Transcript PROSTATE CANCER

PROSTATE CANCER
(Module 3 of
Renal/Prostate Disease)
Bill Lyons, M.D.
UNMC Geriatrics & Gerontology
PROSTATE CANCER:
LEARNING OBJECTIVES
 Epidemiology and
General Principles
 Treatment Approaches,
Vigorous vs. Frail
 Androgen Deprivation
Therapy: Benefits and
Burdens
BACKGROUND
 Most common non-skin cancer in men
 Second-most-common cause of cancer
mortality in American men
 Lifetime risk of prostate cancer: 16%
 Risk of dying of the disease 3.4%
BACKGROUND, cont.
 Many/most elderly men die with, not of,
prostate cancer
 Hence controversy regarding screening for
and treating early-stage disease
 Damage done to normal tissue by treatment
(radiation, surgery) may exceed that from
untreated indolent cancer
BACKGROUND, cont.
 Prostate cancer
diagnosed




Elevated PSA
TURP pathology
Local urologic
symptoms
Metastatic symptoms
(esp. bone)
NATURAL HISTORY OF EARLY
PROSTATE CANCER
 Johansson et al: population-based cohort



Mean observation period 21 years
N = 223 men
Early stage: T0-T2 NX M0
 Most early-stage tumors have indolent course
 Local progression, metastatic disease can
arise over longer term
 “Findings  early radical treatment, notably
among patients with estimated LE > 15 yr”
OVERALL APPROACH TO
TREATMENT
 Mortimer &
McElhaney’s Schema
 Approach depends on
function, co-morbidity
GENERAL SCHEMA: CANCER
CONFINED TO GLAND
 Good Function, Low Comorbidity:

Prostatectomy vs. radiation treatment
 Poor Function, High Comorbidity:

Consider watchful waiting
GENERAL SCHEMA: LOCAL
EXTENSION OF DISEASE
 To capsule, seminal vesicle, bladder, rectum,
or pelvic nodes
 Good Function, Low Comorbidity:

Radiation + GnRH agonist
 Poor Function, High Comorbidity:

Consider GnRH agonist alone
GENERAL SCHEMA: DISEASE
OUTSIDE THE PELVIS
 Initial approach:
 Good Function, Low Comorbidity:


Castration (androgen deprivation therapy) +
antiandrogen (eg, flutamide)
AKA “Combined androgen blockade”
 Poor Function, High Comorbidity:

Same
GENERAL SCHEMA: DISEASE
OUTSIDE THE PELVIS
 If disease has progressed:
 Good Function, Low Comorbidity:

Stop antiandrogen treatment
 Poor Function, High Comorbidity:

Same
GENERAL SCHEMA: DISEASE
OUTSIDE THE PELVIS
 If disease progresses still further:
 Good Function, Low Comorbidity

Consider chemotherapy
 Poor Function, High Comorbidity

Symptomatic management
RISING PSA AFTER LOCAL
TREATMENT
 After RRP, typically check PSA q 3 mo

Rising PSA, short doubling time predict
disease progression
 After radiation treatment, PSA declines


Typically nadir < 1.0 ng/mL reached
Three consecutive increases from nadir
signifies biochemical failure
ANDROGEN DEPRIVATION
THERAPY
 Generally first-line
therapy for advanced
prostate cancer, also
used as adjuvant for
local treatment of highrisk disease
 Medical now more
common than
orchiectomy, outcomes
similar
ANDROGEN DEPRIVATION
THERAPY, cont.
 GnRH agonists – leuprolide, goserelin




Depot injections, subcutaneous implants
Decrease pituitary release of LH
Castration levels of testosterone w/in 3 wks
Initial testosterone surge


Flare of metastatic disease, bone pain
Some start androgen receptor blocker beforehand
ANDROGEN DEPRIVATION
THERAPY: BENEFITS
 In advanced prostate cancer:





Reduced bone pain
Fewer pathologic fractures
Reduced incidence of spinal cord compression
Reduced incidence of ureteral obstruction
Survival? Unclear
ANDROGEN DEPRIVATION
THERAPY: ADVERSE EFFECTS
 Decreased libido and erectile dysfunction
 Hot flashes in up to 80%
 Osteoporosis with increased risk of fracture
 Mood and cognitive effects
 Body composition: lean  fat
 Increased fasting glucose, cholesterol
 Anemia
 Gynecomastia
ANDROGEN DEPRIVATION
THERAPY: ADVERSE EFFECTS
 Check BMD at baseline;
start Ca + D
 Bisphosphonates


Osteoporosis
Bony metastases of
androgen-independent
prostate cancer
ADVANCED PROSTATE CANCER
 …almost always becomes androgen-
independent after some time on ADT
 Duration of ADT response in metastatic
disease typically 14-20 months
 Options:


Hormone receptor blockers (flutamide,
bicalutamide, nilutamide)
Ketoconazole – decreases adrenal androgen
synthesis
REFERENCES AND READINGS
 Baum N. Clinical Geriatrics 2005;13(5):23-
26.
 Johansson JE et al. JAMA 2004; 291:27132719
 Mortimer JE, McElhaney J. Cancers in the
Geriatric Population. Chapter 30 in:
Landefeld CS et al. Current Geriatric
Diagnosis and Treatment, 2004, McGraw-Hill.
REFERENCES AND READINGS
 Sharif N et al. JAMA 2005;294:238-244.
 Stoller ML, Carroll PR. Urology. Chapter 23
in: Tierney LM Jr, McPhee SJ, Papadakis
MA, Current Medical Diagnosis & Treatment,
2004, McGraw-Hill.
Post test 1
An 82-year-old patient of yours is diagnosed with
prostate cancer, and pelvic imaging strongly suggests
he has extensive involvement of pelvic lymph nodes.
Because of his functional dependence (he requires
assistance for bathing and dressing, and he
ambulates with a walker) and comorbidity (he has
poorly-controlled diabetes mellitus, advanced heart
failure, and mild dementia), he is started on
leuprolide injections as sole therapy.
All of the following statements regarding his
androgen deprivation therapy (ADT) are true
EXCEPT:
All of the following statements regarding his
androgen deprivation therapy (ADT) are true
EXCEPT:
(a) Flutamide should be started before the
GnRH agonist, leuprolide.
(b) ADT is expected to reduce his risk of
pathologic fractures.
(c) ADT is expected to prolong his survival.
(d) ADT may exacerbate his cognitive problems.
(e) His bone mineral density should be checked
before treatment begins, and he should be
considered for treatment with a
bisphosphonate.
Correct Answer: (c) ADT is
expected to prolong his survival.
Feedback:(c) is not necessarily a true statement (and
therefore is the correct answer); it is not yet clear that
ADT prolongs survival in men with prostate cancer,
although it does reduce the risk of many
complications. Statement (a) is true, because
androgen blockers reduce the odds of GnRH-induced
flares. Statement (b) is true pathologic fractures are
one complication that occur less frequently when
GnRH agonists are employed. Statement (d) is true,
and should be remembered in the care of patients
like this one who already have cognitive deficits.
Finally, statement (e) is true, because ADT places
patients at risk of treatment-induced osteoporosis.