[Prostate cancer - a disease in transformation]. / Prostatacancer ­ sjukdom i förändring.

This article introduces a series of articles covering some of the most important aspects of contemporary prostate cancer care. After the introduction of the prostate-specific antigen (PSA) blood test and systematic prostate biopsies in the early 1990s, the incidence of localised prostate cancer and the use of radical treatment rose dramatically. Improved diagnostic methods and understanding of the tumour biology now reduce overdiagnosis and pave the way for organised screening. New and more effective treatments, in combination with the stage shift from advanced to localised disease at the time of diagnosis, have reduced the age-standardised prostate cancer specific mortality by half in men under the age of 85 years. The National Prostate Cancer Register of Sweden (NPCR) has evolved over the past 25 years and now comprehensively supports clinical care and is an invaluable research data source. Patients' organisations have emerged as important players on the national arena.

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)

Grupos de riesgo de recidiva bioquímica tras prostatectomía radical de la Asociación Europea de Urología: validación externa e identificación de factores de riesgo de progresión y mortalidad / European Association of Urology biochemical recurrence risk groups after radical prostatectomy: external validation and identification of independent risk factors for progression and death

Contexto La EAU propuso una clasificación del riesgo de progresión y muerte en pacientes con recidiva bioquímica tras prostatectomía radical (PR). Objetivo Validar la clasificación de riesgo de RB de la EAU en nuestro contexto e identificar los factores asociados con la progresión y la muerte. Material y métodos Estudio multicéntrico, retrospectivo y observacional que incluyó a 2140 pacientes sometidos a PR entre 2011 y 2015. Los pacientes con RB fueron identificados y estratificados en grupos de riesgo bajo (TD-PSA >1 año y pGS <8) o alto (TD-PSA <=1 año o pGS=>8). Se calcularon la supervivencia libre de progresión por PSA y supervivencia libre de metástasis (SLP-PSA, SLM), la supervivencia cáncer específica y la supervivencia global (curvas de Kaplan Meier y log-rank test). Se identificaron factores de riesgo independientes (regresión de Cox). Resultados Un total de 427 pacientes experimentaron RB (32,3% de bajo riesgo y 67,7% de alto riesgo). La mediana de SLP-PSA fue de 135,0 m (IC 95% 129,63-140,94) y 115,0 m (IC 95% 104,02-125,98) (p < 0,001) para los grupos de bajo y alto riesgo, respectivamente. Hubo diferencias significativas en la SLM y la supervivencia global entre ambos grupos. El grupo de riesgo de RB de la EAU fue un factor independiente de progresión del PSA (HR 2,55; p 0,009). El tiempo transcurrido entre la PR y la RB fue un factor independiente de aparición de metástasis (HR 0,43; IC 95%: 0,18-0,99; p 0,044) y muerte (HR 0,17; IC 95%: 0,26-0,96; 23 p 0,048). Se hallaron diferencias en la SLM (p 0,001) y la supervivencia cáncer específica (p 0,004) para <12, ≥ 12-<36 y ≥36 meses transcurridos entre la PR y la RB. Otros factores independientes fueron la radioterapia de rescate precoz y el PSA en el momento de aparición de la RB (AU)

Background The EAU proposed a progression and death risk classification in patients with biochemical recurrence after radical prostatectomy (PR). Objective To validate the EAU BCR-risk classification in our setting and to find factors related to progression and death. Material and methods Multicenter, retrospective, observational study including 2140 patients underwent RP between 2011 and 2015. Patients with BCR were identified and stratified in low risk (PSA-DT>1 yr and pGS <8) or high-risk (PSA-DT <=1 yr or pGS=>8) grouping. PSA and metastatic free survival (PSA-PFS, MFS), cancer specific survival and overall survival were calculated (Kaplan Meier curves and log-rank test). Independent risk factors were identified (Cox regression). Results 427 patients experienced BCR (32.3% low-risk and 67.7% high-risk). Median PSA-PFS was 135.0 mo (95% CI 129.63-140.94) and 115.0 mo (95% CI 104.02-125.98) (p < .001), for low and high-risk groups, respectively. There was also significant differences in MFS and overall survival. The EAU BCR risk grouping was independent factor for PSA-progression (HR 2.55, p 0.009). Time from PR to BCR, was an independent factor for metastasis onset (HR 0.43, 95% CI 0.18-0.99; p 0.044) and death (HR 0.17, 95% CI 0.26.0.96; 23 p 0.048). Differences in MFS (p 0.001) and cancer specific survival (p 0.004) were found for <12, ≥12-<36 and≥36 months from PR to BCR. Others independent factors were early salvage radiotherapy and PSA at BCR. Conclusions High-risk group is a prognostic factor for biochemical progression, but it has a limited accuracy on MP and death in our setting. The inclusion of other factors could increase its predictive power (AU)

The impact of race on survival in metastatic prostate cancer: a systematic literature review.

BACKGROUND: Prostate cancer (PC) is the second most diagnosed cancer in men worldwide. While racial and ethnic differences exist in incidence and mortality, increasing data suggest outcomes by race among men with newly diagnosed PC are similar. However, outcomes among races beyond Black/White have been poorly studied. Moreover, whether outcomes differ by race among men who all have metastatic PC (mPC) is unclear. This systematic literature review (SLR) provides a comprehensive synthesis of current evidence relating race to survival in mPC. METHODS: An SLR was conducted and reported in accordance with PRISMA guidelines. MEDLINE®, Embase, and Cochrane Library using the Ovid® interface were searched for real-world studies published from January 2012 to July 2022 investigating the impact of race on overall survival (OS) and prostate cancer-specific mortality (PCSM) in patients with mPC. A supplemental search of key congresses was also conducted. Studies were appraised for risk of bias. RESULTS: Of 3228 unique records identified, 62 records (47 full-text and 15 conference abstracts), corresponding to 54 unique studies (51 United States and 3 ex-United States) reporting on race and survival were included. While most studies showed no difference between Black vs White patients for OS (n = 21/27) or PCSM (n = 8/9), most showed that Black patients demonstrated improved OS on certain mPC treatments (n = 7/10). Most studies found no survival difference between White patients and Hispanic (OS: n = 6/8; PCSM: n = 5/6) or American Indian/Alaskan Native (AI/AN) (OS: n = 2/3; PCSM: n = 5/5). Most studies found Asian patients had improved OS (n = 3/4) and PCSM (n = 6/6) vs White patients. CONCLUSIONS: Most studies found Black, Hispanic, and AI/AN patients with mPC had similar survival as White patients, while Black patients on certain therapies and Asian patients showed improved survival. Future studies are needed to understand what aspects of race including social determinants of health are driving these findings.

The Imperative for Population-based Cancer Registration of All Metastatic Cancers.

Metastases are the main cause of morbidity and mortality from solid tumors. Surprisingly, population-based cancer registries in various countries, including the National Cancer Institute's Surveillance, Epidemiology, and End Results program in the United States, only capture data on individuals diagnosed with cancers that are metastatic at diagnosis (M1). Metastatic recurrences of previously diagnosed, initially nonmetastatic tumors are missed. Devasia and colleagues specify an illness-death model for chronic disease and estimate that in prostate cancer, which has a large pool of primary disease that may or may not progress to metastases, about half of all metastatic cancers arise as recurrences from initially nonmetastatic disease. Capturing all incident metastatic cancer cases across all tumor types in population-based cancer registries, not only based on initial stage at diagnosis, would be critical to better understand the disparities in metastatic disease burden and the effectiveness of primary prevention, screening, and therapies for primary and metastatic disease. See related article by Devasia et al., p. 659.

Effect of type of definitive treatment on race-based differences in prostate cancer-specific survival.

BACKGROUND: Racial and ethnic disparities in prostate cancer (PCa) mortality are partially mediated by inequities in quality of care. Intermediate- and high-risk PCa can be treated with either surgery or radiation, therefore we designed a study to assess the magnitude of race-based differences in cancer-specific survival between these two treatment modalities. METHODS: Non-Hispanic Black (NHB) and non-Hispanic White (NHW) men with localized intermediate- and high-risk PCa, treated with surgery or radiation between 2004 and 2015 in the Surveillance, Epidemiology and End Results database were included in the study and followed until December 2018. Unadjusted and adjusted survival analyses were employed to compare cancer-specific survival by race and treatment modality. A model with an interaction term between race and treatment was used to assess whether the type of treatment amplified or attenuated the effect of race/ethnicity on prostate cancer-specific mortality (PCSM). RESULTS: 15,178 (20.1%) NHB and 60,225 (79.9%) NHW men were included in the study. NHB men had a higher cumulative incidence of PCSM (p = 0.005) and were significantly more likely to be treated with radiation than NHW men (aOR: 1.89, 95% CI: 1.81-1.97, p < 0.001). In the adjusted models, NHB men were significantly more likely to die from PCa compared with NHW men (aHR: 1.18, 95% CI: 1.03-1.35, p = 0.014), and radiation was associated with a significantly higher odds of PCSM (aHR: 2.10, 95% CI: 1.85-2.38, p < 0.001) compared with surgery. Finally, the interaction between race and treatment on PCSM was not significant, meaning that no race-based differences in PCSM were found within each treatment modality. CONCLUSIONS: NHB men with intermediate- and high-risk PCa had a higher rate of PCSM than NWH men in a large national cancer registry, though NHB and NHW men managed with the same treatment achieved similar PCa survival outcomes. The higher tendency for NHB men to receive radiation was similar in magnitude to the difference in cancer survival between racial and ethnic groups.

A Detailed Evaluation of the Effect of Prostate-specific Antigen-based Screening on Morbidity and Mortality of Prostate Cancer: 21-year Follow-up Results of the Rotterdam Section of the European Randomised Study of Screening for Prostate Cancer.

BACKGROUND: Considering the long natural history of prostate cancer (PCa), long-term results of the European Randomised Study of Screening for PCa (ERSPC) are crucial. OBJECTIVE: To provide an update on the effect of prostate-specific antigen (PSA)-based screening on PCa-specific mortality (PCSM), metastatic disease, and overdiagnosis in the Dutch arm of the ERSPC. DESIGN, SETTING, AND PARTICIPANTS: Between 1993 and 2000, a total of 42376 men, aged 55-74 yr, were randomised to a screening or a control arm. The main analysis was performed with men aged 55-69 yr (n = 34831). Men in the screening arm were offered PSA-based screening with an interval of 4 yr. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Intention-to-screen analyses with Poisson regression were used to calculate rate ratios (RRs) of PCSM and metastatic PCa. RESULTS AND LIMITATIONS: After a median follow-up of 21 yr, the RR of PCSM was 0.73 (95% confidence interval [CI]: 0.61-0.88) favouring screening. The numbers of men needed to invite (NNI) and needed to diagnose (NND) to prevent one PCa death were 246 and 14, respectively. For metastatic PCa, the RR was 0.67 (95% CI: 0.58-0.78) favouring screening. The NNI and NND to prevent one metastasis were 121 and 7, respectively. No statistical difference in PCSM (RR of 1.18 [95% CI: 0.87-1.62]) was observed in men aged ≥70 yr at the time of randomisation. In the screening arm, higher rates of PCSM and metastatic disease were observed in men who were screened only once and in a selected group of men above the screening age cut-off of 74 yr. CONCLUSIONS: The current analysis illustrates that with a follow-up of 21 yr, both absolute metastasis and mortality reduction continue to increase, resulting in a more favourable harm-benefit ratio than demonstrated previously. These data do not support starting screening at the age of 70-74 yr and show that repeated screening is essential. PATIENT SUMMARY: Prostate-specific antigen-based prostate cancer screening reduces metastasis and mortality. Longer follow-up shows fewer invitations and diagnoses needed to prevent one death, a positive note towards the issue of overdiagnosis.

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.).

Identificación de parámetros pronósticos relativos a la técnica quirúrgica en pacientes tratados mediante prostatectomía radical robótica / Identifying prognostic parameters related to surgical technique in patients treated by robotic radical prostatectomy

Introducción y objetivo Los factores más estudiados en pacientes tratados mediante prostatectomía radical robótica son antígeno prostático específico (PSA) y las características patológicas de la biopsia y la pieza de prostatectomía. Los factores asociados a la técnica quirúrgica han sido poco estudiados y con resultados controvertidos. El objetivo es identificar todos los factores posibles de la cirugía y su relación con la supervivencia libre de enfermedad (SLE) y de metástasis. Pacientes y métodos Estudio prospectivo aprobado por el Comité de Ética, en pacientes intervenidos de prostatectomía radical robótica desde enero del 2009 con seguimiento mínimo de cinco años. Analizamos como posibles factores pronósticos: el cirujano, el tiempo quirúrgico, la pérdida sanguínea, el acceso fascial, las técnicas de continencia, la preservación de la fascia, las bandeletas neurovasculares, el cuello vesical, la uretra, la curva de aprendizaje y las complicaciones quirúrgicas. Realizamos comparaciones univariables y emparejadas de supervivencia mediante la estimación de Kaplan-Meier y long-rank tests. El nivel de significancia para comparaciones múltiples se estableció con ajuste False Discovery Rate (p ajustada [padj]). Resultados Cohorte de 667 pacientes con mediana de seguimiento de 69 meses. En el análisis univariante, el cirujano (padj = 0,018), la conservación de ligamentos puboprostáticos (padj = 0,02), la preservación de fascia endopélvica (padj = 0,001) y realizar suspensión parauretral (padj < 0,001) son factores de mal pronóstico para la SLE. La preservación de la fascia también afecta negativamente a la supervivencia libre de metástasis (SLM) (padj = 0,04). Las cirugías previas abdominales, la próstata, el tiempo de intervención, el sangrado, el tipo de uretra residual, el lóbulo medio, el acceso fascial, la conservación de bandeletas o cuello vesical, no tienen significancia estadística (AU)

Introduction and objective The most frequently studied factors in patients treated by robotic radical prostatectomy are PSA and pathological features of the biopsy and prostatectomy specimen. Studies on the factors associated with the surgical technique are scarce and with controversial results. The objective is to identify all possible surgical factors and their relationship with disease-free and metastasis-free survival. Patients and Method Prospective study approved by the Ethics Committee, including patients who underwent robotic radical prostatectomy since January 2009 with a minimum follow-up of 5 years. Surgeon, surgical time, blood loss, fascial access, continence techniques, preservation of the fascia, neurovascular bundles, bladder neck, urethra, learning curve and surgical complications, were analyzed as possible prognostic factors. We performed univariate and matched comparisons of survival using Kaplan-Meier estimation and long-rank tests. The significance level for multiple comparisons was established with False Discovery Rate-adjustment (adjusted p). Results Cohort of 667 patients with a median follow-up of 69 months. In univariate analysis, surgeon (adjp = 0.018), preservation of puboprostatic ligaments (adjp = 0.02), preservation of endopelvic fascia (adjp = 0.001) and performing periurethral suspension (adjp < 0.001) are poor prognostic factors for disease-free survival. Fascia preservation also negatively affects metastasis-free survival (adjp = 0.04). Previous abdominal surgeries, prostate, surgical time, blood loss, type of residual urethra, middle lobe, fascial access, fascia or bladder neck preservation, have no statistical significance. Conclusions The surgeon and specific aspects of the surgical technique are determining factors in disease-free survival. Preservation of the fascia is the only factor that negatively affects metastasis-free survival (AU)

Prostate cancer disparities among American Indians and Alaskan Natives in the United States.

BACKGROUND: Americans Indians and Alaska Natives face disparities in cancer care with lower rates of screening, limited treatment access, and worse survival. Prostate cancer treatment access and patterns of care remain unknown. METHODS: We used Surveillance, Epidemiology, and End Results data to compare incidence, primary treatment, and cancer-specific mortality across American Indian and Alaska Native, Asian and Pacific Islander, Black, and White patients. Baseline characteristics included prostate-specific antigen (PSA), Gleason score (GS), tumor stage, 9-level Cancer of the Prostate Risk Assessment risk score, county characteristics, and health-care provider density. Primary outcomes were first definitive treatment and prostate cancer-specific mortality (PCSM). RESULTS: American Indian and Alaska Native patients were more frequently diagnosed with higher PSA, GS greater than or equal or 8, stage greater than or equal to cT3, high-risk disease overall (Cancer of the Prostate Risk Assessment risk score ≥ 6), and metastases at diagnosis than any other group. Adjusting for age, PSA, GS, and clinical stage, American Indian or Alaska Native patients with localized prostate cancer were more likely to undergo external beam radiation than radical prostatectomy and had the highest rates of no documented treatment. Five-year PCSM was higher among American Indian and Alaska Natives than any other racial group. However, after multivariable adjustment accounting for clinical and pathologic factors, county-level demographics, and provider density, American Indian and Alaska Native patient PCSM hazards were no different than those of White patients. CONCLUSIONS: American Indian or Alaska Native patients have more advanced prostate cancer, lower rates of definitive treatment, higher mortality, and reside in areas of less specialty care. Disparities in access appear to account for excess risks of PCSM. Focused health policy interventions are needed to address these disparities.

Estudio poblacional de casuística y morbimortalidad de la prostatectomía radical en España / Population based study of morbidity and mortality rates associated to radical prostatectomy cases in Spain

Introducción: No existe ningún estudio poblacional que contabilice en número de prostatectomías radicales (PR) realizadas España, ni la morbimortalidad de dicha intervención.Nuestro objetivo es estudiar la morbimortalidad de la PR en España desde el 2011 al 2015 y evaluar la variabilidad geográfica. Material y métodos: Diseñamos un estudio observacional retrospectivo de todos los pacientes intervenidos de PR en España durante cinco años consecutivos (2011-2015) a partir de los datos registrados en el Conjunto Mínimo Básico de Datos (CMBD).Hemos estudiado la distribución del número de casos y la variabilidad intercomunitaria en términos de morbilidad y de estancia hospitalaria, así como el impacto del volumen quirúrgico medio anual por cada centro en dichas variables. Resultados: Entre los años 2011-2015 se han realizado un total de 37.725 PR en 221 hospitales españoles públicos del sistema nacional de salud. La edad media de la serie fue 63,9 ± 3,23 años. El 50% de las PR se han realizado por vía abierta, y un 43,4% se han intervenido en hospitales de < 500 camas. Encontramos una gran variabilidad en la distribución de los casos intervenidos en las distintas Comunidades Autónomas (CCAA Las comunidades que realizan un mayor número de prostatectomías son Andalucía, Cataluña, Galicia y Madrid. La tasa de complicaciones a nivel nacional es de 8,6%, siendo las más frecuentes la hemorragia y necesidad de transfusión (5,3 y 4%, respectivamente). Encontramos importantes diferencias en las tasas de hemorragia y en la estancia hospitalaria entre las distintas CCAA, que se mantienen tras ajustar por las características del paciente y del tipo de hospital. Al estudiar el volumen quirúrgico anual de cada hospital vemos que el impacto en la tasa de hemorragia o transfusión es lineal sin embargo en la estancia a partir de 60 PR/año la estancia se mantiene estable en torno a cinco días. (AU)

Introduction: There is no population-based study that accounts for the number of radical prostatectomies (RP) carried out in Spain, nor regarding the morbidity and mortality of this intervention.Our objective is to study the morbidity and mortality of RP in Spain from 2011 to 2015 and to evaluate the geographic variation. Material and methods: We designed a retrospective observational study of all patients submitted to RP in Spain during five consecutive years (2011-2015). The data was extracted from the «Conjunto Mínimo Básico de Datos» (CMBD).We have evaluated geographic variations in terms of morbidity and hospital stay, and the impact of the mean annual surgical volume for each center on these variables. Results: Between 2011-2015, a total of 37,725 RPs were performed in 221 Spanish public hospitals. The mean age of the series was 63.9 ± 3.23 years. Of all RPs, 50% were performed through an open approach, and 43.4% have been operated on in hospitals with < 500 beds. We observed an important variability in the distribution of the cases operated on in the different regions. The regions that perform more RPs are Andalusia, Catalonia, Galicia, and Madrid. Our study shows a complication rate of 8.6%, with hemorrhage and the need for transfusion being the most frequent (5.3 and 4%, respectively). There are significant differences in bleeding rates and hospital stay among regions, which are maintained after adjusting for patient characteristics and type of hospital. When studying the annual surgical volume of each hospital, we find that the impact on the rate of hemorrhage or transfusion is linear; however, hospital stay remains stable at around 5 days from 60 RPs/year (AU)

An analysis of time trends in breast and prostate cancer mortality rates in Lithuania, 1986-2020.

BACKGROUND: Breast cancer (BC) and prostate cancer (PC) mortality rates in Lithuania remain comparatively high despite the ongoing BC and PC screening programmes established in 2006. The aim of this study was to investigate time trends in BC and PC mortality rates in Lithuania evaluating the effects of age, calendar period of death, and birth-cohort over a 35-year time span. METHODS: We obtained death certification data for BC in women and PC in men for Lithuania during the period 1986-2020 from the World Health Organisation database. Age-standardised mortality rates were analysed using Joinpoint regression. Age-period-cohort models were used to assess the independent age, period and cohort effects on the observed mortality trends. RESULTS: Joinpoint regression analysis indicated that BC mortality increased by 1.6% annually until 1996, and decreased by - 1.2% annually thereafter. The age-period-cohort analysis suggests that temporal trends in BC mortality rates could be attributed mainly to cohort effects. The cohort effect curvature showed the risk of BC death increased in women born prior to 1921, remained stable in cohorts born around 1921-1951 then decreased; however, trend reversed in more recent generations. The period effect curvature displayed a continuous decrease in BC mortality since 1991-1995. For PC mortality, after a sharp increase by 3.0%, rates declined from 2007 by - 1.7% annually. The period effect was predominant in PC mortality, the curvature displaying a sharp increase until 2001-2005, then decrease. CONCLUSIONS: Modestly declining recent trends in BC and PC mortality are consistent with the introduction of widespread mammography and PSA testing, respectively, lagging up to 10 years. The study did not show that screening programme introduction played a key role in BC mortality trends in Lithuania. Screening may have contributed to favourable recent changes in PC mortality rates in Lithuania, however the effect was moderate and limited to age groups < 65 years. Further improvements in early detection methods followed by timely appropriate treatment are essential for decreasing mortality from BC and PC.

External beam radiation therapy treatment factors prognostic of biochemical failure free survival: A multi-institutional retrospective study for prostate cancer.

BACKGROUND AND PURPOSE: The goal of this work is to identify specific treatment planning and delivery features that are prognostic of biochemical failure-free survival (BFFS) for prostate cancer patients treated with external beam radiotherapy (EBRT). MATERIALS AND METHODS: This study reviewed patients diagnosed with localized prostate adenocarcinoma between 2005 and 2016, and treated with EBRT on a Varian linear accelerator at one of the four cancer centers in Alberta, Canada. BFFS was calculated using the Kaplan-Meier estimator. Patient demographics, tumor characteristics, and EBRT treatment planning and delivery factors, were collected for each patient. The patient cohort was split into a training dataset with patients from two centers and a validation dataset with patients from another two centers. A random survival forest was used to identify features associated with BFFS. RESULTS: This study included 2827 patients with a median follow-up of 6.4 years. The BFFS for this cohort collectively was 84.9% at 5 years and 69.3% at 10 years. 2519 patients from two centers were used for model training and 308 patients from two different centers were used for model validation. The prognostic features were Gleason score, prostate-specific antigen (PSA) at diagnosis, clinical T stage, CTV D99, pelvic irradiation, IGRT frequency, and PTV V98. Variables including bladder volume, dose calculation algorithm, PTV D99, age at diagnosis, hip prosthesis, number of malignancies, fiducial marker usage, PTV volume, RT modality, PTV HI, rectal volume, hormone treatment, PTV D1cc, equivalent PTV margin, IGRT type, and EQD2_1.5 were unlikely to be prognostic. A random survival forest using only the seven prognostic variables was built. The Harrell's concordance index for the model was 0.65 for the whole training dataset, 0.62 for out-of-bag samples of the training dataset, and 0.62 for the validation dataset. CONCLUSION: EBRT features prognostic of BFFS were identified and a random survival forest was developed for predicting prostate cancer patients' BFFS after EBRT.

SNPs at SMG7 Associated with Time from Biochemical Recurrence to Prostate Cancer Death.

BACKGROUND: A previous genome-wide association study identified several loci with genetic variants associated with prostate cancer survival time in two cohorts from Sweden. Whether these variants have an effect in other populations or if their effect is homogenous across the course of disease is unknown. METHODS: These variants were genotyped in a cohort of 1,298 patients. Samples were linked with age, PSA level, Gleason score, cancer stage at surgery, and times from surgery to biochemical recurrence to death from prostate cancer. SNPs rs2702185 and rs73055188 were tested for association with prostate cancer-specific survival time using a multivariate Cox proportional hazard model. SNP rs2702185 was further tested for association with time to biochemical recurrence and time from biochemical recurrence to death with a multi-state model. RESULTS: SNP rs2702185 at SMG7 was associated with prostate cancer-specific survival time, specifically the time from biochemical recurrence to prostate cancer death (HR, 2.5; 95% confidence interval, 1.4-4.5; P = 0.0014). Nine variants were in linkage disequilibrium (LD) with rs2702185; one, rs10737246, was found to be most likely to be functional based on LD patterns and overlap with open chromatin. Patterns of open chromatin and correlation with gene expression suggest that this SNP may affect expression of SMG7 in T cells. CONCLUSIONS: The SNP rs2702185 at the SMG7 locus is associated with time from biochemical recurrence to prostate cancer death, and its LD partner rs10737246 is predicted to be functional. IMPACT: These results suggest that future association studies of prostate cancer survival should consider various intervals over the course of disease.

Association of 5α-Reductase Inhibitors With Prostate Cancer Mortality.

Importance: There is evidence that 5α-reductase inhibitors (5-ARIs), a standard treatment of benign prostate hyperplasia, are associated with a decrease in the incidence of prostate cancer (PCa). However, studies to date have had conflicting results regarding the association with prostate cancer mortality (PCM). Objective: To evaluate the association of treatment with 5-ARIs with PCM in men without a prior diagnosis of PCa. Design, Setting, and Participants: This population-based cohort study was conducted in Stockholm, Sweden, between January 1, 2007, and December 31, 2018, and included 429 977 men with a prostate-specific antigen (PSA) test within the study period. Study entry was set to 1 year after the first PSA test. Data were analyzed from September 2021 to December 2021. Exposures: After their initial PSA test, men with 2 or more newly dispensed prescriptions of 5-ARI, finasteride, or dutasteride were considered 5-ARI users (n = 26 190). Main Outcomes and Measures: Primary outcome was PCM. Cox proportional hazards regression models were used to calculate multivariable-adjusted hazard ratios (HRs) and 95% CIs for all-cause mortality and PCM. Results: The study cohort included 349 152 men. The median (IQR) age for those with 2 or more filled prescriptions of 5-ARI was 66 (61-73) years and 57 (50-64) years for those without. The median follow-up time was 8.2 (IQR, 4.9-10) years with 2 257 619 person-years for the unexposed group and 124 008 person-years for the exposed group. The median exposure to treatment with 5-ARI was 4.5 (IQR, 2.1-7.4) years. During follow-up, 35 767 men (8.3%) died, with 852 deaths associated with PCa. The adjusted multivariable survival analysis showed a lower risk of PCM in the 5-ARI group with longer exposure times (0.1-2.0 years: adjusted HR, 0.89; 95% CI, 0.64-1.25; >8 years: adjusted HR, 0.44; 95% CI, 0.27-0.74). No statistically significant differences were seen in all-cause mortality between the exposed and unexposed group. Men treated with 5-ARIs underwent more PSA tests and biopsies per year than the unexposed group (median of 0.63 vs 0.33 and 0.22 vs 0.12, respectively). Conclusions and Relevance: The results of this cohort study suggest that there was no association between treatment with 5-ARI and increased PCM in a large population-based cohort of men without a previous PCa diagnosis. Additionally, a time-dependent association was seen with decreased risk of PCM with longer 5-ARI treatment. Further research is needed to determine whether the differences are because of intrinsic drug effects or PCa testing differences.

Competing risk of the specific mortality among Asian-American patients with prostate cancer: a surveillance, epidemiology, and end results analysis.

BACKGROUND: Adopted the competing-risk model to investigate the relevant factors affecting the prostate cancer (PCa)-specific mortality among Asian-American PCa patients based on the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: The information of 26,293 Asian-American patients diagnosed with PCa between 2004 and 2015 were extracted from the SEER 18 database. Subjects were divided into three groups: died of PCa, died of other causes, survival based on the outcomes at the end of 155 months' follow-up. Multivariate analysis was performed by the Fine-gray proportional model. Meanwhile, subgroup analyses were conducted risk stratification by race and age. RESULTS: Age ≥ 65 years [Hazard ratio (HR) = 1.509, 95% confidence interval (CI) 1.299-1.754], race (HR = 1.220, 95% CI 1.028-1.448), marital status (unmarried, single or widowed, HR = 1.264, 95% CI 1.098-1.454), tumor grade II (HR = 3.520, 95% CI 2.915-4.250), the American Joint Committee on Cancer (AJCC) stage (T3: HR = 1.597, 95% CI 1.286-1.984; T4: HR = 2.446, 95% CI 1.796-3.331; N1: HR = 1.504, 95% CI 1.176-1.924; M1: HR = 9.875, 95% CI 8.204-11.887) at diagnosis, radiotherapy (HR = 1.892, 95% CI 1.365-2.623), regional nodes positive (HR = 2.498, 95% CI 1.906-3.274) increased risk of PCa-specific mortality for Asian-American PCa patients, while surgical (HR = 0.716, 95% CI 0.586-0.874) reduced the risk. CONCLUSION: The study findings showed that age, race, marital status, tumor grade (II), AJCC stages (T3, T4, N1, M1) at diagnosis, radiotherapy, regional nodes positive and surgery was associated with the specific mortality of PCa patients among Asian-Americans.

Predicting biochemical-recurrence-free survival using a three-metabolic-gene risk score model in prostate cancer patients.

BACKGROUND: Biochemical recurrence (BCR) after initial treatment, such as radical prostatectomy, is the most frequently adopted prognostic factor for patients who suffer from prostate cancer (PCa). In this study, we aimed to construct a prognostic model consisting of gene expression profiles to predict BCR-free survival. METHODS: We analyzed 70 metabolic pathways in 152 normal prostate samples and 494 PCa samples from the UCSC Xena dataset (training set) via gene set enrichment analysis (GSEA) to select BCR-related genes and constructed a BCR-related gene risk score (RS) model. We tested the power of our model using Kaplan-Meier (K-M) plots and receiver operator characteristic (ROC) curves. We performed univariate and multivariate analyses of RS using other clinicopathological features and established a nomogram model, which has stronger prediction ability. We used GSE70770 and DFKZ 2018 datasets to validate the results. Finally, we performed differential expression and quantitative real-time polymerase chain reaction analyses of the UCSC data for further verification of the findings. RESULTS: A total of 194 core enriched genes were obtained through GSEA, among which 16 BCR-related genes were selected and a three-gene RS model based on the expression levels of CA14, LRAT, and MGAT5B was constructed. The outcomes of the K-M plots and ROC curves verified the accuracy of the RS model. We identified the Gleason score, pathologic T stage, and RS model as independent predictors through univariate and multivariate Cox analyses and constructed a nomogram model that presented better predictability than the RS model. The outcomes of the validation set were consistent with those of the training set. Finally, the results of differential expression analyses support the effectiveness of our model. CONCLUSION: We constructed an RS model based on metabolic genes that could predict the prognosis of PCa patients. The model can be easily used in clinical applications and provide important insights into future research on the underlying mechanism of PCa.

SP/NK1R system regulates carcinogenesis in prostate cancer: Shedding light on the antitumoral function of aprepitant.

AIMS: Prostate cancer continues to be one of the main global health issues in men. Neuropeptide substance P (SP) acting via neurokinin-1receptor (NK1R) promotes tumorigenicity in many human malignant tumors. However, its pro-tumorigenic functions and the therapeutic effects of its inhibition in prostate cancer remain unclear. METHODS: MTT assay was employed for measuring cellular proliferation and cytotoxicity. mRNAs and proteins expression levels were evaluated by qRT-PCR and western blot assay, respectively. Gelatinase activity was assessed by zymography. The migration ability was defined using wound-healing assay. Flow cytometry was employed to evaluate the cell cycle distribution. We also performed an in vivo experiment in a mouse model of prostate cancer to confirm the in vitro therapeutic effect of targeting the SP/NK1R system. RESULTS: We found a noticeable increase in the expression of the truncated isoform of NK1R as an oncogenic NK1R splice variant in tumor cells. We also demonstrated that SP promotes both proliferative and migrative phenotypes of prostate cancer through modifying cell cycle-related proteins (c-Myc, cyclin D1, cyclin B1, p21), and apoptosis-related genes (Bcl-2 and Bax), promoting cell migration and increasing MMP-2 and MMP-9 expression and activity, while aprepitant administration could remarkably reverse these effects. SP also stimulated tumor growth in vivo, which was correlated with shorter survival times, while aprepitant reversed this effect and led to significantly longer survival time. SIGNIFICANCE: Our findings suggest that SP/NK1R system may serve as a novel therapeutic target in prostate cancer and support the possible candidacy of aprepitant in future prostate cancer therapy.