Tumours of the Urinary System 1: Prostate and Testicular Cancers

Question 1

what are tumours of the urinary system?

Answer 1

prostate and testicular cancer

Question 2

describe the mortality of prostate cancer in the uk?

Answer 2

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

Question 3

describe the epidemiology of postate cancer?

Answer 3

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

Question 4

what is the aetiology and associated risk factors for men with prostate cancer?

Answer 4

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)

Question 5

how is the presentation and diagnosis for prostate cancer?

Answer 5

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

Question 6

what are presenting symptoms for localised prostate cancer?

Answer 6

Question 7

what are presenting symptoms of metastatic prostate cancer?

Answer 7

Question 8

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

Answer 8

b. Asymptomatic (i.e. incidentally noted)

Question 9

what is PSA?

Answer 9

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

Question 10

what are normal serum ranges for PSA?

Answer 10

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

Question 11

what are causes of an elevated PSA?

Answer 11

• UTI
  
  • chronic prostatitis
  • instrumentation (e.g. catheterisation)
  • physiological (e.g. ejaculation)
  • recent urological procedure
  • BPH
  • prostate cancer

Question 12

how do you differentiate between transient and persistent PSA rise?

Answer 12

To differentiate between transient vs persistent rise, recheck PSA in at least 3 weeks (i.e. 8 half-lives)

Question 13

Levels of PSA and cancer probability (PPV):

Answer 13

0-1.0: 5%

1.0-2.5: 15%

2.5–4.0: 25%

4.0-10: 40%

>10: 70%

Question 14

how is prostate cancer diagnosed?

Answer 14

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

Question 15

summarise the diagnostic workup for prostate cancer?

Answer 15

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

Question 16

why is screening not preffered in diagnosis of prostate cancer?

Answer 16

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

Question 17

what is grading?

Answer 17

Grading is assessment of aggressiveness, based on histological differentiation; biopsy samples are needed.

Question 18

what is staging?

Answer 18

assessment of spread, based on clinical (PSA, DRE) and radiological assessment

Question 19

what is staging classified into?

Answer 19

clinical staging system (i.e. localised, locally advanced, metastatic and castrate-resistant/hormone-refractory stage)

TNM staging system

Question 20

what is the gleason grading of prostate cancer?

Answer 20

Summated to give Gleason SUM core

Question 21

how can localised prostate cancer be staged?

Answer 21

Digital rectal examination (local or T-stage)
PSA
MRI (local staging)
CT (regional and distant staging)
Bone scan (distant staging)

Question 22

For purposes of treatment and prognosis, useful to divide prostate cancer into 4 clinical stages:

Answer 22

Localised stage
Locally advanced stage
Metastatic stage
Castrate-resistant/Hormone-refractory stage

Question 23

what is the treatment for localised prostate cancer?

Answer 23

Watchful waiting
Radiotherapy
External-beam
Brachytherapy
Radical prostatectomy
Open
Laparoscopic
Robotic
Others under investigation
Ablative therapy (cryotherapy, HIFU, laser, photodynamic therapy, nanoparticle therapy, etc.)

Question 24

what is the treatment for locally advanced prostate cancer?

Answer 24

Watchful waiting
Hormone therapy followed by surgery
Hormone therapy followed by radiation
Hormone therapy alone
Intermitted hormone therapy (clinical research)

Question 25

what are types of hormonal therapy for prostate cancer?

Answer 25

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)

Question 26

Chemical castration (i.e. LHRH analogue – goserelin, leuprorelin; or LHRH antagonists e.g. Degarelix)

Answer 26

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

Question 27

Anti-androgens (e.g. Bicalutamide, Flutamide, Cyproterone acetate)

Answer 27

inhibits androgen receptors
Not effective on its own; must be used with LHRH analogue (for tumour flare or MAB)

Question 28

Oestrogens (i.e. diethylstilboestrol)

Answer 28

inhibits LHRH and testosterone secretion, inactivates androgens and has direct cytotoxic effect on prostatic epithelial cells

Question 29

what are complications of metastatic and hormone refractory prostate cancer?

Answer 29

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

Question 30

what is standard treatment or metastatic prostate cancer?

Answer 30

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

Question 31

what supportive treatments are available for metastatic and hormone refractory prostate cancer?

Answer 31

Supportive treatment: e.g. palliative radiotherapy to bony metastases, nephrostomy, zoledronic acid, palliative care support, etc.

Question 32

when is the hormone refractory stage reached?

Answer 32

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

Question 33

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

Answer 33

e. Radical chemotherapy

Question 34

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

Answer 34

b. Compared with ad-hoc opportunistic PSA testing, screening for prostate cancer is beneficial because it saves lives

Question 35

what is the presentation of testicular cancer?

Answer 35

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

Question 36

describe the aetiology and incidence of testicular cancer?

Answer 36

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

Question 37

how is testicular cancer diagnosed?

Answer 37

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)

Question 38

what are tumour markers for testicular cancer?

Answer 38

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

Question 39

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

Answer 39

e. Para-aortic lymph nodes

Question 40

what treatment is availbale for testicular cancer?

Answer 40

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

Question 41

describe the pathology of testicular cancer?

Answer 41

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)

Question 42

who is mainly affected by seminomatous GCT?

Answer 42

Mainly affects 30-40 year olds