CASTRATION RESISTANT PROSTATE
CANCER: NOT GRANDPA’S DISEASE
Arash Rezazedeh Kalebasty, MD
P
rostate cancer remains one of the most
common malignancies among men.
PSA screening resulted in an increased
rate of diagnosis of this disease. Men who are
diagnosed with an early stage of disease can
expect a high rate of cure with surgical and
radiotherapy approaches. Over time there has
been a significant improvement in techniques
for radical prostatectomy utilizing robotic
surgery. Radiation therapy can be delivered
with modern techniques including image guided radiation therapy,
intensity modulated radiation therapy and proton therapy. Other
techniques including Cryotherapy are available in United States for
local recurrence of prostate cancer after radiation therapy.
There is ongoing research to tease out the “high risk” prostate
cancer to avoid the morbidity of surgery and radiation for what
ultimately would be indolent disease. These methods include serial
MRIs of the prostate gland and image-guided biopsy for patients
who are offered watchful waiting over time. Gene expression profiles
on prostate cancer biopsy material can help with determination of
“high risk” disease.
Despite high rates of cure with definitive treatment of localized
disease, metastatic disease leads to death in majority of patients.
Metastatic adenocarcinoma of the prostate gland has a good initial
response to lowering testosterone to castrated levels. This response
sometimes last for several years. Cardiac morbidity, loss of bone,
central obesity, loss of muscle mass and metabolic changes are among
long term side effects of androgen deprivation therapy (ADT).
Literature suggests that statins as well as metformin - data only in
diabetics at this time - may have a role in management of prostate
cancer. Bone health remains an important part of management of
prostate cancer.
Metastatic prostate cancer eventually becomes “castration resistant.” Generally cancer starts to behave more aggressively in this
state. Historically metastatic castration resistant prostate cancer
(mCRPC) was treated with second line hormonal therapy. This
class of hormones led to a short response followed by disease progression and death.
There has been significant improvement in the treatment of
prostate cancer in the last decade. Docetaxel was the first chemotherapy that showed a survival advantage in patients with mCRPC.
Interestingly it has been suggested that its effect on disease control
is very likely to be via an androgen receptor pathway. Second line
chemotherapy with Cabazitaxel has shown efficacy with improved
survival.
Research has shown that despite disease progression on castrated
patients, the tumor remains hormone dependent. In fact, it was
shown that prostate cancer cells can produce androgen to activate
androgen receptor and continue to grow. Further work on the androgen axis led to the discovery of Abirateron Acetate, which blocks
the androgen synthesis in adrenal gland and prostate cancer cells. It
is an oral therapy. Common side effects of this compound result from
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LOUISVILLE MEDICINE
relative hyperaldosteronism causing hypertension, peripheral edema
and hypokalemia. Liver toxicity is of concern and liver enzymes
have to be monitored over time. Low dose prednisone has to be
taken with abiraterone to attenuate the resulted hyperaldosteronism.
Enzalutamide was the second oral therapy, which was introduced
to the market for treatment of mCRPC. It is a potent androgen receptor blocker and needs to be taken once daily. Enzalutamide showed
improved survival in both the pre-chemotherapy and post-chemotherapy state for patients with mCRPC. The side effect profile for
this agent was generally favorable. Common side effects include
diarrhea and fatigue. One study showed a 0.9 percent risk of seizure.
Metastatic CRPC was the first cancer which w