Muscle-invasive bladder cancer (MIBC) continues to pose a significant health challenge, as conventional neoadjuvant chemotherapy (NAC) has shown limited improvements in efficacy outcomes. Recent clinical trials suggest that combining NAC with immune checkpoint blockade (NAC.NICB) may enhance therapeutic efficacy. This study aimed to explore the short-term therapeutic efficacy and outcomes of NAC.NICB compared to NAC in real-world settings for the treatment of MIBC. A total of 100 patients with MIBC who received either NAC or NAC.NICB were included in the study. The treatment efficacy of the NAC and NAC.NICB groups was evaluated based on pathological complete response (pCR) and the rate of pathological downstaging through post treatment pathological assessment. In the NAC.NICB group, clinical characteristics were compared between patients who achieved pCR and those who did not, using the independent samples t-test or the Mann-Whitney U test. Overall, 71 patients received NAC and 29 patients received NAC.NICB. At baseline, the NAC.NICB group exhibited higher T and N stages compared to the NAC group. However, 48.3% (14/29) of the patients in the NAC.NICB group achieved pCR, which was significantly higher than that observed in the NAC group (18/71, 25.4%; p = 0.034). In addition, the pathological downstaging rate in the NAC.NICB group was higher than that of the NAC group (75.9% vs. 47.9%; p = 0.014). The disease control rate (DCR) in the NAC.NICB group was higher than that observed in the NAC group (96.6% vs. 77.5%; p = 0.020). Higher pretreatment hemoglobin levels (p = 0.018) or lower platelet levels (p = 0.026) in patients undergoing NAC.NICB therapy may serve as a potential predictor for achieving a higher pCR rate. Neoadjuvant chemotherapy combined with immune checkpoint blockade improves pCR and pathological downstaging rates in MIBC, highlighting the benefits of neoadjuvant chemoimmunotherapy for MIBC.

You have accessJournal of UrologyCME1 Apr 2023MP29-05 TREATMENT PATTERN AND HEALTH-RELATED QUALITY OF LIFE (HRQOL) OF PATIENTS (PTS) WITH METASTATIC CASTRATION-RESISTANT PROSTATE CANCER (MCRPC) IN THE UNITED STATES (US) Neal Shore, Lawrence Karsh, Daniel Shevrin, James Symanowski, Daniel Lin, Jeff Turner, David Russell, Yi Song, James Spalding, Filipa Negreiro, and David Penson Neal ShoreNeal Shore More articles by this author , Lawrence KarshLawrence Karsh More articles by this author , Daniel ShevrinDaniel Shevrin More articles by this author , James SymanowskiJames Symanowski More articles by this author , Daniel LinDaniel Lin More articles by this author , Jeff TurnerJeff Turner More articles by this author , David RussellDavid Russell More articles by this author , Yi SongYi Song More articles by this author , James SpaldingJames Spalding More articles by this author , Filipa NegreiroFilipa Negreiro More articles by this author , and David PensonDavid Penson More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003257.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Therapeutic advances in the management of mCRPC have given clinicians multiple treatment options and the potential for sequencing therapeutic agents, increasing the complexity of treatment decisions. This study aims to describe the treatment patterns and HRQoL of pts with mCRPC in the US from 2015 to 2021. METHODS: This prospective, observational, multicentre study (TRUMPET) enrolled male adult pts who initiated treatment for mCRPC from 147 urology and oncology sites in the US. The data from routine clinic visits and periodic HRQoL questionnaires were collected from Mar 2015 to Apr 2021. The study outcomes assessed patterns of care and HRQoL outcomes (Functional Assessment of Cancer Therapy-Prostate [FACT-P] and Brief Pain Inventory – Short Form [BPI-SF]) associated with mCRPC management. Descriptive analyses were used to evaluate results. RESULTS: Among the enrolled patients, the full analysis set included 832 patients with M1 mCRPC; the safety analysis set included 869 patients with M1 mCRPC. The median duration from initial diagnosis to baseline visit was 4.9 years, median initial prostate-specific antigen (PSA) level at diagnosis was 16.3 ng/mL, and mean (SD) Gleason score was 8.0 (1.18). Novel hormonal therapy (NHT) (enzalutamide and/or abiraterone) and immunotherapy were the most frequent initial treatments (Table). During the follow-up period, 43.8% (n=381) discontinued from the study before the first treatment switch, while 50.1% (n=435) switched treatment, with the majority of pts switching to NHT (n=280, 32.2%). At 1 year follow-up, cumulative first switches were 128 of 158 (81%) from immunotherapy to NHT, 41 of 88 (47%) switched from NHT to a different NHT, 11 of 17 (65%) switched from first-generation anti-androgens (AA) to NHT, 19 of 26 (73%) switched from chemotherapy to NHT, and 6 of 11 (55%) switched from radionuclide therapy to NHT. HRQoL measures showed similar trends (overlapping confidence intervals) of mean change from baseline across different first-line treatment options, irrespective of the initial treatment. CONCLUSIONS: NHT was the preferred first and second-line treatment option in pts with M1 mCRPC. HRQoL was similar regardless of initial treatment. Source of Funding: This study was funded by Astellas Pharma Inc. and Pfizer Inc., the co-developers of enzalutamide. © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e382 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Neal Shore More articles by this author Lawrence Karsh More articles by this author Daniel Shevrin More articles by this author James Symanowski More articles by this author Daniel Lin More articles by this author Jeff Turner More articles by this author David Russell More articles by this author Yi Song More articles by this author James Spalding More articles by this author Filipa Negreiro More articles by this author David Penson More articles by this author Expand All Advertisement PDF downloadLoading ...

OBJECTIVE:Immune checkpoint inhibitors (ICI) have significantly improved the treatment efficacy of a variety of malignant tumors. However, patients may experience a series of special side effects during treatments with ICI. Immune-related myositis after ICI treatment is characterized by autoimmune rheumatic and musculoskeletal damage, which is relatively rare. To analyze the clinical characteristics and outcomes of ICI-associated myositis in urological tumors, we summarized the clinical manifestations, electrophysiological and pathological characteristics, treatments and outcomes in 8 patients.METHODS:The clinical data of the 8 patients with immune-related myositis after ICI treatment for urological tumors treated in the Department of Urology, Peking University First Hospital from March 2018 to March 2022 were retrospectively analyzed for demographic characteristics, drug regimen, clinical symptoms, laboratory indices, electromyography examination, pathological manifestations and outcomes.RESULTS:The eight patients included 2 females and 6 males with a median age of 68 years, all treated with ICI for urological neoplasms, including 2 upper tract urothelial carcinoma (UTUC), 3 renal cell carcinoma (RCC), and 3 bladder cancer (BCa). The median time between the first ICI treatment and the detection of immune-related myositis was 39.5 days, and the median duration of treatment was 2 sessions. The main symptoms were muscle pain and weakness, 5 cases with ptosis, 3 cases with secondary rhabdomyolysis, 5 cases with myocarditis, 1 case with myasthenia gravis, and 1 case with enterocolitis. Among them, patients with immune-related myocarditis had a shorter interval from the first anti-programmed cell death protein-1 (PD-1) therapy to the onset of immune-related myositis (P=0.042) compared with patients without myocarditis. The 8 patients had significant elevation of transaminases and muscle enzyme profile indexes, and 5 patients showed positive auto-antibodies. 3 patients had perfected muscle biopsies and showed typical skeletal muscle inflammatory myopathy-like pathological changes with CD3+, CD4+, CD8+, CD20+ lymphocytes and CD68+ macrophage infiltration. After the diagnosis of immune-related myositis, all the 8 patients immediately discontinued ICI therapy and improved after intravenous administration of methylprednisolone alone or in combination with gamma-globulin.CONCLUSION:Immune-related myositis after ICI treatment is an immune-related adverse reactions (irAEs) with unique clinical and pathological features, commonly combined with cardiovascular adverse reactions. Immediate discontinuation of ICI and initiation of glucocorticoid therapy may improve the patient's condition in a timely manner.

Background After radical prostatectomy, the optimal length of postoperative catheterization time remains to be determined. This study investigates the impact of catheter removal time on urinary continence and overactive bladder (OAB) symptoms after robot-assisted radical prostatectomy (RARP). Methods Four hundred and thirty-two consecutive patients underwent RARP by a single surgeon between Nov 2020 and Oct 2021. Time to catheter removal was categorized into 7, 10, and ≥14 days. Continence was defined as no more than 1 pad used or no more than 20 g of urine leakage per 24 hours. The patients’ continence rates and overactive bladder symptom score (OABSS) were assessed at 48 hours, 1 week, 4, 12, and 24 weeks after catheter removal. Results Overall, continence rates were 37.3% 48 hours after catheter removal, 54.4% 1 week, 77.5% 4 weeks, 92.1% 12 weeks, and 97.9% 24 weeks after catheter removal. The median time to regain continence was 1 week. At 4 weeks after catheter removal, the continence rate in the ≥14 days group (70.5%) was significantly lower than the 7 days group (86.3%) and 10 days group (83.0%) (P=0.001). In a univariate Cox regression analysis, the presence of diabetes, higher pre-operative OABSS, and a catheterization time of 10 days were associated with worse continence recovery. The mean OABSS of patients in the continent group were significantly lower than the incontinent group at 48 hours, 4, 12 and 24 weeks after catheter removal. At 24 weeks after catheter removal, the mean OABSS in the 7 days group was significantly lower than in other groups. Conclusions Early catheter removal (7 days) was associated with better continence results and lower OABSS at 4 and 24 weeks after catheter removal respectively.

BACKGROUND:Secondary jejunal tumor from renal cell carcinoma (RCC) is extremely rare in clinical practice and is easily missed and misdiagnosed because of the low incidence and atypical symptoms.CASE SUMMARY:A 38-year-old male patient was diagnosed pathologically with left RCC after radical nephrectomy in 2012. The patient then suffered multiple lung metastases 2 years later and was treated with oral sorafenib without progression for 6 years. In 2020, an emergency intestinal segmental resection due to intestinal obstruction was required, and postoperative pathology confirmed a jejunal secondary tumor from RCC. The patient had a smooth recovery following surgery. Three months after surgery, the patient was diagnosed with left adrenal metastasis, and subsequent sintilimab therapy has stabilized his condition.CONCLUSION:This report is written to remind urologists and pathologists of the potential for small intestinal secondary tumors when a patient with a history of RCC seeks treatment for digestive symptoms. Enteroscopy and abdominal contrast-enhanced computed tomography are essential means of examination, but severe cases require immediate surgical intervention despite the lack of a preoperative examination to distinguish tumor attributes.

A 69-year old man presented with high-risk metastatic prostate cancer. After 7 months of androgen deprivation therapy (ADT), he progressed to metastatic castration resistant prostate cancer. We suggested him comprehensive therapy, including Abiraterone, chemo-therapy, radio-therapy, platinum chemo-therapy and Enzalutamide, which proved effective with his long term survival.

OBJECTIVE:To observe the early efficacy and toxicity of docetaxel combined with carboplatin in patients with metastatic castration-resistant prostate cancer (mCRPC). METHODS:From May 2017 to July 2019, fifteen patients with mCRPC treated in Peking University First Hospital were collected. The median age was 70 years (43-77 years), and the pathological types were all adenocarcinoma, which was confirmed as distant metastasis by imaging examination. They were given the chemotherapy of docetaxel combined with carboplatin. The specific method was as follows: each cycle was 28 days. Androgen deprivation therapy was administered routinely throughout the treatment period. Blood routine, liver and kidney function, blood clotting function and prostate-specific antigen (PSA) tests were performed before each cycle. Docetaxel was administered intravenously on the first day of each cycle at a dose of 75 mg/m2, and carboplatin was administered intravenously on the second day at the dose calculated by Calvert formula. The main outcome measures including PSA decline range, pain remission rate and occurrence of adverse reactions were observed and analyzed. RESULTS:Among the 15 patients, 12 had completed at least 4 cycles of chemotherapy and had short-term efficacy evaluation. PSA decline range > 50% was observed in 8 patients (66.7%). Among the 9 patients with bone pain, remarkable pain relief was observed in 4 patients (44.4%). Among the 4 patients with measurable metastatic lesions, 2 achieved partial response, 1 was evaluated as stable disease, and 1 was evaluated as progressive disease. The main adverse reactions of chemotherapy included bone marrow suppression, gastrointestinal reactions, fatigue and neurological disorders, and most of them were within the tolerable range. CONCLUSION:This report is a case series study of docetaxel combined with carboplatin in the treatment of mCRPC reported in China and the conclusions are representative. The chemotherapy of docetaxel combined with carboplatin has positive short-term efficacy and high safety in patients with mCRPC, which is worthy of further promotion and exploration in clinical practice.

Recent studies indicate mammalian target of rapamycin (mTOR) may play an important role in PCa progression and drug resistance. Here, we investigated the effects of a novel mTORC1/C2 dual inhibitor, AZD2014, on naive and docetaxel (Doc)-pre-treated castration-resistant PCa (CRPC) cells and explored its therapeutic potential in CRPCs. In the current study, AZD2014 has a greater inhibitory effect against 4EBP1 and AKT phosphorylation than rapamycin in CRPC cells and prevented the feedback activation of AKT signalling. Importantly, AZD2014 suppressed CRPC cell growth in vitro by suppressing proliferation, apoptosis, cell cycle arrest at G1 phase and autophagy to a greater extent than rapamycin. Moreover, AZD2014 was more efficacious than rapamycin in inhibiting migration, invasion and EMT progression in Doc-sensitive and Doc-resistant CRPC cells. Overall, AZD2014 showed significant antitumour effects. Thereby, the current study highlights a reliable theoretical basis for the clinical application of AZD2014 in both Doc-sensitive and Doc-resistant CRPCs.

OBJECTIVETo evaluate urinary continence recovery time and risk factors of urinary continence recovery after robot-assisted laparoscopic radical prostatectomy (RARP).METHODSFrom January 2019 to January 2021, a consecutive series of patients with localized prostate cancer (cT1-T3, cN0, cM0) were prospectively collected. RARP with total anatomical reconstruction was performed in all the cases by an experienced surgeon. Lymph node dissection was performed if the patient was in high-risk group according to the D'Amico risk classification. The primary endpoint was urinary continence recovery time after catheter removal. Postoperative and pathological variables were analyzed. Continence was rigo-rously analyzed 48 hours, 1 week, 4 weeks, 12 weeks, and 24 weeks after catheter removal. Continence was evaluated by recording diaper pads used per day, and all the patients were instructed to perform the 24-hour pad weight test until full recovery of urinary continence. The patient was defined as continent if no more than one safety pad were needed per day, or no more than 20-gram urine leakage on the 24-hour pad weight test. Time from catheter removal to full recovery of urinary continence was recorded, and risk factors influencing continence recovery time evaluated.RESULTSIn total, 166 patients were analyzed. The mean age of the enrolled patients was 66.2 years, and the median prostate specific antigen (PSA) was 8.51 μg/L. A total of 59 patients (35.5%) had bilateral lymphatic dissection, and 28 (16.9%) underwent neurovascular bundle (NVB) preservation surgery. Postoperative pathology results showed that stage pT1 in 1 case (0.6%), stage pT2 in 77 cases (46.4%), stage pT3 in 86 cases (51.8%), and positive margins in 28 patients (16.9%). Among patients who underwent lymph node dissection, lymph node metastasis was found in 7 cases (11.9%). Median continence recovery time was one week. The number of the continent patients at the end of 48 hours, 1 week, 4 weeks, 12 weeks, and 24 weeks were 65 (39.2%), 32 (19.3%), 34 (20.5%), 24 (14.5%), and 9 (5.4%). Two patients remained incontinent 24 weeks after catheter removal. The continence rates after catheter removal at the end of 48 hours, 1 week, 4 weeks, 12 weeks, and 24 weeks were 39.2%, 58.4%, 78.9%, 93.4%, and 98.8%, respectively. Univariate COX analysis revealed that diabetes appeared to influence continence recovery time (OR=1.589, 95%CI: 1.025-2.462, P=0.038). At the end of 48 hours, 4 weeks, 12 weeks, and 24 weeks after catheter removal, the mean OABSS score of the continent group was significantly lower than that of the incontinent group.CONCLUSIONRARP showed promising results in the recovery of urinary continence. Diabetes was a risk factor influencing continence recovery time. Bladder overactive symptoms play an important role in the recovery of continence after RARP.

553 Background: UTUC is a potentially lethal malignancy and PD1-1/PD-L1 antibodies have shown promising efficacy. Although it had been explored in patients of their PD-L1 expression level who were enrolled in clinical trials, most of them were not Chinese. China has a larger patient population in CKD patients, yet may cause a different level of PD-L1 expression. Methods: Patients of locally resectable disease were enrolled and tumor tissues were collected for VENTANA PD-L1 (SP263) Assay (Roch). High and Low expression levels were determined according to the interpretation guide. Clinical and pathological data were collected and statistical analyses were done by SPSS 20. Results: A total of 190 patients diagnosed with UTUC were enrolled. Forty-one (21.6%) patients were identified as high PD-L1 expression. PD-L1 expression were significantly higher in high tumor grade (p=0.001), higher T stage (≤T2 vs. >T3, p=0.002), with divergent differentiation (squamous/ glandular/ sarcomatoid vs. pure UC, p=0.005), higher neutrophil/lymphocyte ratio (NLR≤3 vs. >3, p=0.045) and higher platelet/lymphocyte ratio (PLR<150 vs.≥150, p=0.006). Notably, patients with CKD stage 3 or higher (eGFR <60ml/min/1.73m2) had comparable PD-L1 high expression population (p=0.34). The HR for metastatic free survival was 2.65 in high expression patients (95% CI 1.17~5.97, p=0.019). Conclusions: China has a large population of UTUC with CKD stage 3 or higher who are ineligible for cisplatin and call for new treatment such as PD-L1/PD1 antibody. No difference was found in different CKD groups. UTUC seems to have lower proportion of PD-L1 high expression compared to bladder cancer. Whether it is due to more N-linked glycosylation that masked the detection or there might be other reasons inlayed stilled remain further study to find out.[Table: see text]

e17516 Background: DDR gene alterations(GAs) are prevalent in cancer and play key roles in tumorigenesis, progression and therapeutic response. However, the molecular profile of DDR in genitourinary cancer is still lacking in Asian. In this study, we assessed DDR GAs for better understanding therapeutic implications. Methods: Patients(pts) diagnosed with genitourinary cancer were enrolled. Tumors and plasma samples were collected for next-generation sequencing with Acornmed panel(2.0 Mbp) containing 808 cancer-related genes, including 34 DDR genes(Jonathan, et al.). OncoKB and COSMIC were used to identify GAs status including deleterious, unknown significance, and wild type(wt). Results: A total of 140 pts were enrolled with 56 pts of prostate cancer(PC), 55 pts of renal cell cancer(RCC) and 29 pts of urothelial cancer(UC). Metastatic diseases were accounted for 33.5%. A total of 127 tumor tissues and 109 baseline plasma samples were collected, including 96 matched tissue/plasma samples. A total of 109 pts(77.9%) harbored at least one GA in DDR pathway. UC carried the most DDR GAs(93.1 %), followed by PC(75%) and RCC(72.7%). After stratifying GA status, the most commonly deleterious GAs were ATM(n = 5); FANCA(n = 4); ERCC2, BRCA1, ATR, CHEK2(n = 2 each); MSH6, ERCC4, BRCA2, PALB2(n = 1 each).Tumor mutation burden(TMB) was significantly different among pts with deleterious, unknown significance and wt in PC(Mean: 17.8 vs 9.065 vs 4.468; p = 0.0003). Notably, DDR GAs were more likely to present in pts with metastatic disease(80.95% vs 62.50%), deleterious DDR GAs as well(14.29% vs 8.33%). Conclusions: DDR pathways are frequently altered in genitourinary cancer, especially UC in China. DDR GAs were significantly associated with higher TMB in PC. A higher prevalence was identified in metastatic disease. Comprehensive genomic profiling of DDR GAs highlights the clinical and therapeutic implication. Further exploration of the deleterious nature and alterations of unknown significance are required. [Table: see text]

A 34-year old young man presented with prostate cancer with ductal adenocarcinoma component and neuroendocrine differentiation. After multidisciplinary consultation, a suggestion of comprehensive treatment, including androgen-deprivation therapy, chemotherapy, radiotherapy and radionuclide therapy, was given to him. The therapeutic response was not satisfactory. After genetic testing, a germline mutation of BRCA1 gene was detected. By combination therapy with PARP inhibitor, Olaparib, a short-term disease control was obtained.

目的:评价二线阿西替尼治疗晚期肾癌患者的疗效及安全性.方法:回顾性分析2009年10月～2011年9月于我院泌尿外科诊治的15例接受二线阿西替尼治疗的晚期肾癌患者.所有患者均接受肾根治性切除手术,病理均为透明细胞癌.11例患者一线舒尼替尼治疗后进展,4例患者一线免疫治疗后进展.二线治疗方案:初始剂量5 mg、2次/d,连续4周为一周期直至疾病再次进展或不可耐受的严重毒副反应.若患者对药物耐受好,剂量可增至7 mg、2次/d,或10 mg、2次/d,若毒副反应重则剂量减至3 mg、2次/d.结果:Kaplan-Meier生存分析提示这15例患者中位总位生存期(OS)23.0(18.0～28.0)个月.二线阿西替尼治疗的中位无进展生存期(PFS)为7.0(1.5～47.0)个月.根据RECIST标准评价最佳疗效:完全缓解(CR)0例(0),部分缓解(PR)3例(20.0％),疾病稳定(SD)8例(53.3％),疾病进展(PD)4例(26.7％).多数不良反应多为1～2级,3～4级不良反应有蛋白尿2例(13.3％),腹泻1例(6.7％),呕吐2例(13.3％),乏力消瘦2例(13.3％),高血压5例(33.3％),手足皮肤反应1例(6.7％),口腔黏膜炎1例(6.7％),肝酶升高1例(6.7％),脑梗死1例(6.7％),上消化道出血1例(6.7％).通过减量或暂停药,多数不良反应可以耐受.结论:二线阿西替尼治疗晚期肾癌可取得较长的OS和PFS,二线治疗有较高疾病控制率,且不良反应多可耐受.

2019年欧洲泌尿外科学会(EAU)年会有关前列腺癌诊断和治疗方面的进展精彩纷呈。回顾本届EAU会议上相关的信息，本文重点阐述前列腺癌诊断和治疗方面的进展和热点问题，具体分为前列腺癌的影像学诊断及靶向穿刺进展、根治手术、局灶治疗、药物治疗以及免疫治疗进展5个部分，并结合文献进行深入解读。

目的探讨DDD肾肿瘤评分系统对于肾肿瘤手术的指导意义。方法选择北京大学第一医院泌尿外科2013年1月至2017年9月收治2977例病理诊断为肾细胞癌的患者进行病例回顾,筛选病例资料包含泌尿系增强CT的患者561例,收集患者的年龄、性别、手术方式等数据,对其术前CT或磁共振进行回顾分析并进行RENAL及DDD（D1为位于肾内的肿瘤的最长径;D2为肿瘤边界距离肾髓质或肾窦和集合系统的最短距离;D3肿瘤距离肾动静脉主干的距离）系统评分。将各径线D1、D2、D3评分与手术方式进行Mann-Whitney秩和检验,进一步使用Mann-Whitney秩和检验方法,比较不同DDD系统评分与RENAL评分对手术方式的决策影响。结果 RENAL及DDD系统评分均可分为3组:低度、中度、高度。对于肾部分切除（PN）与肾根治性切除（RN）的比较分析,RENAL及DDD系统评分差异具有统计学意义（P ＜0.001）,评分越低,行肾部分切除术的比率越高。对于腹腔镜肾部分切除术（LPN）与腹腔镜肾根治性切除术（LRN）,RENAL及DDD系统评分差异具有统计学意义（P ＜0.001）,评分越低,行腹腔镜部分肾切除的比率越高。对于LRN及开放肾根治切除术（ORN）的比较分析显示,低分组及中分组在使用RENAL及DDD系统评分差异均无统计学意义（P值分别为0.135和0.602）,但是低分组与高分组比较时两评分系统差异均具有统计学意义（P值分别为0.025和＜0.018）,评分越高,行开放肾根治性切除术的比率越高。结论 DDD肾肿瘤评分系统评分是一种直观简便的描述肾肿瘤解剖特征的综合评估体系,具有良好的稳定性,可以反映肾肿瘤手术的难度,协助临床医师进行肾肿瘤的手术决策。

Background Chemotherapy with Docetaxel (Doc) is efficient in a subset of prostate cancer (PCa) cases; however, most patients ultimately develop resistance to Docetaxel. The tumor immune microenvironment and secreted cytokines play a substantial role in development of resistance to chemotherapy. Our previous study has demonstrated that CD4+ T cells in prostate tumor microenvironment contribute to PCa progression; meanwhile, we found increased CD4+ T-cell infiltration in tumor area after Doc treatment; however, their effects on PCa chemosensitivity remain unclear. Here, we aim to explore the role and mechanisms of CD4+ T cells in PCa chemotherapy sensitivity. Methods CD4+ T-cell infiltration in Doc-treated paraffin-embedded specimens from transurethral resection of prostate, radical prostatectomy, or bone metastasis was detected by immunohistochemistry. The castration-resistant PCa cell lines-C4-2 and CWR22RV1, and CD4+ T-cell lines-HH and Molt-3 were used in the coculture system. After coculture with the lymphocytes, PCa cell chemosensitivity was detected by cell counting kit-8, terminal deoxynucleotidyl transferase dUTP nick-end labeling assays, and Western blot analysis. Various cell cytokines were determined by cytokine arrays and reverse-transcription polymerase chain reaction. The recombinant human C-C motif chemokine ligand 5 (CCL5) was added to PCa cells for further confirming its effects and anti-CCL5 antibody was used for neutralization. S3I-201, a signal transducer and activator of transcription 3 (STAT3) inhibitor, was added to the coculture system to detect STAT3 role in chemosensitivity. Tumor xenografts in nude mice were used for confirming effects of CD4+ T cells in vivo study. Results We found more infiltrated CD4+ T cells in human PCa lesions than in the adjacent noncancerous tissues after Doc treatment. In vitro cell line study confirmed that CD4+ T cells increase the PCa Doc resistance. Quantative polymerase chain reaction and cytokine arrays indicated that after coculture with PCa, CD4+ T cells could secrete large amounts of CCL5. Moreover, CCL5 stimulation enhanced PCa resistance to Doc, and anti-CCL5 antibody could partly reverse this process. We found that CD4+ T cells could activate P-STAT3 signaling via secreting CCL5 and adding a STAT3 inhibitor can reverse the chemoresistance. In vivo mouse model with xenografted 22RV1 cells and CD4+ T cells also confirmed the in vitro results. Conclusions Together, our results indicate that infiltrating CD4+ T cells could promote PCa chemotherapy resistance via modulation of the CCL5/STAT3 signaling pathway.

Objective To summarize the characteristics of clinical manifestation of bone flare after the treatment with new endocrine therapy in patients with metastatic castration-resistant prostate cancer (mCRPC) in order to evaluate the curative effect of patients properly and determine the reasonable treatment strategy.Methods We retrospectively analyzed the clinical data of two patients with mCRPC performed "bone flare" defined as PSA decline and bone metastases progression in the initial treatment with new endocrine therapy in Urology Department of Peking University First Hospital,and analyzed the clinical characteristics and treatment methods with the relative literature.Case 1,a 79-year-old man,presented with frequent urination and prostate-specific antigen (PSA) was 115.900 ng/ml,was diagnosed as prostate cancer (cT3N0M1) with bone metastasis.After androgen deprivation therapy of 24 months,PSA elevated and multiple bone metastases progressed.The patient was diagnosed with mCRPC and then began the treatment of enzalutamide.Case 2,a 62-year-old man,complained about emaciation and frequent urination,was diagnosed with prostate cancer(cT4N1M1)with bone and lymph metastases.After androgen deprivation therapy of 22 months,PSA elevated and multiple bone metastases progressed.The patient was diagnosed with mCRPC and then began the treatment of abiraterone.Results Case 1 was treated with enzalutamide and 2 months later PSA decreased from 133.400 ng/ml to 5.530 ng/ml,while bone scan showed multiple bone metastases,part of which was newly metastatic lesions.6 months later,the number of metastatic lesions kept stable,and part of lesions presented metabolism decrease.8 months later,the number of metastatic lesions began to decrease.1 year later,the patient started to receive chemical therapy because of the progression of the disease.After 5 cycles of chemotherapy,PSA progression occurred and chemotherapy was stopped.Liver failure and disseminated intravascular coagulation caused death in June 2016.Case 2 was treated with abiraterone and 2 months later PSA decreased from 54.820 ng/ml to 3.580 ng/ml,while bone scan showed multiple bone metastases,part of which was newly metastatic lesions.6 months later,the number of metastatic lesions began to decline.10 months later,the number of metastatic lesions kept stable.The treatment of abiraterone was continued so far and the patient was in a stable condition.Conclusions Enzalutamide and abiraterone,two new endocrine therapy,are determined as preferred methods for the treatment of mCRPC.The bone scanning is required to evaluate the possibility of "bone flare" which is defined as PSA decline and bone metastases progression in the initial treatment.These patients should be evaluated to make appropriate clinical decision.

Objective To present a DDD scoring system to access the surgical complexity of renal tumors to assist in the surgical decision-making process. Methods We retrospectively evaluated 561 patients who were histopathologically diagnosed with renal cell carcinoma with available imaging data between January 2013 and September 2017. The surgical approaches, as well as RENAL and DDD scores, were compared. We performed a review of the available English literature published in the last decade and relating to the surgical anatomy pertinent to renal mass excision, and established a solid single renal mass scoring system, the DDD nephrometry score, based on the three most reproducible and pertinent features that characterize the critical anatomical attributes of renal tumors. Each feature in our nephrometry score was designated by an English letter, forming the acronym DDD: (D1)iameter (scores tumor size as the maximal diameter inside the kidney), (D2)epth of the deepest portion of the tumor with the medulla and collecting system or sinus, and (D3) istance (shortest from the mass to the main renal vessels). The points of D1, D2, and D3 were summed as DDD score and tumors were stratified into three complexity levels. The relationships between each D variate and the operation method options were tested by the Mann-Whitney rank sum test. The further Mann-Whitney rank sum test was used to compare the different effects of DDD nephrometry score and RENAL score on surgery method choice. Results In this cohort, 383 (68.3%) patients were men and 178 (31.7%) were women. The mean age was (57.3±11.9) years, and mean BMI was (25.1±3.5) kg/m2. Mean D1 was (4.3±2.0) cm. D2 was 1 pt in 50 (8.9%) patients, 2 pts in 110 (19.6%), and 3 pts in 401 (71.5%). D3 was 1 pt in 357 (63.6%) patients, 2 pts in 33 (5.9%), and 3 pts in 171 (30.5%). There were 36 (6.4%), 186 (33.2%), and 339 (60.4%) patients in the low, moderate, and high DDD score groups, and 140 (25.0%), 289 (51.5%), and 132 (23.5%) in the low, moderate, and high RENAL score groups, respectively. Regarding surgical procedures, 329 (58.6%) patients′ tumors were removed by radical nephrectomy (RN), in which 47 (8.4%) were removed by open radical nephrectomy (ORN) and 282 (50.2%) by laparoscopic radical nephrectomy (LRN); 232 (41.4%) patients′ tumors were removed by partial nephrectomy (PN), in which 32 (5.7%) were removed by open partial nephrectomy (OPN) and 200 (35.7%) by laparoscopic partial nephrectomy (LPN). For partial nephrectomy (PN) rate, significant differences were observed between any two RENAL or DDD score groups (P<0.001 for all), and there was a higher PN rate with the lower score group. Likewise, the same results were observed in the laparoscopic group, and the laparoscopic partial nephrectomy (LPN) rate was higher with the lower score group (P<0.001 for all). As for laparoscopic nephrectomy (LRN) or open nephrectomy (ORN), differences were not significant between low and moderate RENAL or DDD score groups (P=0.135 and P=0.602, respectively), but significant between the low and high groups (P=0.025, <0.018). High DDD score and RENAL groups had significant more patients undergoing ORN than low and moderate groups, respectively. Conclusions DDD score is based on only three variants and all of them are intuitive and pellucid. Even junior urologists and radiologists could easily master this system and it can be measured easily on preoperative CT images. The DDD score could be used to reflect the surgical complexity and assist to make treatment decisions for patients with renal tumors. Key words: Renal cell carcinoma; Surgical procedures; DDD score; RENAL score

Objective To validate a nomogram model based on prostate health index (PHI) for predicting prostate cancer (PCa). Methods The pre-operation serum and clinical data were collected for suspected PCa patients (aged 34 to 90 years), who visited Peking University First Hospital from August 2015 to May 2017 and received transrectal ultrasound-guided prostate biopsy. A total of 391 suspected PCa with total prostate-specific antigen (tPSA)>4 ng/ml were selected into this study, including 235 cases with tPSA level of 4-10 ng/ml and 156 cases with tPSA>10 ng/ml. The p2PSA was tested in all cases and then PHI was calculated. The biopsy results were considered as the gold standard to diagnose PCa. The nomogram model established in Shanghai based on PHI, age and prostate volume was validated in all cases enrolled in this study. Receiver operator curves (ROC) were used to assess the ability of nomogram model to predict PCa. Results Of 391 male patients included in this study, 175(44.8%)were finally diagnosed as PCa. ROC curves indicated that, the area under the curve (AUC) of the nomogram model for predicting PCa among 391 cases was higher than that of the traditional indicator tPSA (AUC: 0.786 vs 0.578, P<0.000 1). And f/t(AUC: 0.786 vs 0.672, P=0.000 2). For those people with tPSA level of 4-10 ng/ml, the AUC of the nomogram model was also higher than that of tPSA (AUC: 0.720 vs 0.513, P=0.000 3) and f/t(AUC: 0.720 vs 0.626, P=0.042 5). Conclusion The nomogram model based prostate health index (PHI) was validated to have a good auxiliary diagnostic value for PCa in our center.(Chin J Lab Med, 2018, 41: 536-540) Key words: Prostatic neoplasms; Prostate-specific antigen; Protein Precursors; ROC curve; Health status