RESUMO
PURPOSE: To present a systematic review of the different therapeutic sequences in metastatic castration-resistant prostate cancer (mCRPC). METHODS: Evidence acquisition on therapeutic sequences in mCRPC was performed by a MEDLINE search using combination of the following key words: "prostate cancer," "metastatic," "castration resistant," "enzalutamide," "abiraterone," "treatment sequencing," "cabazitaxel," "docetaxel." A total of 17 studies were included for analysis. RESULTS: Different sequences have been reported for the treatment of mCRPC: docetaxel after abiraterone, cabazitaxel after docetaxel and abiraterone, abiraterone after cabazitaxel and docetaxel, abiraterone after docetaxel and enzalutamide, and enzalutamide after docetaxel and abiraterone. There are arguments from the preclinical observations suggesting a cross-resistance between docetaxel and abiraterone, and between abiraterone and enzalutamide in mCRPC. Despite limitations, several retrospective clinical reports support these data. CONCLUSION: No study of high level of evidence is available to support any recommendation on sequential treatment for mCRPC. There are only clues that prospective clinical studies need to confirm.
Assuntos
Androstenos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Feniltioidantoína/análogos & derivados , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Taxoides/administração & dosagem , Benzamidas , Docetaxel , Resistencia a Medicamentos Antineoplásicos , Quimioterapia Combinada , Humanos , Masculino , Metástase Neoplásica , Nitrilas , Feniltioidantoína/administração & dosagem , Neoplasias de Próstata Resistentes à Castração/patologiaRESUMO
BACKGROUND: In view of the marked molecular heterogeneity of prostate cancer (PCa), clinical and pathologic parameters alone may be unreliable for predicting disease outcomes after surgical intervention. The development of biomarkers may be helpful to estimate tumor heterogeneity and stratify patients in terms of their risk of progression. Levels of v-ets avian erythroblastosis virus E26 oncogene homolog (ERG), trefoil factor 3 (TFF3), and serine peptidase inhibitor, Kazal type 1 (SPINK1) are commonly elevated in PCa, but it is unclear whether the evaluation of these 3 markers can help to discriminate patients who will have different clinical outcomes. The authors investigated whether assessment of ERG, TFF3, and SPINK1 expression could help to define clinically relevant, distinct subsets of patients with PCa. METHODS: The cohort consisted of 279 men with PCa who underwent radical prostatectomy at Henri Mondor Hospital. Expression levels of ERG, TFF3, and SPINK1 were evaluated immunohistochemically in the prostatectomy specimens. Potential associations of ERG, TFF3, and SPINK1 with age, prostate-specific antigen (PSA), tumor stage, Gleason score, and biochemical recurrence, defined by PSA failure, were investigated. RESULTS: Although prognostic significance was not observed for ERG or TFF3, an exclusive pattern of expression was demonstrated for TFF3 and ERG. SPINK1 expression was observed exclusively in a subgroup of cancers that expressed TFF3 (41 of 175 tumors). Moreover, SPINK1 positivity was identified as predictive of biochemical recurrence in univariate (P = .0009) and multivariate (P = .0003) analyses. CONCLUSIONS: The current results suggest that ERG and TFF3 characterize 2 distinct subsets of PCa, with a more aggressive subgroup of TFF3-expressing tumors that express SPINK1. Together, these findings support a rationale of screening for these biomarkers for prognostic purposes and molecular subtyping of the disease.
Assuntos
Biomarcadores Tumorais/metabolismo , Proteínas de Transporte/metabolismo , Peptídeos/metabolismo , Neoplasias da Próstata/metabolismo , Transativadores/metabolismo , Adulto , Idoso , Progressão da Doença , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Próstata/metabolismo , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/cirurgia , Risco , Regulador Transcricional ERG , Fator Trefoil-3 , Inibidor da Tripsina Pancreática de KazalRESUMO
BACKGROUND: Proper usage of renal tumor biopsy (RTB) remains to be determined in the setting of renal tumors diagnosis, particularly in the elderly population. The aim of the study was to evaluate the perioperative and pathological results of RTB in a population of patients over 75 and to compare the performance of the procedure to their younger counterparts. MATERIAL AND METHODS: Systematic RTB were prospectively performed in a single center between 2009 and 2012. Patients' and tumor characteristics, operative and pathological results were collected. Data were compared between patients under and over 75 years old. Particular attention was paid to influence of RTB on treatment decision-making. RESULTS: A total of 180 patients were included (137 patients <75 years and 43 > 75 years). Size of tumor, clinical stage, radiological aspect and RENAL score were not statistically different between patients under or over 75 years. No difference was observed between the 2 groups regarding complication rate (2.9% vs. 0%, respectively, Pâ¯=â¯0.625). One hundred fifty-seven patients (87.2%) had a positive diagnosis at first RTB, with no difference between the 2 groups regarding histology (Pâ¯=â¯0.942). After biopsy, only 73.1% of patients <75 years and 70.7% of patients >75 years had concordance between radiological and histological findings (Pâ¯=â¯0.919). Treatment decision was challenged after RTB in 21.8% of patients <75 years and in 25.0% of patients >75 years. CONCLUSIONS: RTB was as safe and accurate in the eldest population, as it is in the general population, and should be performed routinely considering its influence on patient management strategy.