PSA Screening for Prostate Cancer

1. PSA Screening for Prostate Cancer Ross Moskowitz, MD Resident Physician AtreyaDash, MD Assistant Clinical Professor

2. Objectives • Overview of Prostate Cancer • What is screening? • What are advantages? • What are the disadvantages? • What should an individual do?

3. What is Prostate Cancer? The prostate is a gland located in a critical area in the pelvis near the rectum, bladder and urethra Purpose is to liquefy semen Adjacent to the urethral sphincter (urine control valve) and the neurovascular bundles (nerves responsible for erections)

4. What is Prostate Cancer? Other than skin cancer, prostate cancer is the most common cancer in American men The second leading cause of cancer death in the U.S. Second to only lung cancer as the leading cause of cancer death in American men About 1 man in 36 will die of prostate cancer

5. What is Prostate Cancer?

6. What is Prostate Cancer? About 1 man in 6 will be diagnosed with prostate cancer during his lifetime Nearly two thirds are diagnosed in men aged 65 or older Rare before age 40 Average age of diagnosis is about 67 The American Cancer Society estimates for the U.S. in 2012: 241,740 new cases will be diagnosed 28,170 men will die of prostate cancer

7. What is Prostate Cancer?

8. What is Prostate Cancer? Most men diagnosed with prostate cancer do not actually die from it More than 2.5 million men in the U.S. who have been diagnosed with prostate cancer at some point are still alive today There are also differences between races in diagnosis and outcomes

9. What is Prostate Cancer?

10. Cancer Incidence and Death Rates* by Site, Race, and Ethnicity†, US, 2004-2008 *Per 100,000, age adjusted to the 2000 US standard population. Race and ethnicity categories are not mutually exclusive; persons of Hispanic origin may be of any race. Data based on Contract Health Service Delivery Areas, comprising about 55% of the US American Indian/Alaska Native population; for more information, please see: Espey DK, Wu XC, Swan J, et al. Annual report to the nation on the status of cancer, 1975-2004, featuring cancer in American Indians and Alaska Natives. Source: Incidence: NAACCR, 2011. Data are collected by cancer registries participating in the National Cancer Institute’s SEER program and the Centers for Disease Control and Prevention’s National Program of Cancer Registries. Mortality: National Center for Health Statistics 2011. American Cancer Society, Surveillance Research, 2012

11. What is Screening? • Screening is actually a disease prevention strategy called: secondary prevention • Primary prevention • Prevent a disease before it can ever start • Daily aspirin to prevent heart disease • Smoking cessation to prevent lung cancer

12. Secondary Prevention Identifying a disease before a patient has symptoms Without symptoms patient unable to complain about a problem that needs evaluation Relies on some sort of test where both disease being tested and test itself meet acceptable criteria

13. Principles of Screening The disease being screened is public health burden There is a phase where the disease is detectable and prevalent Treatment exists for the detected disease Early detection improves outcome with acceptable side effects Screening tests are acceptable to the population, inexpensive and effective

14. Principles of Screening(PSA) The PSA test and its use for Prostate Cancer meet these criteria PSA is a simple blood test No special requirements such as fasting Measures the level of Prostate Specific Antigen However, not so simple to interpret and explain

15. Principles of Screening(PSA) • Early detection improves outcome with acceptable side effects • Reduces cancer deaths • Acceptability of side effects depends on the individual • Screening tests are acceptable to the population, inexpensive and effective • Effective in reducing cancer deaths • Inexpensive • Again acceptability to individuals and its application in a population is a problem

16. Issues in favor of prostate cancer screening The long period of time before symptoms allows for early detection Cancer causing death is bad, but the spread of disease is also bad due to painful symptoms and need for palliative treatment Screening is convenient and cheap PSA (blood test) DRE (digital rectal exam, palpate for nodules/irregularities)

17. Issues in favor of prostate cancer screening Treatments for early disease Variety of choices Surgery, radiation, and other ablative treatments One choice is observing the cancer until gets worse Active surveillance Watchful waiting

18. Issues against prostate cancer screening High prevalence of non-aggressive disease Most patients will not have problems even if their cancer is left alone Inconsistency of disease progression It is unknown how a cancer will behave

19. Screening more harmful than beneficial? • A large number proportion of the cancers detected will be insignificant • Potential for over-diagnosis • There are side effects of the treatment but unpredictable if will occur and severity • A problem of the test itself • A problem of how the test is applied

20. What Does a High PSA Mean and What Next? There is no cutoff level for PSA The risk of finding cancer, and more advanced disease, increases as PSA level increases The PSA is useful in conjunction with a physical exam of the prostate (DRE) If the PSA level and exam warrant, the next step is to perform a prostate biopsy

21. Prostate Biopsy The biopsy is usually an office procedure A minor prep with use oral antibiotics and an enema or other laxative before An ultrasound probe is inserted into the rectum There is a separate channel within the probe to insert the biopsy gun

22. Prostate Biopsy Local anesthetic is injected and the prostate is measured and examined In the U.S. 12 cores are typically obtained Should be only mild discomfort The firing of the gun can be disconcerting Risks Blood in urine, bowel movements, and semen Urinary tract infection Severe infection, requiring hospitalization and intravenous antibiotics

23. What is the most up to date information? • We know treating prostate cancer saves some people from dying from prostate cancer • This is from a randomized controlled trial from Sweden where one group of patients had their prostates surgically removed versus a comparison group that was observed • Bill-Axelson A, et al.; Radical prostatectomy versus watchful waiting in early prostate cancer. N Engl J Med. 2011 364(18):1708-1717

24. What else did the Swedish study tell us? • Some people are helped more than others • Patients younger than 65 had greater benefit • Even patients with less aggressive cancers benefitted • Number needed to treat • This the number of patients who were operated on to prevent one patient from dying from prostate cancer • In the revised estimate from 2011 • Overall: 15 men to save one • In men younger than 65: 7 to save one

25. Are there studies about screening? • Three recent studies • Prostate Lung Colorectal Ovarian Screening Study performed in the U.S. • European Randomized Screening Prostate Cancer (ERSPC) Study • Göteborg Sweden cohort of ERSPC • Each study has a weakness • Derive conflicting conclusions

26. Are there studies about screening? • A summary of these studies • Number needed to screen to prevent one prostate cancer death: • As many as 1410 men to as low as 293 men • Number needed to treat for prostate cancer to prevent one death (from a group of patients identified by screening): • As many as 48 men to as low as 12 men

27. What are the side effects? • Small risks with biopsy • Side effects are mainly associated with treatment • The likelihood and severity of the side effects depend on the treatment selected and patient characteristics, but are not readily predictable • The issue is that these side effects can have a detrimental effect on quality of life

28. Treatments Surgical removal Radiation Administered from an outside energy source focused on the prostate Radioactive seed implants Hormonal blockade No typically given as primary treatment Newer ablative treatments Observation Least organic side effects in the absence of disease progression Side effects Urinary Incontinence Bother related to obstruction or irritation Sexual Loss of erections Loss of libido Bowel Irritation Risk of fistula Vitality Related to use of hormonal therapy What are the side effects?

29. Hormonal Blockage (androgen deprivation therapy) Medications: Leuprolide (Leupron): This is typically given as an IM depot shot, it is a LH-RH (lutenizing hormone releasing hormone) analog which stops the cascade that leads to testosterone production, which in turn feeds prostate cancer Anti-androgens: block the body’s use of androgens Flutamide, biclutamide, nilutamide Bilateral orchietomy (removal of the testicles) may also be performed as a surgical form of androgen deprivation therapy What are the side effects?

30. Hormonal Blockage (androgen deprivation therapy) Typical Side effects Decrease in libido, erections, and energy Hot flashes Decrease in testicle size Pain (bone/muscle/joints), flu like symptoms These side effects are hard to predict, but usually are more pronounced in the elderly, and so these medications are often poorly tolerated What are the side effects?

31. Should I get screened?(Practical) • Am I at risk for cancer including a lethal cancer • What is my race? • Do I have first degree relatives with prostate cancer? • How is my overall health? • How old am I? • What are my other health problems? • What is my risk of cardiovascular disease?

32. Should I get screened?(Experts) • American Society of Clinical Oncology (ASCO) • In men with a life expectancy <10years, it is recommended that general screening for prostate cancer with total PSA be discouraged, because harms seem to outweigh potential benefits • U.S. Preventive Services Task Force (May 22, 2012) • The USPSTF recommends against PSA-based screening for prostate cancer (grade D) • Clinicians are encouraged to not screen patients unless the individual understands the potential benefits and harms

33. Should I get screened?(Experts) • American Urologic Association • PSA the only widely available test for prostate cancer when interpreted appropriately, it provides important information in the diagnosis, pre-treatment staging or risk assessment and monitoring of prostate cancer patients. • American Cancer Society • Informed decision making process • Age at which to start and some details vary • But even “Expert Panels” have their biases

34. Problem based learning (PBL) Cases Here we will present two complex and advanced prostate cancer cases that illustrate the issues that arise in geriatric patients with metastatic prostate cancer

35. PBL Cases 78 year old male with history of prostate cancer This was diagnosed two years ago at the time of transurethral resection of prostate (TURP) surgery (procedure to open prostatic urethra for improved ability to void) Gleason score (grade of severity) was 4+3=7 (6 least severe, 10 most severe) No further intervention (watchful waiting) and PSA followed and was found to be 36.9 (very elevated)

36. PBL Cases Past Medical History: Hypertension, CVA/TIA, seizure disorder, arrhythmia, arthritis, hyperlipidemia, GERD Current Issues: Possible metastatic disease to thoracic spine Elevation in creatinine (worsening kidney function) Renal ultrasound showed left hydronephrosis (blocked urine outflow from left kidney)

37. PBL Cases Interventions: Prostate cancer  Leuprolide injections Then elected to have bilateral orchiectomy to stop testosterone production altogether Decreased kidney function Operating room for endoscopic resection to open left ureteral orifice and placement of stent to allow left kidney to drain efficiently

38. PBL Cases 92 year old male found to have PSA of 88 Biopsy performed (Gleason 5+5=10, most severe) Thought to initially to have a diagnosis of rectal cancer, but confirmed to be locally advanced prostate cancer Patient with history of urinary retention and obstructed voiding symptoms, received a vaporization procedure of prostate 2 years ago (no tissue for diagnosis obtained)

39. PBL Cases Past Medical History: Coronary artery disease (history of myocardial infarction), atrial fibrillation, melanoma, chronic kidney disease Current Issues: Locally advance prostate cancer causing urethral and ureteral obstruction Leading to worsening lower urinary tract symptoms (incontinence) and worsening renal function

40. PBL Cases Interventions: Prostate cancer  Radiation therapy, then hormonal therapy (leuprolide) Decreased kidney function/ureteral obstruction Managed with bilateral nephrostomy tubes (percutaneous flank tubes that drain urine, require changes by interventional radiologist every few months) Has led to multiple hospital admissions for urinary tract infections and worsening renal function

41. PBL Cases Discussion: Should these patients have had more aggressive initial treatment? Yes: May have avoided or delayed local advancement or metastatic disease No: Poor surgical candidate, and possibly avoid quality of life decreasing interventions Should these patients have been screened? Yes: May have be diagnosed sooner, received treatment sooner, and have not required these morbid interventions No: Advanced age with multiple comorbidities, questionable life expectancy >10yrs and still uncertain if they will die from prostate cancer

42. Thank You