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Background Although prostate MRI is routinely used for the detection and staging of localized prostate cancer, imaging-based assessment and targeted molecular sampling for risk stratification are an active area of research. Purpose To evaluate features of preoperative MRI and MRI-guided biopsy immunohistochemistry (IHC) findings associated with biochemical recurrence (BCR) of prostate cancer after surgery. Materials and Methods In this retrospective case-control study, patients underwent multiparametric MRI before MRI-guided biopsy followed by radical prostatectomy between 2008 and 2016. Lesions were retrospectively scored with the Prostate Imaging Reporting and Data System (PI-RADS) (version 2) by radiologists who were blinded to the clinical-pathologic results. The IHC staining, including stains for the ETS-related gene, phosphatase and tensin homolog, androgen receptor, prostate specific antigen, and p53, was performed with targeted biopsy specimens of the index lesion (highest suspicion at MRI and pathologic grade) and scored by pathologists who were blinded to clinical-pathologic outcomes. Cox proportional hazards regression analysis was used to evaluate associations with recurrence-free survival (RFS). Results The median RFS was 31.7 months (range, 1-101 months) for 39 patients (median age, 62 years; age range, 47-76 years) without BCR and 14.6 months (range, 1-61 months) for 40 patients (median age, 59 years; age range, 47-73 years) with BCR. MRI features that showed a significant relationship with the RFS interval included an index lesion with a PI-RADS score of 5 (hazard ratio [HR], 2.10; 95% CI: 1.05, 4.21; P = .04); index lesion burden, defined as ratio of index lesion volume to prostate volume (HR, 1.55; 95% CI: 1.2, 2.1; P = .003); and suspicion of extraprostatic extension (EPE) (HR, 2.18; 95% CI: 1.1, 4.2; P = .02). Presurgical multivariable analysis indicated that suspicion of EPE at MRI (adjusted HR, 2.19; 95% CI: 1.1, 4.3; P = .02) and p53 stain intensity (adjusted HR, 2.22; 95% CI: 1.0, 4.7; P = .04) were significantly associated with RFS. Conclusion MRI features, including Prostate Imaging Reporting and Data System score, index lesion burden, extraprostatic extension, and preoperative guided biopsy p53 immunohistochemistry stain intensity are associated with biochemical relapse of prostate cancer after surgery. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Costa in this issue.
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Biopsia Guiada por Imagen , Inmunohistoquímica , Imágenes de Resonancia Magnética Multiparamétrica , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/cirugía , Anciano , Estudios de Casos y Controles , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Prostatectomía , Neoplasias de la Próstata/patología , Estudios RetrospectivosRESUMEN
PURPOSE: Prostate cancer is predominantly indolent at diagnosis with a small fraction (15% to 25%) representing aggressive subtype (Gleason score 7-10), which is prone to metastatic progression. It is critical to explore noninvasive assays for the early detection of this aggressive subtype, when it still can be treated effectively. Additionally, there is an emerging need to develop markers that perform equally well across races, as racial differences in the prevalence and mortality of prostate cancer has become evident. MATERIALS AND METHODS: First catch, nondigital rectal examination urine specimens were collected from patients undergoing diagnostic biopsy. Total RNA was extracted from urinary exosomes and a quantitative expression assay protocol using droplet digital polymerase chain reaction was developed for detection of candidate genes in exosomal mRNAs from urine. Clinical performance for the gene expression assay was evaluated to predict high grade cancer (Gleason score 7-10) from low grade cancer (Gleason score 6) and cancer negative cases at biopsy. Assay performance was examined in combination with standard of care to determine improvement in model prediction. RESULTS: In a racially diverse patient cohort a 2-gene panel (PCA3, PCGEM1), in combination with standard of care variables, significantly improved the prediction of high grade cancer at diagnosis compared to standard of care variables alone (AUC 0.88 vs 0.80, respectively, p=0.016). Decision curve analysis showed that there is a benefit of adopting the gene panel for detection of high grade cancer compared to standard of care alone. CONCLUSIONS: This study highlights the potential for developing broadly applicable prostate cancer diagnostic biomarker panels for aggressive prostate cancer using our novel gene expression assay platform.
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Exosomas/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Adulto , Anciano , Anciano de 80 o más Años , Biopsia , Estudios de Cohortes , Diagnóstico Diferencial , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de la Próstata/orinaRESUMEN
BACKGROUND: Predicting the clinical course of prostate cancer is challenging due to the wide biological spectrum of the disease. The objective of our study was to identify prostate cancer prognostic markers in patients 'sera using a multi-omics discovery platform. METHODS: Pre-surgical serum samples collected from a longitudinal, racially diverse, prostate cancer patient cohort (N = 382) were examined. Linear Regression and Bayesian computational approaches integrated with multi-omics, were used to select markers to predict biochemical recurrence (BCR). BCR-free survival was modeled using unadjusted Kaplan-Meier estimation curves and multivariable Cox proportional hazards analysis, adjusted for key pathologic variables. Receiver operating characteristic (ROC) curve statistics were used to examine the predictive value of markers in discriminating BCR events from non-events. The findings were further validated by creating a training set (N = 267) and testing set (N = 115) from the cohort. RESULTS: Among 382 patients, 72 (19%) experienced a BCR event in a median follow-up time of 6.9 years. Two proteins-Tenascin C (TNC) and Apolipoprotein A1V (Apo-AIV), one metabolite-1-Methyladenosine (1-MA) and one phospholipid molecular species phosphatidic acid (PA) 18:0-22:0 showed a cumulative predictive performance of AUC = 0.78 [OR (95% CI) = 6.56 (2.98-14.40), P < 0.05], in differentiating patients with and without BCR event. In the validation set all four metabolites consistently reproduced an equivalent performance with high negative predictive value (NPV; > 80%) for BCR. The combination of pTstage and Gleason score with the analytes, further increased the sensitivity [AUC = 0.89, 95% (CI) = 4.45-32.05, P < 0.05], with an increased NPV (0.96) and OR (12.4) for BCR. The panel of markers combined with the pathological parameters demonstrated a more accurate prediction of BCR than the pathological parameters alone in prostate cancer. CONCLUSIONS: In this study, a panel of serum analytes were identified that complemented pathologic patient features in predicting prostate cancer progression. This panel offers a new opportunity to complement current prognostic markers and to monitor the potential impact of primary treatment versus surveillance on patient oncological outcome.
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Prostatectomía , Neoplasias de la Próstata , Teorema de Bayes , Biomarcadores , Progresión de la Enfermedad , Humanos , Masculino , Clasificación del Tumor , Recurrencia Local de Neoplasia , Pronóstico , Antígeno Prostático Específico , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/cirugíaRESUMEN
PURPOSE: The aim of this study was to identify the effects of subsequent prostate needle biopsies after the baseline biopsy on health related quality of life with time. We compared men with and without prostate cancer, and men who did and did not undergo followup prostate needle biopsy. MATERIALS AND METHODS: Included in analysis were patients enrolled in the Center for Prostate Disease Research Multicenter National Database between 2007 and 2015 who had low or favorable intermediate risk prostate cancer, were on active surveillance and underwent prostate needle biopsy for suspicion of prostate cancer. Patients completed the EPIC (Expanded Prostate Cancer Index Composite) and the RAND SF-36 (36-Item Short Form Health Survey) after baseline biopsy and at regular followup intervals. Mean health related quality of life was compared with time between patients who did and did not undergo subsequent prostate needle biopsies following baseline. RESULTS: Of the 637 patients included in study 129 (20.3%) with prostate cancer were on active surveillance and 508 (79.7%) were in the noncancer group. In the cancer and noncancer groups mean ± SD followup was 34.7 ± 16.9 and 31.6 ± 14.6 months, respectively. Of the patients with prostate cancer 54 (60.7%) underwent subsequent prostate needle biopsies compared with 114 (27.1%) without cancer. No significant impact on health related quality of life was observed in men who underwent subsequent prostate needle biopsies during a 5-year period. CONCLUSIONS: A subsequent prostate needle biopsy is required in most active surveillance protocols and in men with persistent suspicion of prostate cancer. Our analysis shows that subsequent prostate needle biopsies do not significantly impact health related quality of life.
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Neoplasias de la Próstata/diagnóstico , Calidad de Vida , Espera Vigilante/métodos , Anciano , Biopsia con Aguja/efectos adversos , Biopsia con Aguja/normas , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Próstata/patología , Neoplasias de la Próstata/patología , Encuestas y Cuestionarios/estadística & datos numéricos , Resultado del Tratamiento , Espera Vigilante/normasRESUMEN
INTRODUCTION: To assess the impact of primary and secondary therapies for high- and intermediate-risk prostate cancer on health-related quality of life (HRQoL). MATERIALS AND METHODS: A prospective study was initiated in 2007 at Center for Prostate Disease Research Multicenter National Database sites. Longitudinal patterns in HRQoL from baseline (pre-treatment) to 5 years post-diagnosis were examined for patients with high- and intermediate-risk prostate cancer, treated by radical prostatectomy (RP) or external beam radiation therapy (EBRT). Change in HRQoL was modeled using linear regression models fit with generalized estimating equations. The probability of maintaining HRQoL was compared between patients receiving RP only versus RP with secondary treatment. RESULTS: Of 445 men with high- and intermediate-risk prostate cancer, 228 underwent RP and 143 had EBRT± androgen deprivation therapy (ADT). Fifty received secondary therapy (EBRT and/or ADT or chemotherapy) after RP. RP patients showed a greater decline over time in sexual function and bother and urinary function compared to EBRT±ADT patients. Patients who had secondary therapy after RP were less likely to maintain their HRQoL compared to those who had RP alone. These differences were most pronounced for sexual and hormonal function. CONCLUSIONS: Prostate cancer patients experience significant declines in HRQoL after primary therapy. Additional secondary therapy after RP, in the form of EBRT and/or ADT, appears to be responsible for further deterioration in HRQoL outcomes.
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Recurrencia Local de Neoplasia/terapia , Prostatectomía/métodos , Neoplasias de la Próstata/psicología , Neoplasias de la Próstata/terapia , Calidad de Vida , Radioterapia de Alta Energía/métodos , Anciano , Antagonistas de Andrógenos/administración & dosificación , Bases de Datos Factuales , Supervivencia sin Enfermedad , Humanos , Modelos Lineales , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Invasividad Neoplásica/patología , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Estudios Prospectivos , Prostatectomía/mortalidad , Neoplasias de la Próstata/mortalidad , Neoplasias de la Próstata/patología , Dosificación Radioterapéutica , Radioterapia de Alta Energía/mortalidad , Medición de Riesgo , Análisis de Supervivencia , Resultado del Tratamiento , Estados UnidosRESUMEN
The androgen receptor is one of the key targets for prostate cancer treatment. Despite its less satisfactory effects, chemotherapy is the most common treatment option for metastatic and/or castration-resistant patients. There are constant needs for novel anti-prostate cancer therapeutic/prevention agents. Curcumin, a known chemo-preventive agent, was shown to inhibit prostate cancer cell growth. This study aimed to unravel the inhibitory effect of curcumin in prostate cancer through analyzing the alterations of expressions of curcumin targeting genes clusters in androgen-dependent LNCaP cells and androgen-independent metastatic C4-2B cells. Hierarchical clustering showed the highest number of differentially expressed genes at 12 h post treatment in both cells, suggesting that the androgen-dependent/independent manner of curcumin impacts on prostate cancer cells. Evaluation of significantly regulated top canonical pathways highlighted that Transforming growth factor beta (TGF-ß), Wingless-related integration site (Wnt), Phosphoinositide 3-kinase/Protein Kinase B/ mammalian target of rapamycin (PIK3/AKT(PKB)/mTOR), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) signaling were primarily inhibited, and Phosphatase and tensin homolog (PTEN) dependent cell cycle arrest and apoptosis pathways were elevated with curcumin treatment. The short term (3-24 h) and long term (48 h) effect of curcumin treatment revealed 31 and four genes modulated in both cell lines. TGF-ß signaling, including the androgen/TGF-ß inhibitor Prostate transmembrane protein androgen-induced 1 (PMEPA1), was the only pathway impacted by curcumin treatment after 48 h. Our findings also established that MYC Proto-Oncogene, basic helix-loop-helix (bHLH) Transcription Factor (MYC) signaling was down-regulated in curcumin-treated cell lines. This study established, for the first time, novel gene-networks and signaling pathways confirming the chemo-preventive and cancer-growth inhibitory nature of curcumin as a natural anti-prostate cancer compound.
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Antineoplásicos/farmacología , Curcumina/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Hormonas/metabolismo , Andrógenos/metabolismo , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular/efectos de los fármacos , Biología Computacional/métodos , Perfilación de la Expresión Génica , Ontología de Genes , Humanos , Masculino , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Proto-Oncogenes Mas , Transducción de Señal/efectos de los fármacosRESUMEN
BACKGROUND: Prostate cancer patients diagnosed with low- and intermediate-risk disease have several treatment options. Decisional regret after treatment is a concern, especially when poor oncologic outcomes or declines in health-related quality of life (HRQoL) occur. This study assessed determinants of longitudinal decisional regret in prostate cancer patients attending a multidisciplinary clinic and treated with radical prostatectomy (RP), external beam radiation therapy (EBRT), brachytherapy (BT), or active surveillance (AS). METHODS: Patients newly diagnosed with prostate cancer at the Walter Reed National Military Medical Center who attended a multidisciplinary clinic were enrolled into a prospective study from 2006 to 2014. The Decision Regret Scale was administered at 6, 12, 24, and 36 months posttreatment. HRQoL was also assessed at regular intervals using the Expanded Prostate Cancer Index Composite and 36-item RAND Medical Outcomes Study Short Form questionnaires. Adjusted probabilities of reporting regret were estimated via multivariable logistic regression fitted with generalized estimating equations. RESULTS: A total of 652 patients met the inclusion criteria (395 RP, 141 EBRT, 41 BT, 75 AS). Decisional regret was consistently low after all of these treatments. In multivariable models, only African American race (odds ratio, 1.67; 95% confidence interval, 1.12-2.47) was associated with greater regret across time. Age and control preference were marginally associated with regret. Regret scores were similar between RP patients who did and did not experience biochemical recurrence. Declines in HRQoL were weakly correlated with greater decisional regret. CONCLUSION: In the context of a multidisciplinary clinic, decisional regret did not differ significantly between treatment groups but was greater in African Americans and those reporting poorer HRQoL. Cancer 2017;123:4252-4258. © 2017 American Cancer Society.
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Toma de Decisiones , Emociones , Neoplasias de la Próstata/psicología , Neoplasias de la Próstata/terapia , Calidad de Vida , Negro o Afroamericano/psicología , Negro o Afroamericano/estadística & datos numéricos , Factores de Edad , Anciano , Braquiterapia/psicología , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Prostatectomía/psicología , Neoplasias de la Próstata/etnología , Neoplasias de la Próstata/patología , Radioterapia/psicología , Riesgo , Factores de Tiempo , Espera VigilanteRESUMEN
PURPOSE: Active surveillance is an important alternative to definitive therapy for men with low risk prostate cancer. However, the impact of active surveillance on health related quality of life compared to that in men without cancer remains unknown. In this study we evaluated health related quality of life outcomes in men on active surveillance compared to men followed after negative prostate needle biopsy. MATERIALS AND METHODS: A prospective study was conducted on men who were enrolled into the Center for Prostate Disease Research Multicenter National Database and underwent prostate needle biopsy for suspicion of prostate cancer between 2007 and 2014. Health related quality of life was assessed at biopsy (baseline) and annually for up to 3 years using SF-36 and EPIC questionnaires. Health related quality of life scores were modeled using generalized estimating equations, adjusting for baseline health related quality of life, and demographic and clinical characteristics. RESULTS: Of the 1,204 men who met the initial eligibility criteria 420 had a negative prostate needle biopsy (noncancer comparison group). Among the 411 men diagnosed with low risk prostate cancer 89 were on active surveillance. Longitudinal analysis revealed that for most health related quality of life subscales there were no significant differences between the groups in adjusted health related quality of life score trends over time. CONCLUSIONS: In this study most health related quality of life outcomes in patients with low risk prostate cancer on active surveillance did not differ significantly from those of men without prostate cancer. A comparison group of men with a similar risk of prostate cancer detection is critical to clarify the psychological and physical impact of active surveillance.
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Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/patología , Calidad de Vida , Espera Vigilante , Adulto , Anciano , Biopsia con Aguja , Bases de Datos Factuales , Estudios de Seguimiento , Indicadores de Salud , Humanos , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
BACKGROUND: For patients with low-risk prostate cancer (PCa), active surveillance (AS) may produce oncologic outcomes comparable to those achieved with radical prostatectomy (RP). Health-related quality-of-life (HRQoL) outcomes are important to consider, yet few studies have examined HRQoL among patients with PCa who were managed with AS. In this study, the authors compared longitudinal HRQoL in a prospective, racially diverse, and contemporary cohort of patients who underwent RP or AS for low-risk PCa. METHODS: Beginning in 2007, HRQoL data from validated questionnaires (the Expanded Prostate Cancer Index Composite and the 36-item RAND Medical Outcomes Study short-form survey) were collected by the Center for Prostate Disease Research in a multicenter national database. Patients aged ≤75 years who were diagnosed with low-risk PCa and elected RP or AS for initial disease management were followed for 3 years. Mean scores were estimated using generalized estimating equations adjusting for baseline HRQoL, demographic characteristics, and clinical patient characteristics. RESULTS: Of the patients with low-risk PCa, 228 underwent RP, and 77 underwent AS. Multivariable analysis revealed that patients in the RP group had significantly worse sexual function, sexual bother, and urinary function at all time points compared with patients in the AS group. Differences in mental health between groups were below the threshold for clinical significance at 1 year. CONCLUSIONS: In this study, no differences in mental health outcomes were observed, but urinary and sexual HRQoL were worse for patients who underwent RP compared with those who underwent AS for up to 3 years. These data offer support for the management of low-risk PCa with AS as a means for postponing the morbidity associated with RP without concomitant declines in mental health.
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Salud Mental , Prostatectomía , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/cirugía , Calidad de Vida , Espera Vigilante , Anciano , Estado de Salud , Humanos , Masculino , Persona de Mediana Edad , Vigilancia de la Población , Estudios Prospectivos , Encuestas y CuestionariosRESUMEN
TP53 is one of the most frequently altered genes in prostate cancer. The precise assessment of its focal alterations in primary tumors by immunohistochemistry (IHC) has significantly enhanced its prognosis. p53 protein expression and lymphovascular invasion (LVI) were evaluated for predicting metastatic progression by IHC staining of representative whole-mounted prostate sections from a cohort of 189 radical prostatectomy patients with up to 20 years of clinical follow-up. Kaplan-Meier survival curves were used to examine time to distant metastasis (DM) as a function of p53 expression and LVI status. TP53 targeted sequencing was performed in ten tumors with the highest expression of p53 staining. Nearly half (49.8%) of prostate tumors examined showed focal p53 expression while 26.6% showed evidence of LVI. p53(+) tumors had higher pathologic T stage, Grade Group, Nuclear Grade, and more frequent LVI. p53 expression of > 5% and LVI, individually and jointly, are associated with poorer DM-free survival. TP53 mutations were detected in seven of ten tumors sequenced. Four tumors with the highest p53 expression harbored likely pathogenic or pathogenic mutations. High levels of p53 expression suggest the likelihood of pathogenic TP53 alterations and, together with LVI status, could enhance early prognostication of prostate cancer progression.
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Próstata , Neoplasias de la Próstata , Humanos , Inmunohistoquímica , Masculino , Pronóstico , Próstata/patología , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/cirugía , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
BACKGROUND: There is substantial variability in prostate cancer (PCa) mortality rates across Caucasian American (CA), African American (AA), Asian, and Hispanic men; however, these estimates are unable to disentangle race or ethnicity from confounding factors. The current study explores survival differences in long-term PCa outcomes between self-reported AA and CA men, and examines clinicopathologic features across self-reported CA, AA, Asian, and Hispanic men. METHODS: This retrospective cohort study utilized the Center for Prostate Disease Research (CPDR) Multi-center National Database from 1990 to 2017. Subjects were consented at military treatment facilities nationwide. AA, CA, Asian, or Hispanic men who underwent radical prostatectomy (RP) for localized PCa within the first year of diagnosis were included in the analyses. Time from RP to biochemical recurrence (BCR), BCR to metastasis, and metastasis to overall death were evaluated using Kaplan-Meier unadjusted estimation curves and adjusted Cox proportional hazards regression. RESULTS: This study included 7067 men, of whom 5155 (73%) were CA, 1468 (21%) were AA, 237 (3%) were Asian, and 207 (3%) were Hispanic. AA men had a significantly decreased time from RP to BCR compared to CA men (HR = 1.25, 95% CI = 1.06-1.48, p = 0.01); however, no difference was observed between AA and CA men for a time from BCR to metastasis (HR = 0.73, 95% CI = 0.39-1.33, p = 0.302) and time from metastasis to overall death (HR = 0.67, 95% CI = 0.36-1.26, p = 0.213). CONCLUSIONS: In an equal access health care setting, AA men had a shorter survival time from RP to BCR, but comparable survival time from BCR to metastasis and metastasis to overall death.
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Salud Militar , Neoplasias de la Próstata , Masculino , Humanos , Estudios Retrospectivos , Recurrencia Local de Neoplasia/patología , Neoplasias de la Próstata/patología , Prostatectomía , Antígeno Prostático Específico , Estudios de CohortesRESUMEN
In prostate cancer, emerging data highlight the role of DNA damage repair genes (DDRGs) in aggressive forms of the disease. However, DDRG mutations in African American men are not yet fully defined. Here, we profile germline mutations in all known DDRGs (N = 276) using whole genome sequences from blood DNA of a matched cohort of patients with primary prostate cancer comprising of 300 African American and 300 European Ancestry prostate cancer patients, to determine whether the mutation status can enhance patient stratification for specific targeted therapies. Here, we show that only 13 of the 46 DDRGs identified with pathogenic/likely pathogenic mutations are present in both African American and European ancestry patients. Importantly, RAD family genes (RAD51, RAD54L, RAD54B), which are potentially targetable, as well as PMS2 and BRCA1, are among the most frequently mutated DDRGs in African American, but not in European Ancestry patients.
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Negro o Afroamericano , Neoplasias de la Próstata , Negro o Afroamericano/genética , Daño del ADN/genética , Mutación de Línea Germinal , Humanos , Masculino , Mutación , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patologíaRESUMEN
BACKGROUND: Previous research exploring the role of race on prostate cancer (PCa) outcomes has demonstrated greater rates of disease progression and poorer overall survival for African American (AA) compared to Caucasian American (CA) men. The current study examines self-reported race as a predictor of long-term PCa outcomes in patients with low and favorable-intermediate risk disease treated with external beam radiation therapy (EBRT). METHODS: This retrospective cohort study examined patients who were consented to enrollment in the Center for Prostate Disease Research Multicenter National Database between January 01, 1990 and December 31, 2017. Men self-reporting as AA or CA who underwent EBRT for newly diagnosed National Comprehensive Cancer Network-defined low or favorable-intermediate risk PCa were included. Dependent study outcomes included: biochemical recurrence-free survival, (ii) distant metastasis-free survival, and (iii) overall survival. Each outcome was modeled as a time-to-event endpoint using race-stratified Kaplan-Meier estimation curves and multivariable Cox proportional hazards analysis. RESULTS: Of 840 men included in this study, 268 (32%) were AA and 572 (68%) were CA. The frequency of biochemical recurrence, distant metastasis, and deaths from any cause was 151 (18.7%), 29 (3.5%), and 333 (39.6%), respectively. AA men had a significantly younger median age at time of EBRT and slightly higher biopsy Gleason scores. Multivariable Cox proportional hazards analyses demonstrated no racial differences in any of the study endpoints. CONCLUSIONS: These findings reveal no racial disparity in PCa outcomes for AA compared to CA men, in a long-standing, longitudinal cohort of patients with comparable access to cancer care.
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Neoplasias de la Próstata , Masculino , Humanos , Estudios Retrospectivos , Neoplasias de la Próstata/patología , Clasificación del Tumor , Negro o Afroamericano , Población BlancaRESUMEN
Within the text we describe a 66-year-old male with a history of prostate cancer (PCa), incidentally found to have left-sided hydronephrosis and a left ureteral lesion. Ureteroscopy was employed to visualize the lesion, a biopsy was taken, and a double J stent was placed. The lesion was of prostatic origin and the patient was subsequently started on androgen deprivation therapy (ADT). 6 months following the procedure, the patient's PSA had decreased and his hydronephrosis had resolved. We are the first to report treating a ureteral metastasis from PCa and its associated hydronephrosis solely with ADT and double J stenting, respectively.
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ANXA2 (Annexin A2 or Annexin II) is a calcium dependent phospholipid binding protein with diverse cellular functions. While ANXA2 is either absent or expressed focally in the prostate epithelium of well and moderately differentiated tumours, it is highly expressed in a subset of poorly differentiated tumours. Here we examined the association between ANXA2 expression and tumour progression, with consideration of ERG expression status and patient race (Caucasian American and African American). We evaluated ANXA2 and ERG expression in index tumours by immunohistochemistry of whole mounted prostate sections and tissue microarrays derived from radical prostatectomies of 176 patients, matched for long term post-radical prostatectomy follow-up of up to 22 years (median 12.6 years), race and pathological stage. Expression of ERG and ANXA2 was analysed for correlation with grade group (GG), and pathological T (pT) stage. Kaplan-Meier estimation curves were used to examine associations between ANXA2 or ERG expression and biochemical recurrence (BCR) free survival, and distant metastasis free survival. Significant associations were found between ANXA2(+) index tumours and poorest grade groups (GG 4-5, p=0.0037), and worse pathological stage (pT 3-4, p=0.0142). Patients with ANXA2(+) prostate tumours showed trends towards earlier BCR and metastatic progression. ANXA2(+)/ERG(-) tumours were found to be associated with GG 4-5; ANXA2(-)/ERG(+) tumours, with GG 1-2 (p=0.0036). ANXA2 expression was not associated with patient race. The association between high ANXA2 expression and prostate tumours of higher grade (GG 4-5) and stage (pT 3-4) suggests a potential use for ANXA2 as a prognostic biomarker of aggressive prostate cancer.
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Anexina A2 , Pronóstico , Neoplasias de la Próstata , Anexina A2/análisis , Anexina A2/metabolismo , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/metabolismo , Progresión de la Enfermedad , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Próstata/patología , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Regulador Transcripcional ERG/análisis , Regulador Transcripcional ERG/metabolismoRESUMEN
Prostate-specific antigen (PSA) screening for prostate cancer (PCa) is limited by the lack of specificity but is further complicated in the benign prostatic hyperplasia (BPH) population which also exhibit elevated PSA, representing a clear unmet need to distinguish BPH from PCa. Herein, we evaluated the utility of FLNA IP-MRM, age, and prostate volume to stratify men with BPH from those with PCa. Diagnostic performance of the biomarker panel was better than PSA alone in discriminating patients with negative biopsy from those with PCa, as well as those who have had multiple prior biopsies (AUC 0.75 and 0.87 compared to AUC of PSA alone 0.55 and 0.57 for patients who have had single compared to multiple negative biopsies, respectively). Of interest, in patients with PCa, the panel demonstrated improved performance than PSA alone in those with Gleason scores of 5-7 (AUC 0.76 vs. 0.56) and Gleason scores of 8-10 (AUC 0.74 vs. 0.47). With Gleason scores (8-10), the negative predictive value of the panel is 0.97, indicating potential to limit false negatives in aggressive cancers. Together, these data demonstrate the ability of the biomarker panel to perform better than PSA alone in men with BPH, thus preventing unnecessary biopsies.
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Biomarcadores de Tumor/sangre , Diagnóstico Diferencial , Hiperplasia Prostática/diagnóstico , Neoplasias de la Próstata/diagnóstico , Anciano , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Próstata/metabolismo , Antígeno Prostático Específico/sangre , Hiperplasia Prostática/sangre , Hiperplasia Prostática/patología , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/patologíaRESUMEN
INTRODUCTION: Oncogenic activation of ERG resulting from TMPRSS2-ERG gene fusion is a key molecular genetic alteration in prostate cancer (CaP). The frequency of ERG fusion is variable by race; however, there are limited data available on germline polymorphisms associating with ERG fusion status. The goal of this study is to identify the inherited risk variants associating with ERG status of CaP. MATERIALS AND METHODS: SNP genotyping was performed on the Illumina platform using Infinium Oncoarray SNP chip on blood derived genomic DNA samples from 400 patients treated by radical prostatectomy at a single military institution. ERG status was determined in whole mounted prostate specimens by immuno-histochemistry (IHC) for ERG protein expression. Data analysis approaches included association analyses based on EMMAX and imputation by IMPUTE2. Imputed SNPs were validated by ddPCR. RESULTS: SNP genotyping analysis using imputation identified rs34349373 (p 4.68 × 10 -8 ) and rs2055272 (p 5.62 × 10-8) in TBC1D22B to be significantly associated with ERG fusion status in index tumor and non-index tumor foci. Imputed SNP rs2055272 was further experimentally validated by ddPCR with 98.04% (100/102) concordance. Initial discovery analysis based on SNPs on Oncoarray SNP chip, showed significant (p 10-5) association for SNPs (rs6698333, rs1889877, rs3798999, rs10215144, rs3818136, rs9380660 and rs1792695) with ERG fusion status. The study also replicated two previously known ERG fusion associated SNPs (rs11704416 in chromsome 22; rs16901979 in chromosome 8). CONCLUSIONS: This study identified SNPs associated with ERG status of CaP. IMPACT: The findings may contribute towards defining the underlying genetics of ERG positive and ERG negative CaP patients.
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BACKGROUND: The relationship between race, prostate tumor location, and BCR-free survival is inconclusive. This study examined the independent and joint roles of patient race and tumor location on biochemical recurrence-free (BCR) survival. METHODS: A retrospective cohort study was conducted among men with newly diagnosed, biopsy-confirmed, NCCN-defined low risk CaP who underwent radical prostatectomy (RP) at the Walter Reed National Military Medical Center from 1996 to 2008. BCR-free survival was modeled using Kaplan-Meier estimation curves and multivariable Cox proportional hazards (PH) analyses. RESULTS: There were 539 eligible patients with low-risk CaP (25% African American, AA; 75% Caucasian American, CA). Median age at CaP diagnosis and post-RP follow-up time was 59.2 and 8.1 years, respectively. Kaplan-Meier analyses showed no significant association between race (P = .52) or predominant tumor location (P = .98) on BCR-free survival. In Cox PH multivariable analysis, neither race (HR = 1.18; 95% CI = 0.68-2.02; P = .56) nor predominant tumor location (HR = 1.13; 95% CI = 0.59-2.15; P = .71) was an independent predictor of BCR-free survival. CONCLUSIONS: Neither race nor predominant tumor location was associated with adverse oncologic outcome.
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Recurrencia Local de Neoplasia/epidemiología , Prostatectomía , Neoplasias de la Próstata/mortalidad , Adulto , Negro o Afroamericano/estadística & datos numéricos , Anciano , Biopsia , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Estudios de Seguimiento , Humanos , Calicreínas/sangre , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/sangre , Recurrencia Local de Neoplasia/prevención & control , Pronóstico , Modelos de Riesgos Proporcionales , Próstata/patología , Próstata/cirugía , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/cirugía , Estudios Retrospectivos , Medición de Riesgo/métodos , Medición de Riesgo/estadística & datos numéricos , Estados Unidos/epidemiología , Población Blanca/estadística & datos numéricosRESUMEN
INTRODUCTION: Combined radiotherapy and hormonal treatment are recommended for intermediate- and high-risk prostate cancer (CaP). This study compared the long-term effects on health-related quality of life (HRQoL) of intermediate- and high-risk CaP patients managed with radiation therapy (RT) with vs. without hormone therapy (HT). METHODS: Patients with intermediate- and high-risk CaP enrolled in the Center for Prostate Disease Research diagnosed from 2007 to 2017 were included. EPIC and SF-36 questionnaires were completed and HRQoL scores were compared for patients receiving RT vs. RTâ¯+â¯HT at baseline (pretreatment), 6, 12, 24, 36, 48, and 60 months after CaP diagnosis. Longitudinal patterns of change in HRQoL were modeled using linear regression models, adjusting for baseline HRQoL, age at CaP diagnosis, race, comorbidities, National Comprehensive Cancer Network (NCCN) risk stratum, time to treatment, and follow-up time. RESULTS: Of 164 patients, 93 (56.7%) received RT alone and 71 (43.3%) received RTâ¯+â¯HT. Both groups reported comparable baseline HRQoL. Patients receiving RT+HT were more likely to be NCCN high risk as compared to those receiving only RT. The RTâ¯+â¯HT patients experienced worse sexual function, hormonal function, and hormonal bother than those who only received RT; however, HRQoL recovered over time for the RTâ¯+â¯HT group. No significant differences were observed between groups in urinary and bowel domains or SF-36 mental and physical scores. CONCLUSION: Combined RTâ¯+â¯HT treatment was associated with temporary lower scores in sexual and hormonal HRQoL compared with RT only. Intermediate- and high-risk CaP patients should be counseled about the possible declines in HRQoL associated with HT.
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Antineoplásicos Hormonales/efectos adversos , Quimioradioterapia/efectos adversos , Neoplasias de la Próstata/terapia , Calidad de Vida , Radioterapia de Intensidad Modulada/efectos adversos , Anciano , Antagonistas de Andrógenos/efectos adversos , Quimioradioterapia/métodos , Defecación/efectos de los fármacos , Defecación/efectos de la radiación , Estudios de Seguimiento , Humanos , Modelos Lineales , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Modelos Psicológicos , Estudios Prospectivos , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/mortalidad , Neoplasias de la Próstata/psicología , Radioterapia de Intensidad Modulada/métodos , Medición de Riesgo/estadística & datos numéricos , Factores de Riesgo , Autoinforme/estadística & datos numéricos , Conducta Sexual/efectos de los fármacos , Conducta Sexual/psicología , Conducta Sexual/efectos de la radiación , Resultado del Tratamiento , Micción/efectos de los fármacos , Micción/efectos de la radiaciónRESUMEN
Although ~40% of screen-detected prostate cancers (PCa) are indolent, advanced-stage PCa is a lethal disease with 5-year survival rates around 29%. Identification of biomarkers for early detection of aggressive disease is a key challenge. Starting with 52 candidate biomarkers, selected from existing PCa genomics datasets and known PCa driver genes, we used targeted mass spectrometry to quantify proteins that significantly differed in primary tumors from PCa patients treated with radical prostatectomy (RP) across three study outcomes: (i) metastasis ≥1-year post-RP, (ii) biochemical recurrence ≥1-year post-RP, and (iii) no progression after ≥10 years post-RP. Sixteen proteins that differed significantly in an initial set of 105 samples were evaluated in the entire cohort (n = 338). A five-protein classifier which combined FOLH1, KLK3, TGFB1, SPARC, and CAMKK2 with existing clinical and pathological standard of care variables demonstrated significant improvement in predicting distant metastasis, achieving an area under the receiver-operating characteristic curve of 0.92 (0.86, 0.99, p = 0.001) and a negative predictive value of 92% in the training/testing analysis. This classifier has the potential to stratify patients based on risk of aggressive, metastatic PCa that will require early intervention compared to low risk patients who could be managed through active surveillance.