Tumours of the Urinary System 1: Prostate and Testicular Cancers Flashcards
what are tumours of the urinary system?
prostate and testicular cancer
describe the mortality of prostate cancer in the uk?
Prostate cancer is the 2nd commonest cause of cancer death in men
> 12,000 deaths per year (2018)
Mortality rates highest in men aged ≥90 years
75% of deaths occur in men aged ≥75 years
Mortality rates improving due to improvements in treatment of advanced disease
describe the epidemiology of postate cancer?
75% of new cases are aged >65 years
1% of new cases are aged <50 years
However, 45% of new cases <70 years
Trend likely to change with greater proportion of younger men being diagnosed
what is the aetiology and associated risk factors for men with prostate cancer?
Age
Race/Ethnicity
- African or Afro-Caribbean men have highest risk
- Caucausian men have moderate risk
- East Asian men have lowest risk
Geography
- Northwest Europe/North America/Caribbean/Australia vs Asia/Africa/Central & South America
Family history
- first degree relative (2x risk)
- HPC1; BRCA1 & 2 (5x)
- Lynch syndrome (HNPCC) (2-5x)
- hereditary prostate cancer accounts for up to 10% of all cases
Obesity/Overweight
- almost 10% increase in risk per 5-unit increase in BMI for advanced prostate cancer but conversely 6% lower risk for localised prostate cancer (i.e. risk of delayed diagnosis)
Diet
- Men of African ancestry living in Western countries have higher risk of prostate cancer vs men living in Africa
- Observational studies have shown that some diets (e.g. red meat, high saturated fats and calcium) are associated with prostate cancer development, whereas some (e.g. selenium, omega-3 and anti- oxidants) may be protective (low certainty of evidence)
how is the presentation and diagnosis for prostate cancer?
80% of newly diagnosed prostate cancers are localised
Mostly asymptomatic (i.e. do NOT have cancer-specific symptoms)
Diagnosed through opportunistic ad hoc PSA testing (not screening!)
PSA is prostate specific but not necessarily cancer-specific
what are presenting symptoms for localised prostate cancer?
what are presenting symptoms of metastatic prostate cancer?
What is the commonest mode of presentation for prostate cancer?
a. Frank haematuria
b. Asymptomatic (i.e. incidentally noted)
c. Acute urinary retention
d. Symptoms of benign prostatic enlargement and obstruction
e. Bone pain
b. Asymptomatic (i.e. incidentally noted)
what is PSA?
Kallikrein serine protease - liquifies semen
Produced by glands of prostate - may leak into serum
Normal serum range 0-4.0 μg/mL
Age-specific range; levels increase with age
< 50 years: 2.5 is upper limit
50-60 years: 3.5 is upper limit
60-70 years: 4.5 is upper limit
>70 years: 6.5 is upper limit
what are normal serum ranges for PSA?
Age-specific range; levels increase with age
< 50 years: 2.5 is upper limit
50-60 years: 3.5 is upper limit
60-70 years: 4.5 is upper limit
>70 years: 6.5 is upper limit
what are causes of an elevated PSA?
- UTI
- chronic prostatitis
- instrumentation (e.g. catheterisation)
- physiological (e.g. ejaculation)
- recent urological procedure
- BPH
- prostate cancer
how do you differentiate between transient and persistent PSA rise?
To differentiate between transient vs persistent rise, recheck PSA in at least 3 weeks (i.e. 8 half-lives)
Levels of PSA and cancer probability (PPV):
0-1.0: 5%
1.0-2.5: 15% 2.5–4.0: 25% 4.0-10: 40% >10: 70%
how is prostate cancer diagnosed?
Vast majority of patients present with raised age-specific PSA (commonest) or abnormal prostate on digital rectal examination (DRE)
Work-up involves pre-biopsy prostate multiparametric MRI (or mpMRI) scan, which identifies areas of interest to biopsy
Biopsy performed either by TRUS-guided biopsies (local anaesthetic) or MRI-fusion targeted biopsies (general anaesthetic) depending on MRI scan findings
MRI does not exclude nor confirm prostate cancer diagnosis, merely guides biopsies and provides levels of suspicion (PIRADS score)
MRI also provides staging information should a diagnosis of prostate cancer is subsequently made (T and N stage information)
Further staging may be needed (e.g. bone scan or CT-chest, abdomen and pelvis) depending on index of suspicion for metastatic disease
summarise the diagnostic workup for prostate cancer?
Serum PSA estimation (age-specific PSA range)
Digital rectal examination (palpate for abnormal nodules and provides clinical T-stage information)
Pre-biopsy prostate mpMRI (guides biopsy and provides clinical T and N stage information)
Biopsy performed either by TRUS-guided biopsies (local anaesthetic) or MRI-fusion targeted biopsies (general anaesthetic) depending on MRI scan findings
Additional staging (for M-stage) may be required
Patients with limited life expectancy (<10 years) do not need full workup
why is screening not preffered in diagnosis of prostate cancer?
Wilson-Junger criteria not met
Level 1 evidence (i.e. RCTs and meta-analysis) that screening does not improve cancer-specific survival (compared with standard practice)
Screening leads to over-diagnosis and over-treatment of harmless cancers
what is grading?
Grading is assessment of aggressiveness, based on histological differentiation; biopsy samples are needed.
what is staging?
assessment of spread, based on clinical (PSA, DRE) and radiological assessment
what is staging classified into?
clinical staging system (i.e. localised, locally advanced, metastatic and castrate-resistant/hormone-refractory stage)
TNM staging system
what is the gleason grading of prostate cancer?
Summated to give Gleason SUM core
how can localised prostate cancer be staged?
Digital rectal examination (local or T-stage)
PSA
MRI (local staging)
CT (regional and distant staging)
Bone scan (distant staging)
For purposes of treatment and prognosis, useful to divide prostate cancer into 4 clinical stages:
Localised stage
Locally advanced stage
Metastatic stage
Castrate-resistant/Hormone-refractory stage
what is the treatment for localised prostate cancer?
Watchful waiting
Radiotherapy
External-beam
Brachytherapy
Radical prostatectomy
Open
Laparoscopic
Robotic
Others under investigation
Ablative therapy (cryotherapy, HIFU, laser, photodynamic therapy, nanoparticle therapy, etc.)
what is the treatment for locally advanced prostate cancer?
Watchful waiting
Hormone therapy followed by surgery
Hormone therapy followed by radiation
Hormone therapy alone
Intermitted hormone therapy (clinical research)
what are types of hormonal therapy for prostate cancer?
Surgical castration (i.e. bilateral orchidectomy)
Chemical castration (i.e. LHRH analogue – goserelin, leuprorelin; or LHRH antagonists e.g. Degarelix)
Anti-androgens (e.g. Bicalutamide, Flutamide, Cyproterone acetate)
Oestrogens (i.e. diethylstilboestrol)
Chemical castration (i.e. LHRH analogue – goserelin, leuprorelin; or LHRH antagonists e.g. Degarelix)
LHRH analogues eventually downregulates androgen receptors by negative feedback
tumour flare in first week of therapy (hence need an anti-androgen during this period)
LHRH antagonists DO NOT cause tumour flare
Notwithstanding tumour flare, LHRH analogues or antagonists are used on their own (i.e. monotherapy) except for Maximum Androgen Blockade (i.e. combination of LHRH analogues/antagonists and anti-androgens) for castrate-resistant/hormone-refractory stage
Anti-androgens (e.g. Bicalutamide, Flutamide, Cyproterone acetate)
inhibits androgen receptors
Not effective on its own; must be used with LHRH analogue (for tumour flare or MAB)
Oestrogens (i.e. diethylstilboestrol)
inhibits LHRH and testosterone secretion, inactivates androgens and has direct cytotoxic effect on prostatic epithelial cells
what are complications of metastatic and hormone refractory prostate cancer?
Bone: pain, pathological fractures, anaemia, spinal cord compression
Rectal: constipation, bowel obstruction
Ureteric: obstruction resulting in renal failure
Pelvic lymphatic obstruction: lymphoedema, DVT
Lower urinary tract dysfunction: haematuria, acute urinary retention
what is standard treatment or metastatic prostate cancer?
Immediate hormonal therapy is standard of treatment for metastatic prostate cancer, plus Docetaxel chemotherapy in fit patients; alternative treatments apart from chemotherapy is Abiraterone or Enzalutamide combined with hormonal therapy and steroids
what supportive treatments are available for metastatic and hormone refractory prostate cancer?
Supportive treatment: e.g. palliative radiotherapy to bony metastases, nephrostomy, zoledronic acid, palliative care support, etc.
when is the hormone refractory stage reached?
will be reached in 18-24 months of hormonal therapy
Management is continuing with hormonal therapy combined with Docetaxel, Abiraterone or Enzalutamide if not already given earlier; alternatives include other chemotherapy drugs (e.g. Cabazitaxel)
Diethylstilboestrol can be tried (high risk of thromboembolic and cardiovascular complications); median response time 4 months
Median survival of metastatic HRPC stage is 15-18 months with new treatments
The following are reasonable treatment options for low-risk localised prostate cancer except:
a. External beam radiotherapy b. Active surveillance c. Brachytherapy d. Radical prostatectomy e. Radical chemotherapy
e. Radical chemotherapy
The following statements about screening for prostate cancer are true except:
a. PSA is the best available screening test b. Compared with ad-hoc opportunistic PSA testing, screening for prostate cancer is beneficial because it saves lives c. If screening is advocated, it should be performed for men at risk of prostate cancer rather than the entire male population d. Screening for prostate cancer is not currently advocated e. For suspicious cases detected by screening, there is a need to undergo a definitive test to confirm or exclude presence of prostate cancer
b. Compared with ad-hoc opportunistic PSA testing, screening for prostate cancer is beneficial because it saves lives
what is the presentation of testicular cancer?
Usually
Painless lump
Less often
tender inflamed swelling
history of trauma (although trauma NOT a risk factor)
symptoms/signs from nodal or distant metastasis
- para-aortic lymph nodes
- chest
- bone
describe the aetiology and incidence of testicular cancer?
One of the commonest cancers of young men
Peak incidence in third decade
Risk factors:
Undescended testis (up to 10x increase in relative risk)
Infertility
Atrophic testis;
Genetic abnormalities (i.e. hereditary)
Chromosomal abnormalities (e.g. Klinefelter syndrome),
Race (Caucasians)
Previous cancer in contralateral testis
Aetiology is unknown but Testicular Germ Cell Neoplasia In-Situ (TGCNIS) is a precursor lesion
how is testicular cancer diagnosed?
Lump in testis = testicular tumour until proven otherwise
Differential diagnoses:
- infection (i.e. epididymo-orchitis)
- epididymal cyst
- missed testicular torsion
MSSU
Testicular ultrasound scan is the most important imaging test
Tumour markers (to aid diagnosis and provides staging information)
what are tumour markers for testicular cancer?
Blood for tumour markers is taken at diagnosis (i.e. baseline) and repeated after surgery to ensure clearance (if tumour markers persist, indicates metastatic disease)
Up to 70% of testicular cancers will have abnormal tumour markers
For testicular cancer, the main lymphatic spread to regional lymph nodes occurs in which group of lymph nodes?
a. Scrotal lymph nodes b. Inguinal lymph nodes c. Pelvic lymph nodes (i.e. internal iliac chain) d. Mediastinal lymph nodes e. Para-aortic lymph nodes
e. Para-aortic lymph nodes
what treatment is availbale for testicular cancer?
Radical orchidectomy using an inguinal incision centred over the inguinal canal (i.e. NOT scrotal incision) is essential, as a diagnostic procedure (i.e. to obtain tissue for histology) and therapeutic procedure (may potentially be cured by surgery alone)
Biopsy of testicular mass is NOT performed due to risk of tumour seedling along biopsy track
Occasionally may need biopsy of normal contralateral testis if high risk for germ-cell neoplasia in-situ, but biopsy is only performed if there is NO solid tumour in the normal testis
Further treatment depends on tumour type, stage (TNM) and grade
describe the pathology of testicular cancer?
Germ cell tumour (GCT) (95%) vs Non-GCT (5%)
GCT:
Seminomatous GCT (classical, spermatocytic, or anaplastic)
Non-seminomatous GCT (teratoma, yolk sac, choriocarcinoma, mixed GCT)
Non-GCT (sex cord/stromal cells):
Leydig
Sertoli
Lymphoma rare (usually in older men)
who is mainly affected by seminomatous GCT?
Mainly affects 30-40 year olds
