Analysis of Factors Influencing Bone Metastasis in Prostate Cancer and Diagnostic Value of Serum PSA, CysC and D-D

Objective: This study aims to analyse factors influencing bone metastasis in prostate cancer and the diagnostic value of serum prostate-specific antigen (PSA), and D-dimer (D-D) combined with cystatin C (CysC) in bone metastasis of prostate cancer. Methods: Data of 116 patients with prostate cancer admitted to our hospital were retrospectively analysed. They were divided into two groups: Bone metastasis group (46 cases) and non-bone metastasis group (70 cases). Univariate and multivariate logistic regression analyses were used to determine factors influencing bone metastasis in prostate cancer. The values of serum PSA, D-D and CysC were identified using a receiver operating characteristic diagnostic curve. Results: Of the 116 patients, 46 had bone metastases and 70 had non-bone metastases. Among 46 patients with bone metastasis, 8 cases (17.39%) had single bone metastasis and 38 cases (82.61%) had multiple bone metastasis. Based on the univariate analysis, bone metastasis was associated with increases in Gleason score, clinical stage, lymph node metastasis, systemic inflammatory response index, fibrinogen to albumin ratio and alkaline phosphatase and fibrinogen levels. The Gleason score was higher than 8 points, the clinical stages ranged from T3 to T4 and the serum levels of PSA, D-D and CysC were higher in the bone metastasis group (p < 0.05). The combined value of serum PSA, D-D and CysC in the diagnosis of bone metastasis in prostate cancer was higher than the three indicators alone. Conclusions: Lymph node metastasis in T3–T4 clinical stages with Gleason score >8 was a risk factor for bone metastasis in prostate cancer (all p < 0.05). The risk of bone metastasis in patients with prostate cancer increases with increasing Gleason clinical stage and the occurrence of lymph node metastasis. Serum PSA, D-D and CysC have certain diagnostic value in the diagnosis of bone metastasis, and their combination has the highest value (AU)

Functional Outcomes After Localized Prostate Cancer Treatment.

Importance: Adverse outcomes associated with treatments for localized prostate cancer remain unclear. Objective: To compare rates of adverse functional outcomes between specific treatments for localized prostate cancer. Design, Setting, and Participants: An observational cohort study using data from 5 US Surveillance, Epidemiology, and End Results Program registries. Participants were treated for localized prostate cancer between 2011 and 2012. At baseline, 1877 had favorable-prognosis prostate cancer (defined as cT1-cT2bN0M0, prostate-specific antigen level <20 ng/mL, and grade group 1-2) and 568 had unfavorable-prognosis prostate cancer (defined as cT2cN0M0, prostate-specific antigen level of 20-50 ng/mL, or grade group 3-5). Follow-up data were collected by questionnaire through February 1, 2022. Exposures: Radical prostatectomy (n = 1043), external beam radiotherapy (n = 359), brachytherapy (n = 96), or active surveillance (n = 379) for favorable-prognosis disease and radical prostatectomy (n = 362) or external beam radiotherapy with androgen deprivation therapy (n = 206) for unfavorable-prognosis disease. Main Outcomes and Measures: Outcomes were patient-reported sexual, urinary, bowel, and hormone function measured using the 26-item Expanded Prostate Cancer Index Composite (range, 0-100; 100 = best). Associations of specific therapies with each outcome were estimated and compared at 10 years after treatment, adjusting for corresponding baseline scores, and patient and tumor characteristics. Minimum clinically important differences were 10 to 12 for sexual function, 6 to 9 for urinary incontinence, 5 to 7 for urinary irritation, and 4 to 6 for bowel and hormone function. Results: A total of 2445 patients with localized prostate cancer (median age, 64 years; 14% Black, 8% Hispanic) were included and followed up for a median of 9.5 years. Among 1877 patients with favorable prognosis, radical prostatectomy was associated with worse urinary incontinence (adjusted mean difference, -12.1 [95% CI, -16.2 to -8.0]), but not worse sexual function (adjusted mean difference, -7.2 [95% CI, -12.3 to -2.0]), compared with active surveillance. Among 568 patients with unfavorable prognosis, radical prostatectomy was associated with worse urinary incontinence (adjusted mean difference, -26.6 [95% CI, -35.0 to -18.2]), but not worse sexual function (adjusted mean difference, -1.4 [95% CI, -11.1 to 8.3), compared with external beam radiotherapy with androgen deprivation therapy. Among patients with unfavorable prognosis, external beam radiotherapy with androgen deprivation therapy was associated with worse bowel (adjusted mean difference, -4.9 [95% CI, -9.2 to -0.7]) and hormone (adjusted mean difference, -4.9 [95% CI, -9.5 to -0.3]) function compared with radical prostatectomy. Conclusions and Relevance: Among patients treated for localized prostate cancer, radical prostatectomy was associated with worse urinary incontinence but not worse sexual function at 10-year follow-up compared with radiotherapy or surveillance among people with more favorable prognosis and compared with radiotherapy for those with unfavorable prognosis. Among men with unfavorable-prognosis disease, external beam radiotherapy with androgen deprivation therapy was associated with worse bowel and hormone function at 10-year follow-up compared with radical prostatectomy.

The Value of Combined Detection of Serum PSA, MALAT1 and TMPRSS2-ETV1 in Evaluating the Progress and Prognosis of Prostate Cancer

Objective: To explore the prognostic value of combined detection of serum prostate specific antigen (PSA), lung cancer metastasis-associated transcript 1 (MALAT1), transmembrane serine protease 2 (TMPRSS2), and erythropoietin-specific transforming gene variant 1 (ETV1) in prostate cancer. Methods: Ninety patients with prostate cancer who were treated in hospital were divided into two groups according to tumor node metastasis stage: Stage I−II group (n = 34) and stage III−IV group (n = 56). The serum levels of PSA, MALAT1, and TMPRSS2-ETV1 were detected in both groups and correlated with prostate cancer status to determine their value as indicators of disease progression and prognosis. Results: Age, body mass index (BMI), and Gleason score differed significantly between the study group and the control group (p < 0.05). The expression levels of serum PSA and MALAT1 were higher in group III–IV than in group I–II, and the positive expression rate of TMPRSS2-ETV1 was significantly higher in group III–IV than in the control group (p < 0.05). Pearson’s correlation analysis showed that serum PSA, MALAT1, and TMPRSS2-ETV1 were significantly correlated with prostate cancer (p < 0.05). Differences in PSA levels correlated with differences in age, BMI, type of pathology, and Gleason score, whereas differences in serum MALAT1 levels correlated with differences in age, BMI, and type of pathology. Gleason scores differed significantly between patients with positive and negative TMPRSS2-ETV1 indicators (p < 0.05). Multivariate logistic regression analysis showed that serum PSA, MALAT1, and TMPRSS2-ETV1 were independent risk factors affecting the prognosis of prostate cancer (p < 0.05). The areas under the curve (AUCs) of serum PSA, MALAT1, and TMPRSS2-ETV1 as prognostic predictors in prostate cancer were 0.692, 0.731, and 0.709, respectively, whereas the AUC of the combination was 0.819 (AU)

Terapia de privación de andrógenos en el cáncer de próstata localizado. Situación actual y tendencias futuras / Androgen deprivation therapy in localized prostate cancer. Current status and future trends

Introducción El cáncer de próstata (CaP) se ha reconocido como una enfermedad sensible a los andrógenos desde las investigaciones de Huggins y Hodges en 1941, quienes, gracias a estos hallazgos, recibieron el Premio Nobel en 1966. Aquí se originó el desarrollo de la terapia de privación de andrógenos (TPA) como tratamiento para los pacientes con CaP. Objetivo Resumir las indicaciones actuales de la TPA en el CaP localizado. Adquisición de la evidencia Hemos realizado una investigación bibliográfica exhaustiva en inglés y español, centrada en las principales indicaciones de la TPA en el CaP localizado. Síntesis de la evidencia En la actualidad, las indicaciones de la TPA como monoterapia en el CaP localizado se han limitado a situaciones específicas, a pacientes que no desean o no pueden recibir ninguna forma de tratamiento local y que tienen un PSA-DT<12 meses y un PSA>50 ng/mL, un tumor poco diferenciado o síntomas locales molestos relacionados con la enfermedad. La TPA puede utilizarse en combinación con tratamiento local en diferentes escenarios. Aunque el tratamiento neoadyuvante con TPA antes de la cirugía con intención curativa no tiene un impacto oncológico claro, el CaP es una enfermedad heterogénea y en el futuro podría haber un grupo de pacientes con enfermedad localizada de alto riesgo que se beneficiaran de este tratamiento. Conclusiones Necesitamos optimizar el tratamiento con TPA en el CaP localizado, seleccionando a los pacientes en función de las características de su enfermedad. Dado que el arsenal terapéutico evoluciona día a día, es necesario el desarrollo de nuevos ensayos clínicos, así como el estudio molecular en los pacientes, para identificar a aquellos que podrían beneficiarse de un tratamiento multimodal temprano (AU)

Introduction Prostate cancer (PCa) has been recognized as an androgen-sensitive disease since the investigations from Huggins and Hodges in 1941. Thanks to these findings, they received the Nobel Prize in 1966. This was the beginning of the development of androgen deprivation therapy (ADT) as treatment for patients with PCa. Objective To summarize the current indications of ADT in localized PCa. Evidence acquisition We conducted a comprehensive English and Spanish language literature research, focused on the main indications for ADT in localized PCa. Evidence synthesis Nowadays, the indications for ADT as monotherapy in localized PCa have been limited to specific situations, to patients unwilling or unable to receive any form of local treatment if they have a PSA-DT<12 months, and either a PSA>50 ng/mL, a poorly differentiated tumor, or troublesome local disease-related symptoms. ADT can be used in combination with local treatment in different scenarios. Although neoadjuvant treatment with ADT prior to surgery with curative intent has no clear oncological impact, as a future sight, PCa is a heterogeneous disease, and there could be a group of patients with high-risk localized disease that could benefit. Conclusions We need to optimize the treatment with ADT in localized PCa, selecting the patients accordingly to their disease characteristics. Given that the therapeutic armamentarium evolves day by day, there is a need for the development of new clinical trials, as well as a molecular studies of patients to identify those who might benefit from an early multimodal treatment (AU)

Factores clínicos e histológicos predictores de reclasificación en pacientes incluidos en programa de vigilancia activa de cáncer de próstata / Clinical and histological predictive factors of reclassification of prostate cancer patients on active surveillance

Introducción y objetivo La vigilancia activa (VA) se ha establecido como estrategia terapéutica en pacientes con cáncer de próstata de bajo riesgo. Se han identificado factores demográficos y anatomopatológicos que aumentan la probabilidad de reclasificar a los enfermos. Materiales y métodos Se han recogido datos analíticos e histopatológicos de 116 pacientes incluidos en VA desde 2014. Se ha realizado un análisis univariante con X2, t de Student y Tau de Kendall, un análisis multivariante según regresión logística y se han calculado las curvas de Kaplan-Meier. Resultados De los 116 pacientes en VA, la mediana de edad al diagnóstico fue 66 años y la mediana de seguimiento fueron 13 meses (2-72). De todos ellos, 61 (52,6%) siguen en vigilancia mientras que 55 (47,4%) han salido del programa, la mayoría por progresión histológica (52 pacientes [45,2%]), realizándose prostatectomía radical en 27 (49,1%). El volumen prostático (Vp) ≤ 60cc y el número de cilindros positivos >1 en la biopsia diagnóstica (p = 0,05) se asociaron con mayor tasa de reclasificación en el análisis univariante (p < 0,05). En el análisis multivariante, estas dos variables se correlacionaron significativamente con una mayor tasa de reclasificación (Vp ≤ 60 cc: OR 4,39, p = 0,04; >1 cilindro positivo en la biopsia diagnóstica: OR 2,48, p = 0,03). Conclusiones Se ha objetivado que el volumen ecográfico inicial y el número de cilindros positivos en la biopsia diagnóstica son factores de riesgo independientes para la reclasificación. El antígeno prostático específico (PSA) inicial, la lateralidad de los cilindros afectos y la densidad de PSA no fueron elementos predictores de progresión en nuestra serie (AU)

Introduction and Objective Active surveillance (AS) has been established as a therapeutic strategy in patients with low-risk prostate cancer. Demographic and anatomopathological factors that increase the probability of reclassifying patients have been identified. Materials and Methods Laboratory and histopathological data were collected from 116 patients included on AS since 2014. Univariate analysis was performed with Chi-square, t-student and Kendall's Tau, multivariate analysis according to logistic regression and Kaplan-Meier curves were calculated. Results Of the 116 patients in AS, the median age at diagnosis was 66 years and the median follow-up was 13 months (2-72). Of these, 61 (52.6%) are still on surveillance, while 55 (47.4%) have left the program, mostly due to histological progression (52 patients (45.2%)); radical prostatectomy was performed in 27 (49.1%). Prostate volume (PV) ≤ 60cc and the number of positive cylinders > 1 in diagnostic biopsy (p = 0.05) were associated with higher reclassification rate in univariate analysis (p < 0.05). Multivariate analysis showed that these two variables significantly correlated with higher reclassification rate (PV 60 cc: OR 4.39, p = 0.04; > 1 positive cylinder at diagnostic biopsy: OR 2.48, p = 0.03). Conclusions It has been shown that initial ultrasound volume and the number of positive cylinders in the diagnostic biopsy are independent risk factors for reclassification. Initial PSA, laterality of the affected cylinders and PSA density were not predictive factors of progression in our series (AU)

Impact of a negative confirmatory biopsy on risk of disease progression among men on active surveillance for prostate cancer.

OBJECTIVE: Most prostate cancer active surveillance (AS) protocols suggest a confirmatory biopsy within 12 to 18 months of diagnosis to mitigate the risk of unsampled high-grade disease. We investigate whether the results of confirmatory biopsy impact AS outcomes and could be used to tailor surveillance intensity. METHODS: We retrospectively reviewed our institutional database of prostate cancer patients managed by AS from 1997 to 2019 who underwent confirmatory biopsy and ≥3 biopsies overall. Biopsy progression was defined as either an increase in grade group or an increase in the proportion of positive biopsy cores to >34% and was compared between patients with a negative vs positive confirmatory biopsy using the Kaplan-Meier method and Cox proportional hazards regression. RESULTS: We identified 452 patients meeting inclusion criteria for this analysis, of whom 169 (37%) had a negative confirmatory biopsy. With a median follow-up of 6.8 years, 37% of patients progressed to treatment, most commonly due to biopsy progression. A negative confirmatory biopsy was significantly associated with biopsy progression-free survival in multivariable analysis (HR 0.54, 95% CI 0.34-0.88, P = 0.013), adjusting for known clinical and pathologic factors, including use of mpMRI prior to confirmatory biopsy. Negative confirmatory biopsy was also associated with an increased risk of adverse pathologic features at prostatectomy but not with biochemical recurrence among men who ultimately underwent definitive treatment. CONCLUSIONS: A negative confirmatory biopsy is associated with a lower risk of biopsy progression. While the increased risk of adverse pathology at time of definitive treatment sounds a small cautionary note regarding decreasing surveillance intensity, the majority of such patients have a favorable outcome on AS.

American Indian/Alaska Native men are less likely to receive prostate-specific antigen testing and digital rectal exams from primary care providers than White men: a secondary analysis of the National Ambulatory Medical Care Survey from 2012-2018.

PURPOSE: (1) Identify the proportion of primary care visits in which American Indian/Alaska Native (AI/AN) men receive a prostate-specific antigen test (PSAT)and/or a digital rectal exam (DRE), (2) describe characteristics of primary care visits in which AI/AN receive PSA and/or DRE, and (3) identify whether AI/AN receive PSA and/or DRE less often than non-Hispanic White (nHW) men. METHODS: This was a secondary analysis of the National Ambulatory Medical Care Survey (NAMCS) during 2013-2016 and 2018 and the NAMCS Community Health Center (CHC) datasets from 2012-2015. Weighted bivariate and multivariable tests analyzed the data to account for the complex survey design. RESULTS: For AI/AN men, 1.67 per 100 visits (95% CI = 0-4.24) included a PSATs (or PSAT) and 0 visits included a DRE between 2013-2016 and 2018. The rate of PSA for non-AI/AN men was 9.35 per 100 visits (95% CI = 7.78-10.91) and 2.52 per 100 visits (95% CI = 1.61-3.42) for DRE. AI/AN men were significantly less likely to receive a PSA than nHW men (aOR = 0.09, 95% CI = 0.01-0.83). In CHCs, AI/AN men experienced 4.26 PSAT per 100 visits (95% CI = 0.96-7.57) compared to 5.00 PSAT per 100 visits (95% CI = 4.40-5.68) for non-AI/AN men. DRE rates for AI/AN men was 0.63 per 100 visits (95% CI = 0-1.61) compared to 1.05 per 100 (95% CI = 0.74-1.37) for non-AI/AN men. There was not a statistically significant disparity in the CHC data regarding PSA (OR = 0.91, 95% CI = 0.42-1.98) or DRE (OR = 0.75, 95% CI = 0.15-3.74), compared to nHW men. CONCLUSION: Efforts are needed to better understand why providers may not use PSA and DRE with AI/AN men compared to nHW men.

Low-Value Prostate-Specific Antigen Screening in Older Males.

Importance: The US Preventive Services Task Force guidelines advise against prostate-specific antigen (PSA) screening for prostate cancer in males older than 69 years due to the risk of false-positive results and overdiagnosis of indolent disease. However, this low-value PSA screening in males aged 70 years or older remains common. Objective: To characterize the factors associated with low-value PSA screening in males 70 years or older. Design, Setting, and Participants: This survey study used data from the 2020 Behavioral Risk Factor Surveillance System (BRFSS), a nationwide annual survey conducted by the Centers for Disease Control and Prevention that collects information via telephone from more than 400 000 US adults on behavioral risk factors, chronic illnesses, and use of preventive services. The final cohort comprised male respondents to the 2020 BRFSS survey who were categorized into the following age groups: 70 to 74 years, 75 to 79 years, or 80 years or older. Males with a former or current prostate cancer diagnosis were excluded. Main Outcomes and Measures: The outcomes were recent PSA screening rates and factors associated with low-value PSA screening. Recent screening was defined as PSA testing within the past 2 years. Weighted multivariable logistic regressions and 2-sided significance tests were used to characterize factors associated with recent screening. Results: The cohort included 32 306 males. Most of these males (87.6%) were White individuals, whereas 1.1% were American Indian, 1.2% were Asian, 4.3% were Black, and 3.4% were Hispanic individuals. Within this cohort, 42.8% of respondents were aged 70 to 74 years, 28.4% were aged 75 to 79 years, and 28.9% were 80 years or older. The recent PSA screening rates were 55.3% for males in the 70-to-74-year age group, 52.1% in the 75-to-79-year age group, and 39.4% in the 80-year-or-older group. Among all racial groups, non-Hispanic White males had the highest screening rate (50.7%), and non-Hispanic American Indian males had the lowest screening rate (32.0%). Screening increased with higher educational level and annual income. Married respondents were screened more than unmarried males. In a multivariable regression model, discussing PSA testing advantages with a clinician (odds ratio [OR], 9.09; 95% CI, 7.60-11.40; P < .001) was associated with increased recent screening, whereas discussing PSA testing disadvantages had no association with screening (OR, 0.95; 95% CI, 0.77-1.17; P = .60). Other factors associated with a higher screening rate included having a primary care physician, a post-high school educational level, and income of more than $25 000 per year. Conclusions and Relevance: Results of this survey study suggest that older male respondents to the 2020 BRFSS survey were overscreened for prostate cancer despite the age cutoff for PSA screening recommended in national guidelines. Discussing the benefits of PSA testing with a clinician was associated with increased screening, underscoring the potential of clinician-level interventions to reduce overscreening in older males.

Biochemically recurrent prostate cancer: rationalisation of the approach to imaging.

AIM: To assess the utility of magnetic resonance imaging (MRI) in addition to the additive benefit of the conventional imaging techniques, computed tomography (CT) and nuclear medicine (NM) bone scintigraphy, for investigation of biochemical recurrence (BCR) post-prostatectomy where access to prostate specific membrane antigen (PSMA) positron-emission tomography (PET)-CT is challenging. MATERIALS AND METHODS: Relevant imaging over a 5-year period was reviewed. Ethical approval was granted by the internal review board. All patients with suspected BCR, defined as a PSA ≥0.2 ng/ml on two separate occasions, underwent a retrospective imaging review. This was performed on PACS archive search database in a single centre using search terms "PSA" and "prostatectomy" in the three imaging methods; MRI, CT, and NM bone scintigraphy. All PSMA PET CT performed were recorded. RESULTS: One hundred and eighty-five patients were identified. Patients with an MRI pelvis that demonstrated distant metastases (i.e., pelvic bone metastases or lymph node involvement more cranial to the bifurcation of the common iliac arteries) were more likely to have a positive CT and/or NM bone scintigraphy. The Pearson correlation coefficient between the findings of M1 disease at MRI pelvis and the presence of distant metastases at CT thorax, abdomen, pelvis and NM bone scintigraphy was calculated at 0.81 (p<0.01) and 0.91 (p<0.01) respectively. CONCLUSION: An imaging strategy based on risk stratification and technique-specific selection criteria leads to more appropriate use of resources, and in turn, increases the yield of conventional imaging methods. MRI prostate findings can be used to predict the additive value of CT/NM bone scintigraphy allowing a more streamlined approach to their use.

A big data-based prediction model for prostate cancer incidence in Japanese men.

To define a normal range for PSA values (ng/mL) by age and create a prediction model for prostate cancer incidence. We conducted a retrospective analysis using 263,073 observations of PSA values in Japanese men aged 18-98 years (2007-2017), including healthy men and those diagnosed with prostate cancer. Percentiles for 262,639 PSA observations in healthy men aged 18-70 years were calculated and plotted to elucidate the normal fluctuation range for PSA values by age. Univariable and multivariable logistic regression analyses were performed to develop a predictive model for prostate cancer incidence. PSA levels and PSA velocity increased with age in healthy men. However, there was no difference in PSA velocity with age in men diagnosed with prostate cancer. Logistic regression analysis showed an increased risk of prostate cancer for PSA slopes ranging from 0.5 to 3.5 ng/mL/year. This study provides age-specific normal fluctuation ranges for PSA levels in men aged 18-75 years and presents a novel and personalized prediction model for prostate cancer incidence. We found that PSA slope values of > 3.5 ng/mL/year may indicate a rapid increase in PSA levels caused by pathological condition such as inflammation but are unlikely to indicate cancer risk.

Rendimiento de la PET/TC con 11C-colina en el seguimiento del cáncer de próstata / Effectiveness of 11C-choline PET/CT in prostate cancer surveillance

Objetivo Analizar el rendimiento diagnóstico de la PET/TC con 11C-colina en el seguimiento del cáncer de próstata (CaP), especialmente en pacientes con antígeno prostático específico (PSA)>1ng/ml. Material y métodos Se evaluaron retrospectivamente 329 exploraciones PET/TC con 11C-colina de 191 pacientes (68,2±7,2 años) con CaP con recaída bioquímica o en seguimiento (PSA en el momento de la PET/TC: 13,0±84,2ng/ml). El tratamiento inicial fue prostatectomía radical en 81 pacientes y otros tratamientos (radioterapia, quimioterapia, hormonoterapia) en 110. La PET/TC se adquirió 20min después de la inyección de 555-740MBq de 11C-colina. El seguimiento mínimo fue superior a 12 meses. Resultados Doscientas diecinueve (66,6%) de las 329 exploraciones PET/TC fueron positivas. El porcentaje de positivos fue significativamente mayor en los pacientes con otro tratamiento inicial diferente a la prostatectomía radical (85,6 frente a 43,6%, respectivamente). Ciento treinta PET/TC (59,4%) mostraron recidiva local, 48 (21,9%) a distancia y 41 (18,7%) local más a distancia. El abordaje terapéutico inicial se modificó en 139 casos (63,5%). De las 81 PET/TC con 11C-colina realizadas con PSA<1ng/ml, 23 (28,4%) fueron positivas. El abordaje terapéutico inicial se modificó en 9 (11,1%). Tres de 63 pacientes (4,8%) fallecieron por CaP. Conclusiones La PET/TC con 11C-colina demostró su eficacia en el seguimiento y la reestadificación del CaP, incluso en pacientes con PSA sérico<1ng/ml. El rendimiento diagnóstico fue diferente según el tratamiento inicial al que fueron sometidos los pacientes, siendo mayor en aquellos tratados inicialmente con otros tratamientos distintos de la PR prostatectomía radical (AU)

Aim Our aim was to analyse the performance of 11C-choline PET/CT in prostate cancer (PCa) surveillance, especially in patients with prostate specific antigen (PSA)<1ng/ml. Material and methods Three hundred and twenty-nine 11C-choline PET/CT examinations from 191 patients (68.2±7.2 years) submitted for PCa surveillance or biochemical recurrence were retrospectively evaluated (PSA at study was 13.0±84.2ng/ml). Main initial treatment was radical prostatectomy in 81 patients, and other treatments (radiotherapy, chemotherapy, hormonotherapy) in 110. PET/CT was acquired 20min after injection of 555-740MBq of 11C-choline. Minimum follow-up was 12 months. Results Two hundred and nineteen (66.6%) out of the 329 PET/CT examinations were positive. The percentage of positive examinations was significantly higher in patients with other initial treatment than radical prostatectomy compared to patients with radical prostatectomy (85.6 vs. 43.6%, respectively). One hundred and thirty PET/CT (59.4%) showed local recurrence, 48 (21.9%) distant recurrence, and 41 (18.7%) local plus distant recurrence. Initial therapeutic approach was changed in 139 cases (63.5%). In the subgroup of 81 11C-choline PET/CT scans performed with PSA<1ng/ml, 23 (28.4%) showed a positive result. Initial therapeutic approach was changed in 9 (11.1%). Three (4.8%) out of 63 patients died as per PCa. Conclusions 11C-choline PET/CT demonstrated its effectiveness in PCa surveillance and restaging, even in patients with serum PSA<1ng/ml. The diagnostic performance was different depending on the initial treatment, been higher in patients with non-surgical treatment (AU)

Fifteen-Year Outcomes after Monitoring, Surgery, or Radiotherapy for Prostate Cancer.

BACKGROUND: Between 1999 and 2009 in the United Kingdom, 82,429 men between 50 and 69 years of age received a prostate-specific antigen (PSA) test. Localized prostate cancer was diagnosed in 2664 men. Of these men, 1643 were enrolled in a trial to evaluate the effectiveness of treatments, with 545 randomly assigned to receive active monitoring, 553 to undergo prostatectomy, and 545 to undergo radiotherapy. METHODS: At a median follow-up of 15 years (range, 11 to 21), we compared the results in this population with respect to death from prostate cancer (the primary outcome) and death from any cause, metastases, disease progression, and initiation of long-term androgen-deprivation therapy (secondary outcomes). RESULTS: Follow-up was complete for 1610 patients (98%). A risk-stratification analysis showed that more than one third of the men had intermediate or high-risk disease at diagnosis. Death from prostate cancer occurred in 45 men (2.7%): 17 (3.1%) in the active-monitoring group, 12 (2.2%) in the prostatectomy group, and 16 (2.9%) in the radiotherapy group (P = 0.53 for the overall comparison). Death from any cause occurred in 356 men (21.7%), with similar numbers in all three groups. Metastases developed in 51 men (9.4%) in the active-monitoring group, in 26 (4.7%) in the prostatectomy group, and in 27 (5.0%) in the radiotherapy group. Long-term androgen-deprivation therapy was initiated in 69 men (12.7%), 40 (7.2%), and 42 (7.7%), respectively; clinical progression occurred in 141 men (25.9%), 58 (10.5%), and 60 (11.0%), respectively. In the active-monitoring group, 133 men (24.4%) were alive without any prostate cancer treatment at the end of follow-up. No differential effects on cancer-specific mortality were noted in relation to the baseline PSA level, tumor stage or grade, or risk-stratification score. No treatment complications were reported after the 10-year analysis. CONCLUSIONS: After 15 years of follow-up, prostate cancer-specific mortality was low regardless of the treatment assigned. Thus, the choice of therapy involves weighing trade-offs between benefits and harms associated with treatments for localized prostate cancer. (Funded by the National Institute for Health and Care Research; ProtecT Current Controlled Trials number, ISRCTN20141297; ClinicalTrials.gov number, NCT02044172.).

Ethnic differences in the age-related distribution of serum prostate-specific antigen values: A study in a Taiwanese male population.

This study investigates age-specific prostate-specific antigen (PSA) distributions in Taiwanese men and recommends reference ranges for this population after comparison with other studies. From January 1999 to December 2016, a total of 213,986 Taiwanese men aged above 19 years old without history of prostate cancer, urinary tract infection, or prostate infection were recruited from the Taiwan MJ cohort, an ongoing prospective cohort of health examinations conducted by the MJ Health Screening Center in Taiwan. Participants were divided into seven age groups. Simple descriptive statistical analyses were carried out and quartiles and 95th percentiles were calculated for each group as reference ranges for serum PSA in screening for prostate cancer in Taiwanese men. Serum PSA concentration correlated with age (r = 0.274, p<0.001). The median serum PSA concentration (5th to 95th percentile) ranged from 0.7 ng/ml (0.3 to 1.8) for men 20-29 years old (n = 6,382) to 1.6 ng/ml (0.4 to 8.4) for men over 79 years old (n = 504). The age-specific PSA reference ranges are as follows: 20-29 years, 1.80 ng/ml; 30-39 years, 1.80 ng/ml; 40-49 years, 2.0 ng/ml; 50-59 years, 3.20 ng/ml; 60-69 years, 5.60 ng/ml; 70-79 years, 7.40 ng/ml; over 80 years, 8.40 ng/ml. Almost no change occurred in the median serum PSA value in men 50 years old or younger, while a gradual increase was observed in men over 50. Taiwanese men aged 60 years above showed higher 95th percentile serum PSA values compared to Caucasian men and men in other Asian countries but were closer to those of Asian American and African American men. Results indicate significantly different PSA levels correlating to different ethnicities, suggesting that Oesterling's age-specific PSA reference ranges might not be appropriate for Taiwanese men. Our results should be further studied to validate the age-specific PSA reference ranges for Taiwanese men presented in this study.

Evaluation of sexual function after dutasteride treatment in patients with once-negative prostate biopsy and benign prostate hyperplasia.

INTRODUCTION: Patients with benign prostatic hyperplasia are usually treated with 5α-reduced inhibitors (5ARIs) such as finasteride and dutasteride. However, studies on the influence of 5ARIs on sexual function have been controversial. In this study, we evaluated the impact of dutasteride treatment for erectile function in patients with once-negative prostate biopsy and benign prostate hyperplasia. PATIENTS AND METHODS: 81 patients with benign prostate hyperplasia were enrolled in a one-armed prospective study. They were administrated 0.5 mg/day of dutasteride for 12 months. Patient characteristics and changes of International Prostate Symptom Score (IPSS) and International Index of Erectile Function (IIEF)-15 scores at baseline and 12 months after dutasteride administration were examined. RESULTS: The mean ± standard deviation (SD) age of the patients was 69.4 ± 4.9 years and the prostate volume was 56.6 ± 21.3 mL, respectively. The mean ± SD prostate volume and PSA levels were decreased 25.0 and 50.9%, respectively, after 12 months of dutasteride administration. IPSS total, voiding subscore, storage subscore, and quality of life score significantly improved after 12 months of dutasteride administration. No statistically significant change in IIEF-total score from 16.3 ± 13.5 to 18.8 ± 16.0 (p = 0.14), IIEF-EF score from 5.1 ± 6.9 to 6.4 ± 8.3 (p = 0.13) were observed. There was no decrease in erectile function severity. CONCLUSION: Twelve months administration of dutasteride for patients with BPH improved urinary function and did not increase the risk of sexual dysfunction.

Uso del antígeno prostático específico (PSA) para el cribado de cáncer de próstata en la población de 70 años o más de una zona de salud urbana, 2018-2020. Un estudio transversal / Prostate cancer screening with Prostate-Specific Antigen (PSA) to men over 70 years old in an urban health zone, 2018–2020: A cross-sectional study

Objetivos Cuantificar, describir el origen y estimar el coste de las solicitudes de antígeno prostático específico (PSA) con fines de cribado a varones de 70 años o más realizadas en una zona de salud urbana. Métodos Estudio transversal. Se obtuvieron todas las determinaciones de PSA a pacientes adscritos a una zona de salud entre los años 2018 y 2020. Se clasificaron retrospectivamente como cribado (PSAc) o no, de acuerdo a criterios preestablecidos revisando historiales clínicos. Se comparó la edad de los pacientes sometidos a cribado con aquellos que no lo fueron. Se calcularon tasas de solicitud por centros y solicitantes de acuerdo a la población de referencia provista por el padrón municipal (VM70). Se estimó el coste consultando las tarifas de facturación. Resultados Fueron estudiadas 2.036 PSA, de 888 hombres ≥ 70 años, y 350 clasificadas como cribado. Se diagnosticaron seis adenocarcinomas. Se estimaron 76,07 PSAc/1.000 VM70-año con origen en cualquier centro, 1,45 solicitudes por individuo cribado, y una prevalencia de 15,71%; población media de referencia de 1.534 hombres (DE 45,37). Los pacientes sometidos a cribado (edad media 75 años, DE 4,04) fueron más jóvenes que aquellos no cribados (media 76,5, DE 4,81). Se estimó un coste del cribado de 9.751 €. Conclusiones Se describe la epidemiología y estima el coste de los cribados con PSA a varones ≥ 70 años sin cáncer prostático en nuestra zona, en atención primaria y hospitalaria. Se trata de una práctica habitual, predominantemente en atención primaria, y en magnitud similar a la reportada en la bibliografía estatal. (AU)

Objectives To describe the epidemiology and estimate the cost of Prostate-Specific Antigen (PSA) screening tests to men ≥ 70 years old in an urban health zone. Methods A cross-sectional study was performed. We obtained every PSA test made in the health zone from 2018 to 2020, and classified them retrospectively as screening (PSAc) or not according to pre-established criteria, reviewing electronic health records. Testing rates were calculated by centres and clinical specialities. The standard population was provided by the city register of inhabitants (VM70). Cost estimation was made using our health system's price list. ResultsTwo thousand and thirty six PSA, of 888 men ≥ 70 years old were obtained, and 350 met screening classification criteria. Six adenocarcinomas were diagnosed from those tests. We estimated 76.07 PSAc/1000 VM70-year from any centre, 1.45 tests for each screened individual, and 15.71% prevalence. The standard population was 1534 men (mean 2018-2020, SD 45.37). Patients who were screened (median age 75, SD 4.04) were younger than those not screened. We estimated a total screening test cost of 9,751 €. Conclusions The epidemiology and cost of PSA screening tests to men ≥ 70 years old are reported, both in primary health care and in the hospital. PSA screening tests are common practice amongst professionals attending elderly men in our health zone, mostly in primary care. The screening testing rate of men without prostate cancer is similar to that reported in the literature. (AU)

Clinical Value of Magnetic Resonance Imaging Combined With Serum Prostate-specific Antigen, Epithelial Cadherin and Early Prostate Cancer Antigen 2 In Diagnosis of Prostate Cancer.

AIM: To explore the clinical value of magnetic resonance imaging (MRI) combined with serum prostate specific antigen (PSA), epithelial cadherin (sE-cadherin) and early prostate cancer antigen-2 (EPCA-2) in prostate cancer (PC) diagnosis. PATIENTS AND METHODS: Fifty patients with PC and 50 with benign prostatic hyperplasia (BPH) confirmed by pathology from January 2020 to July 2021 were studied retrospectively. All patients underwent MRI and measurement of the serum levels of PSA, EPCA-2, and sE-cadherin. The diagnostic accuracy and efficacy of these methods was compared between the groups. RESULTS: In MRI diagnosis of PC, lesions were mainly located in the peripheral zone; T2-weighted imaging of this zone showed low signal intensity, with different degrees of prostate enlargement. BPH had a clear boundary, complete capsule and central zone hyperplasia and uneven signal nodules. PC and BPH had different degrees of prostate enlargement. Serum levels of PSA, sE-cadherin and EPCA-2 in the cancer group were significantly higher than those in the BPH group (p<0.05). The diagnostic concordance of combined assessment of MRI, PSA, sE-cadherin, and EPCA-2 in differentiating PC from BPH was 93%, which was significantly higher than these approaches used alone (84%, 79%, 81% and 82%, respectively; p<0.05). The area under the receiver operating characteristics curve for the combined approach in PC diagnosis was 0.900, which was significantly higher than those for the individual methods (0.840, 0.730, 0.760 and 0.810, respectively; Z=2.343, p=0.004). CONCLUSION: MRI combined with PSA, sE-cadherin and EPCA-2 can improve the sensitivity and accuracy of PC diagnosis and has potential as a guiding scheme for early diagnosis of PC.

¿Es el intervalo libre de docetaxel un factor predictivo para el cáncer de próstata resistente a la castración? / Is docetaxel-free interval a predictive factor for castration-resistant prostate cancer?

Objetivo: El cáncer de próstata (CaP) es el segundo tumor sólido más frecuente en los varones y la quinta causa de muerte relacionada con el cáncer. En los estadios avanzados de la enfermedad se administran tratamientos paliativos en lugar de terapias curativas, por lo que, conocer los posibles indicadores predictivos, parece importante. Se revisaron retrospectivamente los pacientes con cáncer de próstata resistente a la castración (CPRC) que recibieron quimioterapia con docetaxel (Dx). El objetivo de este estudio fue investigar si el intervalo libre de Dx podría tener un valor predictivo para el CaP e influir en las terapias secuenciales.Material y métodos: Este ensayo clínico se realizó en 104 pacientes en la Clínica de Oncología de la Universidad de Medeniyet en 2018-2020. Todos los pacientes con CPRC metastásico recibieron Dx como primer tratamiento y fueron sometidos a terapia dirigida al receptor de andrógenos (ARAT, por sus siglas en inglés) tras la progresión de la enfermedad. Se analizó el tiempo hasta la progresión de los pacientes después de la terapia con Dx y los efectos sobre el tratamiento secuencial.Resultados: Posterior al tratamiento con Dx, los pacientes recibieron ARAT (abiraterona [ABI] n: 49 [47,1%] y enzalutamida [ENZ] n: 54 [51,9%]) como tratamiento de segunda línea, excepto un paciente que recibió cabazitaxel. Hubo una relación estadísticamente significativa entre el intervalo libre de Dx y la duración de la respuesta al ARAT (p<0,001). El tiempo de respuesta al tratamiento con ARAT fue <10,5 meses en todos los pacientes con un período de intervalo libre de Dx<9 meses.Conclusiones: Nuestros resultados avalan la hipótesis de que el intervalo libre de Dx puede ser un factor predictivo para el CPRC. El CPRC podría clasificarse como enfermedad sensible al Dx o resistente al Dx en función del intervalo libre de Dx; y la decisión sobre los tratamientos posteriores podría tomarse con base en esta información. (AU)

Objective: Prostate cancer (PCa) is the second most common solid tumor in men and the fifth leading cause of cancer-related death. In advanced stage, palliative treatments are used instead of curative therapies. Therefore, finding predictive indicators seems crucial. Patients with castration-resistant prostate cancer (CRPC) that received Dx chemotherapy have been retrospectively reviewed. The aim of this study was to investigate whether docetaxel (Dx)-free interval could have a predictive value for PCa and influence other sequential therapies.Material and methods: This clinical trial study was performed on 104 patients at Medeniyet University Oncology Clinic in 2018-2020. All CRPC patients had metastases, received Dx as first-line treatment and underwent androgen receptor axis targeted (ARAT) therapy after disease progression. We analyzed patients’ progression time after Dx therapy and the effects on sequential treatment.Results: After Dx therapy, all patients received ARAT (abiraterone (ABI) n: 49 (47.1%) and enzalutamide (ENZ) n: 54 (51.9%)) as a second-line treatment, except for one patient who received cabazitaxel. There was a statistically significant relationship between the Dx-free interval and duration of response to ARAT (P<.001). The response time of ARAT treatment was <10.5 months in all patients whose Dx-free interval period was <9 months.Conclusions: Our findings support the theory that Dx-free interval can be a predictive factor for CRPC. CRPC disease can be classified as Dx-sensitive disease or Dx-resistance disease, based on the Dx-free interval. Decision on subsequent treatments could be made considering this information. (AU)

[Matrix metalloproteinase 14 and plasma kallikrein 1 may be potential biomarkers in the diagnosis and treatment of sepsis: a proteomics and bioinformatics analysis].

OBJECTIVE: To analyze protein profiles in septic patients, and to find potential new targets for the diagnosis and treatment of sepsis. METHODS: A cross sectional observational study was conducted. From January to December 2019, 12 septic patients and 9 healthy volunteers were recruited in the emergency intensive care unit (EICU) of the emergency department of the Affiliated Hospital of Southwest Medical University. The peripheral blood of the two groups was collected for protein mass spectrometry analysis, and the data-independent acquisition technology was used to obtain the expression data of each protein. The obtained data was imported into the online network tool Integrated Differential Expression and Pathway analysis (IDEP2), the data underwent ID converted and were homogenized to verify their comparability, and then principal component analysis was used to eliminate outlier data. Then data with P < 0.05, log2fold change (FC) > 1 or log2FC < -1 were considered to have a statistically significant difference, and the differential proteins were screened out. On the DAVID website, the screened differential proteins would be analyzed by gene ontology (GO), and the biological process, cellular components, and molecular function of the proteins would be analyzed. Protein enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed. Protein-protein interaction (PPI) analysis was performed through the Search Tool for the Retrieval of Interacting Genes Database (STRING) website to find closely related proteins. RESULTS: The data in this study were shown to be comparable after normalization. A total of 125 differential proteins were screened, of which 99 were up-regulated and 26 were down-regulated. GO enrichment analysis discovered that these proteins were mainly extracellular, with cellular regulatory functions and catalytic functions involved in biological regulation, metabolic process and immune process. KEGG pathway analysis suggested that these proteins were involved in amino acid, carbohydrate metabolism and immune-related pathways. PPI analysis showed that key proteins included matrix metalloproteinase 14 (MMP14), fibulin 1 (FBLN1), plasma kallikrein 1 (KLKB1), etc., and finally screened out MMP14 and KLKB1, which were closely related to inflammation and immunity. Both might be potential new targets for early diagnosis and treatment of sepsis. CONCLUSIONS: MMP14 and KLKB1 may be potential biomarkers for the diagnosis, treatment and prognosis of sepsis.