Castrate sensitive prostate cancer Flashcards
When is it appropriate to start androgen deprivation therapy
Newly diagnosed metastatic prostate cancer or in disseminated disease following definitive treatment (radical prostatectomy or radiotherapy). However men with locally recurrent disease may be candidates for local salvage therapy
What is an appropriate regimen for starting androgen deprivation therapy
Bicalutamide (androgen receptor antagonist) 50mg once daily for 3 weeks, continuing for 5 weeks then stopping. And zoladex (GnRH agonist) depot 10.8mg 3monthly starting on the 3rd week after starting bicalutamide
What is the purpose of ADT
ADT is palliative and the initial management for patients with disseminated prostate cancer. It can normalize serum levels of PSA in >90% or patients and produces objective tumour responses in 80-90%%
Aims of management in advanced prostate cancer
Prolong survival, minimise complications and maintain quality of life
When does prostate cancer become castrate resistent
Following relapse of initial systemic hormone therapy (ADT)
What is the primary manifestation of widely disseminated prostate ca
Osteoblastic axial skeletal metastases (the pelvis is the most common site of locoregional recurrence)
What are the two modalities of androgen deprivation therapy
Bilateral orchiectomy (surgical castration) or medical castration
When might bilateral orchiectomy be preferable over medical castration
When an immediate decrease in testosterone is necessary (e.g. impending cord compression of urinary bladder outlet obstruction) or in countries when costs of maintaining therapy are a barrier
Why does ADT work
In most cases, prostate cancer that has not previously been treated with systemic therapy is dependent on androgen for its continued growth
What does ADT target
ADT targets the hypothalamic-pituitary axis
How are androgens produced in males
90-95% of circulating testosterone is produced in the testicles in response to luteinizing hormone (LH), produced from the anterior pituitary in response to GnRH from the hypothalamus. The adrenal glands produce the remainder of the circulating androgens.
How can ADT be made more effective
A chemotherapy agent - abiraterone or docetaxel - may be added. This has been shown to significantly prolong overall survival compared with ADT monotherapy
How does abiraterone work?
There is potential loss of efficacy of ADT due to intracellular conversion of steroids precursors to androgenic steroids within prostate cancer cells. Abiraterone blocks this conversion.
What are the side effects of ADT
- Loss of lean body mass, increased body mass and decreased muscle strength.
- Sexual dysfunction including loss of libido, usually developing within the first several months and is followed by erectile dysfunction
- Loss of bone mineral density causing osteoporosis and increased risk of fracture. Compounded by the presence of bony metastasis.
- Vasomotor instability (cutaneous vasodilation), manifested by hot flushes
- Fatigue or lack of energy
- Behavioural or neurologic effects
- Cardiovascular and metabolic abnormalities
What is the purpose of starting bicalutamide prior to zoladex (combined androgen blockade)
With the initiation of treatment with GnRH agonists (i.e. Zoladex), there is a transient surge in LH before levels fall which may cause a disease flare - particularly concerning in clinical settings such as impending cord compression or urinary tract outflow obstruction. By using bicalutamide for 4-6 weeks a tumour flare is prevented, and zoladex can be administered at 2-4 weeks
