Disease burden and mortality forecast of prostate cancer in Wuhan in 2010-2019 / 公共卫生与预防医学

Objective To analyze the data of prostate cancer in Wuhan from 2010 to 2019, understand the characteristics and trends of incidence, mortality, and YLL, and provide decision-making basis for Wuhan's cancer prevention and control strategies. Methods Data on deaths and incident cases of prostate cancer in Wuhan from 2010 to 2019 and from 2013 to 2017, respectively, were collected from the Wuhan Death Monitoring System. Indicators such as incidence rate, mortality rate, and years of life lost due to premature death (YLL) of prostate cancer in Wuhan were calculated using Excel 2016 and Python. The Bayesian Age-Period-Cohort Model (BAPC) was used to predict the mortality rate of prostate cancer in Wuhan from 2020 to 2024. The trend changes were described using the annual average percentage change (AAPC). Results From 2010 to 2019, the incidence, mortality, and YLL rates of prostate cancer in Wuhan showed an overall increasing trend (AAPC >0, P <0.05). The standardized mortality and incidence rates in the central urban area were significantly higher than those in the outer urban area, and the age group of 85 and above had the highest incidence and mortality rates. The age group of 0-54 had the largest increase in incidence and mortality rates. From 2020 to 2024, prostate cancer in Wuhan is expected to continue to increase slightly (an increase of 0.94%). Conclusion The incidence, mortality, and YLL rates of prostate cancer in Wuhan are showing an overall increasing trend, and this trend may continue. The characteristics are higher in the central urban area than in the outer urban area, and higher in the older age group than in the younger age group. Targeted measures need to be taken, and screening for high-risk populations should be strengthened.

Clinical Efficacy of Qingxin Zishen Decoction on Hot Flashes After Endocrine Therapy for Prostate Cancer and Its Preliminary Mechanism / 中国实验方剂学杂志

ObjectiveTo observe the clinical effect of Qingxin Zishen decoction on hot flashes after endocrine therapy for prostate cancer and explore its therapeutic mechanism. MethodA total of 60 patients who met the criteria and were admitted to Jiangsu Province Hospital of Chinese Medicine from December 2021 to December 2022 were collected and randomly divided into a treatment group and a control group， with 30 cases in each group. The treatment group was treated with Qingxin Zishen decoction， while the control group was only given routine nursing. The observation period of this study was eight weeks. The improvement of hot flash frequency， hot flash degree， hot flash score， ISS score， and TCM syndrome score were observed in the two groups before and after treatment. The changes of serum endothelin-1 （ET-1）， nitric oxide （NO）， calcitonin gene-related peptide （CGRP）， prostate specific antigen （PSA）， and testosterone were detected. ResultIn terms of efficacy， after treatment， the frequency， degree， and score of hot flashes， ISS score， and TCM syndrome score decreased in the treatment group （P<0.05）. Compared with the control group， all indicators were better in the treatment group （P<0.05）. In terms of laboratory indicators， after treatment， the serum NO level in the treatment group was increased. ET-1 level was decreased. The ratio of ET-1/NO was decreased， and the CGRP level was decreased （P<0.05）. However， testosterone and PSA levels were not significantly changed . Compared with the control group， after treatment， the serum NO level in the treatment group was higher， and the level of ET-1 was lower. The ratio of ET-1/NO and the CGRP level were lower （P<0.05）. There were no significant differences in testosterone and PSA levels between the two groups. ConclusionQingxin Zishen decoction can significantly improve hot flashes in patients with prostate cancer after endocrine therapy. The mechanism of Qingxin Zishen decoction may be to improve the vasomotor function by regulating the expression level of vasomotor factors， so as to treat hot flashes.

Pharmacotherapy plan for metastatic hormone-sensitive prostate cancer：a network meta-analysis / 中国药房

OBJECTIVE To determine the optimal therapeutic plan for metastatic hormone-sensitive prostate cancer （mHSPC）， and to provide reference for clinical decision-making. METHODS Retrieved from Medline， Embase， BIOSIS preview， the Cochrane Library and ClinicalTrials. gov systematically， randomized controlled trials about mHSPC therapy， with overall survival （OS） and radiographic progression-free survival （rPFS） as efficacy outcomes and the incidence of serious adverse events （SAEs） as safety outcome， were collected during the inception-Mar. 2022. Two researchers independently screened the literature， extracted data， and evaluated the risk of bias for the included study before conducting a Bayesian network meta-analysis. RESULTS Eight studies with 9 437 patients were finally included. The effectiveness and safety of 7 therapy plans were compared [abiraterone acetate， apalutamide， darolutamide+docetaxel， docetaxel， enzalutamide， standard non-steroidal antiandrogen （SNA） in addition to ADT， and ADT alone]. In terms of efficacy index， the most beneficial regimen （except for ADT+SNA） for OS was ADT+darolutamide+docetaxel （HR＝0.54， 95%CI of 0.44-0.66）， followed by ADT+abiraterone acetate （HR＝0.64，95%CI of 0.57- 0.71）， apalutamide （HR＝0.65， 95%CI of 0.53-0.79）， enzalutamide （HR＝0.66， 95%CI of 0.53-0.82）； the least beneficial regimen for OS was ADT+docetaxel （HR＝0.79， 95%CI of 0.71-0.88）. The most beneficial regimen （except for ADT+SNA） for rPFS was ADT+enzalutamide （HR＝0.39， 95%CI of 0.30-0.50）， followed by ADT+apalutamide （HR＝0.48， 95%CI of 0.39- 0.60）， abiraterone acetate （HR＝0.57， 95%CI of 0.51-0.64）， docetaxel （HR＝0.62， 95%CI of 0.56-0.69）. The results of the tumor- loading subgroup analysis were the same. In terms of safety， ADT+darolutamide+docetaxel （OR＝25.86， 95%CI of 14.08-51.33）， and ADT+docetaxel （OR＝23.35， 95%CI of 13.26-44.81） were associated with markedly increased SAEs； the incidence of SAEs caused by ADT+abiraterone acetate （OR＝1.42，95%CI of 1.10-1.82） was slightly increased， and those of other therapy plans had no significant difference. CONCLUSIONS Compared with ADT alone， ADT+ darolutamide+docetaxel may provide the most significant OS benefit， but the incidence of SAEs is increased greatly； compared with ADT+docetaxel， ADT+abiraterone acetate， apalutamide or enzalutamide provide more OS benefits. ADT+enzalutamide provide optimal rPFS benefits with no increased SAEs.

circCPA4 induces malignant behaviors of prostate cancer via miR-491-5p/ SHOC2 feedback loop

ABSTRACT Objective: circCPA4 has been defined to be an oncogenic gene. This study examined whether circCPA4 regulates Prostate Cancer (PC) development and revealed its molecular mechanism. Methods: PC tissues and PC cell lines were collected, in which circCPA4/miR-491-5p/SHOC2 levels were evaluated by RT-qPCR and immunoblot. Colony formation assay and EdU assay assessed cell proliferation, flow cytometry measured apoptosis, and Transwell assessed invasion and migration. Ki-67, cleaved caspase-3, E-cadherin, and N-cadherin were evaluated by immunoblot. Based on the luciferase reporter assay and RIP assay the authors investigated the targeting relationship between circCPA4/miR-491-5p/SHOC2. The effect of circCPA4 on tumor growth was evaluated by xenotransplantation in nude mice. Results: circCPA4 and SHOC2 levels were abundant while miR-491-5p expression was low in PC. Loss of circCPA4 decreased the proliferation and EdU-positive rate of PC cells, enhanced apoptosis, and inhibited invasion, migration, and EMT. Upregulation of circCPA4 forced the malignant behaviors of PC cells, and this promotion could be abolished when miR-491-5p was overexpressed or SHOC2 was silenced. CircCAP4 competitively decoyed miR-491-5p mediating SHOC2 expression. circCAP4 suppression inhibited PC tumor growth. Conclusion: circCAP4 acts as a novel oncogenic factor in PC, accelerating the malignant behavior of PC cells via miR-491-5p/SHOC2 interaction. This novel ceRNA axis may be a potential target for PC drug development and targeted therapy in the future.

Hospitalization and mortality rates of malignant prostatic neoplasms in Brazil: A cross-sectional study from 2008 to 2018

Abstract Prostate cancer (PCa) is a highly prevalent condition among men worldwide, resulting in reduced quality of life and increased costs to health systems due to hospitalization and death. This study aimed to explore and understand the evolution of PCa in Brazil from 2008 to 2018. Data were obtained from the National Health System Department of Informatics (DATASUS) using code C61 for malignant prostatic neoplasms. We presented the hospitalization and mortality rates in a temporal-, regional- and age-dependent manner. From 2008 to 2018, a year-dependent increase in hospital admissions due to PCa was reported in Brazil, in which the Southeast region showed the highest prevalence. Men aged ≥80 and those 70-79 years old had similar hospitalization rates, followed by men aged 60-69, 50-59, 40-49 and 30-39 years old. Similarly, an increase in deaths due to PCa was reported during this period, with the highest rates seen in the Southeast. Men aged ≥80 years had higher mortality rates, followed by those aged 70-79, 60-69, 50-59, 40-49 and 30-39 years old. The results obtained indicate an age- and region-dependent increase in PCa morbidity and mortality in Brazil overtime and may contribute to the ongoing discussion on the role and future perspective of the health care system in Brazil.

Application of Magnetic Resonance Imaging and Transrectal Ultrasound Image Fusion Targeted Transperineal Biopsy Technique Using Electromagnetic Needle Tracking Under Local Anaesthesia / 肿瘤防治研究

Objective To explore the effect and safety of magnetic resonance imaging and transrectal ultrasound (mpMRI-TRUS) image fusion targeted transperineal biopsy technique using electromagnetic needle tracking under local anesthesia. Methods We retrospectively analyzed the clinical and pathological data of 81 patients with mpMRI-TRUS image fusion targeted transperineal prostate biopsy using electromagnetic needle tracking under local anesthesia. Visual analog scale (VAS) and visual numeric scale (VNS) were used to evaluate the pain level and satisfaction of patients during prostate biopsy (VAS-1 and VNS-1), one hour after puncture (VAS-2 and VNS-2), and one day after surgery (VAS-3 and VNS-3). The perioperative clinical data and tumor positive rate of postoperative biopsy were recorded. Results The average prostate volume of 81 patients was 53.39±29.46 cm3. The PSA values of patients with PI-RADS scores of 2, 3, 4, and 5 were 9.14±2.31, 9.95±4.10, 14.77±6.36, and 32.17±24.39 ng/ml, respectively. The scores of VAS-1, VAS-2, and VAS-3 were 1.70±0.73, 1.16±0.58, and 0.53±0.55, respectively; the scores of VNS-1, VNS-2, and VNS-3 were 2.74±0.44, 3.69±0.46, and 3.84±0.37, respectively. The average surgical time was 17.47±3.44 minutes. Postoperative pathological results showed that the tumor positive rate of targeted prostate biopsy was 64.20%. According to the PI-RADS score for subgroup analysis, the tumor positive rates of patients with PI-RADS scores of 2, 3, 4, and 5 were 21.43%, 44.44%, 61.11%, and 96.77%, respectively. After transperineal prostate biopsy, gross hematuria occurred in 19.75% patients, and urinary retention occurred in 3.70%. The latter were relieved after symptomatic treatment. All patients did not experience complications, such as perineal puncture area hematoma, urinary tract infection, hematospermia, hematoma in perineal puncture area, urinary tract infection, hematospermia, vagus nerve reaction, or septic shock. Conclusion For suspected prostate cancer patients, mpMRI-TRUS image fusion targeted transperineal biopsy technique using electromagnetic needle tracking under local anesthesia is a feasible and easily tolerated surgical procedure. It has good safety and high tumor positive-detection rate, indicating that this technique is worthy of further clinical promotion and application.

Casual Association Between Coffee Intake and Prostate Cancer Based on Two-sample Mendel Randomization / 肿瘤防治研究

Objective To assess the causal relationship between coffee intake and prostate cancer risk by using the two-sample Mendel randomization (MR) method. Methods The genome-wide association study (GWAS) data on coffee intake (exposure) and prostate cancer (outcome) were obtained from two independent data sets in UK Biobank. The inverse variance weighted method (IVW), weighted median estimator method (WME), and MR-Egger method were used for MR analyses. The OR value and 95%CI were used to represent the association between coffee intake and prostate cancer. In addition, the MR-Egger method was performed for pleiotropic and heterogeneity tests, and the leave-one-out method was used for sensitivity analysis. Results A total of 38 SNP were selected as instrumental variables. The IVW method showed that coffee intake might reduce the risk of prostate cancer (OR=0.994; 95%CI: 0.990-0.999; P=0.009). The WME method obtained the same conclusions (OR=0.991; 95%CI: 0.985-0.999; P=0.018), but MR-Egger regression did not find a causal relationship between coffee intake and prostate cancer (OR=0.992; 95%CI: 0.983-1.000; P=0.084). The MR-Egger method showed no pleiotropy (intercept=4.2E-5; P=0.581) or heterogeneity (Q=27.20; P=0.854) among the instrumental variables. The sensitivity analysis indicated that the conclusion was robust. Conclusion Two-sample Mendel randomization analysis reveals that coffee consumption might reduce the risk of prostate cancer.

Correlation Between Wnt5a Expression and Vasculogenic Mimicry in Prostate Cancer Tissues / 肿瘤防治研究

Objective To investigate the correlation of Wnt5a expression and vasculogenic mimicry (VM) in prostate cancer tissues, and analyze their relationships with cancer stem cells (CSCs) characteristics and epithelial–mesenchymal transition (EMT). Methods Immunohistochemistry was conducted to detect the expression of Wnt5a in 50 prostate cancer tissues and 50 benign prostatic hyperplasia tissues. The expression levels of CD133, vimentin, and E-cadherin were detected in the prostate cancer tissues, and CD34/PAS double staining was used to detect VM structures. We analyzed the difference in Wnt5a level between prostate cancer and benign prostatic hyperplasia tissues, the clinical significance of Wnt5a and VM, the relationship of Wnt5a expression and VM, and the relationships of Wnt5a expression and VM with CD133, Vimentin, E-cadherin. Results The expression of Wnt5a was significantly higher in prostate cancer tissues than in benign prostatic hyperplasia (P < 0.05). A positive correlation was observed between Wnt5a expression and VM (P < 0.05). The expression levels of Wnt5a and VM were positively correlated with those of CD133 and vimentin (P < 0.05). Wnt5a expression and VM were positively correlated with Gleason score, vas deferens invasion and lymphatic metastasis (P < 0.05) of prostate cancer, and VM was also positively correlated with T stage of prostate cancer (P < 0.05). Conclusion The expression level of Wnt5a in prostate cancer tissues is elevated and positively related with VM formation. Wnt5a expression and VM are correlated with cancer stem cells characteristics and the expression of epithelial–mesenchymal transition marker proteins.

Outcomes of Salvage Robotic-assisted Radical Prostatectomy in the last decade: systematic review and perspectives of referral centers

ABSTRACT Purpose: Salvage robotic-assisted radical prostatectomy (S-RARP) has gained prominence in recent years for treating patients with cancer recurrence following non-surgical treatments of Prostate Cancer. We conducted a systematic literature review to evaluate the role and outcomes of S-RARP over the past decade. Materials and Methods: A systematic review was conducted, encompassing articles published between January 1st, 2013, and June 1st, 2023, on S-RARP outcomes. Articles were screened according to PRISMA guidelines, resulting in 33 selected studies. Data were extracted, including patient demographics, operative times, complications, functional outcomes, and oncological outcomes. Results: Among 1,630 patients from 33 studies, radiotherapy was the most common primary treatment (42%). Operative times ranged from 110 to 303 minutes, with estimated blood loss between 50 to 745 mL. Intraoperative complications occurred in 0 to 9% of cases, while postoperative complications ranged from 0 to 90% (Clavien 1-5). Continence rates varied (from 0 to 100%), and potency rates ranged from 0 to 66.7%. Positive surgical margins were reported up to 65.6%, and biochemical recurrence ranged from 0 to 57%. Conclusion: Salvage robotic-assisted radical prostatectomy in patients with cancer recurrence after previous prostate cancer treatment is safe and feasible. The literature is based on retrospective studies with inherent limitations describing low rates of intraoperative complications and small blood loss. However, potency and continence rates are largely reduced compared to the primary RARP series, despite the type of the primary treatment. Better-designed studies to assess the long-term outcomes and individually specify each primary therapy impact on the salvage treatment are still needed. Future articles should be more specific and provide more details regarding the previous therapies and S-RARP surgical techniques.

Humoral and Cellular Immunology in Human Prostate Cancer: Plasma Cells and T and B Lymphocytes / Inmunología Humoral y Celular en el Cáncer de Próstata Humano: Células Plasmáticas y Linfocitos T y B

SUMMARY: In solid and malignant tumors, innate and adaptive immunity are combined in antitumor responses. This study aimed to analyze the activation of plasma cells and the correlation between the infiltration of B and T lymphocytes with the degree of malignancy or Gleason grade in human prostate biopsies diagnosed with cancer. Prostate cancer biopsies were obtained from the Clinical Hospital of Universidad de Chile (n=70), according to the bioethical norms of the institution. Histological sections of 5µm thickness were processed for immunohistochemistry with primary antibodies against BL and total TL (HRP/DAB). Recognition and quantification were performed under a Leica DM750 optical microscope. Microsoft Excel and GraphPad software were used for the statistical study. Correlation coefficient (Pearson) and mean comparison tests (Kruskal-Wallis and Dunn) and p≤ 0.05 were developed. B and T lymphocyte populations were inversely interregulated in prostate cancer (Gleason) (r= -0.46). Their relationship with Gleason grade is variable according to lymphocyte type (LB vs. Gleason r= -0.0.47 and LT vs. Gleason r= -0.21). Histological diagnosis of prostate cancer correlates with a predominance of LT. The malignancy of the pathology correlates with a predominance of LTs, according to the Gleason grade. The increased knowledge of B and T lymphocyte infiltration and plasma cell activation could be used to better target clinical trials on treatments based on immune system responses. Immunotherapy could be a new paradigm to apply better antitumor therapy strategies.

En tumores sólidos y malignos, la inmunidad innata y adaptativa se combinan en respuestas antitumorales. Este estudio tuvo como objetivo analizar la activación de células plasmáticas y la correlación entre la infiltración de linfocitos B y T con el grado de malignidad o grado de Gleason en biopsias de próstata humana diagnosticadas con cáncer. Las biopsias de cáncer de próstata se obtuvieron del Hospital Clínico de la Universidad de Chile (n=70), de acuerdo con las normas bioéticas de la institución. Secciones histológicas de 5 µm de espesor fueron procesadas para inmunohistoquímica con anticuerpos primarios contra LB y LT total (HRP/DAB). El reconocimiento y las cuantificaciones se realizaron bajo un microscopio óptico Leica DM750. Para el estudio estadístico se utilizaron los programas Microsoft Excel y GraphPad. Se desarrollaron pruebas de coeficiente de correlación (Pearson) y comparación de medias (Kruskal-Wallis y Dunn) y p≤ 0.05. Los resultados muestran que las poblaciones de linfocitos B y T están inversamente interreguladas en el cáncer de próstata (r= -0,4578). Su relación con el grado de Gleason es variable según el tipo de linfocito (LB vs Gleason r= -0,47* y LT vs Gleason r= -0,21). Se concluye que la malignidad del cáncer de próstata se correlaciona con un predominio de LT, versus el grado de Gleason. El mayor conocimiento de la infiltración de linfocitos B y T y la activación de células plasmáticas podría aprovecharse para una mejor orientación de ensayos clínicos en tratamientos basados en las respuestas del sistema inmunitario. La inmunoterapia podría ser un nuevo paradigma para aplicar mejores estrategias de terapias antitumorales.

Factores pronósticos de metástasis ósea en pacientes con cáncer de próstata / Predictive factors for bone metastasis in patients with prostate cancer i: en

El adenocarcinoma de próstata es considerado una de las neoplasias más frecuentes en hombres mayores de 60 años, y su metástasis ósea constituye una de las complicaciones de peor pronóstico. Objetivo: Estimar los factores pronósticos de metástasis ósea en pacientes con cáncer de próstata. Métodos: Se realizó un estudio analítico de 73 pacientes con cáncer de próstata, asistidos en el Hospital Oncológico Conrado Benítez de Santiago de Cuba en el período 2018-2022. Entre las variables analizadas figuraron: edad, color de la piel, manifestaciones clínicas, tiempo de aparición de la metástasis ósea, grado de diferenciación celular, nivel de antígeno prostático específico y diagnóstico imagenológico. Resultados: En la serie predominó el grupo etario de 60-69 años (50,7 %) y el promedio de edad fue de 67 años; asimismo, prevalecieron los pacientes de piel negra, el dolor óseo como síntoma más frecuente y el diagnóstico imagenológico de metástasis ósea por tomografía axial computarizada (48,0 %). Se observó un aumento proporcional de los valores del antígeno prostático específico y de la puntuación de Gleason en relación con la aparición de metástasis. Conclusiones: Los factores pronósticos que permiten estimar la presencia de metástasis ósea en pacientes con cáncer de próstata son la edad avanzada, el color negro de la piel y los valores de antígeno prostático específico por encima de 20 ng/mL.

Prostate adenocarcinoma is considered one of the most frequent neoplasms in men over 60 years, and bone metastasis constitutes one of the complications with the worst prognosis. Objective: Estimate the predictive factors for bone metastasis in patients with prostate cancer. Methods: An analytic study of 73 patients with prostate cancer was carried out. They were assisted at Conrado Benítez Cancer Hospital in Santiago de Cuba during 2018-2022. The variables analyzed included: age, skin color, clinical manifestations, onset time of bone metastasis, degree of cellular differentiation, prostate-specific antigen level and imaging diagnosis. Results: In the series there was a prevalence of the 60-69 age group (50.7%) and the average age was 67 years; also, dark skinned patients, bone pain as more frequent symptom and imaging diagnosis of bone metastasis by computerized axial tomography prevailed (48.0%). A proportional increase of prostate-specific antigen values and Gleason punctuation was observed in relation to the metastasis onset. Conclusions: The predictive factors for estimating the presence of bone metastasis in patients with prostate cancer are the advanced age, black skin color and prostate-specific antigen values above 20 ng/mL.

Controversias en radioterapia adyuvante en cáncer de próstata localizado

La elección del momento más adecuado para realizar radioterapia en el tratamiento del cáncer de próstata es controversial ya que puede ser realizada inmediatamente posterior a la prostatectomía o como tratamiento de rescate ante una recaída. En este artículo, se realiza una búsqueda del tema, se seleccionan los ensayos clínicos con mayor evidencia y se analizan los resultados. Si bien existe beneficio en la radioterapia adyuvante, este resultado no se encuentra en todos los pacientes y sí se asocia a mayor toxicidad genitourinaria tardía, por lo tanto, la clave está en la selección del tratamiento según el paciente específico.

The choice of the most appropriate time to perform radiotherapy in the treatment of prostate cancer is controversial since it can be performed immediately after prostatectomy or as rescue treatment in case of relapse. In this article, a search for the topic is carried out, the clinical trials with the greatest evidence are selected and the results are analyzed. Although there is benefit in adjuvant radiotherapy, this result is not found in all patients and it is associated with greater late genitoutinary toxicity, therefore, the key is in the selection of treatment according to the specific patient.

Prostatectomía radical citorreductora comparado a no realizar tratamiento local en pacientes con cáncer de próstata metastásico / Cytoreductive radical prostatectomy versus no local treatment in patients with metastatic prostate cancer

Introducción El cáncer de próstata es uno de los cánceres más frecuentes en Chile, con 8157 nuevos casos en 2020. A nivel mundial, 5 a 10% de los hombres presentan metástasis al diagnóstico, y la terapia de deprivación androgénica con o sin quimioterapia es el estándar de cuidado para estos pacientes. El uso de tratamiento local en este contexto tiene una recomendación formal debido a la falta de evi-dencia de alta calidad. Algunos estudios retrospectivos han intentado dilucidar el beneficio de la cirugía sobre el tumor primario en el contexto de la enfermedad metastásica, ya que se ha demostrado que es un tratamiento local eficaz para otras neoplasias metastá-sicas. A pesar de estos esfuerzos, el beneficio de la prostatectomía radical citorreductora como tratamiento local en estos pacientes sigue sin estar claro. Métodos Se realizó una búsqueda en Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, que se mantiene mediante el cribado de múltiples fuentes de información, incluyendo MEDLINE, EMBASE y Cochrane, entre otras. Se extrajeron los datos de las revisiones sistemáticas, se volvieron a analizar los datos de los estudios primarios, se realizó un metanálisis y se generó una tabla de resumen de resultados utilizando el enfoque GRADE. Resultados y conclusiones Se identificaron 12 revisiones sistemáticas, que incluían siete estudios primarios en total, ninguno de los cuales era un ensayo alea-torizado controlado. Sólo seis de esos siete estudios primarios se utilizaron en el resumen de resultados. A pesar de la falta de evi-dencia de alta calidad, los resultados de este resumen muestran los beneficios de realizar la cirugía en el tumor primario en términos de mortalidad por cualquier causas, mortalidad específica por cáncer y progresión de la enfermedad. También se observó un bene-ficio potencial en las complicaciones locales relacionadas con la progresión del tumor primario, lo que apoya la realización de esta intervención en pacientes con enfermedad metastásica. La ausencia de recomendaciones formales subraya la necesidad de evaluar los beneficios de la cirugía caso por caso, presentando la evidencia disponibles a los pacientes para un proceso de toma de decisiones compartido, teniendo en cuenta las futuras complicaciones locales que podrían ser difíciles de manejar.

Introduction Prostate cancer is one of the most frequent cancers in Chile, with 8157 new cases in 2020. Worldwide, 5 to 10% of men have metastatic disease at diagnosis, and androgen deprivation therapy with or without chemotherapy is the standard of care for these patients. The use of local treatment in this setting has no formal recommendation due to the lack of high- quality evidence. Some retrospective studies have sought to elucidate the benefit of surgery on the primary tumor in the setting of metastatic disease since it has been proven to be an effective local treatment for other metastatic malignant diseases. Despite these efforts, the benefit of cytoreductive radical prostatectomy as local treatment in these patients remains unclear. Methods We searched Epistemonikos, the largest database of systematic reviews in health, which is main-tained by screening multiple information sources, including MEDLINE, EMBASE, and Cochrane, among others. We extracted data from systematic reviews, reanalyzed data from primary studies, conducted a meta- analysis, and generated a summary results table using the GRADE approach. Results and conclusions We identified 12 systematic reviews, including seven studies in total, none of which was a trial. Only six of those seven primary studies were used in the results summary. Despite the lack of high- quality evidence, the results summary shows the benefits of performing surgery on the primary tumor in terms of all- cause mortality, cancer- specific mortality, and disease progression. There was also a potential benefit in local complications related to the progression of the prima-ry tumor, supporting the implementation of this intervention in patients with metastatic disease. The absence of formal recommendations highlights the need to evaluate the benefits of surgery on a case- by- case basis, presenting the available evidence to patients for a shared decision- making process and considering future local complications that could be difficult to manage.

Effects of Xihuang Pills on proliferation and apoptosis of prostate cancer LNCaP cells based on AR/m TOR signaling pathway / 中国中药杂志

Based on the androgen receptor(AR)/mammalian target of rapamycin(mTOR)signaling pathway, the effects of Xihuang Pills-medicated serum on the proliferation and apoptosis of prostate cancer LNCaP cells were investigated. The drug-containing serum of SD rats was prepared by intragastric administration of Xihuang Pills suspension. The effects of low-, medium-, and high-dose Xihuang Pills-containing serum on the in vitro proliferation of LNCaP cells were detected by cell counting kit-8(CCK-8). Flow cytometry was used to detect the apoptosis level of LNCaP cells after intervention with different concentrations of Xihuang Pills. Protein expression of cleaved cysteinyl aspartate-specific proteinase caspase-3(cleaved caspase-3), B-cell lymphoma-2(Bcl-2), and AR as well as the phosphorylation level of mTOR protein were detected by Western blot. The results showed that compared with the blank serum, the drug-medicated serum could blunt the activity of LNCaP cells. Low-, medium-, and high-dose Xihuang Pills-containing serum could significantly increase the cell apoptosis rate, increase the expression of cleaved caspase-3 protein, decrease the expression of Bcl-2 protein, reduce the expression of AR protein, and down-regulate the level of phosphorylated mTOR(p-mTOR). To study the effect of Xihuang Pills on the growth of LNCaP cells in vivo, different doses of Xihuang Pills were used to intervene in the subcutaneous graft model in nude mice inoculated with LNCaP cells. The expression levels of AR, mTOR, p-mTOR, Bcl-2, and cleaved caspase-3 were detected by Western blot. The results showed that the volumes of subcutaneous graft tumor in the low-dose, medium-dose, and high-dose Xihuang Pills groups significantly decreased compared with that in the model group. The weight of subcutaneous transplanted tumor in each group with drug intervention was significantly lower than that in the model group. Compared with the model group, the low-dose, medium-dose, and high-dose Xihuang Pills groups showed increased cleaved caspase-3 protein expression, decreased Bcl-2 and AR protein expression, and reduced p-mTOR protein expression. Further experiments showed that AR agonist R1881 could block the anti-proliferation and pro-apoptotic effects of Xihuang Pills. The mechanism of Xihuang Pills against prostate cancer is related to the inhibition of the AR/mTOR signaling pathway, inhibition of LNCaP cell proliferation, and induction of apoptosis in cancer cells.

Diagnostic Efficacy of 68Ga-Labeled Prostate-Specific Membrane Antigen and 18F-Labeled Sodium Fluoride PET/CT in Prostate Cancer With Bone Metastasis / 中国医学科学院学报

Objective To compare the efficiency of 68Ga-labeled prostate-specific membrane antigen (68Ga-PSMA-11) and 18F-labeled sodium fluoride (18F-NaF) PET/CT in the diagnosis of bone metastasis in the patients with prostate cancer.Methods The prostate cancer patients suspected of bone metastasis who underwent 68Ga-PSMA-11 PET/CT and 18F-NaF PET/CT from January 2018 to January 2021 were included in this study.The number of lesions,maximum standardized uptake value (SUVmax),and tumor-to-background (T/B) ratio were compared between the two methods.Results 18F-NaF PET/CT detected more metastases than 68Ga-PSMA-11 PET/CT (310 vs.264,P<0.001).The median SUVmax[23.2 (16.4,33.4) vs.4.1 (2.5,5.6)] and median T/B ratio[7.0 (4.9,9.9) vs.6.7 (3.7,9.6)] of 18F-NaF PET/CT were higher than those of 68Ga-PSMA-11 PET/CT (all P<0.001).With the number of lesions as the indicator,the sensitivity,specificity,accuracy,positive predictive value,and negative predictive value of 18F-NaF PET/CT were 100.0%,92.0%,92.0%,98.7%,and 100.0% respectively,and those of 68Ga-PSMA-11 PET/CT were 85.2%,94.0%,79.2%,98.9%,and 50.5%,respectively.Conclusion 18F-NaF PET/CT is superior to 68Ga-PSMA-11 PET/CT in the detection of bone metastases of prostate cancer.

Baicalin Antagonizes Prostate Cancer Stemness via Inhibiting Notch1/NF-κB Signaling Pathway / 中国结合医学杂志

OBJECTIVE@#To investigate the molecular mechanisms underlying the effect of baicalin on prostate cancer (PCa) progression both in vivo and in vitro.@*METHODS@#The in situ PCa stem cells (PCSCs)-injected xenograft tumor models were established in BALB/c nude mice. Tumor volume and weight were respectively checked after baicalin (100 mg/kg) treatment. Hematoxylin-eosin (HE) staining was used to observe the growth arrest and cell necrosis. mRNA expression levels of acetaldehyde dehydrogenase 1 (ALDH1), CD44, CD133 and Notch1 were determined by reverse transcription-polymerase chain reaction. Protein expression levels of ALDH1, CD44, CD133, Notch1, nuclear factor κB (NF-κB) P65 and NF-κB p-P65 were detected by Western blot. Expression and subcellular location of ALDH1, CD44, CD133, Notch1 and NF-κB p65 were detected by immunofluorescence analysis. In vitro, cell cycle distribution and cell apoptosis of PC3 PCSCs was assessed by flow cytometry after baicalin (125 µmol/L) treatment. The migration and invasion abilities of PCSCs were assessed using Transwell assays. Transmission electron microscopy scanning was utilized to observe the structure and autophagosome formation of baicalin-treated PCSCs. In addition, PCSCs were infected with lentiviruses expressing human Notch1.@*RESULTS@#Compared with the control group, the tumor volume and weight were notably reduced in mice treated with 100 mg/kg baicalin (P<0.05 or P<0.01). Histopathological analysis showed that baicalin treatment significantly inhibited cell proliferation and promoted cell apoptosis. Furthermore, baicalin treatment reduced mRNA and protein expression levels of CD44, CD133, ALDH1, and Notch1 as well as the protein expression of NF-κB p-P65 in the xenograft tumor (P<0.01). In vitro, the cell proliferation of PCSCs was significantly attenuated after treatment with 125 µmol/L baicalin for 72 h (P<0.01). The cell migration and invasion rates were decreased following treatment with baicalin for 48 and 72 h (P<0.01). Baicalin notably induced cell apoptosis and seriously damaged the structure of PCSCs. The mRNA and protein expressions of CD133, CD44, ALDH1 and Notch1 in PCSCs were significantly downregulated following baicalin treatment (P<0.01). Importantly, the inhibitory effects of baicalin on PCa progression and stemness were reversed by Notch1 overexpression (P<0.05 or P<0.01).@*CONCLUSION@#Mechanistically, baicalin exhibited a potential therapeutic effect on PCa via inhibiting the Notch1/NF-κB signaling pathway and its mediated cancer stemness.

Development and validation of a predictive model for the risk of positive after transperineal ultrasound-guided prostate biopsy / 中华泌尿外科杂志

Objective:To develop a nomogram to predict the probability of prostate cancer after transeperineal prostate biopsy, and verify the diagnostic efficacy and clinical applicable value of the model.Methods:The clinicopathologic data of 475 patients who underwent prostate biopsy at Yijishan Hospital of Wannan Medical College between January 2019 to August 2021 were retrospectively reviewed. Of all the patients, 367 patients from January 2019 to December 2020 were in the development cohort and 108 patients from January 2021 to August 2021 were in the validation cohort. Patients in the development cohort were (68.86±9.00) years old. The tPSA level was 13.6(8.6, 23.3)ng/ml, and Prostate Imaging Reporting and Data System (PI-RADS) score was 4(3, 4) points. Patients in the validation cohort were (68.89±8.67) years old. The tPSA was 13.1(8.7, 25.6)ng/ml, and PI-RADS score was 4 (3, 5) points. Univariate and multivariate logistic regression were used to analyze prostate cancer risk factors in the development cohort. Then the nomogram prediction model was established by the risk factors. The prediction model's performance was evaluated using receiver operating characteristic (ROC) curves, calibration maps, and decision curve (DCA) analysis in the development cohort. The performance of the model was verified in the validation cohort.Results:The pathological results showed 180 patients with prostate cancer and 187 patients without prostate cancer in the development cohort. The validation cohort included 53 patients with and 55 without prostate cancer. Based on the results of the univariate and multivariate logistic regression analysis, this model incorporates factors including age ( OR=1.059, P=0.003), platelet-to-monocyte ratio (PMR) ( OR=0.002, P=0.011), f/tPSA ( OR=0.009, P=0.020), and PI-RADS score ( OR= 3.076, P<0.001). The calibration curve revealed a great agreement. Internal validation of the nomogram showed that the area under the ROC curve was 0.845 (95% CI 0.794-0.895). The Hosmer-Lemeshow test was also performed( χ2=1.476, P=0.224). The validation group with an area under the ROC curve was 0.869 (95% CI 0.797-0.941). The results of the decision curve analysis indicated that the decision curve was located above the positive and negative lines in the threshold range of 10% to 90%, within which the model has clinical application. Conclusions:The nomogram, which combines patient age, PMR, f/t PSA, and PI-RADS scores, has high predictive efficacy for prostate cancer and has clinical application value.

Function and regulatory mechanism of androgen receptor variant 7 in castration resistant prostate cancer / 中华泌尿外科杂志

Androgen receptor (AR) plays a key regulatory role in the development of castration resistant prostate cancer (CRPC), and the level of constitutive active variants represented by androgen receptor variant 7 (AR-V7) is increasing during the progress of CRPC, which can be used as a molecular marker of disease progress and prognosis of patients with CRPC. It is an important target to overcome castration resistance and improve the quality of life and survival of patients. In this paper, the function of AR-V7 and its molecular regulation mechanism in CRPC are reviewed. The research shows that the generation of AR-V7 is related to the structural rearrangement of AR gene, gene amplification and the selective splicing of AR gene transcripts, and it is affected by the coordinated regulation of multiple signal pathway molecules such as TGF-β; AR-V7 changes the transport and nuclear localization mechanism of AR protein, and further affects the transcriptional expression of downstream target genes. AR-V7 antagonizes AR activity and blocks the differentiation process driven by AR and androgen, and inhibits the expression of tumor suppressor genes to stimulate the proliferation of tumor cells, thus promoting the progress of Pca. Related targeting studies have revealed AR-V7 targets and CRPC treatment strategies. Currently, they mainly focus on AR-V7 protein degradation, mRNA expression inhibition and N-terminal domain targeting intervention. With the development of in-depth research, the molecular mechanism of AR-V7 in the progress of Pca will be gradually clarified, which will certainly play a greater role in the prevention and treatment of CRPC.

Research progress of radiation therapy for oligo-metastatic prostate cancer / 中华泌尿外科杂志

In this report, we have reviewed the research progress in the involvement, efficacy and prediction of biomarkers of radiotherapy in oligo-metastatic prostate cancer. According to the timing of metastasis, oligo-metastases can be divided into four categories: de-novo oligo-metastasis, oligo-recurrence, oligo-progression and oligo-persistence. The use of radiotherapy in oligo-metastases of prostate cancer is becoming more and more important, which can be used not only for primary radiotherapy in newly diagnosed oligo-metastasis patients, but also for metastatic radiotherapy in oligo-recurrence patients. In addition, studies are trying to conduct full coverage of primary and metastatic radiotherapy for 4 types of oligometastases.

The efficacy analysis of moderately hypofractionated IMRT combined with androgen deprivation therapy for locally advanced prostate cancer / 中华放射医学与防护杂志

Objective:To investigate the efficacy and adverse reactions of moderately hypofractionated intensity modulated radiation therapy (IMRT) combined with androgen deprivation therapy (ADT) for locally advanced prostate cancer (LAPC).Methods:This study retrospectively analyzed the medical records of 40 LAPC patients who were admitted in The Second Hospital of Dalian Medical University during 2014-2020. The planning gross target volume (PGTV) dose for prostate gland and seminal vesicle gland was 64.8-70.0 Gy/25-28 f, 2.4-2.8 Gy/f and the dose of PGTVnd in 20 cases with positive pelvic lymph nodes was 60.0-64.4 Gy/25-28 f, 2.3-2.4 Gy/f. The dose of planning target volume (PTV) for the drainage area of pelvic lymph nodes was 45.0-50.4 Gy/25-28 f. The enrolled patients were treated with long-term ADT, including neoadjuvant, simultaneous, and adjuvant therapies. The efficacy and adverse reactions were evaluated. The prognostic factors affecting the biochemical failure-free survival (BFFS) were analyzed.Results:The median follow-up time was 31 months. The 2- and 3-year overall survival (OS) rates were 100% and 96.9%, respectively. The 1-, 2-, and 3-year BFFS rates were 90%, 76.8% and 72%, respectively. The 1-, 2-, and 3-year distant metastasis-free survival (DMFS) rates were 92.2%, 82.8% and 75.1%, respectively. Gleason (GS) score ( χ2=10.00, P < 0.05) and adjacent tissue invasion ( χ2=8.85, P<0.05) were prognostic factors related to BFFS for LAPC. Adjacent tissue invasion and GS 9-10 were independent poor prognostic factors. The incidence of acute urinary adverse reaction and rectal injury (grade≥2) was 7.5% and 20%, respectively. The incidence of late urinary adverse reaction and rectal injury (grade≥2) was 12.5% and 17.5%, respectively. Adverse reactions at grade 3-4 did not occur. Conclusions:The moderately hypofractionated IMRT combined with ADT is feasible for LAPC treatment, achieving satisfactory survival effects. 70 Gy/25-28 f, 2.5-2.8 Gy/f is a safe and effective moderate hypofraction scheme. Adjacent tissue invasion and GS score are prognostic factors related to BFFS for LAPC.