1. © Copyright Annals of Internal Medicine, 2009 Ann Int Med. 164 (1): ITC1-1. In the Clinic Prostate Cancer

2. © 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

3. © 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

4. © 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

5. © 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

6. © 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 69, and men with life expectancy <10 years

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

8. © 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

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

10. © 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 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

11. © 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

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

13. © 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

14. © 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

15. © 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

16. © 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

17. © 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

18. © 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

19. © 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

20. © 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

21. © 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

22. © 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

23. © 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

24. © 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

25. © 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