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.

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.

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.

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.

Application and Development of Artificial Intelligence in A Pathological Study of Urinary System Tumors / 肿瘤防治研究

Global Cancer Statistics for 2020 show that urinary system tumors account for approximately 13% of the total number of cancers. At present, the diagnostic methods of urinary system tumors are imaging, endoscopy, and pathological examination. As the gold standard of tumor diagnosis, pathological examination has problems such as lack of pathologists and long operation time. Artificial intelligence (AI), with a strong ability for pathology image recognition and feature analysis, can be used as an auxiliary diagnosis. It has realized automatic diagnosis, typing, staging, grading, and prognosis prediction in several urinary system tumors. However, AI still has many shortcomings, which limit its clinical application. This article will review the progress of AI and its application in the pathological study of urinary system tumors.

Research Progress on Effects of Different Treatments on Prostate Cancer with Atrial Fibrillation and Prevention Strategies / 肿瘤防治研究

Atrial fibrillation (AF) is one of the most common clinical arrhythmias. As the population ages, there is an upward trend in its prevalence. The risk factors associated with increased risk of AF include old age, diabetes, hypertension, and cancer. Studies have shown that in all age groups, the risk of death, hospitalization expenses, and hospitalization time of cancer patients with AF were higher than that without AF. Thus, increased systemic inflammation, electrolyte abnormalities, and neurohormonal changes in patients with prostate cancer (PCa) lead to a significantly higher incidence of AF than other cancers. However, the treatment of prostate cancer, including surgery, chemotherapy and radiotherapy, may also increase the risk of AF. In this review, relevant literatures are collected to understand the mechanism of AF in patients with PCa, determine the relationship between PCa and AF and its effect on hospitalized prognosis, and provide strategies for the prevention and treatment of AF in patients with PCa.

Progress in A Real-world Study of Abiraterone Acetate Versus Docetaxel in Patients with Metastatic Hormone-sensitive Prostate Cancer / 肿瘤防治研究

The safety and survival benefits of abiraterone acetate and docetaxel in the treatment of patients with metastatic hormone-sensitive prostate cancer have been confirmed by randomized controlled trials and clinical studies abroad. However, real-world studies remain lacking. In this article, we review the progress of real-world studies of abiraterone acetate and docetaxel in the treatment of patients with metastatic hormone-sensitive prostate cancer and the problems faced in clinical practice against the background of differentiated real-world studies. Further research is needed to address clinically important issues, such as individualized dosing, combination dosing, and monitoring of adverse effects.

Evaluation of Therapeutic Response to Endocrine Therapy for Prostate Cancer by MRI Diffusion-weighted Imaging Based on PI-RADSv2.1 / 肿瘤防治研究

Objective To investigate the value of MRI diffusion-weighted imaging (DWI) technique in endocrine therapy for prostate cancer (PCa) based on PI-RADSv2.1. Methods A retrospective analysis of 57 patients with pathologically confirmed PCa was conducted. All patients underwent multi-parametric MRI (mpMRI) according to PI-RADS v2.1 technical specifications before biopsy and six months after endocrine therapy. The apparent diffusion coefficient (ADC) values were measured in cancer and non-cancer areas before biopsy and six months after endocrine therapy. Patients were grouped based on the mRECIST criteria and PSA level into responders (n=45) and non-responders (n=12). ROC curves were obtained to assess the correlation between changes in ADC values and PSA values before and after endocrine therapy. Results In the responder group, the ADC value of the cancer areas was increased significantly after endocrine therapy (P<0.001). No statistically significant difference of the ADC value of the cancer areas was found in the non-responder group before and six months after endocrine therapy (P=0.714). The ADC change of responders and non-responder groups were (0.411±0.178)×10-3 mm2/s and (-0.014±0.125)×10-3 mm2/s, respectively (P<0.001); the ADC ratio were (60.603±30.201)% and (-1.096±13.175)%, respectively (P<0.001). The cutoff value of the ADC change was 0.165 (AUC=0.974; sensitivity, 88.89%; specificity, 100.00%; PPV, 100.00%; NPV, 70.59%). The cutoff value of ADC ratio was 16.827% (AUC=0.980; sensitivity, 91.11%; specificity, 100.00%; PPV, 100.00%; NPV, 75.00%). The ADC values were negatively correlated with serum PSA before and after endocrine therapy. Conclusion The ADC change and ADC ratio may be facilitated to monitor the efficacy of endocrine therapy for PCa. The ADC values were negatively correlated with serum PSA.

Clinicopathological Features of Primary Small Cell Neuroendocrine Carcinoma of the Bladder / 中国医学科学院学报

Objective To investigate the clinicopathological features,immunohistochemical features,diagnosis,and relationship with sporadic prostate cancer in primary small cell neuroendocrine carcinoma of the bladder. Methods We retrospectively analyzed the clinical characteristics of 12 patients with primary small cell neuroendocrine carcinoma of the bladder diagnosed at Beijing Chao-Yang Hospital affiliated to Capital Medical University from January 2013 to September 2022.The histological features of primary small cell neuroendocrine carcinoma of the bladder were re-evaluated by two pathologists according to the 2022 revision of the World Health Organization Classification of Tumors of the Urinary System and Male Genital Organs.Electronic medical records were retrieved,and telephone follow-up was conducted from the time of histopathological diagnosis to the death or the end of the last follow-up until January 31,2023. Results The 12 patients include 7 patients in pT3 stage and 1 patient in pT4 stage.Eight patients were complicated with other types of tumors,such as high-grade urothelial carcinoma of the bladder and squamous cell carcinoma.Five patients had sporadic prostate cancer.Immunohistochemical staining showed that 12 (100.0%),10 (83.3%),and 8 (66.7%) patients were tested positive for CD56,Syn,and CgA,respectively.The Ki67 proliferation index ranged from 80% to 90%.Five patients with urothelial carcinoma were tested positive for CK20,GATA3,and CK7.P504S was positive in all the 5 patients with prostate cancer,while P63 and 34βE12 were negative.The follow-up of the 12 patients lasted for 3-60 months.Eight of these patients died during follow-up,with the median survival of 15.5 months.Four patients survived. Conclusions Primary small cell neuroendocrine carcinoma of the bladder is a rare urological tumor with high aggressiveness and poor prognosis.In male patients with bladder prostatectomy,all prostate tissue should be sampled.If prostate cancer is detected,the prostate-specific antigen level should be monitored.

Neoadjuvant radiohormonal therapy for oligo-metastatic prostate cancer: safety and efficacy outcomes from an open-label, dose-escalation, single-center, phase I/II clinical trial / 医学前沿

To evaluate the safety and efficacy of neoadjuvant radiohormonal therapy for oligometastatic prostate cancer (OMPC), we conducted a 3 + 3 dose escalation, prospective, phase I/II, single-arm clinical trial (CHiCTR1900025743), in which long-term neoadjuvant androgen deprivation was adopted 1 month before radiotherapy, comprising intensity modulated radiotherapy to the pelvis, and stereotactic body radiation therapy to all extra-pelvic bone metastases for 4-7 weeks, at 39.6, 45, 50.4, and 54 Gy. Robotic-assisted radical prostatectomy was performed after 5-14 weeks. The primary outcome was treatment-related toxicities and adverse events; secondary outcomes were radiological treatment response, positive surgical margin (pSM), postoperative prostate-specific antigen (PSA), pathological down-grading and tumor regression grade, and survival parameters. Twelve patients were recruited from March 2019 to February 2020, aging 66.2 years in average (range, 52-80). Median baseline PSA was 62.0 ng/mL. All underwent RARP successfully without open conversions. Ten patients recorded pathological tumor down-staging (83.3%), and 5 (41.7%) with cN1 recorded negative regional lymph nodes on final pathology. 66.7% (8/12) recorded tumor regression grading (TRG) -I and 25% (3/12) recorded TRG-II. Median follow-up was 16.5 months. Mean radiological progression-free survival (RPFS) was 21.3 months, with 2-year RPFS of 83.3%. In all, neoadjuvant radiohormonal therapy is well tolerated for oligometastatic prostate cancer.

Research hotspots of prostate cancer at the international conferences on urology in 2022 / 浙江大学学报·医学版

The American Urological Association (AUA), European Association of Urology (EUA) and International Urological Society (SIU) annual meetings were held in 2022. Studies on prostate cancer reported in the meetings mainly focus on the advances of diagnostic biomarkers (such as α-2, 3-1inked sialylation of terminal N-glycan on free PSA density, SelectMDx) and imaging techniques [such as multiparametric magnetic resonance imaging, prostate specific membrane antigen(PSMA)-PET/CT], the new method for prostate biopsy, the new treatments of prostate cancer including [177Lu] Ludotadipep and DROP-IN PSMA probe, and the prognosis assessment of prostate cancer (such as AR-V7). This article provides an overview on the research hotspots of three international academic meetings.

Mismatch repair gene germline mutations in patients with prostate cancer / 浙江大学学报·医学版

OBJECTIVES@#To investigate the prevalence of pathogenic germline mutations of mismatch repair (MMR) genes in prostate cancer patients and its relationship with clinicopathological characteristics.@*METHODS@#Germline sequencing data of 855 prostate cancer patients admitted in Fudan University Shanghai Cancer Center from 2018 to 2022 were retrospectively analyzed. The pathogenicity of mutations was assessed according to the American College of Medical Genetics and Genomics (ACMG) standard guideline, Clinvar and Intervar databases. The clinicopathological characteristics and responses to castration treatment were compared among patients with MMR gene mutation (MMR+ group), patients with DNA damage repair (DDR) gene germline pathogenic mutation without MMR gene (DDR+MMR－ group) and patients without DDR gene germline pathogenic mutation (DDR－ group).@*RESULTS@#Thirteen (1.52%) MMR+ patients were identified in 855 prostate cancer patients, including 1 case with MLH1 gene mutation, 6 cases with MSH2 gene mutation, 4 cases with MSH6 gene mutation and 2 cases with PMS2 gene mutation. 105 (11.9%) patients were identified as DDR gene positive (except MMR gene), and 737 (86.2%) patients were DDR gene negative. Compared with DDR－ group, MMR+ group had lower age of onset (P<0.05) and initial prostate-specific antigen (PSA) (P<0.01), while no significant differences were found between the two groups in Gleason score and TMN staging (both P>0.05). The median time to castration resistance was 8 months (95%CI: 6 months-not achieved), 16 months (95%CI: 12-32 months) and 24 months (95%CI: 21-27 months) for MMR+ group, DDR+MMR－ group and DDR－ group, respectively. The time to castration resistance in MMR+ group was significantly shorter than that in DDR+MMR－ group and DDR－ group (both P<0.01), while there was no significant difference between DDR+MMR－ group and DDR－ group (P>0.05).@*CONCLUSIONS@#MMR gene mutation testing is recommended for prostate cancer patients with early onset, low initial PSA, metastasis or early resistance to castration therapy.

Transrectal ultrasound examination of prostate cancer guided by fusion imaging of multiparametric MRI and TRUS: avoiding unnecessary mpMRI-guided targeted biopsy / 亚洲男科学杂志(英文版)

The purpose of this study was to explore transrectal ultrasound (TRUS) findings of prostate cancer (PCa) guided by multiparametric magnetic resonance imaging (mpMRI) and to improve the Prostate Imaging Reporting and Data System (PI-RADS) system for avoiding unnecessary mpMRI-guided targeted biopsy (TB). From January 2018 to October 2019, fusion mpMRI and TRUS-guided biopsies were performed in 162 consecutive patients. The study included 188 suspicious lesions on mpMRI in 156 patients, all of whom underwent mpMRI-TRUS fusion imaging-guided TB and 12-core transperineal systematic biopsy (SB). Univariate analyses were performed to investigate the relationship between TRUS features and PCa. Then, logistic regression analysis with generalized estimating equations was performed to determine the independent predictors of PCa and obtain the fitted probability of PCa. The detection rates of PCa based on TB alone, SB alone, and combined SB and TB were 55.9% (105 of 188), 52.6% (82 of 156), and 62.8% (98 of 156), respectively. The significant predictors of PCa on TRUS were hypoechogenicity (odds ratio [OR]: 9.595, P = 0.002), taller-than-wide shape (OR: 3.539, P = 0.022), asymmetric vascular structures (OR: 3.728, P = 0.031), close proximity to capsule (OR: 3.473, P = 0.040), and irregular margins (OR: 3.843, P = 0.041). We propose subgrouping PI-RADS score 3 into categories 3a, 3b, 3c, and 3d based on different numbers of TRUS predictors, as the creation of PI-RADS 3a (no suspicious ultrasound features) could avoid 16.7% of mpMRI-guided TBs. Risk stratification of PCa with mpMRI-TRUS fusion imaging-directed ultrasound features could avoid unnecessary mpMRI-TBs.

Investigation of androgen receptor-dependent alternative splicing has identified a unique subtype of lethal prostate cancer / 亚洲男科学杂志(英文版)

A complete proteomics study characterizing active androgen receptor (AR) complexes in prostate cancer (PCa) cells identified a diversity of protein interactors with tumorigenic annotations, including known RNA splicing factors. Thus, we chose to further investigate the functional role of AR-mediated alternative RNA splicing in PCa disease progression. We selected two AR-interacting RNA splicing factors, Src associated in mitosis of 68 kDa (SAM68) and DEAD (Asp-Glu-Ala-Asp) box helicase 5 (DDX5) to examine their associative roles in AR-dependent alternative RNA splicing. To assess the true physiological role of AR in alternative RNA splicing, we assessed splicing profiles of LNCaP PCa cells using exon microarrays and correlated the results to PCa clinical datasets. As a result, we were able to highlight alternative splicing events of clinical significance. Initial use of exon-mini gene cassettes illustrated hormone-dependent AR-mediated exon-inclusion splicing events with SAM68 or exon-exclusion splicing events with DDX5 overexpression. The physiological significance in PCa was investigated through the application of clinical exon array analysis, where we identified exon-gene sets that were able to delineate aggressive disease progression profiles and predict patient disease-free outcomes independently of pathological clinical criteria. Using a clinical dataset with patients categorized as prostate cancer-specific death (PCSD), these exon gene sets further identified a select group of patients with extremely poor disease-free outcomes. Overall, these results strongly suggest a nonclassical role of AR in mediating robust alternative RNA splicing in PCa. Moreover, AR-mediated alternative spicing contributes to aggressive PCa progression, where we identified a new subtype of lethal PCa defined by AR-dependent alternative splicing.