Prostate carcinoma

Question 1

How common is prostate cancer?

Answer 1

Most common cancer in men and 6th common cancer world wide.

80% of men have prostate malignancy changes by 80 years (autopsy results)

Question 2

What is a prostate carcinoma?

Answer 2

Prostate carcinoma = adenocarcinomas arising in peripheral prostate

Question 3

Who does it affect?

Answer 3

Men >50 years

Family hx of prostate or breast cancer (2-3x higher risk)

Black men (1 in 4)

Increased testosterone

Question 4

Which genes predispose you to prostate cancer?

Answer 4

HOXB-13

100’s single nucleotide polymorphisms

BRCA-2 gene (5-7x higher risk)

Question 5

What are the clinical features of prostate carcinoma?

Answer 5

May be asymptomatic

Nocturia

Hesitency

Poor stream

Terminal dribbling

Obstruction

Weight loss ± bone pain => metastases

Question 6

How does prostate carcinoma spread?

Answer 6

Local spread to seminal vesicles, bladder and rectum via lymph or haematogenously (sclerotic bony lesions)

Question 7

What investigations are carried out?

Answer 7

Digital rectum exam (nodular formation)

Prostate specific antigen (PSA) => normal in 30% of small cancers

Transrectal ultrasound + biopsy

Bone scan

MRI => staging

Question 8

What is the management of prostate cancer?

Answer 8

Radical prostectomy if <70yrs => disease free survival, curative

Laparoscopy

Radical ± neoadjuvant & adjuvant hormonal therapy (delivered as external beams or brachytherapy) => also curative

Hormone therapy alone => temporary delays tumour progression. Consider in unfit, elderly patients with high risk profile

Locally advanced disease treated with combined androgen deprivation and radiotherapy

Metastatic disease treated with androgen deprivation to achieve medical castration

Endocrine therapy

Question 9

Which prognostic factors help differentiate between monitoring and aggressive therapy?

Answer 9

Pre-treatment PSA level

Clinical tumour stage (TNM staging)

Biopsy Tumour Gleeson grade (Gleeson score 1-5; 5=worst prognosis)
*Gleeson score based on analysing differentiation of the adenocarcinoma from 2 specimen sites and adding them together.

Question 10

Where does prostate cancer most commonly metastasise to?

Answer 10

Bone metastases => appear as osteosclerotic lesions on x-ray

Question 11

Prostate cancer is the most hormone sensitive malignancy with androgen receptor playing a critical role.

What is endocrine therapy?

Answer 11

1. Gonadotrophin releasing hormone (GnRH) agonists
   => e.g. goserelin and leuprorelin are as effective as orchidectomy at lowering circulating androgens.

=>GnRH first stimulate gonadotrophin, then inhibit it by -ve feedback

=> But in the first week, GnRH produces a surge in LH hormone and testosterone
=> this can lead to flare of metastases, therefore they must be combined with anti-androgen i.e. flutamide

2. Androgen receptor blocker => directly block the action of testosterone on prostate cancer cells
3. Androgen synthesis inhibitors => inhibit CYP17 (key enzyme in testosterone production)
4. Corticosteroids and oestrogen => useful in refractory castration disease

Question 12

Non-hormonal therapy is used in metastatic disease.

Give some examples.

Answer 12

Conventional chemotherapy

PARP inhibitor => prevent repair of DNA strand breaks => cancer death

Bone targeted therapy => bone metastases

Question 13

Complications of prostate cancer?

Answer 13

Hypercalcaemia

Incontinence

Erectile dysfunction

Metastases

Question 14

What is the prognosis of prostate cancer?

Answer 14

10% die in 6 months

10% live to >10 years