Carcinoma of the prostate

Question 1

Carcinoma of the prostate

Pathophysiology of prostatic carcinoma

Answer 1

• Cancer arises in the peripheral prostatic glands rather than in the para-urethral tissue, often slow to intrude on the urethra and cause obstruction
• malignant change can occur in the pseudo-capsule of compressed peripheral glandular tissue after benign prostatectomy
• Prostate cancers nearly all adenocarcinomas with a variable degree of differentiation reflected in their behaviour and aggressiveness of local and metastatic spread
• exception is carcinoma of the prostatic ducts which is urothelial in origin and behaves similarly to bladder cancer

Question 2

Carcinoma of the prostate

Diagnosing

Answer 2

• prostatic cancers secrete a glycoprotein, prostate specific antigen (PSA), detectable in the blood even when the tumour remains confined within the gland
• Other prostatic conditions (e.g. hyperplasia, prostatitis) may cause elevation of PSA but levels over 10–15 nanograms/ml are likely to be caused by cancer
• main prognostic indicators are the presenting PSA level, the PSA velocity (i.e. the rate at which it rises) and the histological grading
• diagnosed incidentally at TURP for presumed benign disease

Question 3

Symptoms and signs of prostatic cancer

Answer 3

• Patients with stage T1 or T2 tumours may be asymptomatic. They may be discovered incidentally or on a routine health check
• present with lower urinary tract symptoms like benign hyperplasia. T3 and T4 tumours present in the same way but develop local symptoms from the primary tumour, e.g. encirclement of the rectum or occlusion of ureters renal failure
• Patients with nodal disease (N+) may have symptoms from local compression (swollen legs) and impaired lymphatic drainage
• older men presenting with backache should always have a rectal examination and PSA assay

Question 4

Management of prostatic carcinoma

Answer 4

Early-stage disease (stages T1 or T2; N0, M0):

• prostatectomy or radical radiotherapy is potentially curative for organ-confined disease
• external beam radiation/Cyber Knife radiotherapy
• radioactive seed implants (brachytherapy)

Locally advanced disease (stages T3 or T4, N0, M0):

• with bladder outlet symptoms, standard transurethral resection may relieve urinary symptoms
• TURP may, however, risk permanent incontinence if the tumour has invaded the sphincter mechanism or the nerves controlling it

Metastatic disease (stage N+ and/or M+):

• Most prostatic cancers are androgen-dependent, at least initially, and hormonal manipulation is the mainstay of treatment of advanced disease

Question 5

Management of prostatic carcinoma

Hormonal therapy

Answer 5

Three main treatment options are available.

LHRH agonists (LHRHa) such as goserelin:

• injected at 4–12 weekly intervals.
• causes initial stimulation of luteinising hormone (LH) release from the pituitary,
• causes increased testicular testosterone secretion for up to 2 weeks.
• then inhibition of LH release by competitively blocking the receptors, resulting in an ‘anorchic’ state.

Removal of both testes by subcapsular orchidectomy:

• removes about 95% of testosterone synthesised
• The testicular capsules are left in situ and these fill with blood clot and preserve the scrotal contour
• Few side effects

Anti-androgen drugs such as cyproterone acetate or flutamide

• block the binding of dihydrotestosterone to its receptor at cellular level and, in contrast to LHRH agonists, block both testicular and adrenal testosterone
• Flutamide may preserve the potential for sexual arousal and preferred treatment for younger patients with advanced disease

Inevitably, prostatic cancer eventually escapes its androgen dependency and becomes refractory to hormonal treatment. The mechanism is unknown but occurs at a mean of 2 years after commencing treatment in M+ and 5 years in N+ M0 disease.

• secondary or salvage treatment with diethylstilbestrol may be of value
• high rate of serious thromboembolic side-effects