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1.
Molecules ; 26(8)2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33918705

RESUMO

Bone metastasis remains a major cause of death in cancer patients, and current therapies for bone metastatic disease are mainly palliative. Bone metastases arise after cancer cells have colonized the bone and co-opted the normal bone remodeling process. In addition to bone-targeted therapies (e.g., bisphosphonate and denosumab), hormone therapy, chemotherapy, external beam radiation therapy, and surgical intervention, attempts have been made to use systemic radiotherapy as a means of delivering cytocidal radiation to every bone metastatic lesion. Initially, several bone-seeking beta-minus-particle-emitting radiopharmaceuticals were incorporated into the treatment for bone metastases, but they failed to extend the overall survival in patients. However, recent clinical trials indicate that radium-223 dichloride (223RaCl2), an alpha-particle-emitting radiopharmaceutical, improves the overall survival of prostate cancer patients with bone metastases. This success has renewed interest in targeted alpha-particle therapy development for visceral and bone metastasis. This review will discuss (i) the biology of bone metastasis, especially focusing on the vicious cycle of bone metastasis, (ii) how bone remodeling has been exploited to administer systemic radiotherapies, and (iii) targeted radiotherapy development and progress in the development of targeted alpha-particle therapy for the treatment of prostate cancer bone metastasis.


Assuntos
Partículas alfa/uso terapêutico , Neoplasias Ósseas/secundário , Neoplasias da Próstata/tratamento farmacológico , Compostos Radiofarmacêuticos/uso terapêutico , Humanos , Ligantes , Masculino , Antígeno Prostático Específico/metabolismo , Compostos Radiofarmacêuticos/química
2.
Medicina (Kaunas) ; 57(1)2021 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-33435132

RESUMO

Background and objectives: Overdiagnosis, overtreatment, and the need for repeated procedures caused by transrectal ultrasound guided prostate biopsies and their related complications places a heavy burden on healthcare systems. This was a prospective cohort validating study to access the clinical accuracy of systematic and MRI-cognitive targeted transperineal prostate biopsies in detecting clinically significant prostate cancer after a previous negative biopsy and persistent suspicion of malignancy. The primary goal was to assess the ability of multiparametric magnetic resonance imaging (mpMRI) to detect clinically significant prostate cancer with an additional goal to assess the diagnostic value of systematic and MRI-cognitive transperineal biopsies. Materials and Methods: In total, 200 patients were enrolled who had rising serum prostate specific antigen (PSA) levels for at least 4 months after a previous negative transrectal ultrasound (TRUS) biopsy. All eligible men underwent 1.5T prostate mpMRI, reported using the Prostate Imaging Reporting and Data System version 2 (PI-RADS v2), followed by a 20-region transperineal prostate systematic biopsy and additional targeted biopsies. Results: Systematic 20-core transperineal prostate biopsies (TPBs) were performed for 38 (19%) patients. Systemic 20-core TPB with additional cognitive targeted biopsies were performed for 162 (81%) patients. Clinically significant prostate cancer (csPC) was detected for 31 (15.5%) patients, of which 20 (64.5%) cases of csPC were detected by systematic biopsy, eight (25.8%) cases were detected by targeted biopsy, and three (9.7%) both by systematic and targeted biopsies. Conclusions: Cognitive mpMRI guided transperineal target biopsies increase the detection rate of clinically significant prostate cancer after a previously negative biopsy. However, in a repeat prostate biopsy setting, we recommend applying a cognitive targeted biopsy with the addition of a systematic biopsy.


Assuntos
Adenocarcinoma/patologia , Biópsia com Agulha de Grande Calibre/métodos , Biópsia Guiada por Imagem/métodos , Imageamento por Ressonância Magnética Multiparamétrica , Próstata/patologia , Neoplasias da Próstata/patologia , Adenocarcinoma/diagnóstico , Adenocarcinoma/metabolismo , Idoso , Estudos de Coortes , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Períneo , Estudos Prospectivos , Antígeno Prostático Específico/metabolismo , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/metabolismo
3.
Cancer Invest ; 39(2): 124-132, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33410359

RESUMO

BACKGROUND: Prostate cancer incidence and mortality in the United States in African Americans (AA) are higher than in Caucasians. Eastern Cuyahoga County in Ohio is majority AA and is considered an underserved population particularly vulnerable to healthcare disparities. There is a paucity of data about shared decision making among high-risk AA men with regard to prostate cancer screening. This study aims to examine shared versus informed decision making (SDM versus IDM) in a randomized, control trial among a large, high-risk AA population. METHODS: Patients were included in annual one-day outreach events, each held over 3 years (2017-2019), and were randomized at each event into IDM (control) and SDM (investigational) groups and then were offered screening via prostate specific antigen (PSA) and digital rectal exam (DRE). The primary endpoints were proportion of participants over 40 who did not demonstrate decisional conflict about prostate cancer screening measured by the SURE score, as well as change of knowledge score about prostate cancer screening. RESULTS: Overall, 175 patients were enrolled in the trial; 79 in the SDM arm and 96 in the IDM arm. The investigational (SDM) arm had 3/79 (3.9%) conflict versus 6/96 (6.4%) in the control (IDM) arm (p = 0.74). With regard to knowledge improvement, the SDM cohort demonstrated improvement following educational tools for 66/79 (81%) of participants versus 76/96 (79%) in the IDM cohort (p = 0.85). There was no difference in the proportion (63%) of participants in either group who found the information very helpful (using a Likert scale). CONCLUSIONS: Our education-based study showed no significant difference between SDM and IDM with regard to decisional conflict about prostate cancer screening. The study also demonstrated significant improvement in knowledge about prostate cancer screening in a high-risk AA population in both groups. Our results should be interpreted with caution due to several limitations; however, the study can serve as a benchmark for future studies in this very important topic.


Assuntos
Afro-Americanos/estatística & dados numéricos , Exame Retal Digital/métodos , Calicreínas/metabolismo , Antígeno Prostático Específico/metabolismo , Neoplasias da Próstata/diagnóstico , Tomada de Decisões , Tomada de Decisão Compartilhada , Detecção Precoce de Câncer , Estudos de Viabilidade , Humanos , Masculino , Educação de Pacientes como Assunto , Neoplasias da Próstata/etnologia , Neoplasias da Próstata/metabolismo , Sensibilidade e Especificidade , Estados Unidos/etnologia
4.
Yonsei Med J ; 61(8): 652-659, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32734728

RESUMO

PURPOSE: The benefits of early administration of androgen-deprivation therapy (ADT) in patients with prostate-specific antigen (PSA)-only recurrent prostate cancer (PCa) following radical prostatectomy (RP) are controversial. We investigated the impact of early versus delayed ADT on survival outcomes in patients with non-metastatic, localized or locally advanced PCa who received radiation therapy (RT) following RP and later developed distant metastasis. MATERIALS AND METHODS: A retrospective analysis was performed on 69 patients with non-metastatic, localized or locally advanced PCa who received RT following RP and later developed distant metastasis between January 2006 and December 2012. Patients were stratified according to the level of PSA at which ADT was administered (<2 ng/mL vs. ≥2 ng/mL). Study endpoints were progression to castration-resistant prostate cancer (CRPC)-free survival and cancer-specific survival (CSS). RESULTS: Patients were stratified according to the criteria of 2 ng/mL of PSA at which ADT was administered, based on the Youden sensitivity analysis. Delayed ADT at PSA ≥2 ng/mL was an independent prognosticator of cancer-specific mortality (p=0.047), and a marginally significant prognosticator of progression to CRPC (p=0.051). During the median follow-up of 81.0 (interquartile range 54.2-115.7) months, patients who received early ADT at PSA <2 ng/mL had significantly higher CSS rates compared to patients who received delayed ADT at PSA ≥2 ng/mL (p=0.002). Progression to CRPC-free survival was comparable between the two groups (p=0.331). CONCLUSION: Early ADT at the PSA level of less than 2 ng/mL confers CSS benefits in patients with localized or locally advanced PCa who were previously treated with RP.


Assuntos
Antagonistas de Androgênios/uso terapêutico , Antígeno Prostático Específico/metabolismo , Prostatectomia , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/cirurgia , Idoso , Progressão da Doença , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia/cirurgia , Prognóstico , Modelos de Riscos Proporcionais , Neoplasias da Próstata/patologia , Neoplasias da Próstata/radioterapia , Radioterapia Adjuvante , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
5.
Clin Nucl Med ; 45(10): 789-791, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32701808

RESUMO

Progression of prostate cancer and prostate-specific antigen (PSA) elevation are closely associated. In fewer than 1% of all cases, disease progression may occur despite low or undetectable PSA levels. In these conditions, androgen deprivation therapy is relatively ineffective, and the prostate cancer progresses very quickly. We present a 65-year-old man with non-PSA-secreting prostate cancer and widespread metastases with rather fair response to Lu-prostate-specific membrane antigen radioligand therapy.


Assuntos
Antígenos de Superfície/metabolismo , Glutamato Carboxipeptidase II/metabolismo , Lutécio/uso terapêutico , Neoplasias da Próstata/patologia , Neoplasias da Próstata/radioterapia , Radioisótopos/uso terapêutico , Idoso , Humanos , Ligantes , Masculino , Metástase Neoplásica , Antígeno Prostático Específico/metabolismo , Neoplasias da Próstata/metabolismo , Resultado do Tratamento
6.
Int J Nanomedicine ; 15: 4289-4309, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32606678

RESUMO

Objective: To construct prostate-specific membrane antigen (PSMA)-targeting, indocyanine green (ICG)-loaded nanobubbles (NBs) for multimodal (ultrasound, photoacoustic and fluorescence) imaging of prostate cancer. Methods: The mechanical oscillation method was used to prepare ICG-loaded photoacoustic NBs (ICG NBs). Then, PSMA-binding peptides were connected to the surface of ICG NBs using the biotin-avidin method to make targeted photoacoustic NBs, namely, PSMAP/ICG NBs. Their particle sizes, zeta potentials, and in vitro ultrasound, photoacoustic and fluorescence imaging were examined. Confocal laser scanning microscopy and flow cytometry were used to detect the binding ability of the PSMAP/ICG NBs to PSMA-positive LNCaP cells, C4-2 cells, and PSMA-negative PC-3 cells. The multimodal imaging effects of PSMAP/ICG NBs and ICG NBs were compared in nude mouse tumor xenografts. Results: The particle size of the PSMAP/ICG NBs was approximately 457.7 nm, and the zeta potential was approximately -23.5 mV. Both confocal laser scanning microscopy and flow cytometry confirmed that the PSMAP/ICG NBs could specifically bind to both LNCaP and C4-2 cells, but they rarely bound to PC-3 cells. The ultrasound, photoacoustic and fluorescence imaging intensities of the PSMAP/ICG NBs in vitro positively correlated with their concentrations. The ultrasound and photoacoustic imaging effects of the PSMAP/ICG NBs in LNCaP and C4-2 tumor xenografts were significantly enhanced compared with those in PC-3 tumor xenografts, which were characterized by a significantly increased duration of ultrasound enhancement and heightened photoacoustic signal intensity (P < 0.05). Fluorescence imaging showed that PSMAP/ICG NBs could accumulate in LNCaP and C4-2 tumor xenografts for a relatively long period. Conclusion: The targeted photoacoustic nanobubbles prepared in this study can specifically bind to PSMA-positive prostate cancer cells and have the ability to enhance ultrasound, photoacoustic and fluorescence imaging of PSMA-positive tumor xenografts. Photoacoustic imaging could visually display the intensity of the red photoacoustic signal in the tumor region, providing a more intuitive imaging modality for targeted molecular imaging. This study presents a potential multimodal contrast agent for the accurate diagnosis and assessment of prostate cancer.


Assuntos
Verde de Indocianina/química , Nanopartículas/química , Imagem Óptica , Técnicas Fotoacústicas , Neoplasias da Próstata/diagnóstico por imagem , Ultrassonografia , Animais , Linhagem Celular Tumoral , Meios de Contraste/química , Fluorescência , Humanos , Masculino , Camundongos Nus , Nanopartículas/ultraestrutura , Tamanho da Partícula , Peptídeos/metabolismo , Antígeno Prostático Específico/metabolismo , Neoplasias da Próstata/terapia , Ligação Proteica
7.
Anticancer Res ; 40(8): 4413-4418, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32727771

RESUMO

BACKGROUND/AIM: To compare the predictive efficacy of National Comprehensive Cancer Network (NCCN) and European Association of Urology (EAU) risk stratification systems in radiotherapy of prostate cancer. PATIENTS AND METHODS: One-thousand-nine-hundred-nine patients treated with definitive (1,074), adjuvant (381), and salvage radiotherapy (454) were analysed. RESULTS: Both systems significantly predicted biochemical-relapse-free-survival, metastasis-free-survival, and disease-free-survival, while only the NCCN system correlated with local-control in the definitive radiotherapy group. In the adjuvant setting, both systems failed to predict all outcomes. In the salvage setting, only the NCCN system significantly predicted biochemical-relapse-free-survival, metastasis-free-survival and disease-free-survival. CONCLUSION: This analysis confirms the efficacy of both systems in definitive radiotherapy and suggests the utility of the NCCN also in salvage radiotherapy.


Assuntos
Neoplasias da Próstata/radioterapia , Radioterapia Adjuvante/estatística & dados numéricos , Terapia de Salvação/estatística & dados numéricos , Idoso , Humanos , Calicreínas/metabolismo , Masculino , Estudos Multicêntricos como Assunto , Estudos Observacionais como Assunto , Antígeno Prostático Específico/metabolismo , Neoplasias da Próstata/metabolismo , Dosagem Radioterapêutica , Estudos Retrospectivos , Medição de Risco , Análise de Sobrevida , Resultado do Tratamento
8.
Clin Nucl Med ; 45(9): 672-678, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32604105

RESUMO

PURPOSE: The aim of this study was to investigate the role of F-fluciclovine PET/CT in the evaluation of prostate cancer (PC) patients after definitive treatment in the presence of undetectable prostate-specific antigen (PSA). PATIENTS AND METHODS: This retrospective study was conducted in PC patients who had undetectable PSA level and underwent fluciclovine PET/CT within a 2-week interval of PSA examination and without interval treatment or other cancer. Patient and tumor characteristics at initial diagnosis, treatment regimens, and findings on fluciclovine PET/CT were collected. Comparisons between groups of positive and negative fluciclovine PET/CT were done by using descriptive statistics. RESULTS: A total of 34 fluciclovine PET/CTs from 34 patients met the inclusion criteria. There were 4 positive (11.8%) and 30 negative fluciclovine PET/CTs (88.2%). All of the patients with positive results had an initial Gleason score of 7 or higher and locally advanced tumor (T3-T4). More common features at the time of diagnosis among positive study patients as compared with negative ones were atypical histologic variants (25% vs 0%) and very high-risk PC (50% vs 30%). Most of the patients with positive study received second-line hormonal therapy (HT) (50%), whereas patients with negative results received first-line HT (53.3%). Chemotherapy naivety was less common among positive patients (75% vs 96.7%). Sites of involvement on positive fluciclovine PET/CTs were pelvic lymph nodes (2/4, 50%), lung and mediastinal lymph node (1/4, 25%), and prostatectomy bed (1/4, 25%). CONCLUSIONS: In the presence of undetectable PSA in PC patients after definitive treatment, fluciclovine PET/CT would benefit most to patients with Gleason score of 7 or higher, high disease burden (T3-T4), and atypical histologic variants at the time of diagnosis, and the ones who have history of second-line HT and/or chemotherapy.


Assuntos
Ácidos Carboxílicos , Ciclobutanos , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Antígeno Prostático Específico/metabolismo , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/metabolismo , Idoso , Humanos , Limite de Detecção , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Neoplasias da Próstata/patologia , Neoplasias da Próstata/terapia , Estudos Retrospectivos
9.
NPJ Syst Biol Appl ; 6(1): 13, 2020 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-32382028

RESUMO

Up to date, screening for prostate cancer (PCa) remains one of the most appealing but also a very controversial topics in the urological community. PCa is the second most common cancer in men worldwide and it is universally acknowledged as a complex disease, with a multi-factorial etiology. The pathway of PCa diagnosis has changed dramatically in the last few years, with the multiparametric magnetic resonance (mpMRI) playing a starring role with the introduction of the "MRI Pathway". In this scenario the basic tenet of network medicine (NM) that sees the disease as perturbation of a network of interconnected molecules and pathways, seems to fit perfectly with the challenges that PCa early detection must face to advance towards a more reliable technique. Integration of tests on body fluids, tissue samples, grading/staging classification, physiological parameters, MR multiparametric imaging and molecular profiling technologies must be integrated in a broader vision of "disease" and its complexity with a focus on early signs. PCa screening research can greatly benefit from NM vision since it provides a sound interpretation of data and a common language, facilitating exchange of ideas between clinicians and data analysts for exploring new research pathways in a rational, highly reliable, and reproducible way.


Assuntos
Detecção Precoce de Câncer/métodos , Neoplasias da Próstata/diagnóstico , Biomarcadores Tumorais , Humanos , Biópsia Guiada por Imagem/métodos , Imagem por Ressonância Magnética/métodos , Masculino , Gradação de Tumores/métodos , Valor Preditivo dos Testes , Próstata/patologia , Antígeno Prostático Específico/metabolismo
10.
Int J Nanomedicine ; 15: 3087-3098, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32431503

RESUMO

Purpose: Aldo-ketoreductase (AKR) 1C3 is crucial for testosterone synthesis. Abnormally high expression/activity of AKR1C3 can promote castration-resistant prostate cancer (CRPC). A mansonone derivative and AKR1C3 inhibitor, 6e, was combined with 4D5 (extracellular fragment of the monoclonal antibody of human epidermal growth factor receptor-2)-modified chitosan to achieve a nanodrug-delivery system (CS-4D5/6e) to treat CRPC. Materials and Methods: Morphologies/properties of CS-4D5/6e were characterized by atomic force microscopy, zeta-potential analysis, and Fourier transform-infrared spectroscopy. CS-4D5/6e uptake was measured by immunofluorescence under confocal laser scanning microscopy. Testosterone in LNCaP cells overexpressing human AKR1C3 (LNCaP-AKR1C3) and cell lysates was measured to reflect AKR1C3 activity. Androgen receptor (AR) and prostate-specific antigen (PSA) expression was measured by Western blotting. CS-4D5/6e-based inhibition of AKR1C3 was evaluated in tumor-xenografted mice. Results: CS-4D5/6e was oblate, with a particle size of 200-300 nm and thickness of 1-5 nm. Zeta potential was 1.39±0.248 mV. 6e content in CS-4D5/6e was 7.3±1.4% and was 18±3.6% for 4D5. 6e and CS-4D5/6e inhibited testosterone production significantly in a concentration-dependent manner in LNCaP-AKR1C3 cells, and a decrease in expression of AKR1C3, PSA, and AR was noted. Half-maximal inhibitory concentration of CS-4D5/6e on LNCaP-AKR1C3 cells was significantly lower than that in LNCaP cells (P<0.05). CS-4D5/6e significantly reduced growth of 22Rv1 tumor xenografts by 57.00% compared with that in the vehicle group (P<0.01). Conclusion: We demonstrated the antineoplastic activity of a potent AKR1C3 inhibitor (6e) and its nanodrug-delivery system (CS-4D5/6e). First, CS-4D5/6e targeted HER2-positive CRPC cells. Second, it transferred 6e (an AKR1C3 inhibitor) to achieve a reduction in intratumoral testosterone production. Compared with 6e, CS-4D5/6e showed lower systemic toxicity. CS-4D5/6e inhibited tumor growth effectively in mice implanted with tumor xenografts by downregulating testosterone production mediated by intratumoral AKR1C3. These results showed a promising strategy for treatment of the CRPC that develops invariably in prostate-cancer patients.


Assuntos
Membro C3 da Família 1 de alfa-Ceto Redutase/antagonistas & inibidores , Antineoplásicos/química , Antineoplásicos/farmacologia , Terapia de Alvo Molecular/métodos , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Animais , Anticorpos Monoclonais/química , Antineoplásicos/administração & dosagem , Linhagem Celular Tumoral , Quitosana/química , Sistemas de Liberação de Medicamentos/métodos , Humanos , Masculino , Camundongos Endogâmicos BALB C , Nanoestruturas/administração & dosagem , Nanoestruturas/química , Naftoquinonas/química , Antígeno Prostático Específico/metabolismo , Neoplasias de Próstata Resistentes à Castração/metabolismo , Neoplasias de Próstata Resistentes à Castração/patologia , Receptor ErbB-2/imunologia , Receptores Androgênicos/metabolismo , Sesquiterpenos/química , Testosterona/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
11.
Proc Natl Acad Sci U S A ; 117(22): 12315-12323, 2020 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-32424106

RESUMO

The androgen receptor (AR) antagonist enzalutamide is one of the principal treatments for men with castration-resistant prostate cancer (CRPC). However, not all patients respond, and resistance mechanisms are largely unknown. We hypothesized that genomic and transcriptional features from metastatic CRPC biopsies prior to treatment would be predictive of de novo treatment resistance. To this end, we conducted a phase II trial of enzalutamide treatment (160 mg/d) in 36 men with metastatic CRPC. Thirty-four patients were evaluable for the primary end point of a prostate-specific antigen (PSA)50 response (PSA decline ≥50% at 12 wk vs. baseline). Nine patients were classified as nonresponders (PSA decline <50%), and 25 patients were classified as responders (PSA decline ≥50%). Failure to achieve a PSA50 was associated with shorter progression-free survival, time on treatment, and overall survival, demonstrating PSA50's utility. Targeted DNA-sequencing was performed on 26 of 36 biopsies, and RNA-sequencing was performed on 25 of 36 biopsies that contained sufficient material. Using computational methods, we measured AR transcriptional function and performed gene set enrichment analysis (GSEA) to identify pathways whose activity state correlated with de novo resistance. TP53 gene alterations were more common in nonresponders, although this did not reach statistical significance (P = 0.055). AR gene alterations and AR expression were similar between groups. Importantly, however, transcriptional measurements demonstrated that specific gene sets-including those linked to low AR transcriptional activity and a stemness program-were activated in nonresponders. Our results suggest that patients whose tumors harbor this program should be considered for clinical trials testing rational agents to overcome de novo enzalutamide resistance.


Assuntos
Antineoplásicos/administração & dosagem , Resistencia a Medicamentos Antineoplásicos , Feniltioidantoína/análogos & derivados , Neoplasias de Próstata Resistentes à Castração/genética , Receptores Androgênicos/administração & dosagem , Receptores Androgênicos/genética , Idoso , Idoso de 80 Anos ou mais , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Feniltioidantoína/administração & dosagem , Antígeno Prostático Específico/metabolismo , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/metabolismo , Receptores Androgênicos/metabolismo
12.
Sci Rep ; 10(1): 8191, 2020 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-32424131

RESUMO

While alpha-blockers are commonly used to reduce lower urinary tract symptoms in prostate cancer patients receiving radiotherapy, their impact on response to radiotherapy remains unknown. Therefore, this pilot study aimed to retrospectively determine if alpha-blockers use, influenced response to radiotherapy for localised prostate cancer. In total, 303 prostate cancer patients were included, consisting of 84 control (alpha-blocker naïve), 72 tamsulosin and 147 prazosin patients. The main outcomes measured were relapse rates (%), time to biochemical relapse (months) and PSA velocity (ng/mL/year). Recurrence free survival was calculated using Kaplan-Meier analysis. Prazosin significantly reduced biochemical relapse at both two and five-years (2.72%, 8.84%) compared to control (22.61%, 34.52%). Recurrence free survival was also significantly higher in the prazosin group. This remained after multivariable analysis (HR: 0.09, 95% CI: 0.04-0.26, p < 0.001). Patients receiving prazosin had a 3.9 times lower relative risk of biochemical relapse compared to control. Although not statistically significant, tamsulosin and prazosin extended recurrence free survival by 13.15 and 9.21 months respectively. We show for the first time that prazosin may reduce risk of prostate cancer recurrence and delay time to biochemical relapse and provides justification for prospective studies to examine its potential as an adjunct treatment option for localised prostate cancer.


Assuntos
Antagonistas Adrenérgicos alfa/farmacologia , Neoplasias da Próstata/radioterapia , Idoso , Intervalo Livre de Doença , Humanos , Masculino , Projetos Piloto , Antígeno Prostático Específico/metabolismo , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Recidiva , Estudos Retrospectivos
13.
Clin Nucl Med ; 45(7): e334-e335, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32404713

RESUMO

A 72-year-old man with a family history of prostate cancer and initial diagnosis of favorable intermediate risk prostate cancer via biopsy in 2017 elected for active surveillance. Two years later, he underwent prostate biopsy showing intermediate-risk cT1c Nx Mx lesion with Gleason score 3 + 4 = 7 (5 core positive). Transrectal ultrasound showed a prostate volume 28 mL, and the prostate-specific antigen was 8.1. Patient elected to proceed with combination radiation therapy and androgen deprivation therapy.


Assuntos
Adenocarcinoma/diagnóstico por imagem , Radioisótopos de Flúor , Neoplasias da Próstata/diagnóstico por imagem , Fluoreto de Sódio , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Idoso , Antagonistas de Androgênios/uso terapêutico , Biópsia , Humanos , Masculino , Gradação de Tumores , Tomografia por Emissão de Pósitrons , Antígeno Prostático Específico/metabolismo , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Ultrassonografia
14.
Cancer Epidemiol ; 66: 101724, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32361642

RESUMO

BACKGROUND: Prostate-specific antigen (PSA) testing for early detection of prostate cancer is low-value when it is not indicated by guidelines and the harms outweigh the benefits. In this retrospective cohort study, we identify provider and patient factors associated with PSA testing, particularly in situations where testing would be low-value. METHODS: We used electronic health record data from 2011 to 2018 representing 1,738,021 health system encounters in the United States. Using logistic generalized estimating equation models, we examined patient factors (age, comorbid illness, family history, race and prior PSA results), provider factors (gender, specialty, graduation year and medical school rank), and overall time trends associated with PSA testing in low-value and appropriate settings. RESULTS: Comorbid illness (odds ratio (OR) 0.0 for 3+ conditions vs none) and no prior PSA testing (OR 0.2) were associated with a lower likelihood of PSA testing in low-value situations, while family history of prostate cancer (OR 1.6) and high prior PSA test results (OR 2.2 for PSA > 6 vs 0-1) were associated with a greater likelihood. Men aged 55-65 years were at greatest risk for PSA testing in low-value situations. The provider factor associated with PSA testing in low-value situations was specialty, with urologists being most likely (OR 2.3 versus advanced practice providers). Internal medicine physicians were more likely to perform PSA testing during low-value situations (OR 1.3 versus advanced practice providers) but much more likely to order a PSA test where appropriate (OR 2.2). All PSA testing decreased since 2011. CONCLUSION: We identified several patient and provider factors associated with PSA testing in low-value settings. Some aspects suggest attention to relevant factors for PSA testing in low-value settings (e.g. comorbid illness), while others may encourage PSA testing in low-value settings (e.g. family history). The greatest likelihood of PSA testing in low-value settings is among men within the age range most commonly recommended by guidelines.


Assuntos
Detecção Precoce de Câncer/métodos , Programas de Rastreamento/métodos , Antígeno Prostático Específico/metabolismo , Neoplasias da Próstata/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
15.
Sci Rep ; 10(1): 6681, 2020 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-32317750

RESUMO

Bone is the most common site of metastasis in metastatic castration-resistant prostate cancer (mCRPC), which is associated with pain and skeletal events. Radium-223 dichloride (Xofigo) is an alpha-emitting radioactive isotope that can specifically target bone lesions. Herein, we report the results of a retrospective analysis that documents our experience in the use of radium-223. Data from 63 patients (pts) with mCRPC who underwent radium-223 treatment from December 2015 to September 2017 were collected. Radium-223 (55 kBq/kg) was administered every 4 weeks for up to 6 cycles. The primary endpoint was OS. Radium-223 was administered as first line therapy in 11 pts, as second line in 19 pts, as third line in 16 pts and in successive lines in 17 pts; 42 pts out of 63 (67%) completed all six cycles. Within one month after the end of 6 cycles of radium-223, 15 pts out of 42 (35.7%) had achieved PR, 11 pts out of 42 (26.2%) had SD and 14 pts out of 42 (33.3%) had PD. Levels of pain decreased with progressive cycles of radium-223. After a minimum follow-up of 2 months and a maximum of 43 months, median OS was 15 months and median PFS was 8 months. The most frequent radium-223 related toxicity was low grade haematologic toxicity, predominantly G1-G2, that occurred halfway through treatment in about 75% of pts. The favourable results reported herein confirm that radium-223 can be considered well tolerated and effective in mCRPC, and is associated with significant decreases in pain.


Assuntos
Neoplasias de Próstata Resistentes à Castração/terapia , Rádio (Elemento)/uso terapêutico , Idoso , Fosfatase Alcalina/metabolismo , Anemia/complicações , Neoplasias Ósseas/secundário , Estudos de Coortes , Hemoglobinas/metabolismo , Humanos , Estimativa de Kaplan-Meier , Masculino , Dor/etiologia , Antígeno Prostático Específico/metabolismo , Neoplasias de Próstata Resistentes à Castração/sangue , Neoplasias de Próstata Resistentes à Castração/complicações , Neoplasias de Próstata Resistentes à Castração/diagnóstico por imagem
16.
Anticancer Res ; 40(4): 2053-2057, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32234896

RESUMO

BACKGROUND: The present study aimed to evaluate the toxicity and efficacy of stereotactic body radiotherapy (SBRT) for localized prostate cancer. PATIENTS AND METHODS: We investigated 25 patients treated with SBRT of 35 Gy per five fractions from May 2014 to March 2015. RESULTS: The median age of patients was 70 years, four (16%) patients were low risk and 21 (84%) were intermediate risk. Seven (28%) patients received neoadjuvant androgen-deprivation therapy. The median follow-up time was 53 months. Grade 2 acute and late genitourinary toxicities were observed in five (20%) and two (8%) patients and there were no Grade 2 gastrointestinal toxicities. There were no Grade 3 or higher acute or late toxicities at 2 years follow-up. The biochemical relapse-free survival rate at 2 years was 100%. CONCLUSION: SBRT of 35 Gy per five fractions is a promising treatment method in the short term for prostate cancer.


Assuntos
Androgênios/metabolismo , Trato Gastrointestinal/efeitos dos fármacos , Neoplasias da Próstata/radioterapia , Radiocirurgia/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Androgênios/administração & dosagem , Antineoplásicos Hormonais/administração & dosagem , Fracionamento da Dose de Radiação , Trato Gastrointestinal/patologia , Humanos , Masculino , Terapia Neoadjuvante , Próstata/patologia , Próstata/efeitos da radiação , Antígeno Prostático Específico/metabolismo , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Planejamento da Radioterapia Assistida por Computador , Medição de Risco , Resultado do Tratamento
17.
Clin Nucl Med ; 45(5): 389-391, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32149799

RESUMO

An 85-year-old asymptomatic man with suspected biochemical recurrence of prostate cancer underwent an F-fluciclovine PET/CT scan, which revealed a solitary suspicious tracer uptake in the dorsal right corporal body of the proximal pendulous penis. The patient underwent ultrasound-guided fine-needle aspiration of the penile lesion, which revealed metastatic prostate cancer. The patient had definitive external beam radiation therapy 3 years before the examination. At the time of scan, the prostatic-specific antigen (PSA) was only 1.0 ng/mL, although the PSA doubling time was 2.6 months. It is unusual to detect a solitary penile metastasis in a patient with a low level of PSA.


Assuntos
Ácidos Carboxílicos , Ciclobutanos , Neoplasias Penianas/diagnóstico por imagem , Neoplasias Penianas/secundário , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Antígeno Prostático Específico/metabolismo , Neoplasias da Próstata/patologia , Idoso de 80 Anos ou mais , Humanos , Masculino , Neoplasias Penianas/metabolismo
18.
Int Braz J Urol ; 46(3): 383-389, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32167701

RESUMO

INTRODUCTION: Androgen deprivation therapy (ADT) is the mainstay of therapy for advanced prostate cancer. Studies addressing the efficacy of different depot formulations of long acting luteinizing hormone releasing hormone agonists in the Brazilian population are lacking. We aimed to compare the efficacy of three schedules of leuprolide acetate in lowering PSA in a real world population. MATERIALS AND METHODS: We reviewed the medical records of patients with prostate cancer seen at our institution between January 2007 and July 2018. We analyzed patients treated with long-acting leuprolide acetate and grouped these patients into three strata according to the administration of ADT every 1, 3 or 6 months. The primary outcome was the serum prostate specific antigen (PSA) levels at 6 and 12 months after treatment initiation. We used Friedman test to compare the distribution of PSA levels at baseline and at 6 and 12 months within each treatment stratum. We considered two-sided P values < 0.05 as statistically significant. We analyzed toxicity descriptively. RESULTS: We analyzed a total of 932 patients, with a median age of 72 years and a median time since diagnosis of prostate cancer of 8.5 months. ADT was administered monthly in 115 patients, quarterly in 637, and semiannually in 180. Nearly half of the patients had locally advanced disease. In comparison with baseline, median serum PSA levels were reduced at 12 months by at least 99.7% in the three strata (P < 0.001 in all cases). Sexual impotence and hot flashes were the most frequently reported toxicities. CONCLUSION: To our knowledge, this is the largest assessment of real-world data on alternative schedules of leuprolide in a Brazilian population. Our study suggests that PSA levels can be effectively be reduced in most patients treated with monthly, quarterly, or semiannual injections of long-acting leuprolide acetate.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Leuprolida/uso terapêutico , Antígeno Prostático Específico/metabolismo , Neoplasias da Próstata , Acetatos , Idoso , Antagonistas de Androgênios , Brasil , Humanos , Masculino , Estudos Retrospectivos
19.
Jpn J Clin Oncol ; 50(4): 349-356, 2020 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-32147685

RESUMO

From a clinical perspective, prostate-specific membrane antigen (PSMA) is a valuable target for both diagnosis and radioligand therapy (RLT) of prostate cancer. The term 'specific' has been used to characterize a histologic hallmark of overexpression in the membrane of most prostate cancer. Many PSMA ligands have been developed since the previous decade and have been used in several clinical trials and clinical studies. However, procedure, specification, protocol, interpretation criteria, radiation dose, and cost-effectiveness of PSMA ligands have not been fully explained. Regardless of worldwide use of promising PSMA-ligand PET and RLT, it has not been approved in Japan. Expedited introduction of PSMA-ligand PET and RLT to Japan and implementation of clinical study are eager for many patients with prostate cancer.


Assuntos
Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Antígeno Prostático Específico/metabolismo , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/terapia , Compostos Radiofarmacêuticos/uso terapêutico , Humanos , Ligantes , Masculino , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/patologia , Compostos Radiofarmacêuticos/química
20.
Cancer Causes Control ; 31(5): 431-449, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32162172

RESUMO

PURPOSE: The relationship between body mass index (BMI) and prostate cancer remains unclear. However, there is an inverse association between BMI and prostate-specific antigen (PSA), used for prostate cancer screening. We conducted this review to estimate the associations between BMI and (1) prostate cancer, (2) advanced prostate cancer, and (3) PSA. METHODS: We searched PubMed and Embase for studies until 02 October 2017 and obtained individual participant data from four studies. In total, 78 studies were identified for the association between BMI and prostate cancer, 21 for BMI and advanced prostate cancer, and 35 for BMI and PSA. We performed random-effects meta-analysis of linear associations of log-PSA and prostate cancer with BMI and, to examine potential non-linearity, of associations between categories of BMI and each outcome. RESULTS: In the meta-analyses with continuous BMI, a 5 kg/m2 increase in BMI was associated with a percentage change in PSA of - 5.88% (95% CI - 6.87 to - 4.87). Using BMI categories, compared to normal weight men the PSA levels of overweight men were 3.43% lower (95% CI - 5.57 to - 1.23), and obese men were 12.9% lower (95% CI - 15.2 to - 10.7). Prostate cancer and advanced prostate cancer analyses showed little or no evidence associations. CONCLUSION: There is little or no evidence of an association between BMI and risk of prostate cancer or advanced prostate cancer, and strong evidence of an inverse and non-linear association between BMI and PSA. The association between BMI and prostate cancer is likely biased if missed diagnoses are not considered.


Assuntos
Calicreínas/metabolismo , Antígeno Prostático Específico/metabolismo , Neoplasias da Próstata/diagnóstico , Índice de Massa Corporal , Detecção Precoce de Câncer/métodos , Humanos , Masculino , Obesidade/epidemiologia , Sobrepeso/epidemiologia
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