Prostate Cancer Flashcards
What is prostate cancer?
-Adenocarcinoma (>95%) of the prostate gland
=Ca of the acinar or ductal epithelium
=Invade the fibromuscular stroma
-Other pathological types v rare
=mucinous adeno Ca, small cell Ca, Sq Cell Ca, sarcoma
Prostate cancer incidence
-PrCa is the commonest male Ca (after skin Ca)
-PrCa is the 2nd most common cause of male Ca death
-UK
=47,500 new PrCa diagnoses/yr
=11,500 PrCa deaths/yr
-Prevalence
=30% of men in 50s
=70% of men in 80s
-Male lifetime risk of PrCa Dx: 12.5% (1:8)
-Male lifetime risk of PrCa Death: 3% (11,500/yr)
-Only ~15% of men diagnosed with PrCa will die from it
-“most men die with prostate cancer, than from prostate cancer”
Age of onset in prostate cancer
-UK
=47,500 new PrCa diagnoses/yr
=11,500 PrCa deaths/yr
-Prevalence
=30% of men in 50s
=70% of men in 80s
-Afro-caribbean: more aggressive, earlier onset
-FH PrCa / BrCa: increased risk, earlier onset
Sex/ Gender of prostate cancer
-PrCa is a male Ca – of specifically biological males(individuals born male)
-The following people will also have prostates:
=Trans women (or transgender women or transsexual women) who identify and live as women
=Male-assigned non-binary people
=Will have a prostate, regardless of whether they have had genital reconstructive surgery or not
=Can therefore get PrCa or prostate disease
=Trans women who have been taking feminising hormones are still at risk of PrCa [PrCa UK]
Geographical variation of Prostate cancer
Increased Risk
=Western: N America (high fat diet), Scandinavia(reduced sunlight, reduced Vit D)(USA, Europe)
=Afro-caribbean: African-American & Jamaicans have greatest risk
↓ Risk
=Far East, Asia
=Diet: reduced animal fat, oestrogenic protection from soya milk
Risk factors for prostate cancer
increasing age
obesity
Afro-Caribbean ethnicity
family history: around 5-10% of cases have a strong family history
Anabolic steroids
Tall stature
Aetiology of prostate cancer
-Hormonal factors & diet: meat & dairy products; soya protective (phytoestrogens), lycopenes
-Geography
-Race
-FH: 5% of all PrCa hereditary, HPC1/2, BrCa gene mutations
-Mutations TSGs: pTEN, MSR1, p53
-Increased Oncogenes: c-myc, bcl-2
Presentation of prostate cancer
-Asymptomatic: PSA screening
-Symptoms of locally advanced or metastatic disease (LUTS), pelvic pain and urinary symptoms, bladder outlet obstruction (hesitancy, urinary retention), haematuria, haematospermia, pain: back, perineal, testicular, ED
-DRE: asymmetrical, hard, nodular enlargement with loss of median sulcus
-Severity of symptoms is dependent on degree of anatomical involvement
-Symptoms of locally advanced disease: haematospermia, rapid ED, haematuria, urinary retention, obstructive nephropathy (ureteric obstruction), rectal obstruction
-Symptoms of metastatic disease: lumbar back pain, cauda equina syndrome
Describe Gleason’s Pattern Scale: microscopic pathology features
-AdenoCa 95%
-Graded acc to Gleason system(originally on whole-prostate specimens)
-Grade 1-5 acc to degree of differentiation
-Gd 1 well differentiated- well circumscribed nodule
-Gd 5 v poorly diff.; no glandular differentiation
-Gl score = sum of the 2 most common (ie dominant) grades:2-10 (6-10 used in practice)
-Low risk PrCa: Gl 6
-Int risk PrCa: Gl 7
-High risk PrCa: Gl 8-10
Prostate cancer macroscopic pathology features
-70-80% cancers develop in peripheral zone (DRE)
-20% transition zone
-5% central zone
Prostate cancer diagnosis pathway
-Hx & O/E
-DRE
-PSA
-TRUSP Bx: Gl score, now mpMRI and then TRUSBx in selected patients unless unfit for radical Rx (transrectal ultrasound-guided TRUS biopsy). Complications sepsis, pain, fever, haematuria, rectal bleeding
-Staging: mpMRI first ine for suspected clinically localised prostate cancer), Bone Scan if PSA>20 ug/l
PSA and Diagnosis
-PSA: Prostate Specific Antigen
-34kDa glycoprotein produced by Pr epithelial cells – liquefies the ejaculate, and leaks into the circulation
-PSA is Prostate specific, but not Pr cancer specific
-Used as a marker for PrCa
-Insufficiently sensitive (80%) + specific (40-50%) for Dx
- ie PSA may be normal in the presence of PrCa
-and PSA may be abnormally elevated in benign conditions: BPH, UTI, ejaculation, post-catheterisation, urethral instrumentation, prostatitis, retention, vigorous DRE
-PSA is used in PrCa screening, & PrCa follow-up (monitor effects of Rx… & detect recurrence)
-The decision whether or not to Bx is dependent on DRE findings, level of PSA, FH PrCa ….and patient factors/wishes
-There are age-related reference rages for PSA, that can vary locally:
-PSA can be used diagnostically in certain circumstances
-eg 84y man with abnormal DRE (hard + nodular) + PSA~100ug/l = PrCa
=The percentage of free: total PSA may help to distinguish benign disease from cancer. Values of <20% are suggestive of cancer and biopsy is advised
-Digital rectal examination
-Trans rectal USS +/- biopsy
MRI/CT and bone scan for staging
Why is screening in prostate cancer controversial?
-Disease: common, defined Hx, latent stage
-Test: has SEs (urosepsis, haematospermia, retention), PSA insufficiently sensitive nor specific, Bx may “miss” the Ca lesion, may require repeat Bx
-Rx: may not be necessary, sig SEs (ED, UI), may not be curative, may cause ↓QoL
-ERSPC trial: 1,400 men would have to be screened, and 48 treated, to save one life from PrCa. ie NNT is v poor in PrCa screening.
Treatment options in prostate cancer
-Watch and wait- Elderly, multiple co-morbidities, low Gleason score
-Radiotherapy (External)- Both potentially curative and palliative therapy possible. Similar survival figures to surgery. However, radiation proctitis and rectal malignancy are late problems. Brachytherapy is a modification allowing internal radiotherapy.
-Surgery- Radical prostatectomy. Surgical removal of the prostate is the standard treatment for localised disease. The robot is being used increasingly for this procedure. As well as the prostate the obturator nodes are also removed to complement the staging process. Erectile dysfunction is a common side effect.
-Hormonal therapy- Testosterone stimulates prostate tissue and prostatic cancers usually show some degree of testosterone dependence. 95% of testosterone is derived from the testis and bilateral orchidectomy may be used for this reason.
-Pharmacological alternatives include LHRH analogues and anti androgens (which may be given in combination).
-In the UK the National Institute for Clinical Excellence (NICE) suggests that active surveillance is the preferred option for low risk men. It is particularly suitable for men with clinical stage T1c, Gleason score 3+3 and PSA density < 0.15 ng/ml/ml who have cancer in less than 50% of their biopsy cores, with < 10 mm of any core involved.
Treatment and prognosis in prostate cancer
Treatment & Prognosis is dependent on:
=Grade & Stage of disease
=Patient factors (fitness/performance status)
=Benefits: cure, improved survival
=Side-effects: ED, urinary incontinence, lethargy, fatigue, gynaecomastia
-Localised PrCa (T1a/b/c, T2)
=Active surveillance and watchful waiting
=Potentially curative Rx: Radical prostatectomy (RALP, LRP), Brachy-, EBRT, Cryo-, radiotherapy (external beam and brachytherapy)
-Locally Advanced PrCa (T3)
=EBRT + neoadjuvant ADT (hormonal therapy)
=Clinical observation in select patients
=Radical prostatectomy (ED coplication)
=Radiotherapy, may dvelop proctitis, increased risk bladder, colon, rectal cancer
-Metastatic PrCa
=ADT (androgen deprivation therapy=hormonal therapy): Leuprorelin, Goserelin… Degarelix
=Chemo (Docetaxel)
=Cyp17 inhib (Abiraterone)
=Bilateral orchidectomy
