pathological and molecular properties of bladder cancer. Here, we report, by our knowledge, the first bladder cancer organoid-based small molecule screening for epigenetic drugs. We found that SRT1720, a Sirtuin 1 (SIRT1) activator, significantly inhibits the growth of both mouse and human bladder cancer organoids. And it also restrains the development of mouse in situ bladder cancer and human PDX bladder cancer. Mutation of Sirt1 promotes the growth of cancer organoids and decreases their sensitivity to SRT1720, which validate Sirt1 as the target of SRT1720 in bladder cancer. Mechanistically, SRT1720 treatment represses the hypoxia pathway through deacetylating HIF1α by activating Sirt1. Genetic or pharmaceutic inhibitions of HIF mimic the anti-tumor effect of SRT1720. Furthermore, the SIRT1-repressed gene signature is associated with the hypoxia target gene signature and poor prognosis in human bladder cancers. Thus, our study demonstrates the power of cancer organoid-based drug discovery and, in principle, identifies SRT1720 as a new treatment for bladder cancer.

Purpose: Fumarate hydratase–deficient renal cell carcinoma (FH-deficient RCC) is a rare but lethal subtype of RCC. Little is known about the genomic profile of FH-deficient RCC, and the therapeutic options for advanced disease are limited. To this end, we performed a comprehensive genomics study to characterize the genomic and epigenomic features of FH-deficient RCC. Experimental Design: Integrated genomic, epigenomic, and molecular analyses were performed on 25 untreated primary FH-deficient RCCs. Complete clinicopathologic and follow-up data of these patients were recorded. Results: We identified that FH-deficient RCC manifested low somatic mutation burden (median 0.58 mutations per megabase), but with frequent somatic copy-number alterations. The majority of FH-deficient RCCs were characterized by a CpG sites island methylator phenotype, displaying concerted hypermethylation at numerous CpG sites in genes of transcription factors, tumor suppressors, and tumor hallmark pathways. However, a few cases (20%) with low metastatic potential showed relatively low DNA methylation levels, indicating the heterogeneity of methylation pattern in FH-deficient RCC. Moreover, FH-deficient RCC is potentially highly immunogenic, characterized by increased tumor T-cell infiltration but high expression of immune checkpoint molecules in tumors. Clinical data further demonstrated that patients receiving immune checkpoint blockade–based treatment achieved improved progression-free survival over those treated with antiangiogenic monotherapy (median, 13.3 vs. 5.1 months; P = 0.03). Conclusions: These results reveal the genomic features and provide new insight into potential therapeutic strategies for FH-deficient RCC.

Benign prostatic hyperplasia (BPH) occurs most commonly among older men, often accompanied by chronic tissue inflammation. Although its aetiology remains unclear, autoimmune dysregulation may contribute to BPH. Regulatory T cells (Tregs) prevent autoimmune responses and maintain immune homeostasis. In this study, we aimed to investigate Tregs frequency, phenotype, and function in BPH patients and to evaluate adoptive transfer Tregs for immunotherapy in mice with BPH via CD39. Prostate specimens and peripheral blood from BPH patients were used to investigate Treg subsets, phenotype and Treg‐associated cytokine production. Sorted CD39+/− Tregs from healthy mice were adoptively transferred into mice before or after testosterone propionate administration. The Tregs percentage in peripheral blood from BPH patients was attenuated, exhibiting low Foxp3 and CD39 expression with low levels of serum IL‐10, IL‐35 and TGF‐β. Immunohistochemistry revealed Foxp3+ cells were significantly diminished in BPH prostate with severe inflammatory. Although the Tregs subset was comprised of more effector/memory Tregs, CD39 was still down‐regulated on effector/memory Tregs in BPH patients. Before or after testosterone propionate administration, no alterations of BPH symptoms were observed due to CD39‐ Tregs in mice, however, CD39+Tregs existed more potency than Tregs to regulate prostatic hyperplasia and inhibit inflammation by decreasing IL‐1β and PSA secretion, and increasing IL‐10 and TGF‐β secretion. Furthermore, adoptive transfer with functional Tregs not only improved prostate hyperplasia but also regulated muscle cell proliferation in bladder. Adoptive transfer with Tregs may provide a novel method for the prevention and treatment of BPH clinically.

Numerous studies suggested that non-coding RNA modifications play an important role in upper tract urothelial carcinoma (UTUC), but few have depicted the architecture of non-coding RNA on the pathological process of UTUC. We aimed to better understand the pathogenesis of UTUC and provide precision medicine references of non-coding RNA when managing UTUC patients. PubMed, Cochrane Library, Embase, and Scopus were searched for UTUC until December 31, 2020. Methodological quality assessment was conducted according to NIH recommendations. Enrichment analyses and network analyses were conducted to explore the interactions of miRNA with genes and other non-coding RNAs. Survival analyses were performed to validate the novel genes. A total of 12 pairs of UTUC tumors and adjacent normal tissues were also included to validate the gene expressions regulated by miRNAs from the miRNA-gene network. Thirteen studies with 945 patients were eligible, investigating 106 miRNAs mutations. The quality of all the studies was fair to good. Most miRNAs were enriched in tissue/organs, diseases, and specific anti-cancer drugs (false discovery rate0.05). Other non-coding RNAs, i.e.,: miR-34a, DLGAP1-AS1, USP39, and RNA5SP479, were highlighted by network analyses to have potential in the pathogenesis of UTUC. Top hub genes in the miRNA-gene network, namely ZNF460, NUFIP2, and E2F3, were all validated by survival analysis(P0.05). Using own cohort data, the differential expression analyses identified 368 overlapped significant genes, including above 3 hub genes (false discovery rate0.05). Novel biomarkers identified in our studies might play essential roles in UTUC, from the perspectives of the molecule, tissue/organ, diagnosis, treatment, and prognosis. Candidate biomarkers could be significant references for personalized and target therapies.

516 Background: Tri-modality therapy (TMT) is an alternative to radical cystectomy for selected muscle-invasive bladder cancer (MIBC) patients with bladder-preserving will. Neoadjuvant treatment makes chance for imperfect patients to turn into ideal bladder-sparing patients. This phase 2 study aimed to explore the efficacy of neoadjuvant chemotherapy plus tislelizumab followed by radiotherapy as a strategy of bladder-sparing therapy for high risk/locally advanced MIBC (Trial registration number: ChiCTR2100045213). Methods: Pathological and imaging diagnosed cT2-4bN0-3M0-1a MIBC received 3-4 cycles of neoadjuvant chemotherapy (gemcitabine and cisplatin or carboplatin) plus tislelizumab (200mg every three weeks for one year). Radiotherapy (60.4-64.4 Gy /1.8Gy/33-35f to bladder with 50.4 Gy/1.8Gy/28f to pelvic) were given to patients with non- progressed disease (PD) after neoadjuvant therapy. The primary endpoint was complete response rate (CR, including T0/Ta/Tis), and the secondary endpoints were progression-free survival (PFS), bladder-intact disease free survival (BI-DFS), overall survival (OS) and toxicity. Results: The simple size is 43 participants. Until now, 28 patients were included, of which 23 patients received radiotherapy and 16 patients finished efficacy evaluation with imaging and cystoscopic biopsy after radiotherapy. Median follow-up time was 14.2 (1.5-17.4) months (m). Two of the 16 patients were Tis and 14 were T0 after radiotherapy, indicating the primary CR rate were 100%. For the 2 patients with Tis received BCG vaccine intravesical perfusion, and T0 was achieved when the second therapy evaluation. No patient died and only one patient had distant metastasis. The one-year PFS rate, one-year BI-DFS and one-year OS were 100%. Grade 3 and 4 hematological system adverse events were 23.3% and 2.3%. One patient had reduced bladder capacity (100-200 mL) with 2-h intervals of micturition, and 3 patients had frequency with urgency, nocturia and dysuria. Three patients had grade1 immunotherapy related abnormality of thyroidal function and 3 patients suffered from grade 2 myositis. The current bladder-preserving therapies research were well-tolerated with acceptable and manageable toxicities. Conclusions: Neoadjuvant chemotherapy plus tislelizumab followed by radiotherapy showed perfect efficacy and acceptable toxicities, which maybe an optimal strategy for high risk/locally advanced MIBC patients with bladder-preserving willingness. Clinical trial information: ChiCTR2100045213 .

Cisplatin-based chemotherapy remains the primary treatment for unresectable and metastatic muscle-invasive bladder cancers (MIBCs). However, tumors frequently develop chemoresistance. Here, we established a primary and orthotopic MIBC mouse model with gene-edited organoids to recapitulate the full course of chemotherapy in patients. We found that partial squamous differentiation, called semi-squamatization, is associated with acquired chemoresistance in both mice and human MIBCs. Multi-omics analyses showed that cathepsin H (CTSH) is correlated with chemoresistance and semi-squamatization. Cathepsin inhibition by E64 treatment induces full squamous differentiation and pyroptosis, and thus specifically restrains chemoresistant MIBCs. Mechanistically, E64 treatment activates the tumor necrosis factor pathway, which is required for the terminal differentiation and pyroptosis of chemoresistant MIBC cells. Our study revealed that semi-squamatization is a type of lineage plasticity associated with chemoresistance, suggesting that differentiation via targeting of CTSH is a potential therapeutic strategy for the treatment of chemoresistant MIBCs.

Background: It have been reported that polycyclic aromatic hydrocarbons (PAHs) were associated with a variety of diseases, but it is still unclear that whether PAHs are associated with urinary incontinence (UI). This study aims to assess the association between PAHs and UI.Methods: Data were collected from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2016. 10 PAHs were detected totally. UI was diagnosed and distinguished into stress UI (SUI), urgency UI (UUI), and mixed UI (MUI) by answers of self-reported questions. Multivariate logistic regression analyses categorizing PAHs as quartiles were performed to detect the correlation between urinary PAHs and all three UI subtypes. Models were adjusted for common epidemiological factors including demographic and living habits factors.Results: A total of 12,393 participants of NHANES with available urine PAHs and UI data were eligible. No significant differences were observed between characteristics of participants with and without UI. Increasing prevalence of UUI was associated with the highest quantiles of 1-hydroxynapthalene (OR=1.208, 95%CI=1.026-1.422, p for trend=0.036), 1-hydroxyphenanthrene (OR=1.203, 95%CI=1.017-1.423, p for trend=0.004), and 1-hydroxypyrene (OR=1.251, 95%CI=1.062-1.475, p for trend=0.013) compared with the lowest quantiles. Increasing rate of SUI was observed in participants with higher exposure of all 9 PAHs (p for trendConclusion: Our study suggested a positive relationship between U-PAHs and the prevalence of all three types of UI. Almost all PAHs are positively correlated with SUI.

The discovery of novel non-invasive biomarkers for discriminating between prostate carcinoma (PCa) patients and benign prostatic hyperplasia (BPH) patients is necessary to reduce the burden of biopsies, avoid overdiagnosis and improve quality of life. Previous studies suggest that abnormal glycosylation of immunoglobulin gamma molecules (IgGs) is strongly associated with immunological diseases and prostate diseases. Hence, characterizing N-linked intact glycopeptides of IgGs that correspond to the N-glycan structure with specific site information might enable a better understanding of the molecular pathogenesis and discovery of novel signatures in preoperative discrimination of BPH from PCa. In this study, we profiled N-linked intact glycopeptides of purified IgGs from 51 PCa patients and 45 BPH patients by our developed N-glycoproteomic method using hydrophilic interaction liquid chromatography enrichment coupled with high resolution LC-MS/MS. The quantitative analysis of the N-linked intact glycopeptides using pGlyco 2.0 and MaxQuant software provided quantitative information on plasma IgG subclass-specific and site-specific N-glycosylation. As a result, we found four aberrantly expressed N-linked intact glycopeptides across different IgG subclasses. In particular, the N-glycopeptide IgG2-GP09 (EEQFNSTFR (H5N5S1)) was dramatically elevated in plasma from PCa patients, compared with that in BPH patients (PCa/BPH ratio = 5.74, p = 0.001). Additionally, the variations in these N-linked intact glycopeptide abundances were not caused by the changes in the IgG concentrations. Furthermore, IgG2-GP09 displayed a more powerful prediction capability (auROC = 0.702) for distinguishing PCa from BPH than the clinical index t-PSA (auROC = 0.681) when used alone or in combination with other indicators (auROC = 0.853). In conclusion, these abnormally expressed N-linked intact glycopeptides have potential for non-invasive monitoring and pre-stratification of prostate diseases.

Objective: To compare these managements focusing on the efficacy and safety to treat overactive bladder (OAB) in children through network meta-analysis (NMA). Methods: We searched PubMed, Embase, the Cochrane Library Central Register of Controlled Trials (CENTRAL) and the reference lists up to May 1st, 2017. Data from eligible randomized controlled trails (RCT) studies including three different treatment options were extracted. The primary outcome was maximal voiding volume (MVV). We performed pairwise meta-analyses by random effects model and NMA by Bayesian model. We used the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework to assess the quality of evidence contributing to each network estimate. Results: Six RCTs (462 patients) comparing three different interventions fulfilled the inclusion criteria. A low risk of bias was shown for the majority of the study items. The results of NMA showed that compared with antimuscarinic drugs, Parasacral transcutaneous electrical nerve stimulation was associated with significant improvement in the MVV (mean difference [MD] = 58.50, 95% confidential interval [CI]: 45.95–69.52), followed by urotherapy group (MD = 21.03, 95% CI: 11.85–29.97). When it comes to the constipation, antimuscarinic drugs exerted significant benefit than PTENS (odds ratio [OR]: 0.22, 95% CI: 0.01–0.46). No significant difference was found between other treatments. Conclusion: Compared with antimuscarinic drugs, PTENS was associated with significant better efficacy considering MVV, but more constipation events in de novo OAB children. Antimuscarinic drugs showed remarkably better efficacy considering MVV and comparable safety profile compared with urotherapy. Clinicians should take all known safety and compliance of patients into account when choosing an optimal strategy. Keywords: Overactive bladder, Meta-analysis, Anticholinergics, Parasacral transcutaneous electrical nerve stimulation

Objective: Administration of drugs targeting anti-cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) is often associated with serious immune-related adverse events (irAEs). Here, we performed a comprehensive analysis of organ-specific irAEs and treatment-related hematologic abnormalities and musculoskeletal disorders resulting from anti-CTLA-4 treatment. Materials and methods: PubMed, the Cochrane library, Web of Science, and ClinicalTrials.gov were searched for studies between January 1990 and March 2018 reporting AEs associated with anti-CTLA-4 therapies. Results: A total of 11 clinical trials with 7,088 patients were included; of these, data were accessible for 10 on ClinicalTrials.gov. Compared with control therapies (placebo, chemotherapy, radiation therapy, or vaccine), anti-CTLA-4 therapies (ipilimumab and tremelimumab) were associated with an increased risk of serious irAEs, predominantly dermatologic (rash: odds ratio [OR] 3.39, P

This study aimed to further validate the prognostic role of fibrinogen in upper tract urothelial carcinoma (UTUC) in a large Chinese cohort. A total of 703 patients who underwent radical nephroureterectomy were retrospectively identified. Fibrinogen levels of ≥4.025 g l-1 were defined as elevated. Logistic regression analysis was performed to determine the association between fibrinogen and adverse pathological features. Kaplan-Meier analysis and Cox regression models were used to assess the associations of fibrinogen with cancer-specific survival (CSS), disease recurrence-free survival (RFS), and overall survival (OS). Harrell c-index and decision curve analysis were used to assess the clinical utility of multivariate models. The median follow-up duration was 42 (range: 1-168) months. Logistic regression analysis revealed that elevated fibrinogen was associated with higher tumor stage and grade, lymph node involvement, lymphovascular invasion, sessile carcinoma, concomitant variant histology, and positive surgical margins (all P < 0.05). Multivariate Cox regression analysis demonstrated that elevated fibrinogen was independently associated with decreased CSS (hazard ratio [HR]: 2.33; P < 0.001), RFS (HR: 2.09; P < 0.001), and OS (HR: 2.09; P < 0.001). The predictive accuracies of the multivariate models were improved by 3.2%, 2.0%, and 2.8% for CSS, RFS, and OS, respectively, when fibrinogen was added. Decision curve analysis showed an added benefit for CSS prediction when fibrinogen was added to the model. Preoperative fibrinogen may be a strong independent predictor of worse oncologic outcomes in UTUC; therefore, it may be valuable to apply this marker to the current risk stratification in UTUC.

Background: Many studies explored the prognostic value of the modified Glasgow Prognostic Score (mGPS) in urothelial carcinoma (UC), but the results are controversial. This study aimed to quantify the relationship between pretreatment mGPS and survival in patients with UC. Methods: A systematic literature search was conducted using Embase, PubMed, and Web of Science to identify eligible studies published before August 2022. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were used to assess the association between pretreatment mGPS and the prognosis of UC. Results: Thirteen eligible studies involving 12,524 patients were included. A high mGPS was significantly associated with poor overall survival (mGPS 1/0: HR = 1.33, 95% CI 1.12–1.58, p = 0.001; mGPS 2/0: HR = 2.02, 95% CI 1.43–2.84, p < 0.0001), progression-free survival (mGPS 1/0: HR = 1.26, 95% CI 1.03–1.53, p = 0.021; mGPS 2/0: HR = 1.76, 95% CI 1.12–2.77, p = 0.013), recurrence-free survival (mGPS 1/0: HR = 1.36, 95% CI 1.18–1.56, p < 0.0001; mGPS 2/0: HR = 1.70, 95% CI 1.44–2.000, p < 0.0001), and cancer-specific survival (mGPS 2/0: HR = 1.81, 95% CI 1.30–2.52, p < 0.0001). A subgroup analysis of OS also yielded similar results. Conclusions: Evidence suggests that high pretreatment mGPS in UC is closely related to poor survival. Pre-treatment mGPS is a powerful independent prognostic factor in patients with UC.

Background To investigate the expression of estrogen receptor (ER) in prostate tissues of benign prostatic hyperplasia (BPH) individuals, and the effects of estrogen regulating the proliferation and inflammatory expressions of primary prostate stromal cells in BPH. Methods A total of 44 human BPH prostate tissues were collected to explore the expression of ER by immunohistochemistry (IHC). Cell proliferation, mRNA and protein expressions were analyzed in primary prostate stromal cells treated with estrogen or estrogen plus fulvestrant through cell count kit-8 (CCK-8) assay, quantitative real-time polymerase chain reaction (qPCR), IHC and western blot, respectively. Results Firstly, ERβ was positive, and ERα was negative in the transition zone of prostate among all the 44 individuals with BPH. Secondly, the effects could be partially inhibited by fulvestrant, of estrogen promoting the proliferation of primary prostate stromal cells cultured in dulbecco's modified eagle medium (DMEM) supplemented with 2% fetal bovine serum (FBS). Thirdly, estrogen up-regulates the mRNA levels of C-C chemokine receptor type 3 (CCR3), CD40 ligand (CD 40L), C-X-C motif chemokine ligand 9 (CXCL9) and interleukin 10 (IL10), and down-regulates the mRNA levels of C-C chemokine receptor type 4 (CCR4) and interleukin 17C (IL17C). Then, the protein expressions of CCR3, CCR4, CD40L, IL10 and IL17C are positive, and CXCL9 is negative in the third-generation primary prostate stromal cells. Finally, the effects could be partially inhibited by fulvestrant, of estrogen up-regulating the protein levels of CD40L and IL10. Conclusions The expressions of ER in human BPH prostate tissues are zone-dependent. Estrogen promoting the proliferation of primary prostate stromal cells cultured in DMEM supplemented with 2% FBS. The expressions of CCR3, CCR4, CD 40L, IL17C, CXCL9 and IL10 are regulated by estrogen in primary prostate stromal cells.

Background: We are aiming to compare the oncologic outcomes between cryoablation and radiation therapy for low or intermediate risk localized prostate cancer. Methods : Among patients diagnosed between 2004 and 2016 in SEER databases, we identified cases confirmed low or intermediate risk prostate adenocarcinoma treated with radiation treatment (n = 93041) or cryoablation (n = 2350). Propensity score matching (PSM) was performed. Kaplan-Meier method, Cox proportional hazards model were used to calculate cancer specific mortality (CSM) and overall survival (OS) in the unmatched and matched cohort, and in subgroups based on clinical characteristics. Results: A total of 95391 patients who were diagnosed with first prostate adenocarcinoma and treated with radiation treatment (97.54%) or cryoablation (2.46%) were identified. In the matched cohort, cryoablation group has similar CSM (HR 1.13, 95%CI 0.72-1.77, P=0.6) and worse OS (HR 1.20, 95%CI 1.04-1.39, P=0.01) than radiation treatment group in the non-adjusted model as well as those in the adjusted model (HR 1.06, 95%CI 0.68-1.65, P=0.8; HR 1.18, 95%CI 1.02-1.36, P=0.02, respectively). For low risk disease, CSM and OS outcomes were similar between cryoablation and radiation treatment group. Last but not least, for intermediate risk patients, compared with radiation treatment group, cryoablation group has similar CSM (HR 1.26, 95%CI 0.90-1.77, P=0.2) and inferior OS (HR 1.17, 95%CI 1.04-1.32, P=0.01). Conclusion: In summary, for low risk disease, CSM and OS outcomes were similar between cryoablation and radiation treatment group. For intermediate risk disease, we found that radiation treatment group showed superior OS than cryoablation group.

Introduction Prebiopsy multiparametric magnetic resonance imaging (mpMRI) has been increasingly utilized for patients of suspicious prostate cancer (PCa). However, the optimal core number and site for MRI-targeted biopsy have not been clearly elucidated. Evidence acquisition A systematic search in Pubmed, Embase and Ovid up to June 2019 was conducted and we identified studies reporting detection details of every MRI-targeted core. The incremental diagnostic value of performing additional cores was pooled on per-lesion analysis. Our secondary outcome concentrated on detection accuracy for cores of different site within one lesion. Evidence synthesis Five studies comprising 2291 patients were identified to elucidate the association between targeted core number and cancer detection rates. Adding the second core to the first one resulted in 19.8% (range: 13.6-26.7%) increase in the detection rate of clinically significant lesions, and adding the third one to the first two resulted in 11.5% (range: 7.8-14.3%) increase. The incremental value of adding the fourth or the fifth core was 6.0% (4.7%, 6.9%) and 4.1% respectively. Four studies arranging MRI-targeted biopsy of more than two cores in well-determined sequences indicated more positive cores with higher cancer grade through center of the lesions. Conclusions Increasing the number of samples per target from one to two, or two to three resulted in a nonnegligible incremental detection rate of clinically significant lesions, while obtaining more than 3 cores per target provided a diminished incremental value. And performing targeted cores accurately through center of the lesions may help improve diagnostic accuracy.

BackgroundTo retrospectively investigate the clinical characteristics, initial treatment, relapse, therapy outcome, and prognosis of Chinese patients with primary testicular lymphoma (PTL) through analysis of the cases of our institute.MethodsFrom December 2008 to July 2018, all patients with PTL were included in this study. Kaplan-Meier method was used to estimate PFS and OS. The Cox proportional hazards model was used to compare the survival times for groups of patients differing in terms of clinical and laboratory parameters.ResultsAll 28 PTL patients (24 DLBCL, three NK/T lymphomas, and one Burkkit’s lymphoma) with a median age of 65.5 years were included in this study. Six patients were observed recurrence among all the 22 individuals evaluated. Following orchiectomy and systemic chemotherapy, with or without intrathecal prophylaxis, complete response was achieved in 15 (68%) patients. For DLBCL patients, the median progression-free survival (PFS) was 44.63 months (95% CI 17.71–71.56 months), and the median overall survival (OS) was 77.02 months (95% CI, 57.35–96.69 months). For all the DLBCL patients, the 5-year PFS and 5-year OS were 35.4% (95%CI, 14.8–56.0%) and 53.4% (95%CI, 30.1–76.7%). Without further chemotherapy following orchiectomy (HR = 3.4,P = 0.03) were associated with inferior PFS of DLBCL patients. Advanced Ann Arbor stage (HR =5.9,P = 0.009) and high (international prognostic index, IPI) score: 3–5 (HR =3.9,P = 0.04) were correlated with shorter OS of DLBCL patients.ConclusionThis study confirms that PTL is an aggressive malignant with a poor prognosis. Limited Ann Arbor stage, further chemotherapy following orchiectomy, and low IPI score (less than 2) are correlated with superior survival for DLBCL patients.

Introduction Our aim is to compare feasibility and safety of open radical cystectomy (ORC), laparoscopic radical cystectomy (LRC) and robot-assisted radical cystectomy (RARC) for the treatment of bladder cancer through network meta-analysis. Evidence acquisition Eligible articles were identified from electronic databases including PubMed/Medline, Embase, the Cochrane Library and Web of Science up to August 2019 with no language limitations. Studies selection, quality assessment, data extraction and analysis were accomplished by two independent reviewers (DCF and AL) using Cochrane Collaboration's tools. Evidence synthesis After screening 2528 articles, 27 studies were included in the final meta-analysis. In the network meta-analysis, both RARC (MD:83.09, 95% CI: 61.06 to 105.11) and LRC (MD: 49.68, 95% CI: 21.75 to 77.62) showed a longer operative time compared with ORC. Besides, RARC had a longer operative time than LRC (MD: 33.40, 95% CI: 1.35 to 65.45). RARC (MD:-591.86, 95% CI: -879.46 to -304.27) and LRC (MD: -435.28, 95% CI: -854.98 to -15.58) showed a less estimated blood loss (EBL) than ORC; however, the difference in EBL for RARC versus LRC was not significant. RARC (OR: 0.26, 95% CI: 0.14 to 0.50) and LRC (OR: 0.23, 95% CI: 0.13 to 0.43) had a higher blood transfusion rate than ORC; however, the OR between RARC and LRC was not significant. RARC (MD: -1.34, 95% CI: -2.55 to -0.12) and LRC (MD: -1.35, 95% CI: -2.38 to -0.32) took a shorter time to regular diet compared with ORC; however, there was no significant difference between RARC and LRC. Compared with ORC, RARC (MD: -2.37, 95% CI: -3.57 to -1.17) and LRC (MD: -2.22, 95% CI: -4.04 to -0.40) showed a shorter length of stay (LOS); however, the difference in LOS for RARC versus LRC was not significant. RARC, LRC and ORC were comparable with regard to minor complications, major complications, positive surgical margin and lymph node yields. Conclusions Current evidence indicates that minimally invasive approaches could be considered as a feasible and safe alternative to ORC when performed by experienced surgeons in selected patients. Notably, RARC may be more suitable for RC with extracorporeal urinary diversion. Larger well-designed trials are still needed to confirm these findings due to the observational nature of most studies.

499 Background: Bladder-preserving combined-modality therapy has been a popular research field as an alternative to radical cystectomy for selected patients with localized muscle-invasive bladder cancer (MIBC). This real-world study aimed to compare the efficacy of neoadjuvant chemotherapy plus immunotherapy versus chemotherapy alone as one of bladder-sparing therapies for localized MIBC. Methods: Patients with cT2-4bN0-3M0-1a pathological and imaging diagnosed MIBC were included in the study. Either chemotherapy (gemcitabine and cisplatin/carboplatin) plus immunotherapy (PD-1 checkpoint inhibitor, including pembrolizumab，tislelizumab and toripalimab) or chemotherapy alone were given as patients’ wish. The primary endpoint was complete response rate (CR, T0/Ta/Tis), and the secondary endpoints were disease control rate (DCR), progression-free survival (PFS), bladder-intact disease-free survival (BI-DFS) and toxicity. Results: In total, 41 patients were included, 25 in combination group and 16 in chemotherapy group respectively. The baseline characteristics were well balanced in two groups. Median follow-up time was 15.3 ±4.4 months(m). No patient died. The efficacy evaluable population was consisted of 34 pts (22 in combination group; 12 in chemotherapy alone group). The CR rate for combination group was 50.0% and 0 for chemotherapy alone group. One patient suffered from disease progression in combination group and three in chemotherapy group. The DCRs for combination group and chemotherapy group were 95.5% and 66.7%, respectively ( p= 0.003). Twelve patients had radiotherapy and six patients had radical cystectomy followed by neoadjuvant treatments in combination group. And two patients had radiotherapy and three patients had radical cystectomy in chemotherapy group. The one-year PFS rates were 95.5% and 62.5% for combination group and chemotherapy group( p= 0.010), and the one-year BI-DFS were 66.1% versus 27.5% respectively( p= 0.159). The bladder-preserving combined-modality therapies used were well-tolerated with acceptable and manageable toxicities. Grade ¾ hematological system adverse events were 15.9% and 6.4% in combination group and chemotherapy group, respectively ( p= 0.021). Conclusions: Neoadjuvant chemotherapy plus immunotherapy showed better efficacy compared with chemotherapy alone as an important bladder-sparing therapy for locally advanced MIBC with acceptable and manageable toxicities.

Background Pretreatment controlling nutritional status (CONUT) score is a novel index which was used to predict outcomes in cancer patients. We aim to explore the prognostic significance of CONUT score in patients with upper tract urothelial carcinoma (UTUC) after radical nephroureterectomy (RNU). Patients and methods A total of 662 UTUC patients between 2004 and 2016 were retrospectively analyzed. Patients were categorized into three groups based on CONUT score (Normal: 0‐1; Light: 2‐4; Moderate/severe: 5‐12). Associations of CONUT score with oncological outcomes were analyzed using Logistic and Cox regression analysis. Harrell concordance index was used to assess the predictive accuracy of the multivariate models. Subgroup analyses were conducted according to tumor grade and stage. Results The median follow‐up duration was 41 months. Multivariate Logistic analysis showed that high CONUT score was independently associated with high‐grade disease, high pT stage, lymphovascular invasion, sessile carcinoma, variant histology, and positive surgical margins (each P

To identify the impact of albumin-globulin ratio (AGR) on pathologic and survival outcomes in patients with upper tract urothelial carcinoma (UTUC) after radical nephroureterectomy (RNU).We retrospectively reviewed medical records of 620 patients treated with RNU for UTUC at our institution. Logistic regression analysis was used to evaluate the relation between low AGR (1.45) and adverse pathologic features. Kaplan-Meier curves were used to estimate recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) probabilities between 2 groups. Univariable and multivariable Cox regression models were performed to address prognostic factors related to RFS, CSS, and OS.Of the 620 patients, 323 (52.1%) had AGR 1.45. During a median follow-up of 50.0 months (interquartile range, 28-78 months), 277 (44.7%) experienced disease recurrence and 194 (31.3%) died of disease. The results showed that low AGR was significantly associated with adverse pathologic features (all P .05). Kaplan-Meier analysis showed that compared to those with high AGR (≥1.45), patients with low AGR had poorer RFS, CSS, and OS (P .001). After adjusting for the confounding clinicopathologic factors, multivariate analyses showed that AGR 1.45 independently predicted poor RFS (hazard ratio [HR] = 1.321, P = .029), CSS (HR = 1.503, P = .010) and OS (HR = 1.403, P = .015).Low preoperative AGR is an independent predictor of worse pathologic and oncologic outcomes in patients with UTUC after RNU. The application of AGR as an easily assessed blood-based biomarker in predicting the prognosis of patients with UTUC is promising.

Urothelial carcinoma (UC) is the most common type of cancer of the bladder and upper urinary tract, and is characterized by a high risk of recurrence and progression. Urine fluorescence in situ hybridization (FISH) is a technique that detects genetic aberrations in exfoliated cells in the urine, with specific probes for chromosomes 3, 7 and 17 and the p16 gene. To evaluate the diagnostic value of FISH in UC, 119 patients from November 2010 to June 2012 with suspected UC were recruited into a prospective, cross-sectional study and were followed up for 12-30 months. These patients received voided urine cytology and FISH tests, and underwent cystoscopy and/or ureteroscopy as a reference standard. The final diagnoses confirmed 73 patients with UC, located in the bladder, upper urinary tracts or the two. The sensitivity of FISH for detecting UC was superior to cytology, irrespective of tumor grade and stage: Overall, 80.8 vs. 32.9% (P

The high potential for cancer relapse has emerged as a crucial challenge of human bladder cancer treatment. To date, those stem-like bladder cancer cells (BCSCs) have been considered as seeds that induce frequent tumor recurrence. However, the cell origin of cancer stem cells (CSCs) is still a controversial issue, due in part to the findings that CSCs not only origin from normal stem cells but also converted from differentiated tumor cells. Here, we describe a biomaterial 3D collagen I gel culture system, where non-tumorigenic cells can obtain tumorigenic potential and revert back into CSCs through the integrin α2β1/PI3K/AKT/NF-κB cascade, resulting in the tumorigenesis in bladder tissues. Furthermore, inhibiting this integrin α2β1/PI3K/AKT/NF-κB signal pathways can significantly impair the tumorigenic capacity of CSCs. Simultaneously, in vivo studies demonstrate that IFN-γ secreted by T cells can trigger those CSCs into dormancy through the IDO/Kyn/AHR/P27 cascade, which elicit chemotherapy resistance and cancer relapse. To address the challenges of suppressing bladder tumor growth and preventing tumor reoccurrence, we use IDO and integrin α2β1 signal pathway inhibitors combine with chemotherapeutic agents to awaken dormant bladder CSCs and inhibit their tumorigenic ability as well as effectively eliminate CSCs. The therapeutic approaches we propose provide new insights for eradicating tumors and reducing bladder cancer relapse after therapy.

Purpose: We aimed at investigate a series of inflammatory myofibroblastic tumors (IMTs) of urogenital system in multi-centers in China. Materials and methods: Within the pathologic databases at West China Hospital of Sichuan University and the Third People’s Hospital of Chengdu, we identified 33 individuals with IMTs from May 2009 to January 2019 Results: A total of 33 patients with IMTs of urogenital system were identified. The median age of all the individuals was 39.5 years (range 0-74 years). The most common presentations were hematuria (13patients), pain (12 patients), and mass (12 patients). In addition, other clinical symptoms included dysuria, urinary frequency, and fever. Fourteen individuals were diagnosed with anemia, including 10 mild anemia patients and 4 moderate anemia cases. Moreover, neutrophil was the dominant inflammatory cell type. The main positive markers of immunohistochemistry staining included SMA (22/25), MSA (8/9), CD34 (15/17), and CD68 (3/3). Surgery resection was the sole treatment for all the patients. Follow- up was available in 23 patients during a median follow-up period of 78.3 months (range 19.2-118.8 months), and either recurrence or metastasis was detected in any patients except one patients died from retroperitoneum IMTs. Conclusion: This study confirmed that urogenital system IMTs, with potential of recurrence or metastasis, are extremely rare. In summary, although favorable prognosis was observed in IMTs of urogenital system, closely follow-up is essential and needed.

The tumor microenvironment is associated with various tumor progressions, including cancer metastasis, immunosuppression, and tumor sustained growth. Tumor‐associated macrophages (TAMs) are considered an indispensable component of the tumor microenvironment, participating in the progression of tumor microenvironment remodeling and creating various compounds to regulate tumor activities. This study aims to observe enriched TAMs in tumor tissues during bladder cancer development, which markedly facilitated the proliferation of bladder cancer cells and promoted tumor growth in vivo. We determined that TAMs regulate tumor sustained growth by secreting type I collagen, which can activate the prosurvival integrin α2β1/PI3K/AKT signaling pathway. Furthermore, traditional chemotherapeutic drugs combined with integrin α2β1 inhibitor showed intensive anticancer effects, revealing an innovative approach in clinical bladder cancer treatment.