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PURPOSE: Long-term comparative effectiveness research on localized prostate cancer treatments is scarce, and evidence is lacking especially for brachytherapy. The aim of this study was to assess the long-term impact of the side effects of radical prostatectomy, brachytherapy, and external radiation therapy on patients with localized prostate cancer at 10 years, using propensity score analyses. METHODS AND MATERIALS: This was a prospective observational study of a cohort of men who received a diagnosis of clinically localized prostate cancer (clinical stage T1 or T2, low and intermediate risk group) and were treated with radical prostatectomy (n = 139), brachytherapy (n = 317), or external radiation therapy (n = 194). Treatment decisions were jointly made by patients and physicians. Patient-reported outcome (PRO) evaluation included the Expanded Prostate Cancer Index Composite and Short Form-36, administered centrally by telephone interviews before and annually after treatment. The Expanded Prostate Cancer Index Composite covers urinary, bowel, sexual, and hormonal domains. To assess PRO changes over time, while accounting for correlation among repeated measures, generalized estimating equation models adjusted by propensity scores were constructed. RESULTS: The PRO completion rate at 10 years was 85.8%. Generalized estimating equation models showed that the pattern of radical prostatectomy side effects, with substantial urinary incontinence and sexual dysfunction, remained until 10 years after treatment (standard deviation [SD], -1.1 and -1.3, respectively). Brachytherapy produced late deterioration in urinary continence (SD, -0.4) and sexual function (SD, -0.9) that appeared midterm, but the differences from radical prostatectomy remained statistically significant at 10 years (P < .001 after adjusting by propensity score). External radiation therapy showed similar results to brachytherapy, but with bowel bother (SD, -0.3). CONCLUSIONS: Although late deterioration in radiation therapy groups attenuated differences from radical prostatectomy, relevant PRO differences still remained after 10 years. Our findings support that brachytherapy is the treatment option that causes the least impact on PROs; it is therefore an alternative to be considered when making evidence-based decisions on localized prostate cancer treatment.
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Pesquisa Comparativa da Efetividade , Neoplasias da Próstata , Braquiterapia , Estudos de Coortes , Seguimentos , Humanos , Masculino , Medidas de Resultados Relatados pelo Paciente , Estudos Prospectivos , Neoplasias da Próstata/radioterapia , Qualidade de VidaRESUMO
Seminal plasma (SP) contains a unique concentration of miRNA, mostly contained in small extracellular vesicles (sEVs) such as exosomes, some of which could be clinically useful for diagnosis and/or prognosis of urogenital diseases such as prostate cancer (PCa). We optimized several exosome-EV isolation technologies for their use in semen, evaluating EV purifying effectiveness and impact on the downstream analysis of miRNAs against results from the standard ultracentrifugation (UC) method to implement the use of SP sEV_miRNAs as noninvasive biomarkers for PCa. Our results evidenced that commercial kits designed to isolate exosomes/EVs from blood or urine are mostly applicable to SP, but showed quantitative and qualitative variability between them. ExoGAG 3500× g and the miRCURY Cell/Urine/CSF 1500× g methods resulted as equivalent alternative procedures to UC for isolating exosomes/sEVs from semen for nanoparticle characteristics and quality of RNA contained in vesicles. Additionally, the expression profile of the altered semen sEV-miRNAs in PCa varies depending on the EV isolation method applied. This is possibly due to different extraction techniques yielding different proportions of sEV subtypes. This is evidence that the exosome-EV isolation method has a significant impact on the analysis of the miRNAs contained within, with important consequences for their use as clinical biomarkers. Therefore, miRNA analysis results for EVs cannot be directly extrapolated between different EV isolation methods until clear markers for delineation between microvesicles and exosomes are established. However, EV extraction methodology affects combined models (semen exosome miRNA signatures plus blood Prostate specific antigen (PSA) concentration for PCa diagnosis) less; specifically our previously described (miR-142-3p + miR-142-5p + miR-223-3p + PSA) model functions as molecular marker from EVs from any of the three isolation methods, potentially improving the efficiency of PSA PCa diagnosis.
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Biomarcadores Tumorais/normas , Vesículas Extracelulares/metabolismo , MicroRNAs/normas , Neoplasias da Próstata/metabolismo , Sêmen/metabolismo , Adulto , Idoso , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Fracionamento Celular/métodos , Humanos , Biópsia Líquida/métodos , Masculino , MicroRNAs/genética , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologiaRESUMO
There is an urgent need for accurate non-invasive biomarkers for prostate cancer (PCa) diagnosis and disease risk stratification. Previous data suggests that total seminal plasma (SP) represents a source of miRNAs for screening. We have evaluated a panel of eight PCa-associated miRNAs for their potential use as PCa biomarkers in SP by analyzing their levels using RT-qPCR. Multivariate logistic regression modelling and clinical risk assessment were performed for those SP miRNAs statistically altered between PCa and non-PCa (HCt and/or BPH) groups. Our results provide evidence that altered miRNA expression in PCa tissue can also be detected in total SP. We obtained a clinically useful SP miRNA-based combined model (PSA+miR-142-3p+miR-223-3p+miR-93-5p), which improves PCa specificity of the PSA test, for, firstly, predicting the presence of malignant tumors in a sample from the total population and secondly, and more interestingly for clinicians, for predicting PCa in samples from the positive PSA screening test (PSA>4 ng/ml). Additionally, [PSA+miR-30d-5p+miR-93-5p] and [PSA+miR-30d-5p] models have been shown to be useful for predicting the disease aggressiveness with diagnostic accuracy. In conclusion, our results provide evidence that miRNAs in total SP represent a useful target for evaluation for PCa, which technically simplifies the future use of semen miRNA-based models as non-invasive biomarkers to increase the efficiency of PCa diagnosis and prognosis.
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OBJECTIVE: To describe the initial experiencein our center on targeted prostate biopsies (TB) using Magnetic Resonance imaging/ultrasonography (MRI/US) fusion and to compare PCa detection with systematic biopsies (SB). PATIENTS AND ME THODS: A retrospective, descriptive and comparative study was conducted on the first 94 men who underwent TB using MRU/US fusion in our center since February 2017 to March 2018. All patients underwent a protocol of 6-12 cores of systematic biopsies (SB) (except 9) and 2-6 targeted coreson the MRI index lesion. The Hitachi/HiVision Preirus equipment was used with RVS software (Real-time virtual sonography) and a biplane transducer for the fusion imaging procedure. Clinically significant PCa (csPCa) was defined as: at least one core with a Gleason score of 3+4. RESULTS: The proportion of patients diagnosed with PCa was higher in TB compared with SB (p=0.035) and the mean of core performed for diagnosis was lower in TB compared with SB (p<0.001). A trend towards an improved detection of csPCa in TB compared to SB was observed (p=0.063). CONCLUSIONS: The MRI/US fusion targeted biopsies (TB) showed a higher detection rate of PCa, with less cores taken for diagnosis and a tendency to better identification of csCaP compared to SB.
OBJETIVO: El objetivo de este estudio es describir la experiencia inicial en nuestro centro de las primeras 94 Biopsias de Próstata dirigidas (BD) con fusión de imagen ecografía/Resonancia magnética (US/RMmp) y comparar la tasa de detección de CaP con las biopsias sistemáticas.MATERIAL Y MÉTODOS: Se realizó un estudio retrospectivo, descriptivo y comparativo de los primeros 94 pacientes sometidos a BD por fusión de imagen US/RMmp en nuestro centro desde febrero de 2017 hasta marzo de 2018. Todos los pacientes fueron sometidos a un protocolo de 6-12 cilindros de biopsias sistemáticas (BS) (menos 9) y de 2-6 cilindros dirigidos a las lesiones diana visualizadas en la RMmp. Se utilizó el equipo Hitachi/HiVision Preirus con software RVS (Real-time virtual sonography) y un transductor biplanar para la fusión de imagen. Se definió como CaP clínicamente significativo un GS ≥ 3+4 en, al menos, 1 de los cilindros realizados. RESULTADOS: La proporción de detección de CaP fue mayor en las BD que en las BS (p=0,035) y el número de cilindros realizados para su diagnóstico fue menor en las BD comparado con las BS (p<0,001). Se observó una clara tendencia a una mayor identificación de CaP clínicamente significativo (CaPcs) en las BD comparado con las BS (p=0,063). CONCLUSIONES: Comparado con las BS, las BD por fusión de imagen US/RMmp presentaron una mayor tasa de detección de CaP y una tendencia a una mayor identificación de CaPcS con una necesidad menor de cilindros realizados.
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Neoplasias da Próstata/diagnóstico por imagem , Humanos , Biópsia Guiada por Imagem , Imageamento por Ressonância Magnética , Masculino , Gradação de Tumores , Estudos Retrospectivos , Ultrassonografia de IntervençãoRESUMO
Although it is specific for prostatic tissue, serum prostate-specific antigen (PSA) screening has resulted in an over-diagnosis of prostate cancer (PCa) and many unnecessary biopsies of benign disease due to a well-documented low cancer specificity, thus improvement is required. We profiled the expression level of miRNAs contained in semen exosomes from men with moderately increased PSA levels to assess their usefulness, either alone or in addition to PSA marker, as non-invasive biomarkers, for the early efficient diagnosis and prognosis of PCa. An altered miRNA expression pattern was found by a high throughput profiling analysis in PCa when compared with healthy individuals (HCt) exosomal semen samples. The presence of vasectomy was taken into account for the interpretation of results. Fourteen miRNAs were selected for miRNA validation as PCa biomarkers in a subsequent set of semen samples. In this explorative study, we describe miRNA-based models, which included miRNA expression values together with PSA levels, that increased the classification function of the PSA screening test with diagnostic and/or prognostic potential: [PSA + miR-142-3p + miR-142-5p + miR-223-3p] model (AUC:0,821) to discriminate PCa from BPH (Sn:91,7% Sp:42,9% vs Sn:100% Sp:14,3%); and [PSA + miR-342-3p + miR-374b-5p] model (AUC: 0,891) to discriminate between GS ≥ 7 tumours and men presenting PSA ≥ 4 ng/ml with no cancer or GS6 tumours (Sn:81,8% Sp:95% vs Sn:54,5% Sp:90%). The pathway analysis of predicted miRNA target genes supports a role for these miRNAs in PCa aetiology and/or progression. Our study shows semen exosome miRNA-based models as molecular biomarkers with the potential to improve PCa diagnosis/prognosis efficiency. As the next step, further prospective studies on larger cohorts of patients are required to validate the diagnostic and/or prognostic role of the miRNA panel before it could be adopted into clinical practice.
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Biomarcadores Tumorais/metabolismo , Exossomos/metabolismo , MicroRNAs/metabolismo , Neoplasias da Próstata/metabolismo , Sêmen/metabolismo , Adulto , Biópsia/métodos , Progressão da Doença , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Próstata/metabolismo , Próstata/patologia , Antígeno Prostático Específico/metabolismo , Neoplasias da Próstata/patologia , Sensibilidade e EspecificidadeRESUMO
OBJECTIVE: The Patient-Oriented Prostate Utility Scale (PORPUS) is a combined profile and utility-based quality of life measure for prostate cancer patients. Our objectives were to adapt the PORPUS into Spanish and to assess its acceptability, reliability, and validity. METHODS: The PORPUS was adapted into Spanish using forward and back translations and cognitive debriefing. PORPUS was administered jointly with the SF-36 and the Expanded Prostate Index Composite (EPIC) to 480 Spanish prostate cancer patients treated with radical prostatectomy or radiotherapy. The Spanish PORPUS scores' distribution and reliability were examined and compared with the original instrument. To evaluate construct validity, relationships were assessed between PORPUS and other instruments (testing hypotheses of the original PORPUS study), and among known groups defined by side effect severity. RESULTS: Reliability coefficient was 0.76 (similar to the original PORPUS' 0.81). Spanish PORPUS items presented correlations ranging 0.57-0.88 with the corresponding EPIC domains, as in the original PORPUS study (0.60-0.83). Both PORPUS-P and PORPUS-U showed significant differences and large effect sizes (0.94-1.90) when comparing severe versus no problem groups on urinary, bowel, sexual and hormonal side effects defined by EPIC. CONCLUSIONS: A conceptually equivalent Spanish version was obtained, with high reliability and good construct validity, similar to the original Canadian PORPUS version. It can therefore be used to measure health-related quality of life and utilities in Spanish prostate cancer patients.