The HIF1A Functional Genetic Polymorphism at Locus +1772 Associates with Progression to Metastatic Prostate Cancer and Refractoriness to Hormonal Castration

The hypoxia inducible factor 1 alpha (HIF1a) is a key regulator of tumour cell response to hypoxia, orchestrating mechanisms known to be involved in cancer aggressiveness and metastatic behaviour. In this study we sought to evaluate the association of a functional genetic polymorphism in HIF1A with overall and metastatic prostate cancer (PCa) risk and with response to androgen deprivation therapy (ADT). The HIF1A +1772 C>T (rs11549465) polymorphism was genotyped, using DNA isolated from peripheral blood, in 1490 male subjects (754 with prostate cancer and 736 controls cancer-free) through Real-Time PCR. A nested group of cancer patients who were eligible for androgen deprivation therapy was followed up. Univariate and multivariate models were used to analyse the response to hormonal treatment and the risk for developing distant metastasis. Age-adjusted odds ratios were calculated to evaluate prostate cancer risk. Our results showed that patients under ADT carrying the HIF1A +1772 T-allele have increased risk for developing distant metastasis (OR, 2.0; 95%CI, 1.1-3.9) and an independent 6-fold increased risk for resistance to ADT after multivariate analysis (OR, 6.0; 95%CI, 2.2-16.8). This polymorphism was not associated with increased risk for being diagnosed with prostate cancer (OR, 0.9; 95%CI, 0.7-1.2). The HIF1A +1772 genetic polymorphism predicts a more aggressive prostate cancer behaviour, supporting the involvement of HIF1a in prostate cancer biological progression and ADT resistance. Molecular profiles using hypoxia markers may help predict clinically relevant prostate cancer and response to ADT

Gemcitabine as a Therapeutic Alternative during Shortage of BCG: The CHLC (Hospital S. José) Experience

Introdução: Os tumores não músculo invasivos da bexiga devem ser estratificados em grupos de risco de forma a adequar o tratamento após cirurgia a cada doente. Nos tumores de alto risco deve ser realizada terapêutica adjuvante com bacilo de Calmette-Guérin (BCG) intravesical durante 1 a 3 anos. Têm sido reportadas roturas de stock de BCG intravesical, tendo sido o Centro Hospitalar de Lisboa Central (CHLC) afectado nos anos 2014 e 2015, o que obrigou a uma reformulação no tratamento dos doentes que tinham indicação para realização desta terapêutica. A gencitabina poderá ser uma alternativa válida, dado que alguns estudos mostram que poderá ter um papel nos doentes de risco intermédio, como alternativa à mitomicina C, e nos de alto risco, refractários à BCG, com um perfil de toxicidade mais favorável. Material e Métodos: Trata-se de um estudo retrospectivo descritivo que incluiu doentes com tumores da bexiga não musculo-invasivos de alto risco, com início da doença em 2013/2014, afectados pelo período de escassez de BCG no Centro Hospitalar. Resultados: No CHLC, 11 doentes com tumores de alto risco foram submetidos a terapêutica com gencitabina, apenas dois exclusivamente, os restantes sequencialmente com BCG. Apenas dois doentes, tratados com BCG e gencitabina, apresentaram recidiva tumoral. No entanto, um número significativo (6 em 11) sofreram efeitos adversos, dois dos quais que levaram à interrupção da terapêutica. Conclusão: Aparentemente, a gencitabina foi uma boa alternativa de terapêutica adjuvante na ausência do tratamento gold standard (BCG), dada a existência de baixo número de recidivais tumorais, apesar do elevado número de efeitos adversos reportados.info:eu-repo/semantics/publishedVersio

Controversies in the management of advanced prostate cancer

For advanced prostate cancer, the main hormone treatment against which other treatments are assessed is surgical castration. It is simple, safe and effective, however it is not acceptable to all patients. Medical castration by means of luteinizing hormone-releasing hormone (LH-RH) analogues such as goserelin acetate provides an alternative to surgical castration. Diethylstilboestrol, previously the only non-surgical alternative to orchidectomy, is no longer routinely used. Castration reduces serum testosterone by around 90%, but does not affect androgen biosynthesis in the adrenal glands. Addition of an anti-androgen to medical or surgical castration blocks the effect of remaining testosterone on prostate cells and is termed combined androgen blockade (CAB). CAB has now been compared with castration alone (medical and surgical) in numerous clinical trials. Some trials show advantage of CAB over castration, whereas others report no significant difference. The author favours the view that CAB has an advantage over castration. No study has reported that CAB is less effective than castration. Of the anti-androgens which are available for use in CAB, bicalutamide may be associated with a lower incidence of side-effects compared with the other non-steroidal anti-androgens and, in common with nilutamide, has the advantage of once-daily dosing. Only one study has compared anti-androgens within CAB: bicalutamide plus LH-RH analogue and flutamide plus LH-RH analogue. At 160-week follow-up, the groups were equivalent in terms of survival and time to progression. However, bicalutamide caused significantly less diarrhoea than flutamide. Withdrawal and intermittent therapy with anti-androgens extend the range of treatment options. © 1999 Cancer Research Campaig

The Diagnosis of Bladder Cancer

Exame físico (incluindo toque rectal). Ultrasonografia renal e da bexiga e/ou UIV Cistoscopia com descrição de tamanho, e localização do tumor (o diagrama da bexiga deve ser incluído). Urina Tipo II; Citologia urinária, RTU com biópsia da base tumoral. Biópsias de todas as áreas suspeitas; biópsias randomizadas na presença da citologia positiva, tumor >3cm, ou tumor não papilar; biópsia da uretra prostática em casos de Cis ou suspeita de carcionoma in situ. Quando o tumor da bexiga é invasivo e está indicado um tratamento radical, é mandatório RX do tórax, UIV e/ou tomografia axial computorizada abdominal e pélvica, Ultasonografia hepática, cintigrafia óssea se houver sintomas ou se fosfatase alcalina for elevada