Background cardiovascular risk factors in patients of metastatic prostate cancer on androgen deprivation therapy: A retrospective observational study from a tertiary care hospital of Eastern India

Background: Androgen deprivation therapy (ADT) is indispensable part of treatment for metastatic prostate cancer (MPC) patients. There is documented association between ADT and adverse cardiovascular (CV) events, with variability between the different modes. However, there is dearth of evidence on the background CV risk factors of these group of patients at diagnosis. Aims and Objectives: We envisaged this retrospective observational study in the department of oncology to document the background CV risk factors of MPC patients at diagnosis, to help us better select the available ADTs based on their CV risks. Materials and Methods: Over a period of 2 years, all patients registered for treatment with a diagnosis of MPC, indicated for ADT, and available detailed history and background cardiological evaluation at presentation, were included in the study. As indirect indicators of CV risks, history of smoking, presence and treatment of dyslipidemia, and type 2 diabetes mellitus (T2DM), were documented. As direct indicators of CV risks, presence and treatment of hypertension, ischemic heart disease (IHD), congestive cardiac failure (CCF), ECG, and echocardiography changes suggesting cardiac morbidity were documented and the data were analyzed using descriptive statistical methods. Results: Indirect indicators: dyslipidemia, habit of smoking, and T2DM were found in 74%, 29.3%, and 13.3% patients, respectively. Direct indicators: Presence of hypertension, IHD, CCF, abnormalities in ECG, and echocardiography were found in 38.7%, 10.6%, 4%, 28%, and 34.6% patients, respectively. ST-T changes on ECG, low EF, and IHD on echocardiography were seen in 28.5%, 23%, and 26.9%, respectively. Conclusions: MPC patients have a substantial pre-existing CV risk at diagnosis. Our findings warrant a meticulous screening of all MPC patients for CV risk factors, to help in judicious selection of their ADT.

Influence of statins in metastatic castration-resistant prostate cancer patients treated with new antiandrogen therapies: a systematic review and meta-analysis

ABSTRACT Objective To evaluate whether the addition of statins to the new antiandrogens (enzalutamide or abiraterone) affects overall survival in patients with metastatic castration-resistant prostate cancer. Methods We searched studies in English language including the keywords statins, overall survival, and metastatic castration-resistant prostate cancer, at PubMed® (MEDLINE®), Embase and Cochrane databases. Results A total of 195 articles were initially identified, but only four met the inclusion criteria and were selected for the meta-analysis. A total of 955 patients, 632 on the new antiandrogens only group, and 323 on the new antiandrogens + statins group, were analyzed. In all four studies the combination therapy (new antiandrogens + statin) was well tolerated, regardless of which new antiandrogens were used. Neither the type of statin nor the doses and duration of use were well specified in the studies. The combination therapy in metastatic castration-resistant prostate cancer was associated with an overall survival improvement, and a 46% reduction in death (hazard ratio of 0.54; 95%CI 0.34-0.87; p<0.01) in multivariate analysis. Conclusion There seems to be a clinical benefit with the association of statins to the new antiandrogens in patients with metastatic castration-resistant prostate cancer, suggesting longer overall survival with no important collateral effect. However, due to fragility of the studies available in the literature, we are not yet capable of recommending this combination of drugs in the clinical practice. Further randomized prospective studies are warranted to confirm these beneficial outcomes.

Androgen deprivation therapy and side effects: are GnRH antagonists safer? / 亚洲男科学杂志(英文版)

Androgen deprivation therapy (ADT) with gonadotropin-releasing hormone (GnRH) agonists and antagonists is the mainstay of advanced prostate cancer treatment. Both drug classes decrease levels of luteinizing hormone and follicle-stimulating hormones (FSH), thereby lowering testosterone to castrate levels. This is associated with adverse events (AEs), including cardiovascular (CV) disorders, bone fractures, metabolic dysfunction, and impaired cognitive function. This literature review discusses these AEs, with a focus on CV and bone-related events. A hypothesis-generating meta-analysis of six clinical trials showed a potentially increased risk for CV disorders with GnRH agonists versus the GnRH antagonist degarelix. While no study has directly compared GnRH agonists versus antagonists with a primary CV outcome, one hypothesis for this observation is that GnRH agonists lead to initial surges in FSH that may negatively impact CV health, whereas antagonists do not. GnRH agonists are associated with metabolic and cognitive AEs and while data are lacking for GnRH antagonists, no differences in risk are predicted. Other common AEs with ADT include injection site reactions, which are much more common with degarelix than with GnRH agonists, which may reflect differing administration and injection techniques. Future studies are needed to further evaluate and compare the safety profiles of GnRH agonists and antagonists, especially in patients with pre-existing CV disease and other co-morbidities. Physicians should carefully evaluate benefits and risks when prescribing ADT and ensure that side effects are well managed.

Optimal duration of androgen deprivation therapy for moderate and high risk prostate cancer after radiotherapy: A Meta-analysis / 肿瘤

Objective: To systematically evaluate the optimal duration of adjuvant androgen deprivation therapy (ADT) after radiotherapy for prostate cancer. Methods: The CBM, CNKI, Wanfang, PubMed, EMbase, Cochrane Library, Clinical Trials.gov databases were searched by computer. The randomized controlled trial (RCT) on long-term and shortterm ADT for intermediate and high risk non-metastatic prostate cancer after radiotherapy were collected. The retrieval time was from the establishment of these databases to November 5, 2018. After independent screening literature, extracting data and evaluating the quality of the included studies, two researchers used RevMan 5.3 software for Meta-analysis. Results: A total of eight RCTs were selected, including 6 165 patients. Meta-analysis showed that the overall survival (OS) rate in longterm ADT group was higher than that in short-term treatment group [hazard ratio (HR) = 0.75, 95% confidence interval (CI): 0.63-0.89, P = 0.000 7]; the disease-free survival (DFS) rate in long-term ADT group was higher than that in short-term treatment group (HR = 0.81, 95% CI : 0.70-0.94, P = 0.007); the disease-specific survival (DSS) in long-term ADT group was higher than that in short-term treatment group (HR = 0.83, 95% CI : 0.71-0.96, P = 0.01); the local progress (LP) in long-term ADT group was lower than that in short-term treatment group [relative risk (RR) = 0.76, 95% CI : 0.59-0.97, P = 0.03]; the biochemical failure (BF) in long-term ADT group was lower than that in short-term treatment group (RR = 0.66, 95% CI : 0.52-0.83, P = 0.0004); the distant metastasis (DM) in long-term ADT group was lower than that in short-term treatment group (RR = 0.85, 95% CI : 0.74-0.96, P = 0.01). Conclusion: The long-term ADT treatment is superior to the shortterm treatment in OS rate, DFS rate, DSS rate, LP rate, BF rate and DM rate after radiotherapy for moderate and high risk prostate cancer. Due to the limitation of the quantity and quality of the included literatures, the above conclusion need to be verified by higher quality research.

Prognostic value of pretreatment albumin to globulin ratio in prostate cancer patients treated with maximal androgen blockade / 中华老年医学杂志

Objective@#To investigate the prognostic value of pretreatment albumin to globulin ratio(AGR)in prostate cancer(Pca)patients treated with maximal androgen blockade(MAB).@*Methods@#Clinical and pathological data of 210 Pca patients who underwent MAB as first-line therapy between January 2013 and June 2018 were retrospectively analyzed.The ages of patients in our cohort ranged from 61 to 90 years, with a mean of(77.0±6.5)years.According to the cut-off point for AGR calculated by the receiver-operating curve analysis, patients were categorized into two groups: the high-AGR group and the low-AGR group.Clinical and pathological features were compared between the groups.Independent factors affecting prognosis were analyzed by using univariate and multivariate analysis.@*Results@#The median follow-up duration was 44.0 months.Of the 210 patients, 99 cases had castration resistance, 100 patients(47.6%)had disease progression and 67 patients(31.8%)died.The cut-off point for AGR calculated by the receiver-operating curve analysis was 1.56.There were 103 cases in the low-AGR group(AGR<1.56)and 107 cases in the high-AGR group(AGR≥1.56). Univariate analysis revealed that the progression-free survival(PFS), cancer-specific survival(CSS)and overall survival(OS)were lower in the low-AGR group than in the high-AGR group[1.773(1.298~2.442), 1.948(1.220~3.213), 1.965(1.217~2.996), all P<0.05]. Multivariate Cox regression analysis showed that Gleason score, regional lymph nodes and bone metastases and AGR were independent prognostic factors for PFS(P=0.007, 0.040 and 0.022, P=0.031), CSS(P=0.003, 0.035 and 0.041, P=0.009)and OS(P=0.003, 0.026 and 0.023, P=0.002).@*Conclusions@#Pretreatment AGR<1.56 is an independent predictor for poor prognosis in Pca patients treated with MAB.

Prognostic value of pretreatment albumin to globulin ratio in prostate cancer patients treated with maximal androgen blockade / 中华老年医学杂志

Objective To investigate the prognostic value of pretreatment albumin to globulin ratio(AGR) in prostate cancer(Pca)patients treated with maximal androgen blockade(MAB).Methods Clinical and pathological data of 210 Pca patients who underwent MAB as first-line therapy between January 2013 and June 2018 were retrospectively analyzed.The ages of patients in our cohort ranged from 61 to 90 years,with a mean of(77.0-±-6.5)years.According to the cut-off point for AGR calculated by the receiver-operating curve analysis,patients were categorized into two groups:the high-AGR group and the low-AGR group.Clinical and pathological features were compared between the groups.Independent factors affecting prognosis were analyzed by using univariate and multivariate analysis.Results The median follow-up duration was 44.0 months.Of the 210 patients,99 cases had castration resistance,100 patients (47.6％) had disease progression and 67 patients (31.8％)died.The cut-off point for AGR calculated by the receiver-operating curve analysis was 1.56.There were 103 cases in the low-AGR group(AGR＜ 1.56)and 107 cases in the high-AGR group(AGR≥1.56).Univariate analysis revealed that the progression-free survival(PFS),cancer-specific survival (CSS)and overall survival(OS)were lower in the low-AGR group than in the high-AGR group[1.773(1.298～ 2.442),1.948 (1.220 ～ 3.213),1.965 (1.217 ～ 2.996),all P ＜ 0.05].Multivariate Cox regression analysis showed that Gleason score,regional lymph nodes and bone metastases and AGR were independent prognostic factors for PFS (P =0.007,0.040 and 0.022,P =0.031),CSS (P=0.003,0.035 and 0.041,P =0.009)and OS(P=0.003,0.026 and 0.023,P=0.002).Conclusions Pretreatment AGR＜1.56 is an independent predictor for poor prognosis in Pca patients treated with MAB.

Terapia hormonal para agresores sexuales con desórdenes parafílicos / Hormonal drug therapy for sexual offenders with paraphilic disorders

La ocurrencia de casos de pedofilia ha motivado que se evalué la implementación de la castración química mediante la terapia hormonal. El objetivo de esta revisión es evaluar los efectos de la terapia con antiandrógenos en agresores sexuales y con desordenes parafílicos. Se buscaron revisiones sistemáticas y guías de práctica clínica sobre la terapia con anti-andrógenos. Se seleccionaron dos revisiones sistemáticas y una guía de práctica clínica cuya evidencia corresponde a reportes de casos y estudios observacionales. El desenlace primario, recaídas sexuales, solo ha sido evaluado en dos estudios comparativos con medroxiprogesterona. El número pequeño de participantes y el alto porcentaje de abandonos no permiten sacar conclusiones en cuanto a la eficacia. Se reportaron efectos adversos frecuentes. La evidencia disponible es escasa y de baja calidad sobre la eficacia de la terapia hormonal con anti-andrógenos esteroideos y análogos de la GnRH en pacientes con desordenes parafílicos.

Occurrence of pedophilia’s cases has led to the evaluation of the implementation of chemical castration through hormonal therapy. The aim of this review is to evaluate the effects of anti-androgen therapy on sexual offenders with paraphilic disorders. We searched for systematic reviews and clinical practice guidelines on anti-androgen therapy. Two systematic reviews and a clinical practice guide were selected whose evidence corresponds to case reports and observational studies. Primary outcome, sexual relapse, has only been evaluated in two comparative studies with medroxyprogesterone. Small number of participants and high percentage of dropouts do not allow conclusions to be drawn as to efficacy. Frequent adverse effects were reported. Available evidence is scant and of low quality on the efficacy of hormonal therapy with antiandrogens steroids and GnRH analogs in patients with paraphilic disorders.

Long-Lasting Antiandrogen Withdrawal Syndrome in Castration-Resistant Prostate Cancer: Three Cases With Complete Response

This is a case report of 3 patients who had a dramatic and long-term complete response after antiandrogen withdrawal. All 3 patients were diagnosed with advanced or metastatic prostate cancer with a high prostate-specific antigen (PSA) level. For all patients, we started combined androgen blockade as androgen deprivation therapy and the PSA concentration decreased to <0.1 ng/mL, but then started to increase. After discontinuation of antiandrogen the PSA concentration decreased again and has remained below the limit of sensitivity for more than 1 year in all 3 patients.

Androgen deprivation therapy is associated with decreased second primary lung cancer risk in the United States veterans with prostate cancer / 한국역학회지

OBJECTIVES: We investigated whether androgen deprivation therapy (ADT) in prostate cancer patients was associated with a decreased risk for second primary lung cancer in US veterans.METHODS: Prostate cancer diagnoses in the US Veterans Affairs Cancer Registry between 1999 and 2008 were identified. Use of hormonal therapy and diagnoses of second primary lung cancer were determined from the registry. Synchronous prostate and lung cancers, defined as 2 diagnoses made within 1 year, were excluded from the analysis. Cancer-free survival was estimated using the Kaplan-Meier method and hazard ratios were estimated using Cox proportional hazard models.RESULTS: Among the 63,141 identified patients with prostate cancer, 18,707 subjects were eligible for the study. Hormonal therapy was used in 38% of patients and the median follow-up period was 28 months. ADT use was associated with longer lung cancer-free survival in prostate cancer patients (log-rank p=0.01). After adjusting for age, race, smoking and prostate cancer stage, ADT use was associated with decreased lung cancer risk by 15, 21, and 24% after 1, 2, and 3 years, respectively.CONCLUSIONS: ADT in prostate cancer patients may be associated with decreased second primary lung cancer risk among US veterans.

Androgen deprivation therapy is associated with decreased second primary lung cancer risk in the United States veterans with prostate cancer / 한국역학회지

OBJECTIVES: We investigated whether androgen deprivation therapy (ADT) in prostate cancer patients was associated with a decreased risk for second primary lung cancer in US veterans. METHODS: Prostate cancer diagnoses in the US Veterans Affairs Cancer Registry between 1999 and 2008 were identified. Use of hormonal therapy and diagnoses of second primary lung cancer were determined from the registry. Synchronous prostate and lung cancers, defined as 2 diagnoses made within 1 year, were excluded from the analysis. Cancer-free survival was estimated using the Kaplan-Meier method and hazard ratios were estimated using Cox proportional hazard models. RESULTS: Among the 63,141 identified patients with prostate cancer, 18,707 subjects were eligible for the study. Hormonal therapy was used in 38% of patients and the median follow-up period was 28 months. ADT use was associated with longer lung cancer-free survival in prostate cancer patients (log-rank p=0.01). After adjusting for age, race, smoking and prostate cancer stage, ADT use was associated with decreased lung cancer risk by 15, 21, and 24% after 1, 2, and 3 years, respectively. CONCLUSIONS: ADT in prostate cancer patients may be associated with decreased second primary lung cancer risk among US veterans.

Cambios en la densidad mineral ósea en pacientes que reciben terapia de deprivación androgénica para el cáncer de próstata / Changes in bone mineral density in patients receiving androgen deprivation therapy for prostate cancer

Introducción: el cáncer de próstata (CP) es el tumor maligno más frecuente en hombres en Uruguay. La terapia de deprivación androgénica (TDA) es una herramienta valiosa para su tratamiento. Si bien es altamente eficaz, este tratamiento tiene diversos efectos no deseados, entre los que se encuentra la disminución de la densidad mineral ósea. Material y método: realizamos un estudio longitudinal, observacional y prospectivo cuyo objetivo fue determinar si existe disminución de la densidad mineral ósea en los pacientes que reciben TDA para el CP. Se incluyeron pacientes portadores de CP en cualquier estadio que iniciarían tratamiento con TDA en el Servicio de Oncología del Hospital de Clínicas de Montevideo, Uruguay, en el período setiembre de 2012 a agosto de 2013, en quienes se realizó una densitometría ósea (DMO) previo al inicio de la TDA (DMO1) y se repitió a los seis meses de recibir la primera dosis de tratamiento hormonal (DMO2). Para cada región analizada se compararon las medias de densidad ósea medida en g/cm2 en la DMO1 vs DMO2. Resultados: se hizo seguimiento a diez pacientes con una edad mediana de 77 años. Se observó disminución significativa de la densidad mineral ósea en vértebras L3 y L4 (L3: 1.268 g/cm2 a 1.225 g/cm2 p=0,01; L4: 1.247 g/cm2 a 1.227g/cm2 p=0,005), mientras que en los otros puntos evaluados (L1, L2, cuello de fémur y cadera total) también hubo una disminución pero sin alcanzar significancia estadística. Conclusiones: confirmamos que la TDA disminuye la densidad mineral ósea por lo menos en vértebras lumbares 3 y 4 en un relativamente corto plazo (seis meses). Este efecto adverso debe evaluarse, identificarse y prevenirse oportunamente para evitar complicaciones mayores.

Abstract Introduction: prostate cancer is the most frequent malignant tumor in men in Uruguay. Androgenic deprivation therapy (ADT) is a valuable tool to treat this condition. In spite of it being highly effective, this treatment has several non-desirable effects, a reduction in bone mineral density being among them. Material: we conducted a longitudinal, observational and prospective study whose objective was to determine whether there is a reduction in bone mineral density in patients who receive ADT for prostate cancer. Patients who were carriers of prostate cancer undergoing any stage who would start their ADT treatment at the Oncology Unit of the University Hospital of Montevideo from September 2012 through August 2013 were included in the study. All of them underwent a bone densitometry prior to the initiation of ADT (BD1) treatment and it was repeated six months after they received the first dose of hormone treatment (BD2). Measurements of bone density were compared for every region analysed in g/ cm2 in BD1 versus BD2. Results: Ten patients with an average age of 77 years old were followed-up. A significant reduction in bone mineral density was observed in the L3-L4 spinal segment (L3: 1.268 g/cm2 at 1.225 g/cm2 p=0.01; L4: 1.247g/cm2 at 1.227g/cm2 p=0.005), whereas in the other points assessed (L1, L2, femoral neck and total hip) there was a reduction as well, although it did not represent any statistical significance. Conclusions: we confirmed ADT reduces the bone mineral density in lumbar vertebrae L3 and L4 in a relatively short time (six minths). This negative effect needs to be timely assessed, identified and prevented to avoid greater complications.

Resumo Introdução: o câncer de próstata (CP) é o tumor maligno mais frequente em homens no Uruguai. A terapia de deprivação androgênica (TDA) é uma ferramenta valiosa para seu tratamento. Embora seja altamente eficaz, este tratamento apresenta diversos efeitos não desejados, entre eles a diminuição da densidade mineral óssea. Material e método: realizamos um estudo longitudinal, observacional e prospectivo cujo objetivo foi detectar uma possível redução da densidade mineral óssea em pacientes que recebem TDA para CP. Foram incluídos pacientes portadores de CP em qualquer estadio que iniciaram tratamento com TDA no Serviço de Oncologia do Hospital de Clínicas de Montevidéu, Uruguai, no período setembro de 2012 a agosto de 2013; antes do inicio do tratamento foi realizada una densitometria óssea (DMO1) e uma segunda seis meses depois da primeira dose de tratamento hormonal (DMO2). Para cada região analisada foram comparadas as medias de densidade óssea medida en g/cm2 na DM1 versus DMO2. Resultados: dez pacientes com um mediana de idade de 77 anos foram estudados. Observamos uma diminuição significativa da densidade mineral óssea nas vértebras L3 e L4 (L3: 1.268 g/cm2 a 1.225 g/cm2 p=0,01; L4: 1.247g/cm2 a 1.227g/cm2 p=0,005); em outros pontos avaliados (L1, L2, colo de fêmur e quadril total) também houve diminuição porém não era estatisticamente significativa. Conclusões: confirmamos que a TDA diminui a densidade mineral óssea pelo menos nas vértebras lombares 3 e 4 em um prazo relativamente curto (seis meses). Este efeito adverso deve ser avaliado, identificado e prevenido oportunamente para evitar maiores complicações.

Primary Androgen Deprivation Therapy for Prostate Cancer in Koreans: A Retrospective Multicenter Study

PURPOSE: To evaluate the characteristics of patients who received primary androgen deprivation therapy (PADT) for prostate cancer and the clinical efficacy of this treatment. MATERIALS AND METHODS: Two hundred forty patients treated by PADT were reviewed. These patients could not receive definitive therapy owing to old age, patient need, and medical comorbidity. The patients were divided into three groups according to the extent of prostate cancer: localized, locally advanced, and metastatic. Then, prostate-specific antigen (PSA) progression in these groups was analyzed. RESULTS: The median age of the patients was 73.0 years, and the median pretreatment PSA level was 47.0 ng/mL. Of the patients, 91.7% were treated with combined androgen blockade, and 8.3% were treated with monotherapy. Clinical factors for PSA progression were a PSA nadir and a high clinical stage. Estimated PSA recurrence-free median survival time in each group was 57, 24, and 12 months, respectively. A PSA nadir of >0.2 ng/mL and metastatic stage were independent factors for expecting a poor response to PADT (hazard ratio 4.26, p<0.001; and 2.60, p<0.001). CONCLUSIONS: Patients with localized or locally advanced prostate cancer who did not receive definitive therapy had lower PSA progression rates than those at metastatic stage during PADT. Further, a PSA nadir of < or =0.2 ng/mL showed better progression-free survival. Therefore, PADT can be another therapeutic option in well-selected patients with localized or locally advanced prostate cancer and PSA change should be checked carefully.

Impact of intermittent androgen deprivation therapy on prostate volume and lower urinary tract symptoms in patients with prostate cancer combined with prostatic hyperplasia / 中华老年医学杂志

Objective To explore the impact of intermittent androgen deprivation therapy on prostate volume and lower urinary tract symptoms (LUTS) in patients with prostate cancer combined with prostatic hyperplasia (BPH),and to evaluate the clinical effect of intermittent androgen deprivation therapy as compared with conventional drug in patients with BPH.Methods Patients with prostate cancer (n=57) and BPH (n=83) were respectively treated with intermittent androgen deprivation therapy and finasteride combined with alpha-receptor antagonist.Prostate volume,international prostate symptom score (IPSS),quality of life index (QOL) and maximum urinary flow rate (Qmax) in patients were observed before and 1,3,6 and 12 months after treatment.Results The improvements in prostate volume,IPSS,QOL and Qmax were higher in prostate cancer patients treated with intermittent androgen deprivation therapy than in BPH patients treated with finasteride combined with alpha-receptor antagonist (P ＜ 0.05).Conclusions Intermittent androgen deprivation therapy can significantly reduce prostate volume and improve LUTS in patients with prostate cancer,and has a better clinical effect than finasteride combined with alpha-receptor antagonist treatment.

Therapeutic progress in castration-resistant prostate cancer / 肿瘤研究与临床

Prostate cancer represents one of the most common cancer in men, and the treatment of castrate refractory prostate cancer (CRPC) is still a challenge in the clinical practice,as there are few effective therapies to lengthen patients life.Nowadays,with the expansion of knowledge regarding the biology of CRPC,many novel approaches which are currently in development yielded promising results in the clinical setting for patients.

Impact of the National Health Fund policy on hormone treatment for prostate cancer in Jamaica / Repercusión de un subsidio del Fondo Nacional de Salud en la hormonoterapia para el cáncer de próstata en Jamaica

OBJECTIVE: To compare the proportion of patients choosing surgical versus medical castration to treat prostate cancer, before and after the National Health Fund (NHF) of Jamaica began to subsidize hormone therapy. METHODS: A retrospective review was performed at the University Hospital of the West Indies (UHWI), Jamaica. The pathology database at UHWI was searched to identify patients who had prostate biopsies between January 2000 and December 2007. These were combined with records of biopsies at external institutions. Medical records of all patients with positive prostate biopsies were reviewed to determine if they had received androgen deprivation therapy (ADT). Patients were classified as having had surgical castration (bilateral orchiectomy) or medical castration. Chi-square statistics were used to determine the difference in proportions between those choosing medical versus surgical castration before and after March 2005, when the NHF began offering subsidies for ADT drugs. RESULTS: Of the 1 529 prostate biopsies performed during the study period, 680 (44.0 percent) cases of prostate cancer were diagnosed. Of these, 458 patients underwent ADT and had complete records available for analysis. The mean patient age was 72 years. During the entire study period, surgical castration was performed in 265 patients (58.0 percent) and medical castration in 193 (42.0 percent). A greater proportion of orchiectomies were performed before March 2005, rather than after (P < 0.001). Estrogens were the most common method of medical castration used before the NHF subsidy became available (62.0 percent); while luteinizing hormone-releasing hormone analogues (38.0 percent) and antiandrogens (36.5 percent) were most often chosen afterwards. CONCLUSIONS: Surgical castration was more common than medical castration before March 2005. After the NHF began to subsidize the cost of drugs for hormone therapy, medical castration was chosen more often. Increased access to drugs for hormone therapy has changed treatment patterns in Jamaica.

OBJETIVO: Comparar la proporción de pacientes que eligen la castración quirúrgica frente a la castración farmacológica para tratar el cáncer de próstata, antes y después de la creación de un subsidio del Fondo Nacional de Salud (NHF, por sus siglas en inglés) de Jamaica destinado a cubrir los costos de la hormonoterapia. MÉTODOS: Se llevó a cabo un examen retrospectivo en el Hospital Universitario de las Indias Occidentales, Jamaica. Se efectuó una búsqueda en la base de datos de enfermedades de dicho hospital para identificar a los pacientes a quienes se les había practicado una biopsia de próstata entre enero del 2000 y diciembre del 2007. Los datos se combinaron con los registros de biopsias llevadas a cabo en instituciones externas. Se estudiaron las historias clínicas de todos los pacientes con resultados positivos en la biopsia de próstata para determinar si habían recibido tratamiento de supresión androgénica. Los pacientes se clasificaron en dos grupos, según se hubieran tratado mediante castración quirúrgica (orquiectomía bilateral) o farmacológica. Se usó la prueba de la ji al cuadrado para determinar la diferencia en las proporciones entre los pacientes que escogieron la castración quirúrgica y los que escogieron la opción farmacológica antes y después de marzo del 2005, la fecha en la que el NHF empezó a subsidiar los medicamentos de supresión androgénica. RESULTADOS: Entre las 1 529 biopsias de próstata realizadas durante el período de estudio, hubo 680 (44,0 por ciento) casos con diagnóstico de cáncer de próstata. De estos, 458 pacientes habían recibido tratamiento de supresión androgénica y se disponía de sus registros completos para el análisis. La edad media de los pacientes fue de 72 años. Durante el período de estudio, se les practicó castración quirúrgica a 265 pacientes (58,0 por ciento) y castración farmacológica a 193 (42,0 por ciento). La proporción de orquiectomías fue mayor antes de marzo del 2005 que después de esa fecha (P < 0,001). Los estrógenos fueron el método de castración farmacológica más común antes de la creación del subsidio del NHF (62,0 por ciento); a partir de ese momento se eligieron con mayor frecuencia los análogos de la hormona liberadora de la hormona luteinizante (38,0 por ciento) y los antiandrógenos (36,5 por ciento). CONCLUSIONES: La castración quirúrgica era más común que la castración farmacológica antes de marzo del 2005. Después de que el NHF empezó a subsidiar el costo de los medicamentos para el tratamiento hormonal, la opción escogida con más frecuencia fue la castración farmacológica. El mayor acceso a los medicamentos usados en la hormonoterapia ha cambiado los patrones de tratamiento del cáncer de próstata en Jamaica.

Efficacy of Alternative Antiandrogen Therapy for Prostate Cancer That Relapsed after Initial Maximum Androgen Blockade

PURPOSE: We evaluated the effectiveness of second-line maximum androgen blockade (MAB) with an alternative antiandrogen in patients who relapsed after initial MAB. MATERIALS AND METHODS: We retrospectively analyzed 47 patients with prostate cancer who relapsed after initial MAB, including surgical or medical castration combined with antiandrogens, from January 1998 to December 2009. When the serum prostate-specific antigen (PSA) level was increased on three consecutive occasions, we discontinued the antiandrogen and then administered an alternative antiandrogen. Seven patients were assessed for antiandrogen withdrawal syndrome (AWS). The effect of the second-line MAB was evaluated by the serum PSA level, and response was subdivided into > or =50% and or =50% PSA reductions with a mean response duration of 13.4+/-5.4 months. Nine (19.2%) patients reached or =50% PSA reduction group, <50% PSA reduction group, and PSA elevation group was 15.6+/-12.9 months, 11.8+/-6.0 months, and 8+/-6.5 months, respectively. That is to say, it was significantly longer in the responder groups (p=0.038). CONCLUSIONS: Second-line MAB using an alternative antiandrogen is an effective treatment option before cytotoxic chemotherapy in patients who relapse after initial MAB.

Adjuvant Effect of IV Clodronate on the Delay of Bone Metastasis in High-Risk Prostate Cancer Patients: A Prospective Study / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: High-risk prostate cancer patients undergoing treatment often experience biochemical recurrence. The use of bisphosphonates as an adjuvant treatment delays skeletal events, yet whether or not bisphosphonates also delay metastastic development remains to be determined. MATERIALS AND METHODS: A total of 140 high-risk prostate cancer patients who were undergoing definitive treatment and who had clinically organ-confined disease and who suffered from biochemical recurrence were administered intravenous (IV) clodronate. The patients were treated with a radical retropubic prostatectomy (RP) or curative radiotherapy (RTx). Upon androgen deprivation therapy initiation, tri-monthly IV clodronate was added to the treatment to prevent bone demineralization. Twenty-six out of 60 operated cases and 45 out of 80 irradiated cases received bisphosphonate. The length of time until the first bone metastasis was recorded and analyzed. RESULTS: No statistical difference was found for the type of primary treatment (RP or RTx) on the time to the first bone metastasis (95% confidence interval [CI], 0.40 to 2.43; p=0.98). However, there was a clear advantage favoring the group that received bisphosphonate (p<0.001). The addition of bisphosphonate delayed the appearance of the first bone metastasis by seven-fold (95% CI, 3.1 to 15.4; p<0.001). CONCLUSION: Treatment with tri-monthly IV clodronate delayed the time to the first bone metastasis in high-risk prostate cancer patients who were experiencing an increase in the prostate specific antigen level after definitive treatment.

Recovery of hormone sensitivity after salvage brachytherapy for hormone refractory localized prostate cancer

PURPOSE: Recent work has demonstrated the return of hormone sensitivity after palliative chemotherapy in androgen independent prostate cancer. We wished to establish whether a similar phenomenon existed in patients with no exposure to chemotherapy. MATERIALS AND METHODS: A review of “hormone resistant” patients who had received salvage brachytherapy for localized prostate cancer after previous external beam radiotherapy was undertaken. Three patients with subsequent biochemical relapse responded to the rechallenge with hormonal treatment. RESULTS: The series of patients presented here demonstrates this phenomenon occurs after salvage brachytherapy with no exposure to chemotherapy. Recovery of sensitivity is demonstrated both to androgen deprivation and to androgen receptor antagonism. The recovery of hormone sensitivity was surprisingly durable, ranging from eight months to over twenty-one months. CONCLUSIONS: Hormone sensitivity may be recovered after salvage brachytherapy. Potential mechanisms underlying these observations are discussed and the likely central role of the activity of the androgen receptor highlighted. The relevance of these findings to the management of advanced prostate cancer is considered including thoughts on the practice of intermittent anti-androgen therapy.

Changes of sex hormone levels in male acne patients with normal serum testosterone and effect of antiandrogen therapy / 第二军医大学学报

Objective: To observe the sex hormone levels in adolescent male acne patients with normal serum testosterone, and to evaluate the curative effect of antiandrogen therapy. Methods: Totally 40 adolescent male acne patients with normal serum testosterone were evenly randomized into two groups, the treatment group received finasteride plus life-style intervention, and the control group received life-style intervention only. The curative effects were compared between the two groups, and the levels of serum testosterone, dihydrotestosterone (DHT), free testosterone (FT), sex hormone binding globulin (SHBG), and estradiol (E2), and the adverse effects were observed before and after treatment. The curative effects in the treatment group were also observed 3 months after drug withdrawal. Another 40 healthy adolescent males served as normal group for comparison of the baseline hormone levels with ance patients. Results: The patients in our group had significantly higher levels of body fat content, E2 (P<0.05), DHT, and FT (P<0.01), and lower level of SHBG (P<0.05) compared with those in the normal control group. The overall effective rate of the treatment group was 90%, which was significantly higher than that of the control group (25%, P<0.01); the effective rate of the treatment group was 85% 3 months after drug withdrawal. The levels of DHT (P<0.01) and FT (P<0.05) in the treatment group were significantly decreased and the levels of SHBG was significantly increased (P<0.05) after treatment. There were no severe adverse effects in both groups. Conclusion: The adolescent male acne patients with normal serum testosterone have higher body fat content, DHT, FT, E2 and lower SHBF levels. The therapy using finasteride plus life-style is effective) it can greatly improve the serum level of SHBF and reduce adverse effects, with low recurrent rate after drug withdrawal.

Terapia médica de la ginecomastia con tamoxifeno. Influencia del volumen y duración de la ginecomastia en el resultado terapéutico / Influence of size and duration of gynecomastia on its response to treatment with tamoxifen

Background. Gynecomastia is treated when it is painful, there are psychosocial repercussions or it does not revert in less tan two years. It is treated with the antiestrogenic drug tamoxifen, but there are doubts about its effectiveness in high volume gynecomastias or in those lasting more than two years. Aim. To assess the effectiveness and safety of tamoxifen for gynecomastia and the influence of its volume and duration on the response to treatment. Patients and methods. Forty three patients with gynecomastia, aged 12 to 62 years, were studied. Twenty seven patients had a pubertal physiological gynecomastia, in eight it was caused by medications, in four it was secondary to hypogonadism, in three it was idiopathic and in one it was due to toxic exposure. Twenty patients had mastodynia and in 33, gynecomastia had a diameter over 4 cm. It lasted less than two years in 30 patients, more than two years in nine and four did not recall its duration. All were treated with tamoxifen 20 mg/dayfor 6 months. A follow up evaluation was performed at three and six months of treatment. Results. Mastodynia disappeared in all patients at three months. At six months gynecomastia disappeared in 26 patients (62 percent), but relapsed in 27 percent. All gynecomastias caused by drugs with antiandrogen activity disappeared. Fifty two percent of gynecomastias over 4 cm and 90 percent of those of less than 4 cm in diameter disappeared (p<0.05). Fifty six percent of gynecomastias lasting more than two years and 70 percent of those of a shorter duration disappeared (p=NS). Two patients had diarrhea or flushes associated to the therapy. Conclusions: Tamoxifen is safe and effective for the treatment of gynecomastia. Larger lesions have a lower response to treatment.