Transcript Clinical Slide Set. Prostate Cancer

In the Clinic
Prostate Cancer
© Copyright Annals of Internal Medicine, 2009
Ann Int Med. 164 (1): ITC1-1.
How can prostate cancer be prevented?
 Dietary changes and supplements not proven in
prevention
 Lowering intake of animal fat
 Antioxidants or lycopene
 Selenium and vitamin E
 Don’t prescribe 5α-reductase inhibitors for most men
 Don’t prolong life
 Increase sexual dysfunction
 Reduce incidence of low-grade prostate cancer
 Increase incidence of high-grade prostate cancer
© Copyright Annals of Internal Medicine, 2009
Ann Int Med. 164 (1): ITC1-1.
CLINICAL BOTTOM LINE: Prevention...
 Trials don’t support altering diet or taking supplements to
prevent prostate cancer
 5α-reductase inhibitors are not recommended for most men
© Copyright Annals of Internal Medicine, 2009
Ann Int Med. 164 (1): ITC1-1.
Who should clinicians screen for prostate
cancer?
 Screening for prostate cancer is controversial
 Most men with prostate cancer die of another cause
 Curative treatment often causes significant side effects
 Moderate evidence that harms outweigh benefits in 50- to
69-year-olds
 Data inadequate to make recommendations to patients
with significant risk factors:
 African American or first degree family history of prostate
cancer
 Don’t screen men <50 with no risk factors
 Screening unlikely to benefit men >69 or with <10 to 15
years of life expectancy
© Copyright Annals of Internal Medicine, 2009
Ann Int Med. 164 (1): ITC1-1.
What tests should clinicians use for
screening?
 PSA testing is the most useful for screening
 But produces false-positives, false-negatives
 Serum PSA may be elevated due to prostatitis, prostate
biopsies, UTI, prostate massage, or ejaculation
 Sampling error in biopsy process adds uncertainty to the
interpretation of negative results
 Digital rectal exam and imaging methods are less
sensitive and not shown to be effective
© Copyright Annals of Internal Medicine, 2009
Ann Int Med. 164 (1): ITC1-1.
CLINICAL BOTTOM LINE: Screening...
 Screening and treatment may prevent prostate cancer deaths
 Screening also produces false-negatives and false-positives
 Harm from treatments is more likely than benefit
 Treatments commonly cause sexual dysfunction and
distinct patterns of urinary and bowel symptoms
 Shared decision-making that reviews benefits and harms is
essential to any informed decision to screen
 Screening not recommended for men <50 with no risk factors,
most men >69, and men with life expectancy <10 years
© Copyright Annals of Internal Medicine, 2009
Ann Int Med. 164 (1): ITC1-1.
What should you consider when workingup a patient for prostate cancer?
 Awareness that the diagnosis can be harmful
 Potential for overdiagnosis of harmless prostate cancer
is substantial
 Cancer “label” can have negative social, economic and
psychological consequences
 Anxiety can occur when choosing a treatment
© Copyright Annals of Internal Medicine, 2009
Ann Int Med. 164 (1): ITC1-1.
What are the signs and symptoms of prostate
cancer?
 Bone pain (most common symptom)
 Weight loss
 Normocytic anemia
 Cachexia
 Neurologic dysfunction related to spinal cord
compression
 Lower urinary tract obstructive symptoms have low
positive predictive value
© Copyright Annals of Internal Medicine, 2009
Ann Int Med. 164 (1): ITC1-1.
How should clinicians diagnose prostate
cancer?
 Use serum PSA levels and digital rectal exam in men with:
 Hematospermia
 Pelvic pain
 Symptoms of metastatic prostate cancer
 Rapidly progressing lower urinary tract obstructive
symptoms or erectile dysfunction
 Confirm any elevations in serum PSA
 Alternative PSA measures have no proven benefit in
diagnosis
© Copyright Annals of Internal Medicine, 2009
Ann Int Med. 164 (1): ITC1-1.
When should patients be referred to a
specialist for consultation?
 Refer patients to a urologist for transrectal ultrasoundguided biopsy for:
 Confirmed elevations >4.0 ng/mL for serum PSA
 Prostate nodule or suspicious induration on DRE
 Systematic biopsies are subject to sampling error
 Repeat biopsy in men with previously negative results
 Repeat biopsy at 6-12 months for patients with sustained
PSA elevations
 No proven benefit of strategies to enhance yield from
biopsy including imaging, direct sampling of suspicious
areas
© Copyright Annals of Internal Medicine, 2009
Ann Int Med. 164 (1): ITC1-1.
How is prostate cancer staged?
 “Early” or clinically localized prostate cancer
 Confined within prostate capsule
 Local treatments are potentially curative
 Locally advanced cancer
 Extends beyond prostate capsule, including seminal vesicles
 Curative methods often involve radiation and ADT
 Advanced prostate cancer
 Spread to retroperitoneal lymph nodes or to bone
 Treated palliatively
 Use CT and bone scans to stage those at high risk for
advanced and intermediate risk
© Copyright Annals of Internal Medicine, 2009
Ann Int Med. 164 (1): ITC1-1.
© Copyright Annals of Internal Medicine, 2009
Ann Int Med. 164 (1): ITC1-1.
CLINICAL BOTTOM LINE: Diagnosis
and Staging...
 Signs of prostate cancer:
 Rapidly worsening LUTS and impotence
 Hematospermia
 Pelvic pain
 Bone pain
 Refer to urologist when patient has symptoms, abnormal
results on DRE, and confirmed PSA elevations
 Order bone scan and abdominal-pelvic CT if PSA
concentrations ≥20 ng/mL, Gleason score >7, or T3 cancer
© Copyright Annals of Internal Medicine, 2009
Ann Int Med. 164 (1): ITC1-1.
What is the role of shared decision making
and consultation in clinically localized
prostate cancer?
 Patients should solicit input from diagnosing urologist
as well as radiation and medical oncologists
 Choice: to defer or have curative treatment
 Curative treatment may avoid later metastases and death
but often causes significant side effects
 Specific treatments have no proven differences in efficacy
but vary in side effects
 Decision aids present issues and evidence in a balanced,
clear fashion
 Treatment outcomes are better at high-volume
institutions and from high-volume providers
© Copyright Annals of Internal Medicine, 2009
Ann Int Med. 164 (1): ITC1-1.
CLINICAL BOTTOM LINE: Shared
Decision Making...
 Men with clinically localized prostate cancer should choose
treatment based on how they value potential benefits, harms
 They should make shared treatment decisions with surgical,
radiation, and medical oncologists
 Essential information for informed decision making includes:
 Reason for intervention
 Benefits and harms
 Alternative approaches
 Clear statement that the patient has a choice
© Copyright Annals of Internal Medicine, 2009
Ann Int Med. 164 (1): ITC1-1.
How is risk defined in prostate cancer?
 Low-risk cancer
 PSA <10 ng/dL, Gleason score ≤6, clinical tumor
stage ≤T2a
 Intermediate-risk cancer
 PSA 10 to 20 ng/dL, Gleason score 6, clinical tumor
stage T2b or T2c
 High-risk cancer
 PSA ≥20 ng/dL, Gleason score 8 to 10, clinical tumor
stage T3
 Higher PSA or Gleason score increases likelihood
untreated cancer will metastasize and recur after local
treatment
© Copyright Annals of Internal Medicine, 2009
Ann Int Med. 164 (1): ITC1-1.
What options should be considered for
clinically localized prostate cancer?
 Watchful waiting (deferred treatment)
 Active surveillance (monitoring for signs of progression
that trigger curative treatment)
 Radical prostatectomy (RP)
 External-beam radiation therapy (EBRT)
 Brachytherapy
 High-risk cancer: androgen deprivation therapy (AD)
plus radiation
 All active treatments cause side effects
 Deferring until metastases or evidence of more aggressive
cancer increases mortality risk by only a small amount continued
© Copyright Annals of Internal Medicine, 2009
Ann Int Med. 164 (1): ITC1-1.
What is the role of radical prostatectomy
in treatment of prostate cancer?
 Removes the prostate and seminal vesicles
 An effective option in clinically localized prostate cancer
 Results in erectile dysfunction in most men
 Results in urinary incontinence for many men
 Use of nerve-sparing surgery may reduce erectile
dysfunction
 Minimally invasive surgery including robotic surgery
decreases hospital stay and may reduce recovery time
but does not improve outcomes
 May result in small decreases in mortality
© Copyright Annals of Internal Medicine, 2009
Ann Int Med. 164 (1): ITC1-1.
What is the role of external beam
radiotherapy in the treatment of prostate
cancer?
 An effective option in clinically localized or locally
advanced prostate cancer
 Patients with high risk prostate cancer should be treated
with EBRT plus ADT
 Adjuvant ADT may result in improved cancer-specific
survival and in most cases overall survival
 Combined radiation therapy and ADT may be considered
for patients with intermediate risk prostate cancer based
on expert opinion
© Copyright Annals of Internal Medicine, 2009
Ann Int Med. 164 (1): ITC1-1.
What is the role of brachytherapy in the
treatment of prostate cancer?
 Appropriate for men with low risk cancer, especially
non-palpable T1C tumors and minimal or no urinary
obstruction
 EBRT sometimes added to brachytherapy for patients
with palpable nodules and intermediate-risk features
© Copyright Annals of Internal Medicine, 2009
Ann Int Med. 164 (1): ITC1-1.
What are options when PSA level increases
after treatment for localized prostate
cancer or for those who are at high risk
after prostatectomy?
 Monitor serum PSA level regularly after local treatment
 Increase from post-treatment nadir indicates persistent
cancer and high risk for metastasis
 Prostatectomy: aims to remove all tissue
 High-risk findings after prostatectomy:
 radiation therapy or ADT
 Radiation: may leave benign prostate tissue
 “PSA bounce” may occur after radiation treatments end
 ADT may be beneficial
© Copyright Annals of Internal Medicine, 2009
Ann Int Med. 164 (1): ITC1-1.
What are options for patients with newly
diagnosed metastatic prostate cancer?
 Androgen deprivation therapy (ADT)
 GnRH agonists (goserelin, leuprolide): start course of
nonsteroidal antiandrogen 1-2 wks prior to first injection
 GnRH antagonists (degarelix)
 Bilateral orchiectomy
 For extensive metastases:
 Add docetaxel to initial ADT
 If patient progresses on ADT and does not achieve
testosterone < 50 ng/dL offer bilateral orchiectomy
© Copyright Annals of Internal Medicine, 2009
Ann Int Med. 164 (1): ITC1-1.
What options should be considered for
patients with castrate-resistant metastatic
prostate cancer?
 Docetaxel: first-line systemic treatment
 Diethylstilbestrol or nonsteroidal antiandrogen (add to
GnRH agonist)
 Agents that target testosterone production (antiandrogen
enzalutamide, abiraterone acetate)
 Sipuleucel-T
 Radium-223
© Copyright Annals of Internal Medicine, 2009
Ann Int Med. 164 (1): ITC1-1.
Spinal cord compression in prostate
cancer
 A medical emergency!
 Can result in:
 back pain, vertebral tenderness
 perineal numbness
 urinary retention, urinary incontinence
 constipation, fecal incontinence
 Requires spinal magnetic resonance imaging, high-dose
corticosteroids and either radiation therapy or surgery
© Copyright Annals of Internal Medicine, 2009
Ann Int Med. 164 (1): ITC1-1.
CLINICAL BOTTOM LINE: Treatment…
 Options for low-risk prostate cancer
 Watchful waiting (deferred treatment)
 Active surveillance (monitoring for signs of progression
that trigger treatment)
 RP, EBRT, brachytherapy, ADT in conjunction with EBRT
 Options for metastatic prostate cancer
 Surgical castration (bilateral orchiectomy)
 GnRH agonist with nonsteroidal anti-androgen
 GnRH antagonist
 Docetaxel + ADT: for men with extensive bone metastases
 Options for castrate-resistant prostate cancer
 Several treatments briefly prolong survival
© Copyright Annals of Internal Medicine, 2009
Ann Int Med. 164 (1): ITC1-1.