Cáncer de próstata: práctica clínica basada en la evidencia

Reis, Leonardo Oliveira; Sasse, André Deeke; Matheus, Wagner Eduardo; Denardi, Fernandes; Stopiglia, Rafael Mamprim; Silva, Maurício Moreira da; Ferreira, Ubirajara

doi:10.1016/s0210-4806(09)74158-0

Actas Urológicas Españolas

2009

DOI: 10.1016/s0210-4806(09)74158-0

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Cáncer de próstata: práctica clínica basada en la evidencia

Leonardo Oliveira Reis

André Deeke Sasse

Wagner Eduardo Matheus

et al.

Abstract: The existing parameters should be viewed as guidelines of conduct. The final trial on which the clinical procedure or treatment plan is most suitable for a particular patient should be done by a physician, who should discuss the available treatment options with the patient according to the diagnosis.

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Cited by 11 publications

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Old issues and new perspectives on prostate cancer hormonal therapy: the molecular substratum

Reis

2011

Med Oncol

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Secondary hormonal therapy is a treatment option in patients with castration-resistant prostate cancer (CRPC); however, it is underutilized and is room for optimization and improvement. In this context, androgen receptor (AR) is the Achilles' heel, being critically important and various mechanisms ranging from receptor mutations to secondary signaling pathways are responsible for some of the biological heterogeneity, demanding a multimodal approach. A comprehensive review of the peer-reviewed literature is performed on the topic of molecular mechanisms supporting secondary hormonal therapies, including expanded alternative hormonal therapies for CRPC. Essential concepts in clinical treatment of patients with progression on primary hormonal therapy are maintaining the castrate state, accounting for the intermittency phenomenon and sequentially using oral antiandrogens and adrenolytics heading to androgen depletion microenvironment. Survival prolongation, pain relief or measurable improvement in tumor-related symptoms should be persecuted and are considered to be a tangible benefit of obvious worth to the patient. Understanding the underlying molecular substratum is of paramount importance to hormonal therapy optimization in this context once current androgen-depletion strategies are incomplete, and residual androgens as well as alternative routes contribute to sustained AR activity and disease progression to a lethal phenotype. One or many mechanisms may be playing a role, even within the same patient and lastly are potential targets for treatment. Five fundamental mechanisms mediated through the AR to promote tumor growth (three of which depend on ligand signaling) added to the stem cell pathway must be recognized in CRPC. They are persistence of intratumoral androgens as a result of in situ steroidogenesis or adrenal source; AR mutations that allow promiscuous activation by otherwise nonsignaling ligands; wild-type AR gene amplification; alterations in AR coactivator-to-corepressor ratio that impact transcription; outlaw AR pathways that bypass the need for androgens by signaling through crosstalk with other ligand-bound receptors, cytokines, or transactivation of activated tyrosine kinase receptors in the cytosol.

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Old issues and new perspectives on prostate cancer hormonal therapy: the molecular substratum

Reis

2011

Med Oncol

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N-acetyltransferase-2 gene polymorphisms and prostate cancer susceptibility in Latin American patients

et al. 2012

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We investigated the role of N-acetyltransferases (NAT) in prostate cancer (PCa) susceptibility. NAT are polymorphic in the population and metabolize important carcinogenic products directly involved in the tumor initiation process. This prospective case-control study utilized the polymerase chain reaction-based restriction fragment length polymorphism method and comprised a cohort of consecutive 478 individuals: 126 men with prostate cancer; 101 men with benign prostatic hyperplasia (BPH); and a control health population of 177 female and 74 male blood donors from the same region. NAT2 slow or fast acetylators genotypes were determined by the combination of four variant alleles. Lifetime occupational history, dietary patterns, cigarette smoking and other anamnestic data were obtained by interviews. We were not able to find any correlation among smoking, dietary patterns, parameters of tumor aggressiveness or patient outcome and any NAT2 genotypes or phenotypes considered in separate or in different combinations. However, there was an association between NAT2T481C (OR=0.47; 95% CI=0.26-0.84; P=0.01) and NAT2A803G (OR=0.57; 95% CI=0.33-0.97; P=0.04) polymorphisms and PCa protection. Conversely, the presence of NAT2G857A genotype increased the risk of PCa more than 3 times (OR=3.57; 95% CI=1.39-9.15; P=0.005). Slow acetylator NAT2*7A and NAT2*6B genotypes occurred in 10.31% of PCa but in none of BPH patients (P=0.0007). The control health population confirmed the results and allowed the exclusion of possible biases caused by gender influence on genotype inheritance and by the inclusion of not diagnosed prostate diseases patients among the control individuals. We suggest that the investigation of germline polymorphisms of NAT2 gene may be useful in the assessment of Latin American patients at risk of BPH and PCa.

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Management of prostate cancer patients following radiation therapy after radical surgery referred from urology to radiation oncology departments in Spain

et al. 2015

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Cáncer de próstata: práctica clínica basada en la evidencia

Cited by 11 publications

References 53 publications

Old issues and new perspectives on prostate cancer hormonal therapy: the molecular substratum

Old issues and new perspectives on prostate cancer hormonal therapy: the molecular substratum

N-acetyltransferase-2 gene polymorphisms and prostate cancer susceptibility in Latin American patients

Management of prostate cancer patients following radiation therapy after radical surgery referred from urology to radiation oncology departments in Spain

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