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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.
Subject(s)
Humans , Male , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Prostatic Neoplasms, Castration-Resistant/pathology , Prostatic Neoplasms, Castration-Resistant/drug therapy , Treatment Outcome , Androgen Antagonists/therapeutic useABSTRACT
Abstract Objective: To evaluate the effect that external cooling of the salivary glands (ECSG) has on the uptake of gallium-68-labeled prostate-specific membrane antigen (68Ga-PSMA), as an indirect assessment of the capacity of ECSG to reduce the local dose in lutetium-177-PSMA-617 radioligand therapy. Materials and Methods: Ten patients with prostate cancer were submitted to 68Ga-PSMA positron emission tomography/computed tomography with unilateral ECSG. The ECSG was started at 30 min before the injection of the radiotracer and maintained until the end of image acquisition (1 h after injection). Each salivary gland was assessed by determining the maximum, mean, and peak standardized uptake values (SUVmax, SUVmean, and SUVpeak, respectively). The volume of each gland was determined in a volume of interest delineated by a threshold SUVmax of 10%. Paired Student's t-tests were used in order to compare the results. Results: In terms of the SUV parameters, there were no statistically significant differences between the cooled and contralateral salivary glands. However, the mean volume was 27% lower in the cooled parotid glands than in the contralateral parotid glands (p = 0.004). Conclusion: The use of ECSG does not appear to reduce 68Ga-PSMA uptake by the salivary glands. In addition, there is yet no evidence that ECSG is effective in preventing salivary gland toxicity.
Resumo Objetivo: Avaliar o impacto do resfriamento externo de glândulas salivares (REGS) na captação de 68Ga-PSMA como marcador indireto dessa intervenção para redução da dose local na terapia com 177Lu-PSMA. Materiais e Métodos: Dez pacientes com câncer de próstata foram submetidos a PET/CT com 68Ga-PSMA com REGS unilateral. O resfriamento se iniciou 30 minutos antes da injeção do radiofármaco até o fim da aquisição de imagem, 1 hora após a injeção. Cada glândula foi avaliada para os valores de captação padronizados máximo, médio e pico (SUVmáx, SUVmédio e SUVpico, respectivamente). O volume foi definido por um isocontorno usando 10% do SUVmáx. Os resultados foram comparados com o teste t de Student. Resultados: Não houve diferença estatisticamente significante entre os valores de SUV das glândulas resfriadas e seus controles. Houve 27% de redução volumétrica (p = 0,004) nas parótidas resfriadas em comparação ao controle. Conclusão: Não houve redução da captação de 68Ga-PSMA nas glândulas salivares ao REGS. Atualmente não há evidências que suportem essa prática clínica.
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ABSTRACT Background: Non-metastatic castration resistant prostate cancer (M0 CRPC) has seen important developments in drugs and diagnostic tools in the last two years. New hormonal agents have demonstrated improvement in metastasis free survival in M0 CRPC patients and have been approved by regulatory agencies in Brazil. Additionally, newer and more sensitive imaging tools are able to detect metastasis earlier than before, which will impact the percentage of patients staged as M0 CRPC. Based on the available international guidelines, a group of Brazilian urology and medical oncology experts developed and completed a survey on the diagnosis and treatment of M0 CRPC in Brazil. These results are reviewed and summarized and associated recommendations are provided. Objective: To present survey results on management of M0 CRPC in Brazil. Design, setting, and participants: A panel of six Brazilian prostate cancer experts determined 64 questions concerning the main areas of interest: 1) staging tools, 2) treatments, 3) side effects of systemic treatment/s, and 4) osteoclast-targeted therapy. A larger panel of 28 Brazilian prostate cancer experts answered these questions in order to create country-specific recommendations discussed in this manuscript. Outcome measurements and statistical analysis: The panel voted publicly but anonymously on the predefined questions. These answers are the panelists' opinions, not a literature review or meta-analysis. Therapies not yet approved in Brazil were excluded from answer options. Each question had five to seven relevant answers including two non-answers. Results were tabulated in real time. Conclusions: The results and recommendations presented can be used by Brazilian physicians to support the management of M0 CRPC patients. Individual clinical decision making should be supported by available data, however, for Brazil, guidelines for diagnosis and management of M0 CRPC patients have not been developed. This document will serve as a point of reference when confronting this disease stage.
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Humans , Male , Physicians , Prostatic Neoplasms, Castration-Resistant/diagnosis , Prostatic Neoplasms, Castration-Resistant/drug therapy , Perception , Brazil , Treatment Outcome , Patient Selection , ConsensusABSTRACT
El presente trabajo es una revisión bibliográfica y actualización de los diferentes esquemas terapéuticos aprobados y en estudio, de la enfermedad con metástasis en hueso producto del cáncer de próstata avanzado con la condición de resistente a la castración. Aborda generalidades del cáncer de próstata, los mecanismos por los cuales se vuelve resistente a la castración, la aparición de metástasis óseas, la terapéutica enfocada en terapia antiresortiva, (bifosfonatos e inhibidor del Ligando RANK), radiofármacos, radioterapia y nuevas drogas (Cabozantinib)(au)
This is a literature review and update of the different therapeutic options approved and under study, of bone metastases due to castration resistant prostate cancer. It addresses general information of prostate cancer, the mechanisms by which it becomes resistant to castration, the appearance of bone metastases, treatment focused on antiresorptive therapy (bisphosphonates and RANK Ligand inhibitor), radiopharmaceuticals, radiotherapy and new drugs (Cabozantinib).(au)
Subject(s)
Humans , Male , Prostate/pathology , Radiotherapy , Castration , Radiopharmaceuticals , Diphosphonates/pharmacology , Prostatic Neoplasms, Castration-Resistant/therapy , Neoplasm Metastasis/therapy , Therapeutics , Prostate-Specific Antigen , Reference Drugs , RANK LigandABSTRACT
Objective To investigate the safety and efficacy of 177Lu-prostate specific membrane antigen (PSMA)-617 in the treatment of metastatic castration-resistant prostate cancer (mCRPC).Methods From August 2017 to September 2018,11 patients(average age 70.6 years) with mCRPC who underwent 177Lu-PSMA-617 therapy in Nanjing First Hospital were studied.All patients underwent 68Ga-PSMA-11 PET/CT before therapy to assess the tumor radioactive uptake.Blood routine examination and renal function test results were documented before and after therapy to assess the safety.The efficacy was reflected by the changes of prostate specific antigen (PSA) levels and maximum standardized uptake value (SUVmax) on 68Ga-PSMA-11 PET/CT imaging.Paired t test and Wilcoxon's sign rank test were used to analyze the data.Results No acute side effects were observed after therapy of 177Lu-PSMA-617.There were no statistically significant differences after therapy in WBC counts,RBC counts,and PLT,as well as Hb levels (t values:-0.28-1.11,all P＞ 0.05).No kidney toxicity was found.The PSA level after 177Lu-PSMA-617 therapy was significantly lower than that before therapy (80.70 (14.29,1 538.00) μg/L vs 604.60 (88.41,3 980.00) μg/L;u =59,P =0.023).Of the 11 patients,only 2 had elevated PSA levels and disease progression,while the other 9 patients had varying decreases,of which 2/11 decreased by ＞30％ and 7/11 decreased by ＞50％.After therapy,SUVmax of metastatic lesions and metastatic lymph nodes were decreased in 9 and 2 patients respectively.Conclusions 177Lu-PSMA-617 has a good therapeutic value for mCRPC.It is safe and has no obvious side effects.
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The incidence of prostate cancer in China has a rising trend recently. The majority of prostate cancer patients have been in advanced stage at the first diagnosis. Although the endocrine therapy may make prostate cancer under control and improvement in a certain period of time, but almost patients will finally develop to metastatic castration-resistant prostate cancer (mCRPC) with poor prognosis after 18-24 months of remission period. Because mCRPC is difficult to cure, it is urgent to optimize the treatment strategy for improving efficacy. The current evidence shows that the new endocrine drugs such as abiraterone and enzalutamide combined with docetaxel chemotherapy can provide survival benefit for the patients with mCRPC, but there is still a controversy about the optimal using order of these agents. The article reviews the clinical trials on the treatment sequencing of noval endocrine agents in docetaxel-experienced and docetaxel-naive patients with mCRPC in order to provide the basis for the correct selection of treatment strategies, and thus to prolong the overall survival and improve the quality of life of the patients.
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Objective To assess the role of 68Ga-N,N'-bis (2-hydroxy-5-(carboxyethyl) benzyl) ethylenediamine-N,N'-diacetic acid(HBED-CC)-(Ahx) Lys-CO-Glu(PSMA-11) PET/CT on the detection of metastatic lesions from castration-resistant prostate cancer (CRPC).Methods Sixteen patients with CRPC who underwent 68Ga-PSMA-11 PET/CT between January 2015 and November 2015 were recruited in this study.Mean age of patients was (72±9) years.The PSA levels were 4-12 356 μg/L,Gleason score was 7-10.PET/CT was performed at 1 h postinjection of 68Ga-PSMA-11.Patient-based analysis and lesionbased analysis were performed.ROI analysis was used to calculate the tumor uptake (SUVmax).Final diagnosis was based on histopathology and results of other imaging examinations(99Tcm-MDP imaging,MRI).x2 test was used to compare the diagnostic efficiencies of PET and CT.Results No adverse effects were observed in patients.68Ga-PSMA-11 PET/CT showed moderate physiologic uptake in salivary glands and proximal small intestine,with predominant tracer clearance by the kidneys.All patients were positive on 68Ga-PSMA-11 PET/CT.Bone metastasis was found in 16 patients,liver metastasis in 2 patients (5 lesions),and lymph node metastasis in 4 patients (26 lesions).The SUVmax of liver,lymph node and bone metastases were 15.06±2.77,7.54±5.20,19.01± 16.96,respectively.The diagnostic sensitivity,specificity and accuracy on bone metastasis with 68Ga-PSMA-11 PET and CT were 96.30％(52/54) vs 61.11％(33/54),3/3 vs 1/3,96.49％ (55/57) vs 59.65％ (34/57).The sensitivities and accuracies of the two modalities were significantly different(x2=19.943,22.593,both P＜0.01).Conclusions 68Ga-PSMA-11 PET/CT could precisely detect both primary and metastatic lesions of CRPC,suggesting that it is of great value for the clinical management and treatment.
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PURPOSE: Docetaxel-based chemotherapy (DTX) improves overall survival (OS) of men with metastatic castration-resistant prostate cancer (mCRPC). Considering the potential existence of androgen receptors that remain active at this stage, we aimed to assess the impact of the combined use of androgen deprivation therapy (ADT) with DTX for mCRPC. MATERIALS AND METHODS: We performed a single-institutional retrospective analysis of patients with mCRPC who received either DTX alone (DTX group, n=21) or concurrent DTX and ADT (DTX+ADT group, n=26) between August 2006 and February 2014. All patients received DTX doses of 75 mg/m2 every three weeks for at least three cycles. In the DTX+ADT group, all patients used luteinizing hormone releasing hormone agonist continuously as a concurrent ADT. RESULTS: The median follow-up period was 24.0 months (interquartile range 12.0-37.0) for the entire cohort. The median radiographic progression-free survival (rPFS) was 9.0 months and 6.0 months in the DTX+ADT and DTX groups, respectively (log-rank p=0.036). On multivariable Cox regression analysis, concurrent administration of ADT was the only significant predictor of rPFS [hazard ratio (HR)=0.525, 95% confidence intervals (CI) 0.284-0.970, p=0.040]. The median OS was 42.0 and 38.0 months in the DTX+ADT and DTX groups, respectively (log-rank p=0.796). On multivariable analysis, hemoglobin level at the time of DTX initiation was associated with OS (HR=0.532, 95% CI 0.381-0.744, p<0.001). CONCLUSION: In chemotherapy-naive patients with mCRPC, the combined use of ADT with DTX improved rPFS. Our result suggests that the concurrent administration of ADT and DTX is superior to DTX alone.
Subject(s)
Aged , Humans , Male , Middle Aged , Adenocarcinoma/blood , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Disease-Free Survival , Gonadotropin-Releasing Hormone/administration & dosage , Hemoglobins/metabolism , Prostatic Neoplasms, Castration-Resistant/blood , Retrospective Studies , Survival Rate , Taxoids/administration & dosageABSTRACT
Prostate cancer represents the second cancer-related cause of death in North American and Chilean men. The main treatment for incurable stages of disease is surgical or pharmacological castration. However, with time and despite the addition of anti-androgens, the disease progresses to a clinical state that has been commonly referred to as hormone refractory. In recent years, the concept of hormone refractoriness has been challenged and replaced by castration resistance, acknowledging that further and optimal hormonal manipulation can be attained, beyond achieving testosterone levels at castration range. The purpose of this review is to summarize the recent therapeutic breakthroughs in the management of metastatic castrate resistant prostate cancer (mCRPC), with greater emphasis in the newer hormonal therapy agents such as Abiraterone and Enzalutamide. Future combination and sequential treatment strategies are contextualized in the current era of personalized cancer medicine and genomic characterization of prostate cancer.