ON12 Prostate Cancer

Epidemiology​: Median age at diagnosis is [blank_start]66[blank_end] years​. [blank_start]100%[blank_end] 5 year survival rate with local or regional disease​ [blank_start]28.7%[blank_end] 5 year survival rate with distant disease​ 95% are [blank_start]adenocarcinoma[blank_end](cancer that starts in the mucous glands in epithelial tissue). In New Zealand…​ [blank_start]Most common[blank_end] cancer in men (3000 new cases/year, 600 deaths/year)​.

Which of these is NOT a risk factor for prostate cancer?

There is controversy with screening​ for prostate cancer as there is no clear evidence of mortality benefit with screening​.

Screening methods: - Digital rectal exam (circa 1900s)​. [blank_start]Cheap, safe, easy[blank_end] BUT not [blank_start]sensitive[blank_end], poor interobserver reliability, poor [blank_start]compliance[blank_end]​ - PSA blood test (prostate specific antigen)​ Low [blank_start]specificity[blank_end]​. Many other causes (BPH, acute [blank_start]prostatitis[blank_end], urinary [blank_start]retention[blank_end],benign prostatic [blank_start]hypertrophy[blank_end])​.

Select ALL the symptoms of prostate cancer which indicate advanced disease.

Diagnosis​ History and physical exam​. DRE​ and PSA. TRUS - [blank_start]transrectal ultrasound[blank_end] - if one of above positive). [blank_start]Biopsy[blank_end] (confirmative)​

Staging: Stage A​ - [blank_start]Occult or palpable​[blank_end] Stage B​ -[blank_start]Confined to the prostate​[blank_end] Stage C​ - [blank_start]Localised to periprostatic area​[blank_end] Stage D​ - Metastatic disease ​ [blank_start]T0N0M0[blank_end] (non-palpable)​ [blank_start]T1[blank_end]​ - Not palpable or visible by imaging​ [blank_start]T2[blank_end]​ - Confined within prostate​ [blank_start]T3[blank_end]​ - Extends through capsule​ [blank_start]T4​[blank_end] - Fixed or invades adjacent structures (other than seminal vesicles)​

Gleason Score​: Histologic grade of tumor​. Calculated based on dominant [blank_start]histological[blank_end] grades. Scores range from 1 = well [blank_start]differentiated[blank_end] healthy tissue, to 5 = very [blank_start]poorly[blank_end] differentiated​ abnormal tissue. Gleason score = sum of [blank_start]two most common[blank_end] pattern grades ([blank_start]2 to 10[blank_end])​. Higher is worse.

Factors influencing prognosis:​ Extent of [blank_start]tumor[blank_end]​ Histological [blank_start]grade[blank_end] of tumor​ Patient’s [blank_start]age and health​[blank_end] [blank_start]Molecular markers[blank_end] (Bcl-2, Bax, Ki67, p53, p27, E-cadherin, Microvessel density, DNA ploidy, p16)​ PSA level? ​

Initial treatment depends on the stage, Gleason score, presence of symptoms, and life expectancy​. Low risk patients (T1 or T2, GS of [blank_start]2-6[blank_end], PSA<10ng/ml) – excellent survival (10yr)​: [blank_start]Observation​Radiation​[blank_end] Radical [blank_start]prostatectomy ​[blank_end] Life expectancy <10 years​? Observation​ Radiation therapy ​

Nonpharmacological Treatments: Observation​ - DRE and PSA performed every [blank_start]6[blank_end] months and biopsy if signs of [blank_start]progression[blank_end]​ Radiation​ - Effective yet complications ([blank_start]hematuria, impotence, diarrhea, cystitis[blank_end])​ Radical prostatectom y - Complications: [blank_start]blood loss[blank_end], impotence, [blank_start]incontinence[blank_end], fistula​ Bilateral orchiectomy (removal of testes)​. Need [blank_start]androgen deprivation therapy[blank_end]​.

Hormonal Treatment​: Rationale​ - Androgens stimulate prostate cancer cells to [blank_start]grow[blank_end]. Main androgens are [blank_start]testosterone[blank_end] and dihydrotestosterone (DHT)​. Most androgens made by [blank_start]testicles[blank_end] but also by adrenal glands​. Lowering androgen levels makes prostate cancer cells shrink or grow more [blank_start]slowly[blank_end] but does not cure prostate cancer. Indication​ - If cancer cannot be cured by surgery or radiation or [blank_start]remains/relapses[blank_end]​... In combination with radiation therapy if high [blank_start]risk of recurrence[blank_end] (high Gleason)​... OR before radiation to shrink cancer and make radiation more [blank_start]effective[blank_end] .

Pharmacological (hormone) Treatment​: 1. LHRH [blank_start]agonists[blank_end]​ - Reversible method of androgen ablation as effective as orchiectomy​. Puts patient at risk for [blank_start]osteoporosis[blank_end]​. Drugs: [blank_start]Leuprolide, Goserelin,[blank_end] Triptorelin, Histrelin​. 2. GnRH [blank_start]antagonists[blank_end]​ - Works directly in [blank_start]pituitary[blank_end] to reduce testosterone ​ 3. Antiandrogens - Bind to [blank_start]androgen[blank_end] receptors so androgens cannot. Not used alone, typically with LHRH agonists/removal of testicles. Drugs: [blank_start]Flutamide, Bicalutamide, Nilutamide​[blank_end]

Which of these is not an ADR of androgen lowering therapies?