RESUMO
INTRODUCTION: Non-metastatic, castration-resistant prostate cancer (nmCRPC) is an important clinical stage of prostate cancer, prior to morbidity and mortality from clinical metastases. In particular, the introduction of novel androgen-receptor signaling inhibitors (ARSi) has changed the therapeutic landscape in nmCRPC. Given recent developments in this field, we update our recommendations for the management of nmCRPC. METHODS: A panel of 51 invited medical oncologists and urologists convened in May of 2021 with the aim of discussing and providing recommendations regarding the most relevant issues concerning staging methods, antineoplastic therapy, osteoclast-targeted therapy, and patient follow-up in nmCRPC. Panel members considered the available evidence and their practical experience to address the 73 multiple-choice questions presented. RESULTS: Key recommendations and findings include the reliance on prostate-specific antigen doubling time for treatment decisions, the absence of a clear preference between conventional and novel (i.e., positron-emission tomography-based) imaging techniques, the increasing role of ARSis in various settings, the general view that ARSis have similar efficacy. Panelists highlighted the slight preference for darolutamide, when safety is of greater concern, and a continued need to develop high-level evidence to guide the intensity of follow-up in this subset of prostate cancer. DISCUSSION: Despite the limitations associated with a consensus panel, the topics addressed are relevant in current practice, and the recommendations can help practicing clinicians to provide state-of-the-art treatment to patients with nmCRPC in Brazil and other countries with similar healthcare settings.
Assuntos
Neoplasias de Próstata Resistentes à Castração , Neoplasias de Próstata Resistentes à Castração/diagnóstico , Neoplasias de Próstata Resistentes à Castração/terapia , Humanos , Masculino , Estadiamento de Neoplasias , Antineoplásicos/uso terapêutico , Antagonistas de Receptores de Andrógenos/uso terapêutico , Consenso , Brasil , OsteoclastosRESUMO
Objetivos: Caracterizar o perfil genético-clínico de pacientes com fenilcetonúria em Alagoas, diagnosticados e acompanhados pelo Programa Nacional de Triagem Neonatal.Métodos: Pacientes com fenilcetonúria, assistidos pelo Serviço de Referência em Triagem Neonatal de Alagoas, foram submetidos a coleta de sangue para rastrear mutações genéticas determinantes da variação fenotípica da doença. Concomitantemente, os pacientes ou seus responsáveis responderam a um questionário padronizado para coleta de dados clínicos e epidemiológicos.Resultados: Foram acompanhados 20 pacientes, sendo 14 do sexo masculino e seis do sexo feminino, pertencentes a 18 famílias. A idade dos pacientes estudados variou de 3 a 31 anos. Houve consanguinidade parental em 3/18 famílias; recorrência familial 3/18; 3/20 tiveram diagnóstico tardio; 2/20 interromperam temporariamente o tratamento; 1/20 não aderiu ao tratamento; e 6/20 apresentam manifestações clínicas. A análise das mutações foi concluída em 15/20 pacientes. As mutações encontradas no gene da fenilalanina hidroxilase foram: R261Q-homozigose (2 pacientes); V388M/I65T (1); R270K/V388M (1); I65T/L348V (1); IVS10nt11G>A-homozigose (2); V388M/R252W (1); R261Q/I65T (1); IVS10nt11G>A/R252W (1); V388M/IVS10nt11G>A (3); R261Q/R252W (1); R261Q/V388M (1).Conclusões: O genótipo V388M/IVS10nt11G>A foi o mais prevalente. Trinta por cento dos pacientes foram sintomáticos, provavelmente pela natureza das mutações, não adesão ao tratamento, tratamento inadequado e/ou diagnóstico tardio.
Aims: Characterizing the genetic/clinical profile of patients diagnosed with Phenylketonuria in Alagoas, monitored by the National Program of Newborn Screening. Methods: Patients with phenylketonuria, assisted by the Reference Center for Neonatal Screening of Alagoas , underwent blood sampling for detecting genetic determinants for the phenotypic variability of the disease. Concomitantly, patients or their guardians answered a standardized questionnaire for collection of clinical and epidemiological data. Results: Twenty patients (14 males and 6 females), belonging to 18 families, were monitored. Age ranged from 3-31 (mean age 10.35).We found parental consanguinity in 3/18 families; familial recurrence was 3/18; 3/20 had late diagnosis; 2/20 interrupted treatment for some time; 1/20 did not adhere to treatment; and 6/20 had clinical manifestations. Analysis of mutations was concluded in 15/20 patients. Mutations found in the phenylalanine hydroxylase gene were: R261Q-homozygous (2 patients); V388M/I65T (1); R270K/V388M (1); I65T/L348V (1); IVS10nt11G>A-homozygous(2); V388M/R252W (1); R261Q/I65T (1); IVS10nt11G>A/R252W (1); V388M/IVS10nt11G>A (3); R261Q/R252W (1); R261Q/V388M (1).