Genitourinary Cancers Flashcards
What is the role of 5-alpha-reductase inhibitors in prostrate cancer and BPH? And what are their major side effects?
5-AR inhibitors (Finasteride, Dutasteride) work to block conversion of testosterone to DHT (dihydrotestosterone), the most active androgen in the prostrate. They can be used as chemoprevention in men at high risk of prostate cancer and have been shown to reduce the incidence of prostrate cancer, but have no overall survival benefit
They are frequently used in BPH and reduce the PSA by up to 50%, reduce prostrate gland size and volume, and reduce the need for prostrate reducing surgery. These effects occur over 6-12 months
Side effects: gynecomastia, decreased libido, erectile dysfunction
What is the next best step in management for a man with an abnormal prostate on PR exam, but normal PSA and asymptomatic?
Any abnormal DRE warrants urological exam, regardless of serum PSA level. The definitive diagnostic test for prostate cancer is transrectal biopsy with multiple core samples from all parts of the prostate gland.
How should bony metastases in prostate cancer be managed?
- Monthly Bisphosphonates (Zoledronic acid or Pamidronate)
- Radiation therapy
- Radium 223 (alpha-emitting radionucleotide which kills prostate cancer cells without damaging surrounding tissue)
- Sipuleucel-T for hormone refractory prostate cancer (autologous cellular immunotherapy) to activate the patients own dendritic cells to attack the prostate cancer
What agents are used in chemical castration of prostate cancer?
GnRH agonists/antagonists (Goserelin)
- work by competitively binding GnRH receptors on pituitary cells resulting in an initial transient increased release of FSH/LH (‘flare’) with subsequent increased testosterone release from Leydig cells, followed by down-regulation of GnRH receptors and thus decline in pituitary production of FSH/LH
GnRH agonists are used in combination with antiandrogens for combined androgen blockade
- Antiandrogens (Flutamide, Bicalutamide) competitively bind to androgen receptors, inhibiting the binding of testosterone and DHT
Give calcium and cholecalciferol to all men receiving androgen deprivation therapy
Why are GnRH agonists/antagonists recommended prior to radiation therapy in high-risk, locally advanced prostate cancer?
Combination therapy improves overall survival compared with radiation alone
How do you treat hormone-refractory prostate cancer and progressive metastatic disease?
Patients with hormone-refractory or progressive metastatic disease due to prostate cancer may benefit from chemotherapy
Use Docetaxel (taxane - stabilises microtubules) with Prednisolone
This combination has demonstrated a 3-6 month survival benefit
What is the most common solid tumour in young men?
Testicular cancer
95% of testicular tumours are germ cell tumours. What are the 2 classes of germ cell testicular cancers and what significant does this have for prognosis?
Germ cell testicular tumours are classified as either seminomatous or non-seminomatous.
Seminoma (50%):
- good prognosis with very high cure rate
Non-seminoma (50%):
- histological types: embryonal, choriocarcinoma, yolk sac carcinoma, teratoma or mixed type
- have elevated serum AFP
- have poorer prognosis and require more aggressive treatment
What are the risk factors for testicular cancer?
Klinefelter syndrome
Cryptorchidism
FHx testicular cancer
- surgical correction of an undescended testis in early life substantially reduces risk of testicular cancer, but does not eliminate the risk
- testicular cancer can also develop in the normal descended testicle of a patient with cryptorchidism
How do testicular cancers present and what tumour markers are used for testicular cancer?
Unilateral testicular mass or swelling
Acute pain (10%)
Signs and symptoms of metastases (10%)
Gynaecomastia (5%) - d/t elevated bHCG
Testicular cancer serum markers:
- serum alpha-fetoprotein (AFP)
- bHCG
- LDH
** an elevated AFP defines the tumour as a non-seminoma
What are the risk factors for prostrate cancer?
Black men Increasing age Prostate ca in a first degree relative High fat, low-fibre diet Prostatitis
Vasectomy is NOT associated with increased risk of prostate cancer
How do you treat testicular cancer?
All require radical orchidectomy
Seminoma:
- post-orchidectomy, active surveillance vs single agent Carboplatin chemo (1 cycle)
Nonseminona:
- post-orchidectomy, active surveillance OR retroperitoneal lymph node dissection (RLND) OR 2 cycles of multi-agent chemo (platinum, Etoposide and bleomycin)
- active surveillance has 20-30% recurrence rate
What is the predominant histological type of bladder cancer? And what are the risk factors for bladder cancer?
90% of bladder cancers are urothelial (transitional cell) in origin
Risk factors:
Smoking** (risk proportional to pack years)
M>F
Age >60yo
Occupational exposure in metal workers, painters & leather workers
Where do most renal cancers originate, and what are the predominant histological types?
Most renal cancers originate in the renal cortex
Most are clear cell type
10-15% are papillary tumours
10% are chromophobe
Few are oncocytomas
Papillary tumours tend to be early-stage lesions at diagnosis and thus have a better prognosis
What are the risk factors for renal cancer?
Cigarette smoking
Obesity
Occupational exposure (calcium, asbestos, gasoline)
Effects of dialysis (acquired cystic kidney disease)
Von Hippel-Lindau syndrome
*VHL gene mutations results in sporadic clear cell cancer due to over-expression of VEGF (respond to VEGF inhibitors ie. Bevacizumab, Sorafenib, Sunitinib)
