Urology Flashcards
What are the 3 zones of the prostate and their significance?
- Central Zone – Surrounds ejaculatory duct
- Transitional Zone – Commonest site of BPH
- Peripheral Zone – Commonest site of CA Prostate [70-80%]
What are the 3 parts of the urethra?
- Prostatic Urethra
-
Penile Urethra
- Membranous – Fixed, surrounded by external sphincter
- Spongy – Surrounded by corpus spongiosum
How does Prostate CA typically present?
- Incidental Finding – Palpated in DRE, ↑PSA in routine check-up, Microscopic tumour in histologic exam of specimen after prostatectomy for BPH
- Lower Urinary Tract Symptoms [only in very advanced disease]
- Haematuria, Dysuria, Incontinence, Retention [↓common ∵peripheral zone involvement rather than transitional zone]
- Obstructive – DISH
3. Cancer Symptoms
- Constitutional
- Metastatic – Bone pain, Pathological Fractures
- May have + FHx
How does Prostate CA metastasize?
- Locally – Beyond prostatic capsule, seminal vesicle, urethra, bladder base
- Lymphatic – Sacral, Iliac, Para-aortic nodes
- Haematogenous – Lung, Liver, Bone [lumbosacral spine, femur, pelvis]
What PE would you perform for suspected Prostate CA?
- DRE – Asymmetrical area of induration/Hard irregular nodule fixed to pelvic wall
- Assess Metastasis
- Local invasion – ballot kidneys for hydronephrosis
- Bone – Percuss Spine for any tenderness/pathological fractures
Differentials for Palpable nodule on DRE
- Prostate CA
- BPH
- Prostate Calculi
- Prostatitis
What is PSA?
- A glycoprotein secreted by the prostate glandular epithelial cell to liquefy semen
- Majority → semen; Some → blood
- CA prostate produces 10x serum PSA [hence serum PSA is measured]
What causes elevated PSA?
[PSA is organ specific but not disease specific]
- Malignant – Prostate CA
- Benign – BPH, AROU, Prostatitis, Trauma [Biopsy, Instrumentation]
- Physiological – Ejaculation, Cycling, Prostate Massage
Indications for PSA Measurement
[These DO NOT apply to patients with palpable nodule on DRE]
- Patients with CA Prostate for FU
- Patients with BPH if implications of test are explained
- Positive family history
- DO NOT perform if life expectancy <10 years
What is the cut-off for PSA value?
- PSA cut-off values are age-dependent [↑age = ↑cut-off]
- 40s = 2.5 → 50s = 3.5 → 60s = 4.5 → 70s = 6.5
General rule of thumb for PSA interpretation
- PSA < 4ng/mL – Normal; Biopsy not indicated
- 4-10ng/mL – 20% chance of CA; Consider biopsy
- ≥10ng/mL – >50% chance of CA; biopsy indicated
What if the PSA is between 4-10ng/mL?
- Other PSA indices can be used for additional reference
- PSA Density – PSA/Prostate Volume = >0.15 = ↑Probability
- PSA Velocity – Rate of ↑of PSA > 0.75ng//mL/yr = ↑Probability
-
% Free PSA
- 0-10% = >50% probability of CA
- 10-15% = 28%
- 15-20 = 20%
- >25% = 8%
If the PSA is <4 does it rule out Prostate CA?
NO, around 23% patients with prostate CA can have a PSA of ≤3
What are the other laboratory markers for prostate CA?
- Prostate Health Index [PHI] – Uses proPSA; ↑Specific for prostate CA c.f. PSA
- PCA3 – Urine gene based test for prostate specific mRNA
What are the two forms of screening and how is PSA used?
- Organised (Routine) Screening – Organised by authorities; everyone is screened; screening test must be of high standard [meet Wilson’s criteria]
- Opportunistic Screening – Screening requested by the patient
- Wilson’s Criteria – 1) Important PH problem; 2) Natural history well understood; 3) Has recognisable early pre-malignant stage [long progression]; 4) Effective investigations and treatments available; 5) Cost effective test
- PSA screening is not recommended for routine screening as it has poor Spe and Spec PLUS many patients die with Prostate CA; not of it; thus +ve PSA result may → invasive tests done on patients who would not benefit from it
- PSA opportunistic screening done if indicated
Indications for Prostate Biopsy
- Elevated PSA + Age <75yo [if diagnosis would affect treatment decision]
- Palpable nodule on DRE
- Diagnosis of CA prostate in clinically evident metastatic disease
How is prostate biopsy performed?
Trans-rectal Ultrasound [TRUS] guided → 10-12x biopsies taken → labelled according to which area taken
- Hypo-echoic lesion [30% chance of CA]
- Cx [3%] – Bleeding [Haematuria, Haemospermia, PR Bleed], Infection [4% UTI; 1% urosepsis - could be severe]
MRI guided/Robotic assisted biopsy may be done in some centres
How would you manage a patient with sudden onset fever post-TRUS biopsy?
- Treat as Post-TRUS biopsy urosepsis
- Urological emergency urgent management required
- ABC + Vitals → Resuscitate → Hx, PE , Ix + Empirical antibiotics
- PE – must perform DRE for prostate abscess requiring drainage from interventional radiologist
- Most common organism = E. coli
- Augmentin/Ciprofloxacin routinely used for UTI but NOT in this case as prophylactic antibiotics already given before TRUS; organism likely resistant if big guns not used
- Meropenem required
Investigations to stage prostate CA
- Clinical – Palpable nodule = T2 at least
- Histological – TRUS + Biopsy
-
Radiological – Assess local invasion & nodal involvement
- MRI – Endorectal Coli MRI [ERC]
- CT Abdomen + Pelvis
- Metastatic – PET-CT/Bone Scan
[MRI and Bone scan only performed in high risk disease guided by PSA and GS]
How is prostate CA staged?
Prostate CA is staged according to the TMN staging system
T = Tumour Size
- T1 = Not palpable
- T2 = Confined to Prostate
- T3 = Extra-Prostatic spread [Beyond capsule; Seminal vesicle]
- T4 = Spread to adjacent pelvic structures [External Sphincter, Bladder neck, Rectum, Pelvic floor muscles]
M = Metastasis – Either present or not
N = Nodal – Either present or not
What is the Gleason Score and Significance?
- Based on architectural features of prostatic CA cells seen on low power field microscopy
Calculation
- Tumours graded 1 to 5; 1 = most and 5 = least differentiated
- Sum of scores for the two most prevalent differentiation patterns = Gleason score
Significance
- ↑Gleason score = Worse prognosis [15yr mortality rate]
-
Guides further investigation
- GS ≤ 4+3 AND PSA≤20 → No further investigations
- GS ≤ 4+3 AND PSA≥20 → CT/MRI
- GS ≥ 8 AND PSA≤10 → No further investigations
- GS ≥ 8 AND PSA≥10 → CT/MRI
What would you look for in XR spine of a patient with Prostate CA?
- CA prostate is osteoblastic metastasis
- Focus on the pedicles to look for radio-opaque lesions and for symmetry of the pedicles
What are the two variations in Gleason Score calculation?
-
Core Principle – Glandular architecture on low power field microscopy
1. For TRUS biopsy specimen - Most common pattern + Most malignant pattern
1. For prostate specimen following prostatectomy - Most common + Second most common pattern
Principles of Treatment for Prostate CA
- If ≥75yo / Life expectancy ≤10yrs → Conservative [Watchful Waiting]
T1 or 2 + Life expectancy ≥10 yrs
- Conservative – Active Surveillance
- Curative [treatment of choice] – Radical Prostatectomy +/- Radiotherapy
T3 or 4 → Palliative
- Radiotherapy + Androgen Deprivation
Active Surveillance for Prostate CA
- For young [>10yr LE] patients fit for surgery with low risk disease [T1 or 2 & GS<7 + PSA<10] who want to avoid complications of tx [ED, Incontinence]
- Involves frequent PSA testing and biopsies to monitor tumour progression
- Curative treatment required if 1)↑PSA doubling time; 2) Progression of tumour on biopsy [↑grade/extensive]
How do you assess the outcome of radical prostatectomy?
- [Use the mnemonic CUP for ‘Trifecta’ outcomes]
- Continence
- Undetectable PSA
- Potency
Watchful Waiting for Prostate CA
- For old [<10-15yr LE] patients unsuitable for surgery with any stage of disease [Any T & GS<7 + no limit for PSA] to avoid complications of tx
- No need for frequent PSA testing or biopsies
- Palliative treatment if tumour progresses
What are the modalities of curative treatment for Prostate CA?
Radical Prostatectomy +/- Pelvic LN dissection
- Methods – Open [retropubic or perineal approach], Laparoscopic or Robotic
- Cx – ED [30-80%], Bleeding, Incontinence [50% initially; 10% permanent], Bladder neck stenosis [10%], GA risks, Rectal/Bowel injury
Radiotherapy
- Modalities – External Beam [EBRT; 33x]; Brachytherapy [insert radioactive implants]
- Cx – ED [30%], Radiation cystitis, Prostatitis, Proctitis, OAB
What are the modalities of palliative treatment of Prostate CA?
Palliative RT – Prolong survival; Relieve SCI, Symptomatic control
Androgen Deprivation Therapy
-
Castration
- Surgical – Orchiectomy [😊fastest onset, ☹S/E, permanent & psychological]
- Medical – LHRH agonist [Groserelin and Leuprolide]
- Anti-Androgen – Flutamide [Non-steroidal]; Cyproterone acetate
- Oestrogens
Prevent bone loss – Denosumab, Bisphosphonates [alendronate]
Time required for testosterone to fall to post-castration levels in different ADT modalities
- Orchiectomy – 3h
- LHRH antagonist – 3d
- LHRH analogue – 3mo
What is the mechanism of action and the drawbacks of LHRH analogues?
- [Nomenclature – GnRH = LHRH]
- Mechanism – Gonadotropin release in the body is pulsatile; prolonged use of LHRH analogue will lead to negative feedback → inhibit
- Drawbacks
- LHRH analogues can cause initial flare up of disease [↑risk of fractures/cord compression] while the effect is being achieved
- Anti-androgens must be given therefore before LHRH analogue use
How would you manage patients who do not respond to ADT in palliative CA Prostate?
- CA Prostate will progress into castration resistance stage
Secondary Hormonal Manipulation
- Adrenal Suppression – Ketoconazole
- Steroids – Prednisolone
- Progesterone
Chemotherapy – Docetaxel + Prednisolone
What are the side effects of ADT?
[Use the mnemonic ABCDEFG]
- Anaemia
- Bone loss [Osteoporosis]
- CVS risk/Cognitive impairment
- DM/Dyslipidemia
- Erectile Dysfunction
- Flushes (Hot)
- Gynaecomastia
Important Vessels around Prostate
[I Observe Prostate Vessels]
- Iliac – External & Internal Iliac Veins
- Obturator – a & v
- Pudendal vessels
- Vesical – Superior and Inferior arteries
