Prostate Cancer

1. Prostate Cancer

2. 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. 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. 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. 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. 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

7. 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. 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. 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

10. 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. 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

13. 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. 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. 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. 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. 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. 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

19. 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. 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. 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. What are options for patients with newly diagnosed metastatic prostate cancer? • Androgen deprivation therapy (ADT) • GnRH agonists (goserelin, leuprolide): start course of nonsteroidalantiandrogen1-2 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. What options should be considered for patients with castrate-resistant metastatic prostate cancer? • Docetaxel: first-line systemic treatment • Diethylstilbestrol or nonsteroidalantiandrogen (add to GnRHagonist) • Agents that target testosterone production (antiandrogenenzalutamide, abiraterone acetate) • Sipuleucel-T • Radium-223

24. 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. 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