Non-canonical role of Hippo tumor suppressor serine/threonine kinase 3 STK3 in prostate cancer

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Synthesis and automated fluorine-18 radiolabeling of new PSMA-617 derivatives with a CuAAC radiosynthetic approach

In the last decade, the development of new radiopharmaceuticals for the imaging and therapy of prostate cancer has been a highly active and important area of research, especially focusing on the prostate-specific membrane antigen (PSMA), an antigen which is upregulated in prostate, as well as in other tumor cells. A large variety of PSMA ligands have been radiolabeled, to date. Among the various derivatives, PSMA-617 resulted to be one of the most interesting in terms of interaction with the antigen and clinical properties, and its lutetium-177 labeled version has recently been approved by regulatory agencies for therapeutic purposes. For this reasons, the radiolabeling with fluorine-18 of a PSMA-617 derivative might be of interest. Beside other methodologies to radiolabel macromolecules with fluorine-18, the “click-chemistry” approach resulted to be very useful, and the copper-catalyzed azide-alkyne cycloaddition (CuAAC) is considered one of most efficient and reliable. This paper proposes the synthesis of a suitable precursor for the radiolabeling with fluorine-18 of a new PSMA-617 derivative. The whole radiosynthetic procedure has been fully automated, and the final product, which proved to be stable in plasma, has been obtained with radiochemical yield and purity suitable for subsequent preclinical studies.     

Minimally Invasive Treatments for Benign Prostatic Hyperplasia: Systematic Review and Network Meta-Analysis

PurposeTo review and to compare indirectly the outcomes of minimally invasive therapies for the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia.Materials and MethodsA literature search via Medline and Cochrane Central databases was completed for randomized control studies published between January 2000 to April 2020 for the following therapies: Rezum, Urolift, Aquablation, and prostatic artery embolization (PAE). Data on the following variables were included: International prostate symptom score (IPSS), maximum urinary flow rate, quality of life, and postvoid residual (PVR). Standard mean differences between treatments were compared through a meta-analysis using transurethral resection of the prostate (TURP) to assess differences in treatment effect.ResultsThere was no significant difference in outcomes between therapies for IPSS at the 3, 6, and 12-month follow ups. Although outcomes for Rezum were only available out to 3 months, there were no consistently significant differences in outcomes when comparing Aquablation versus PAE versus Rezum. TURP PVR was significantly better than Urolift at 3, 6, and 12 months. No significant differences in minor or major adverse events were noted.ConclusionAlthough significant differences in outcomes were limited, Aquablation and PAE were the most durable at 12 months. PAE has been well studied on multiple randomized control trials with minimal adverse events while Aquablation has limited high quality data and has been associated with bleeding-related complications.     

Metastasis-directed Therapy in Prostate Cancer: Prognostic Significance of the ESTRO/EORTC Classification in Oligometastatic Bone Disease

AimsOligometastatic disease (OMD) represents a spectrum of clinical scenarios and various classification systems have been proposed. Bone-only OMD can occur in patients with advanced prostate cancer and validated decision-making tools are needed to assist patient selection for metastasis-directed therapy. The aim of the present study was to determine the prognostic utility of a classification system for OMD.Materials and methodsA retrospective review was conducted of all patients with bone-only oligometastatic prostate cancer treated with stereotactic body radiotherapy (SBRT) since November 2011. SBRT was delivered using CyberKnife® and gantry-based linear accelerator platforms. All patients were classified into oligometastatic states based on the European Society for Radiotherapy and Oncology/European Organisation for Research and Treatment of Cancer (ESTRO/EORTC) classification system. Kaplan–Meier and Cox regression analyses were carried out to determine the prognostic utility of this classification system.ResultsIn total, 105 patients with 145 osseous metastases were treated over 119 sessions. The median follow-up after SBRT was 23 months (interquartile range 10–39.8). Twelve patients had died after a median time of 31 months. The 3-year metastatic progression-free survival was 23% (95% confidence interval 13–32) and the 3-year overall survival was 88% (95% confidence interval 80–96). Patients in a metachronous oligometastatic state were 4.50 (95% confidence interval 1.19–17.10, P = 0.03) times more likely to experience metastatic progression compared with those with synchronous oligometastases, and 6.69 (95% confidence interval 1.05–42.50, P = 0.04) times more likely to experience any failure. Hazard ratio magnitudes increased for patients in a repeat oligometastatic state. The multivariate model for both metastatic progression-free survival and failure-free survival found prostate-specific antigen doubling time <4 months (P = 0.002; P = 0.05) to independently predict for progression.ConclusionThe ESTRO/EORTC classification of OMD predicts for progression in patients treated with SBRT for bone-only oligometastatic prostate cancer at our institution. Further validation in prospective series over multiple tumour sites is needed. These characterisation factors should be assessed in patients considered for metastasis-directed therapy together with established prognostic features.     

Brachytherapy: An emblematic example of extreme hypofractionated regimen

In order to provide more convenient irradiation regimens for patient comfort, radiation facility organization and health expenses, new hypofractionated protocols have been evaluated. Moderately (dose/fraction: 2.3 to 3 Gy), then ultra (dose/fraction: 5.2 to 6.1 Gy) hypofractionated irradiations were first validated. The current question is: is it possible to go forward using extreme hypofractionated regimens (EHR) based on 1 to 3 fractions. Different irradiation techniques are under investigation. However, brachytherapy remains the smartest way to deliver a high dose in a small volume. We report prospective and retrospective study results which evaluated EHR for breast and prostate brachytherapy. While oncological outcome and toxicity profile appear extremely encouraging for low-risk breast cancer after a 1 to 4 fractions (6.25 to 20 Gy/fraction), the use of a single fraction of 19 to 23 Gy appears debatable for prostate cancer. Brachytherapy represents an emblematic example of EHR but longer follow-up and more mature results are awaited in order to specify the right indications and refine the EQD2 calculation method including new biological and technical factors.     

PSMA-CAR-CIK转基因细胞体外杀伤三种前列腺癌细胞株效率的研究北大核心

目的:本研究通过检测前列腺特异性膜抗原(prostate specific membrane antigen,PSMA)-肿瘤特异性嵌合抗原受体(chimeric antigen receptor,CAR)-细胞因子诱导的杀伤细胞(cytokine induced killer cell,CIK)转基因细胞杀伤三种前列腺癌细胞株的效率,鉴定其用于后期治疗前列腺癌的可行性。方法:通过已经构建的二代PSMA-CAR慢病毒表达载体转染CIK细胞,构建PSMA-CAR-CIK转基因细胞;通过CCK8法检测CIK细胞及PSMA-CAR-CIK转基因细胞杀伤三种前列腺癌细胞株PC3、LNCaP、DU145的效率及效靶比。结果:转基因PSMA-CAR-CIK细胞构建成功;3 h~3.5 h为检测效应细胞对靶细胞细胞毒活性时与CCK8试剂孵育的最佳时间;两种效应细胞均在效靶比为10∶1、15∶1、20∶1时,杀伤率逐步增高,无统计学意义(P>0.05),但与其它组相比差异显著(P<0.05)。结论:两种效应细胞对于前列腺癌细胞的杀伤,只要效靶比达到10∶1的比例,就能起到一个较好的杀瘤效果,并且随着效应细胞的增加,其抗肿瘤能力逐步加强;转基因PSMA-CAR-CIK细胞的构建为CAR技术治疗前列腺癌的临床应用奠定了基础。     

前列腺癌早期诊断的研究进展北大核心

前列腺癌(prostate cancer, PCa)是中老年男性常见恶性肿瘤之一,目前尚缺乏有效的晚期癌症治疗方法,因此早期诊断对于降低PCa死亡率至关重要。近年来,较多研究开发出多种新型诊断方法以改善对PCa诊断的准确性,同时避免过度诊疗,但其有效性及实用性尚需进一步验证。本文对目前新型生物标志物、联合成像技术及风险预测模型等的早期诊断技术进行总结,以期为临床研究提供指导作用。