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Single tertiary cancer center experience on the management of pT3b prostate cancer after robotic-assisted laparoscopic prostatectomy

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Current Urology 2022年第4期16卷 227-231页

作者： Arvind Nayak Omar El-Taji Sugeeta Sukumar John Piedad Aruni Ghose Rob Hughes Roberto Alonzi Peter Ostler Anand Sharma Tim Lane Jim Adshead Nikhil Vasdev Department of Urology East and North Hertfordshire NHS TrustStevenageUK Department of Radiation Oncology Mount Vernon Cancer CentreLondonUK University of Hertfordshire StevenageUK Department of Medical Oncology Mount Vernon Cancer CentreLondonUK

Background:Pathological involvement of the seminal vesicle poses a treatment dilemma following robotic *** status plays an important role in deciding further management.A wide range of treatment options are available,including active monitoring,adjuvant radiotherapy,salvage radiotherapy,and occasionally androgen deprivation *** undergoing postoperative radiotherapy tend to have higher risk of urinary and bowel *** recent RADICALS-RT concluded that adjuvant radiotherapy did not have any benefit compared with salvage *** aim to audit the incidence,margin status,and management of T3b cancer cases at our *** and methods:A retrospective analysis was conducted of all patients diagnosed with pathological T3b(pT3b)prostate cancer following robotic-assisted laparoscopic prostatectomy from January 2012 to July *** parameters analyzed included prostate-specific antigen(PSA),T stage,and age.A chi-square test and 2-tailed t test were used to determine the relationship between categorical and continuous variables,***-Meier survival curves were generated to assess overall survival in patients with pT3b prostate cancer and used to compare unadjusted progression-free survival among those who underwent adjuvant and salvage ***:A total of 83(5%)of 1665 patients who underwent robotic prostatectomy were diagnosed with pT3b prostate cancer between January 2012 and July *** these,36 patients(44%)did not receive any radiotherapy during follow-up,compared with 26 patients(31%)who received adjuvant radiotherapy and 21(25%)who received salvage *** median age of our cohort was 64(SD,6.4)*** PSA at presentation was 12.7 pg/*** margins were seen in 36 patients(43%);however,there was no statistically significant difference between treatment groups(p=0.49).The median overall survival was 96%.There was no significant difference between the adjuvant and

关键词： prostate cancer Radiotherapy Robotic prostatectomy Seminal vesicle T3b

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Chemotherapy and its evolving role in the management of advanced prostate cancer

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Asian Journal of Andrology 2014年第3期16卷 334-340页

作者： Michael T Schweizer Emmanuel S Antonarakis prostate cancer Research Program Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Baltimore Maryland USA

Advanced prostate cancer has been recognized as being responsive to androgen deprivation since the 1940s when Charles Huggins first described the role of surgical castration in managing these patients. However, androgen deprivation only results in transient disease control for the vast majority of men, with those progressing in spite of castrate testosterone levels labeled as having castrate-resistant prostate cancer （CRPC）. Until 2004, the therapeutic arena for these patients had remained stagnant, with no agent having shown a survival gain in the CRPC setting. Two landmark publications changed the prostate cancer treatment landscape by providing ＇level-1 evidence＇ that docetaxel-based chemotherapy led to prolongation in overall survival （OS）. This was followed by the approval of cabazitaxel in 2010 on the basis of Phase III data demonstrating its efficacy in patients pretreated with docetaxel. More recently, a number of next-generation androgen-directed agents （e.g. abiraterone and enzalutamide） have also been shown to lead to a survival benefit in men with CRPC. With so many new treatment options available, a number of questions remain. These include： how to best sequence chemotherapy with these newer hormonal agents, the clinical implication of cross-resistance between taxanes and androgen-directed agents and which subsets of patients may benefit most from early use of chemotherapy. This review will provide an overview of the evolving role of chemotherapy in the management of advanced prostate cancer in the current era.

关键词： cabazitaxel chemotherapy cyclophosphamide docetaxel mitoxantrone prostate cancer taxanes

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PSCA, Cox-2, and Ki-67 are independent, predictive markers of biochemical recurrence in clinically localized prostate cancer： a retrospective study

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Asian Journal of Andrology 2017年第4期19卷 458-462页

作者： Sung Han Kim Weon Seo Park Bo Ram Park Jungnam Joo Jae Young Joung Ho Kyung Seo Jinsoo Chung Kang Hyun Lee Department of Urology Center for Prostate Cancer Research Institute and Hospital of National Cancer Center Goyang Korea Department of Pathology Center for Prostate Cancer Research Institute and Hospital of National Cancer Center Goyang Korea Department of Statistics Biometric Research Branch Clinical Research Coordination Center Research Institute and Hospital of National Cancer Center Goyang Korea.

prostate cancer is the second most common male cancer, with half of all patients going on to develop metastases. To better identify patients at high risk for prostate cancer progression and reduce prostate cancer-related mortality, improved prognostic factors are required. In this study, we used immunohistochemistry （IHC） to determine the prognostic values of multiple tissue biomarkers in hormone-na＇l＇ve prostatectomy specimens of prostate cancer. Using 510 prostatectomy specimens collected between 2002 and 2012, IHC analysis was performed for Cerb-2, Cyclin D1, VEGF, EGFR, Rb, PSCA, p53, Bcl-2, Cox-2, PMS2, and Ki-67 on formalin-fixed paraffin-embedded sections. The Cox proportional hazard model was used to determine the predictive risk factors for biochemical recurrence （BCR） of prostate cancer. During a median 44-month follow-up, 128 （25.1%） patients developed BCR. A multivariate regression analysis revealed that Ki-67 （hazard ratio [HR]. 1.60, P = 0.033）, PSCA （HR： 0.42, P 〈 0.001）, and Cox-2 （HR： 2.05, P = 0.003） were the only significant prognostic tissue markers of BCR. Resection margin status （HR： 1.67, P = 0.010）, pathologic pTO/l/2 stage （vs pT3/4; HR： 0.20, P = 0.002）, preoperative PSA levels （HR.. 1.03, P 〈 0.001）, biopsied （HR： 1.30, P = 0.022） and pathologic （HR： 1.42, P = 0.005） Gleason scores, and prostate size （HR： 0.97, P = 0.003） were significant clinicopathologic factors. The expression of Ki-67, PSCA, and Cox-2 biomarkers along with other clinicopathologic factors were prognostic factors for BCR in patients with clinically localized prostate cancer following radical prostatectomy.

关键词： biomarker immunohistochemistry prostatectomy recurrence tissue microarray

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Prevalence and risk evaluation of cardiovascular disease in the newly diagnosed prostate cancer population in China:A nationwide,multi-center,population-based cross-sectional study

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Chinese Medical Journal 2024年第11期137卷 1324-1331页

作者： Weiyu Zhang Huixin Liu Ming Liu Shi Ying Renbin Yuan Hao Zeng Zhenting Zhang Sujun Han Zhannan Si Bin Hu Simeng Wen Pengcheng Xu Weimin Yu Hui Chen Liang Wang Zhitao Lin Tao Dai Yunzhi Lin Tao Xu Department of Urology Peking University People’s HospitalBeijing 100044China Department of Clinical Epidemiology and Biostatistics Peking University People’s HospitalBeijing 100044China Department of Urology Beijing HospitalNational Center of GerontologyBeijing 100005China Institute of Geriatric Medicine Chinese Academy of Medical SciencesBeijing 100005China Department of Urology Wuhan Union HospitalHuazhong University of Science&TechnologyWuhanHubei 430022China Department of Urology The Third People’s Hospital of ChengduChengduSichuan 610014China Department of Urology West China Hospital of Sichuan UniversityChengduSichuan 610041China Department of Urologic Oncology Tianjin Medical University Cancer Institute&HospitalTianjin 300060China Department of Urology Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China National cancer center Beijing 100021China National Clinical Research center for cancer Beijing 100021China Department of Urology Liaoning Cancer HospitalShenyangLiaoning 110801China Department of Urology The Second Hospital of Tianjin Medical UniversityTianjin 300141China Tianjin Institute of Urology Tianjin Medical UniversityTianjin 300141China Department of Urology Lu’an Affiliated Hospital of Anhui Medical UniversityLu’anAnhui 237322China Department of Urology Renmin Hospital of Wuhan UniversityWuhanHubei 430060China Department of Urology Harbin Medical University Affiliated Cancer HospitalHarbinHeilongjiang 150081China Department of Urology The Second Hospital of Dalian Medical UniversityDalianLiaoning 116023China Department of Urology Surgery Fujian Cancer HospitalFuzhouFujian 350014China Department of Urology Surgery Hunan Cancer HospitalChangshaHunan 410031China Department of Urology Surgery The First Affiliated Hospital of Fujian Medical UniversityFuzhouFujian 350004China

Background:Cardiovascular disease(CVD)has emerged as the leading cause of death from prostate cancer(PCa)in recent decades,bringing a great disease burden *** with preexisting CVD have an increased risk for major adverse cardiovascular events when treated with androgen deprivation therapy(ADT).The present study aimed to explore the prevalence and risk evaluation of CVD among people with newly diagnosed PCa in ***:Clinical data of newly diagnosed PCa patients were retrospectively collected from 34 centers in China from 2010 to 2022 through convenience *** was defined as myocardial infarction,arrhythmia,heart failure,stroke,ischemic heart disease,and *** risk was estimated by calculating Framingham risk scores(FRS).Patients were accordingly divided into low-,medium-,and high-risk groups.χ2 or Fisher’s exact test was used for comparison of categorical ***:A total of 4253 patients were enrolled in the present study.A total of 27.0%(1147/4253)of patients had comorbid PCa and CVD,and 7.2%(307/4253)had two or more *** enrolled population was distributed in six regions of China,and approximately 71.0%(3019/4253)of patients lived in urban *** imaging and pathological evaluation,most PCa patients were diagnosed at an advanced stage,with 20.5%(871/4253)locally progressing and 20.5%(871/4253)showing *** of them initiated prostatectomy(46.6%,1983/4253)or regimens involving ADT therapy(45.7%,1944/4253)for prostate *** the present PCa cohort,43.1%(1832/4253)of patients had hypertension,and half of them had poorly controlled blood *** FRS stratification,as expected,a higher risk of CVD was related to aging and metabolic ***,we also found that patients with treatment involving ADT presented an originally higher risk of CVD than those without *** was in accordance with clinical practice,i.e.,aged patients or patients at advanced oncological stages were inclined to accept sys

关键词： prostate cancer Castration Cardiovascular disease Prevalence Cardiovascular risk

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Integrated analysis of single-cell and bulk transcriptomes uncovers clinically relevant molecular subtypes in human prostate cancer

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Chinese Journal of cancer Research 2025年第01期 90-126页

作者： Tao Ding Lina He Guowen Lin Lei Xu Yanjun Zhu Xinan Wang Xuefei Liu Jianming Guo Fanghong Lei Zhixiang Zuo Jianghua Zheng Department of Urology Yuebei People's Hospital Shantou University Medical College Department of Urology Southern Medical University Affifiliated Fengxian Hospital School of Life Sciences State Key Laboratory of Oncology in South China Cancer Center Collaborative Innovation Center for Cancer Medicine Sun Yat-sen University Department of Urology Fudan University Shanghai Cancer Center Department of Urology Zhongshan HospitalFudan University Department of Urology Tongji Hospital School of Medicine Tongji University Department of Biochemistry School of Medicine Southern University of Science and Technology Department of Pathology Yuebei People's Hospital Shantou University Medical College Central Laboratory Tongji HospitalSchool of Medicine Tongji University Department of Laboratory Medicine Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital

Objective: prostate cancer(PCa) is a complex disease characterized by diverse cellular ecosystems within the tumor microenvironment(TME) and high tumor heterogeneity, which challenges clinically stratified management and reinforces the need for novel strategies to fight against castration-resistant PCa(CRPC).Methods: We performed single-cell RNA sequencing(scRNA-seq) on 10 untreated primary PCa tissues and integrated public scRNA-seq resources from three normal prostate tissues, two untreated primary PCa tissues, and six CRPC tumors to portray a comprehensive cellular and molecular interaction atlas of PCa. We further integrated the single-cell and bulk transcriptomes of PCa to establish a molecular classification ***: scRNA-seq profiles revealed substantial inter-and intra-tumoral heterogeneity across different cell subpopulations in untreated PCa and CRPC tumors. In the malignant epithelial reservoir, cells evolved along decoupled paths in treatment-naive PCa and CRPC tumors, and distinct transcriptional reprogramming processes were activated, highlighting anti-androgen therapy-induced lineage plasticity. Based on the specifically expressed markers of the epithelial subpopulations, we conducted unsupervised clustering analysis in The cancer Genome Atlas prostate adenocarcinoma(TCGA-PRAD) cohort and identified three molecularly and clinically distinct subtypes. The C1 subtype, characterized by high enrichment of CRPC-enriched epithelial cells, had a high risk of rapid development of anti-androgen resistance and might require active surveillance and additional promising intervention treatments, such as integrin A3(ITGA3) + integrin B1(ITGB1) inhibition. The C2 subtype resembled the immune-modulated subtype that was most likely to benefit from anti-LAG3 immunotherapy. The C3 subtype had a favorable ***: Our study provides a comprehensive and high-resolution landscape of the intricate architecture of the PCa TME, and our trichotomic molecu

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Use of androgen deprivation therapy in prostate cancer： indications and prevalence

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Asian Journal of Andrology 2012年第2期14卷 177-186页

作者： Roisin M Connolly Michael A Carducci Emmanuel S Antonarakis prostate cancer Research Program Department of Medical Oncology Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Baltimore MD 21231-1000 USA

Androgens play a prominent role in the development, maintenance and progression of prostate cancer. The introduction of androgen deprivation therapies into the treatment paradigm for prostate cancer patients has resulted in a wide variety of benefits ranging from a survival advantage for those with clinically localized or locally advanced disease, to improvements in symptom control for patients with advanced disease. Controversies remain, however, surrounding the optimal timing, duration and schedule of these hormonal approaches. Newer hormonal manipulations such as abiraterone acetate have also been investigated and will broaden treatment options for men with prostate cancer, This review highlights the various androgen-directed treatment options available to men with prostate cancer, their specific indications and the evidence supporting each approach, as well as patterns of use of hormonal therapies.

关键词： androgen deprivation therapy androgen synthesis anti-androgen prostate cancer

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HoLEP does not affect the overall sexual function of BPH patients： a prospective study

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Asian Journal of Andrology 2014年第6期16卷 873-877页

作者： Sung Hart Kim Hyung-Kook Yang Hahn-Ey Lee Jae-Seung Paick Seung-June Oh Department of Urology Prostate Cancer Center National Cancer Center Goyang Korea Department of Epidemiology and Statistics and cancer Policy Branch of National cancer Control Research Institute National Cancer Center Goyang Korea Department of Urology Seoul National University Hospital Seoul Korea.

We aimed to prospectively evaluate the influence of holmium laser enucleation of the prostate （HoLEP） on the overall postoperative sexual function of benign prostatic hyperplasia （BPH） patients with lower urinary tract symptoms （LUTS） and to explore the relationship between sexual function and LUTS. From January 2010 to December 2011, sixty sexually active consecutive patients with BPH who underwent HoLEP were prospectively enrolled in the study. All patients filled out the Male Sexual Health Questionnaire （MSHQ） for evaluation of their overall sexual function and the International Prostatic Symptom Score （IPSS） for pre- and post-operative 6 months evaluation of their voiding symptoms. The LUTS and sexual function changes were statistically analyzed. The preoperative and 6 months postoperative status of the patients was compared using uroflowmetry and IPSS questionnaires. The analysis revealed significant improvements following HoLEP. Among the sub-domains of the MSHQ, postoperative sexual function, including erection, ejaculation, sexual satisfaction, anxiety or sexual desire, did not significantly change after HoLEP （P 〉 0.05）, whereas satisfaction scores decreased slightly due to retrograde ejaculation in 38 patients （63.3%）. Sexual satisfaction improved significantly and was correlated with the improvements of all LUTS and the quality-of-life （QoL） domains in IPSS after surgery （QoL; relative risk [RR]： -0.293; total symptoms, RR： -0.411; P 〈 0.05）. The nocturia score was associated with the erectile function score （odds ratio 0.318, P = 0.029）. The change in ejaculatory scores did not show significant association with IPSS scores. HoLEP did not influence overall sexual function, including erectile function. In addition, sexual satisfaction improved in proportion with the improvement of LUTS.

关键词： benign prostatic hyperplasia ejaculation erectile dysfunction lasers prostatectomy sex disorders

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Competition for nutrients or cell intrinsic programming?-Metabolic mechanisms behind the tumor promoting immune microenvironment in cancer

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Signal Transduction and Targeted Therapy 2021年第8期6卷 2268-2269页

作者： Yuequn Niu Thomas Mayr Michael H.Muders Rudolf Becker Laboratory for prostate cancer Research Center of PathologyUniversity Hospital BonnBonnGermany

The prevention of anti-tumor immunity is a hallmark of *** and cancer cells depend on glucose for their anabolic *** reprogramming of immune cells is essential to promote the growth of cancer *** a recent study published in Nature,Reinfeld et al.1 pinpointed the mTORCI signaling pathway to be responsible for metabolic reprogramming of the immune cells in the tumor microenvironment(TME).

关键词： Metabolic prevention immunity

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Cytoreductive radical prostatectomy after chemohormonal therapy in patients with primary metastatic prostate cancer

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Asian Journal of Urology 2022年第1期9卷 69-74页

作者： Christa Babst Thomas Amiel Tobias Maurer Sophie Knipper Lukas Lunger Robert Tauber Margitta Retz Kathleen Herkommer Matthias Eiber Gunhild von Amsbergb Markus Graefen Juergen Gschwend Thomas Steuber Matthias Heck Department of Urology Technical University of MunichRechts der Isar Medical CenterMunichGermany Martini-Klinik prostate cancer center HamburgGermany

Objective:Cytoreductive radical prostatectomy(cRP)has been proposed as local treatment option in metastatic hormone-sensitive prostate cancer(mHSPC)to prevent local complications and potentially improve oncological *** this study,we examined the feasibility of a multimodal concept with primary chemohormonal therapy followed by cRP and analyzed prostate size reduction under systemic treatment,postoperative complication rates,as well as early postoperative ***:In this retrospective study,38 patients with mHSPC underwent cRP after primary chemohormonal therapy(3-monthly luteinising hormone-releasing hormone-analogue+six cycles 3-weekly docetaxel 75 mg/m2)at two centers between September 2015 and December ***:Overall,10(26%)patients had high volume and 28(74%)patients had low volume disease at diagnosis,according to CHAARTED *** prostate-specific antigen(PSA)decreased from 65 ng/mL(interquartile range[IQR]35.0-124.5 ng/mL)pre-chemotherapy to 1 ng/mL(IQR 0.3-1.7 ng/mL)*** gland volume was significantly reduced by a median of 50%(IQR 29%-56%)under chemohormonal therapy(p=0.003).Postoperative histopathology showed seminal vesicle invasion in 33(87%)patients and negative surgical margins in 17(45%)*** complications(Grade 3 according to Clavien-Dindo)were observed in 4(11%)patients within 30 *** was reached in 87%of patients after 1 month and in 92%of patients after 6 *** time to castration-resistance from begin of chemohormonal therapy was 41.1 months and from cRP was 35.9 *** PSA-nadir≤1 ng/mL versus>1 ng/mL was a significant predictor of time to castration-resistance after cRP(median not reached versus 5.3 months;pprostate volume under chemohormonal therapy going along with a low postoperative complication and high early continence ***,the oncologic benefit from cRP is still under evaluation.

关键词： Metastatic hormone-sensitive prostate cancer Chemohormonal therapy Cytoreductive radical prostatectomy Feasibility Prevent local complications Continence rate

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Albumin-linked prostate-specific antigen-activated thapsigargin- and niclosamide-based molecular grenades targeting the microenvironment in metastatic castration-resistant prostate cancer

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Asian Journal of Urology 2019年第1期6卷 99-108页

作者： Emmanuel S.Akinboye W.Nathaniel Brennen Samuel R.Denmeade John T.Isaacs Department of Oncology Prostate Cancer ProgramThe Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsThe Johns Hopkins University School of MedicineBaltimoreMDUSA

Localized prostate cancer is curable via annihilation of the entire cancer neighborhood by surgery or local ***,once metastatic,no available therapy is *** vast majority will die despite aggressive systemic combinational androgenablation ***,there is an urgent need for effective systemic therapeutics that sterilize the entire microenvironment in metastatic castration-resistant prostate cancer(mCRPC).To accomplish this goal,advantage can be taken of the unique biology of mCRPC *** their normal cell of origin,mCRPCs retain expression of the prostate-specific differentiation protein,prostate-specific antigen(PSA),which they abundantly secrete into their extracellular fluid(ECF).This unique,and essentially universal,secretion of enzymatically active PSA into the ECF by mCRPCs creates an exploitable therapeutic index for activation of systemically delivered highly lipophilic toxins as“molecular grenades”covalently linked to cysteine-34 of human serum albumin(HSA)via a stable maleimide containing PSA cleavable peptide such that PSA-dependent hydrolysis(i.e.,“detonation”)releases the grenades restrictively within the ECF of *** approach decreases dose-limiting host toxicity while enhancing plasma half-life from minutes to days(i.e.,pharmacokinetic effect)and increasing the tissue concentration of the maleimide coupled albumin delivery(MAD)in the ECF at sites of cancer due to the enhanced permeability of albumin at these sites(i.e.,enhanced permeability and retention effect).This allows the MAD-PSA detonated grenades to circulate throughout the body in a non-toxic *** within sites of mCRPC is there a sufficiently high level of enzymatically active PSA to efficiently“pull the pin”on the grenades releasing their lipophilic cellpenetrant toxins from ***,if a sufficient level of“detonation”occurs,this will kill mCRPC cells,and sterilize the entire PSA-rich metastatic sites via a bystander *** this review,two

关键词： Albumin-linked prodrug Maleimide coupled albumin delivery Thapsigargin Niclosamide

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