© copyright annals of internal medicine, 2009 ann int med. 164 (1): itc1-1. in the clinic prostate...

© Copyright Annals of Internal Medicine, 2009Ann Int Med. 164 (1): ITC1-1.

In the Clinic

Prostate Cancer


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


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


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


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


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


What should you consider when working-up 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


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


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

How should clinicians diagnose prostate cancer?


When should patients be referred to a specialist for consultation?

Refer patients to a urologist for transrectal ultrasound-guided 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


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


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


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


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


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


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


What is the role of radical prostatectomyin 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


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


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


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


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


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


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


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. in the clinic prostate...

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