TP5

Question 1

Cancro da próstata

Answer 1

is an adenocarcinoma, and 80% of cancersorig- 225

inate from the posterior “peripheral zone” of the gland

Question 2

Mutação mais comum

Answer 2

somatic translocation 200
fusing the androgen-responsive gene TMPRSS2 with a gene encoding an ETS-family transcription factor, which could be ERG,
ETV1, ETV4, or ETV6.

• sem relação com o prognóstico

amplification of the androgen receptor(AR) gene and somatic mutations of AR associated with resistance to anti-androgens, a group of drugs that block androgenbinding to AR

Question 3

Fatores de risco cancro da próstata

Answer 3

Age >50
Race (higher risk in African-American men)
Family history
BRCA2 gene mutation

Question 4

Sintomas do cancro da próstata

Answer 4

Frequenturination
Difficulty starting urinary stream
Urgency to urinate
Weak urinary stream
Erectile dysfunction
Pain during urination or
ejaculation
Blood in urine or semen
Bone pain in pelvis, back (spine)
Weight loss
Incontinence ofurine or stool
Weaknessor paralysis of legs

Question 5

Diagnóstico

Answer 5

• Centro de saúde - PSA (4 é o limite máx normal) e toque retal
• Se superior a 4 - biópsia por ultrassom transretal (por PSA elevada ou toque retal confirma nodúlo) - retirar 2 amostras de cada uma das 6 regiões da próstata.

Question 6

Estadiamento

Answer 6

• Gleason score. (1 e 2 não é cancro, 3 a 5)
• PSA
• Tamanho

prostate cancer is most often categorized as metastatic or localized, with localized cancers subdivided among low-, intermediate-, and
high-risk disease.

Question 7

Prognóstico do cancro da próstata

Answer 7

Intermediate- and high-risk cancers warrant staging evaluation, whereas low risk disease, with its characteristic indolent growth pattern, is highly unlikely to demonstrate metastasis.

Question 8

Metástases locais típicos

Answer 8

Osso e linfáticos e retroperitoneu.

Question 9

Metástases prostáticas ósseas

Answer 9

Blásticas e não líticas como a maioria

Question 10

Managementof localized prostate cancer

Answer 10

• active survillance
• active treatment (pacientes jovens ou com cancro intermédio e alto risco)
  
  • cirurgia - prostatectomia
  • radiation - brachytherapy (iodine 125 na próstata, mais nocivo)) and external-beam radiation therapy (EBRT - x ray em várias direções mas não diretamente no órgão)

____
HIGH RISK
EBRT + hormonal - “medical castration”
and androgen deprivation therapy (ADT): erradicação da produção de testosterona - 3 anos

Question 11

Efeitos secundários da ADT próstata

Answer 11

hotflashes (similar to hot flashes experienced by postmenopausal women), weight gain, loss of lean muscle mass, loss of bone density with increased potential for fractures, loss of erections, loss of libido, and potential development of diabetes mellitus and cardiovascular complications.

Question 12

Managementof metastatic prostate cancer

Answer 12

• ADT lifelong

- inibição do recetor de Androgénios

Question 13

Problemas da ADT

Answer 13

ADT offers several years

of disease control before the development of metastatic castration-resistant prostate cancer (mCRPC).

Question 14

tratamento para mCRPC

Answer 14

docetaxel chemotherapy.

• taxano
• estabilização dos microtúbulos levando à morte por impedimento da mitose.

Question 15

Mecanismos de resistência que levam ao mCRPC

Answer 15

• amplification of the AR gene,
• activating mutations of AR,
• expression of aberrantly spliced AR mRNA variants that are insensitive to anti-androgen therapy
• up-regulation of androgen biosynthesis from non-gonadal sources, including the adrenal glands and the cancer cells themselves.

Question 16

Target AR

Answer 16

enzalutamide
- anti-androgeno: competitively bind to the ligand-binding domain of the AR,thusinhibiting translocation of the AR to the nucleus, where the AR recruits other co-factors and
binds the DNAto stimulate transcription
- AR-V7 é resistente.

bicalutamide, nilutamide,
and flutamide - 1ª geração com uma atividade parcial agonista - não são utilizados agr.

_____________

Abiraterone acetate, an orally bioavailable prodrug
ofabiraterone, is a selective inhibitor of CYP17, an enzyme that plays a critical role in testosterone biosynthesis from cholesterol. Inibe testosterona da adrenal, testes e prostata - inib dos mineralocorticoids com um desvio da via para aldosterona (retenção liq e hipocaliémia) - damos prednisolona.

Question 17

Outros tratamentos

Answer 17

Sipuleucel-T
Cabazitaxel
Radium 223