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Based
on metastatic spread
M+ Distant metastatic spread
MX
Presence of distant metastases cannot be assessed
M0 No distant metastasis
M1 Distant metastasis
M1a Involvement of nonregional lymph nodes
M1b Involvement of bone(s)
M1c Involvement of other distant sites
There
is also another classification system that is applicable
to prostate cancer called the Whitmore-Jewett
Classification
-
Stage
A: defined as microscopic cancer confined to the
prostate and not felt by digital rectal exam
-
A1: cancer is well differentiated and confined to
only one site
-
A2: Cancer meets one of two conditions, it is
moderately/poorly differentiated or it is in more
than one site
-
Stage
B: Cancer is large enough to be felt on digital
rectal exam
-
B1: when there is a small nodule on one lobe of the
prostate
-
B2: Can be a large nodule, several small nodules or
a nodule that is poorly differentiated
-
Stage
C: A large cancer that involves almost the entire
gland
-
C1: cancer has spread a small distance beyond the
gland (has not involved other tissue, just grown out
of prostate)
-
C2: Cancer has invaded the neighboring tissue
-
Stage
D: when there is wide spread metastases
-
D1: cancer is in pelvic lymph node
-
D2: cancer has moved to bone or other organs
Treatment Options for Prostate Cancer
-
Watchful waiting: this is the method of treatment
that is the most conservative. A diagnosis of
prostate cancer isn’t a guaranteed death, so depending
on age and other factors this might be the best for
the patient
-
Therapies of curative intent
-
Radical prostatectomy (various approaches)
-
Retropubic: this is the most common
-
Perineal: rarely used anymore unless retropubic
isn’t an option
-
Laparoscopic: not mentioned at all
-
Radiotherapy: one of the best curative therapies and
can be given through external beam radiation or
brachytherapy (implant put into prostate)
-
Cryotherapy: method where probes are used to freeze
the prostate
-
Hormonal therapy—testosterone deprivation
-
LHRH-A
-
Bilateral orchiectomy
-
Antiandrogen
-
Chemotherapy: not used very much because there isn’t a
great effect on the cancer cells
When
a surgeon performs one of these procedures, he/she has
to be careful to preserve the urethral sphincter and the
neurovascular bundle. If the urethral sphincter is
lost, urination will be uncontrolled and if the nerve
supply is lost, the patient won’t be able to achieve an
erection after the surgery.
Table
of Advantages/Disadvantages for each curative treatment
|
Treatment |
Advantages |
Disadvantages |
|
Radical Prostatectomy |
Primary treatment (stage dependent though so if it
has spread outside this procedure isn’t done) |
-Major operation
-Erectile dysfunction (50%)
-Urinary incontinence (10-15%)
-Bowel complications |
|
External Beam radiation |
-Efficacy can be equal to prostatectomy
-Outpatient procedure |
-Erectile dysfunction (due to obliterated blood
vessels)
-Chronic bowel complications
-Incontinence
-Possibility of radiation cystitis (4-5%) |
|
Brachytherapy |
-as effective as EBRT or surgery
-1 time procedure |
-urinary voiding symptoms
-Erectile dysfunction
-rectal discomfort
-Edema
-May worsen the condition by making the prostate
larger
-Can induce strange tumors |
|
Cryotherapy |
-Short term hospital stay
-Relatively non-invasive |
-Erectile dysfunction because you can’t control how
much is freezed outside the prostate
-Urinary problems (usually short term)
-Unknown long term side effects |
Endocrinology of Prostate Cancer
Luteinizing hormone RH and Corticotrophin RH is released
from the hypothalamus. Luteinizing hormone (which
stimulates FSH) and ACTH is then released from the
pituitary gland and act on the Leydig cells of the
testes and the adrenal glands to produce testosterone
which moves out into the circulation. The testosterone
moves into plasma where it interacts with 5 α-reductase
to form DHT. The DHT binds to a receptor and the
complex binds to DNA to promote replication. Remember
that 95% of testosterone comes from Leydog cells while
5% come from other sources
With
that crash course in endocrinology, we can now
understand the hormone therapies.
Current
Treatments:
-
Bilateral orchiectomy: chemical castration which is
irreversible
-
LHRH-A:
used in the US mostly
-
LHRH-A
+ antiandrogen (called CAB)
-
Bilateral orchiectomy +antiandrogen
LHRH-A
|
Mechanism |
uses the negative feedback mechanism of the body
to cause a depletion of luteinizing hormone and a
decrease in testosterone synthesis |
|
Advantages |
-As
effective as bilateral orchiectomy in decreasing
testosterone levels
-Can be administered every 1,3,4 or 12 months
-Potentially reversible so if a cure is found,
patients can regain normal functioning |
|
Disadvantages |
-Hot flashes
-Decreased libido due to decreased testosterone
-Erectile dysfunction
-Early toxicity with a flare reaction |
Antiandrogens
as an
addition to LHRH-A
The
antiandrogens block the androgen receptors (no crap) so
when they are used in conjunction with LHRH-A, the other
5% of testosterone made by other sources than the Leydig
cells is ineffective. The chemical structures were
given but we don’t need to know them, just know that
Casodex is the most common one used.
*When
castration/ LHRH-A therapy is used alone the 5 year
survival rate is 24% in patients with metastatic or
advanced prostate cancer. When antiandrogens are used
the survival increases to 27%.
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