Case Study: Urology 2 & Interactive Tutorial: Urological Cancer Flashcards
History taking in elevated PSA
- Why check, counselled?
- Previous investigations (e.g. previous PSA, any biopsy done)
- Risk factors: **Age, **Race, ***Family history of prostate cancer
- LUTS
- History of UTI, prostatitis, BPH (other causes of ↑ PSA)
- New bone pain, lower limb swelling
- New onset peripheral neurology (if spinal cord involved)
- Anorexia, weight loss
- Coagulopathy
Risk factors for Prostate cancer
- Advanced age
- Family history
- BRCA2
- HNPCC - Race
- Black > Caucasians > Asians
- Poorer survival - Geographical variation
- Western nations - Dietary and lifestyle
P/E of Prostate cancer
- General
- Uraemia
- Cachexia - Abdominal
- Palpable mass
- Bladder
- Ballotable kidneys - DRE
- Prostate
- Anal tone - External genitalia, Scrotal exam
- Neurological exam
Clinical features of Prostate cancer
- Local
- **LUTS
- Recurrent UTI
- **Renal failure
- **Haematuria / Haematospermia
- Malignant priapism (invasion of malignant cells into the cavernosal sinuses and their associated venous systems)
- **Bowel obstruction - General (uncommon)
- Weight loss
- Anorexia
- Malaise - Metastasis
- **Bone
- **LN
- ***Liver / Lung
- Brain - Paraneoplastic (very rare)
- Endocrine
- ***Neurological
- Dermatological
- Haematological
PSA value, Family history and risk of prostate cancer
PSA value:
- Higher PSA —> Higher risk
- ***NO true cut-off normal value for PSA!!! (<=4 can still have cancer!!!)
- Overall risk of Ca prostate and PSA value:
—> <=4: 27%
—> 4.1-10: 41%
—> >10: 69%
—> >20: 87%
Family history:
- 5-10% Ca prostate hereditary
- Familial Ca Breast, BRCA gene (BRCA2)
- Consider genetic tests in selected patients —> may impact on future treatment plans (e.g. targeted therapy)
Is prostate cancer lethal?
- 60% of men >70 yo may have prostate cancer
- Only a small proportion of prostate cancer are clinically significant
- Most patients with prostate cancer die **with prostate cancer but not **from prostate cancer!
PSA screening
Traditional diagnostic pathway of prostate cancer (still used now):
**PSA + **DRE
—> **Transrectal USG guided biopsy (TRUS biopsy)
(NB: Abnormal DRE will warrant prostate biopsy **regardless of PSA level)
Problem with this pathway:
1. Lacks specificity (PSA: organ specific but NOT disease specific)
- overdiagnosis of non-clinically significant prostate cancer
- underdiagnosis of clinically significant prostate cancer
2. Confusion between population screening and early diagnosis
3. Quality of existing screening studies are poor
- European Prostate Cancer Screening Trial (ERSPC): Against PSA screening
- Gothenburg study: NNT closer to breast cancer screening figures
Current best evidence suggest PSA screening:
- Provides only a small reduction in prostate cancer mortality
- No reduction in all cause mortality
- Expose healthy individuals to risk of overdiagnosis + overtreatment + anxiety + SE from treatment
***Current recommendations on PSA screening:
Before PSA screening:
1. Consider in men with life expectancy >10 years
2. Shared decision-making, discuss potential benefits + harms associated
3. If for screening, start at 50 / 45 if have risk factors (e.g. African Americans, 1st degree relative diagnosed <65 yo)
Follow up on PSA screening:
1. **PSA <1 —> repeat test every 4 years
2. **PSA 1-3 —> repeat test every 2 years
3. ***PSA >3 —> more frequent PSA testing (every 1 year) —> consider adjunctive strategies —> biopsy (shared decision making)
PSA test counselling:
1. Benefits of screening + aggressive treatment for prostate cancer have not yet been proven
- if diagnosed with low risk prostate cancer —> need to accept active surveillance
2. DRE + PSA have false positive + false negative results
3. Relatively high risk of further invasive tests
- if have high PSA —> need to **subject to invasive prostate biopsy (otherwise no point of testing PSA)
4. **Aggressive therapy is necessary to achieve benefit following discovery of cancer
5. Risk of mortality / morbidity from treatment
6. Early detection and treatment ***may save lives and avert future cancer related illness
***Diagnosis of Prostate cancer
Traditional diagnostic pathway of prostate cancer (still used now):
**PSA + **DRE
—> **Transrectal USG guided biopsy (TRUS biopsy)
(NB: Abnormal DRE will warrant prostate biopsy **regardless of PSA level)
What can we use to screen / How we can improve?
Paradigm change:
Biochemical + Radiological (PiRADS) —> before Biopsy
- Biochemical
- e.g. **PHI, **PSA density - Radiological (**Pre-biopsy MRI scan)
**Multi-parametric MRI prostate (3 out of 4 sequences):
—> T2
—> ADC / DWI (apparent diffusion coefficient, diffusion-weighted imaging)
—> DCE (dynamic contrast-enhanced)
—> MR Spectrometry
- Identify area of suspicious lesions
- Still can miss up to 20% of cancer (will still need random biopsy even if MRI -ve)
- Likelihood of significant cancer graded by ***PiRADS score (out of 5)
—> 5/5: 88% will have cancer at that lesion - Biopsy (more accurate risk satisfaction)
- ***Transperineal prostate biopsy
- ***MRI-guided prostate biopsy
—> Targeted biopsy
—> Techniques:
——> MRI-Cognitive fusion
——> MRI-US fusion targeted biopsy
——> In-bore MRI
Transrectal USG guided biopsy (TRUS biopsy)
- TRUS probe in rectum
- US imaging of prostate
- Transrectal needle biopsy of prostate
- “Systematic” sampling (but not targeted —> may miss target lesion)
- ***Poor cancer detection rate
Problem with TRUS prostate biopsy:
1. Unreachable areas —> Under-sample prostate —> **High false negative rate
- cannot reach anterior prostate (*CRAP) (>20% of cancer)
- also cannot reach apex / central zone (esp. in large prostate)
- High sepsis risk
- high prevalence of Fluoroquinolone-resistant + ESBL in HK
- TRUS biopsy through **rectal mucosa
- known high risk of sepsis **>5% to over 20%
Currently —> Move towards ***Transperineal prostate biopsy (better + safer)
Transperineal sector biopsies
- Sample prostate directly through perineum
- Many different techniques adopted
- Now used in QMH
Pros:
- Able to hit anterior / anywhere of prostate
- Favourable trajectory to sample prostate —> solve under-sampling problem
- No need bowel prep
- No catheter needed
- No sepsis risk (0%)
- Now feasible under ***LA
Risks:
- Risk of transient urinary retention (∵ more biopsy taken —> swollen prostate after biopsy)
- Transient erectile dysfunction
- Urinary retention
- Bleeding
MRI-guided prostate biopsy
MRI-Cognitive fusion:
Rmb MRI image in brain —> biopsy based on memory of location of lesion on image
Pros:
- Office-based
- **Cheapest
Cons:
- Need very good understanding / interpretation of MRI
- **Learning curve ++
- Accurate?
MRI-US fusion:
Software fuse transrectal USG image with MRI image —> estimate location of suspected area
Pros:
- Office-based
- **Short learning-curve
Cons:
- Needs very good understanding of MRI / radiologist
- **Expensive
In-bore MRI:
Real time sampling of prostate when patient in MRI scanner
Pros:
- Accurate: using ONE imaging modality only
Cons:
- Done by radiologists
- Expensive
- ***Time consuming
- Access
Comparison:
- No difference in detection of clinically significant prostate cancer (although underpowered studies)
More important issues:
1. High quality MpMRI
2. Operator experience in interpreting MRI
3. Operator experience in prostate cancer diagnostics (taking prostate biopsy)
Gleason score
2 scores added up:
1. Score of most predominant pattern
2. Score of highest grade cell
See low power field, overall architecture rather than high power field (conventional high grade / low system)
From Andre Tan:
- Based upon architectural features of prostate cancer cells (with low power field microscopy)
—> closely correlates with clinical behaviour
—> higher score indicates a greater likelihood of having non-organ confined disease + worse outcome after treatment of localised disease
- Tumours graded from 1 to 5, with grade 1 being the most, and grade 5 the least differentiated
- Derived by ***adding together the numerical values for the two most prevalent differentiation patterns (a primary grade and a secondary grade)
***Spectrum of Prostate cancer
Wide spectrum:
1. Localised prostate cancer
- Low risk (non-life-threatening) (10% mortality)
- Intermediate risk (20% mortality)
- High risk (may kill over time if untreated) (35% mortality)
- Locally-advanced prostate cancer (50% mortality)
- Metastatic prostate cancer (70% mortality)
***Stratification of Localised prostate cancer
**D’Amico stratification system:
1. Low risk prostate cancer
- **Gleason 3+3 (out of 10)
- **Selective Gleason 3+4 + Low volume
(- **PSA <=10
- **Stage T1-T2a)
- **Clinically insignificant
- Disease-specific mortality 0.2% at 20 years (very very low)
- Active treatment —> no meaningful benefit, just cause harm
- Patient anxiety +++
- ***Active Surveillance (AS) required —> may cause more anxiety
- Avoid overdiagnosis but also avoid undergrading!!!
- Intermediate risk prostate cancer
- **Gleason 3+4
(- **PSA 10-20
- ***Stage T2b-T2c)
- Can consider radical treatment if life expectancy >10 years - High risk prostate cancer
- **Gleason >4+3 (High PSA / >=T2)
(- **PSA >20
- **Stage T3-T4)
- **High risk of extra-prostatic extension / metastasis if untreated
- **Clinically significant
- **Radical treatment if life expectancy >10 years
- Otherwise ***Watchful waiting (WW)
***Management of Prostate cancer by Risk stratification
- Low risk
- AS
(WW can be option) - Intermediate risk
- Prostatectomy / RT
(AS / WW can be option) - High risk
- Prostatectomy / RT
(AS not an option, WW can be option)
***Treatment of Prostate cancer
- Conservative
- Watchful waiting / Active surveillance - Surgery (Radical prostatectomy)
- Open / Laparoscopic / Robotic-assisted laparoscopy
- Robotic laparoscopic (~oncological outcome to open surgery, early functional outcome maybe better) (gold standard now)
- Aim: Prevent suffering from metastases but NOT prolong patients’ life
- Indication:
—> Intermediate - High risk patients
—> Young patients
Complications:
- Bleeding (3-6% transfusion risk with Robotic prostatectomy (much lower than open surgery (25-30%)))
- Infection
- Rectal / Other visceral injury (<1%)
- **Impotence (50-60%)
- **Incontinence (stress incontinence) (50% early, 5-20% long-term —> advise pelvic floor exercise)
- Anastomotic stenosis (5%)
- RT
- External beam RT
- Intensity-modulated RT
Metastatic disease
4. Androgen deprivation therapy (ADT)
- Surgical castration (Bilateral orchiectomy)
- Medical castration (Anti-androgen, GnRH antagonist, GnRH agonist)
Surgery vs RT:
- No RCT / high quality head-to-head study to show one is superior than the other
