Prostate Cancer Screening:

Prostate Cancer Screening: The Other Side of the Story Tracie Gadler RN, MSN, RNFA, NP-C (Edited by Carol Salem MD) Urologic Oncology Surgery Robotic Surgical Services Nurse Practitioner, Scripps Mercy Hospital

Outcomes Understand function and location of the prostate glad Be informed on prostate cancer screening Identify diagnostic tools and treatment options currently available

Prostate Anatomy

Prostate Anatomy Normal prostate size: 20 grams, by about fifty over half men have enlarged prostates. Data base 738 patients avg size 50.8 (avg age 62.8) Prostate Function: Male accessory gland which secrets fluid into ejaculate

Prostate Cancer (PCA) Prostate cancer occurs when the DNA in prostate cell is changed. Prostate cancer is either inherited or acquired Prostate cancer tends to be slow growing, survival rate at 5 years is 100% and 15 years 91% American Cancer Society Prostate Cancer 2012

Acquired PCA Oncogenes are genes that help cells divide and grow Tumor suppressor genes slow cell division DNA mutations can turn ocogenes on or turn off suppressor genes thus causing cancer Trigger environmental factors, chemicals, radiation American Cancer Society Prostate Cancer 2012

Inherited PCA HPC1 (Hereditary Prostate Cancer Gene) Other inherited genes found across male family members with prostate cancer can include BRCA1 (Breast Cancer Susceptibility Gene or BRCA2 more commonly found in women with females with breast or ovarian cancer Men with first degree relative with PCA have double the risk of developing PCA American Cancer Society Prostate Cancer 2012

Prostate Cancer Facts Prostate Cancer is the most common cancer diagnosed in men (estimated 238,590 in 2013 National Cancer Institute) Yet, Only a small percentage of men die from prostate cancer ( est.10%2013) = second leading cause of cancer death in men (29,720 est. 2013 lives/year).

Prostate Cancer Detection No symptoms of early stage prostate cancer. Usual risk increases after age 50, though can be found at much earlier ages. Increased risk: African-American/ Family History (brother/father/uncle) American Cancer Society 2012

Prostate Cancer Screening No symptoms, so Detection of prostate cancer requires SCREENING

Prostate Cancer Screening The goal of early detection is to reduce the overall morbidity and mortality (side effects and death from the disease )

Consideration Prior to Screening Age Race Risk factors Other illnesses Patient preference Consider health care delivered on an individual basis

Prostate Cancer Detection Screening: Rectal examination PSA (Prostate Specific Antigen) blood test NOT PSA blood test by itself

PSA Prostate Specific Antigen is a glycoprotein enzyme that is secreted by epithelial cells. PSA makes ejaculate liquid and will help to dissolve cervical mucus. Increases in quantity when the glad is damaged or harmed. Most labs consider 0-4ng/mL normal range

Guidelines for PCA Screening Age DRE PSA Age to be screened American Cancer Society American Urologic Society Annual < 2.5 ng/ml > 50 years every 2 years > 45 years if at > 2.5 ng/ml yearly RISK > 40 years if higher RISK Annual Annual > 50 years > 40 if at RISK If >10 years life expectance. RISK: African-American, first degree relative PCA. HIGHER RISK: more then one first degree relative with PCA history.

Different PSA Screening Tests Percent-free PSA PSA Velocity PSA Density Age Specific PSA tests Other

Percent-free PSA (fpsa) Helpful in bx determination PSA is protein bound or unbound fpsa is a ratio unbound PSA: total PSA fpsa lower in PCA <10% = bx 10-25%= strong bx consideration (complexed PSA (cpsa) determines PSA attached to other proteins) American Cancer Society :Prostate Cancer 2012

PSA Velocity (PSAV) Measure of how fast the PSA raises over time Biopsy: PSA >4ng/mL if PSA velocity >0.75 within one year Biopsy: PSA >0.4ng/mL if PSA velocity >0.75 over three PSA blood draws within 18 months of eachother AUA Prostate-Specific Antigen Best Practice Statement 2009

PSA Density (PSAD) PSA levels can be higher in patients with large prostate glands. Volume (transrectal u/s)/ PSA level =PSAD Higher number = greater chance of cancer

Age Related PSA (ng/ml) Age Range Asian- Americans African- American Whites 40-49 yr 0-2.0 0-2.0 0-2.5 50-59 yr 0-3.0 0-4.0 0-3.5 60-69 yr 0-4.0 0-4.5 0-4.5 70-79 yr 0-5.0 0-5.5 0-6.5 AUA Prostate-Specific Antigen Best Practice Statement 2009

Potential Factors Affecting PSA BPH Age Urinary infection Ejaculation Riding Bike Urinary or rectal instrumentation Prostatitis Obesity Medications: Proscar, Avodart, Saw palmetto/testosterone

Rectal examination Perform DRE Important to perform DRE not only for prostate cancer detection but rectal cancers and bleeding.

Prostate Biopsy IF: Abnormal rectal exam and/or Abnormal PSA blood test and Patient desires further work-up THEN: - Prostate Biopsy

Prostate Biopsy Transrectal ultrasound lidocaine gel lidocaine injection antibiotics Potential side effects (3-4%) infection (prostatitis)/urinary retention Bleeding J Urol 168:558,2002;171:247, 2004;174:510,2005.

Transurethral Ultrasound Guided Biopsy Transrectal Ultrasound Guided Biopsy

Evidence Growing body of research. Reduction in the death rate of prostate cancer (since 1990). Obvious shift in finding earlier stage prostate cancers (PSA).

Recommendation: PSA Screening Should INFORM Patients Risks and Benefits of Screening American Medical Association National Cancer Institute American Urologic Association American Cancer Society Do not Discuss (PSA-based prostate cancer screening) - U.S. Preventative Services Task Force

USPSTF Prostate cancer is a serious health problem that affects thousands of men and their families. But before getting a PSA test, all men deserve to know what the science tells us about PSA screening: there is a very small potential benefit and significant potential harms. We encourage clinicians to consider this evidence and not screen their patients with a PSA test unless the individual being screened understands what is known about PSA screening and makes the personal decision that even a small possibility of benefit outweighs the known risk of harms. USPSTF Co-Chair Michael LeFevre, M.D., M.S.P.H. May 22, 2012

USPSTF Based on this work, the Task Force concludes that many men are harmed as a result of prostate cancer screening and few, if any, benefit. A better test and better treatment options are needed. Until these are available, the USPSTF has recommended against screening for prostate cancer. http://www.uspreventiveservicestaskforce.org/prostatecancerscreening.htm

USPSTF RateD: The USPSTF recommends against the service. There is moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits. Suggestions for practice: Discourage the use of this service. http://www.uspreventiveservicestaskforce.org/uspstf/gradespost.htm#drec

USPSTF U.S Department of Health and Human Services 1984 independent group of national experts in prevention and evidence-based medicine that works to improve the health of all Americans by making evidence based recommendations about clinical preventative services, such as screenings 16 VOLUNTEER members medicine/prevention/nursing/pediatrics Government supported activities/research

USPSTF Government supported. Volunteers Not required to have an EXPERT in the field of which they are making a recommendation. Medicare/health care insurance agencies typically weigh these recommendations heavily when considering health care coverage.

Their Evidence USPSTF: Literature Review 80 Articles screenings based primarily on 2 Studies: 1. NIH Prostate, Lung, Colorectal, Ovarian Cancer Screening Trial (PLCO) 2. The European Randomized Study of Screening for Prostate Cancer (ERSPC)

PLCO Study Time: 1993-2006 Population:76,685 men (38,340 intervention/38,345 control) Age: 55-74 yr Intervention Group: annual PSA for 6 years and DRE 4 years Control Group: usual care which sometimes included opportunistic screening By 2009, 57% of the men had been followed for at least 13 years.92% of men followed for 10 years. Natl Cancer Inst 2012; 104:125

PLCO Study Incidence of prostate cancer slightly higher in intervention group (4250 vs 3815) Prostate cancer mortality (death) did not differ significantly between the groups (3.7 vs 3.4 deaths per 10,000 person years) Natl Cancer Inst 2012; 104:125

PLCO Study Problem: Greater than 50% contamination rate in the control group (PSA/rectal examinations) Usual care consisted of any patient or physician performing screening if requested (52% screened by 6 th year) Prescreening of many of them -44%- before enrolling in the trial therefore eliminating some cancers 10 years not enough time re: life expectancy N Engl J Med. 2009 1310-1319; Natl Cancer Inst 2012; 104:125

European Randomized Study Time: Early 1990 s-december 31 2006 Population:182,000 (Core 162,243 55-69 yr) Age: 55-74 yr Intervention group: PSA Screening once every 4 yrs Control group: Unscreened group median follow-up of 11 years New England J Medicine 2009; 360:1320

European Randomized Study Prostate Cancer (ERSPC) Elevated PSA was determined by clinic 2.5-4ng/mL Incidence of prostate cancer 8.2% intervention group vs 4.8% control group Reduced prostate cancer DEATH by 20% 1410 men need to be screened and 48 men treated to prevent 1 death in 10 years. New England J Medicine 2009; 360:1320

ERSPC Problem: High rate of over diagnosis aprox. 50% ERSPC Overdiagnosis defined as the diagnosis in men who would not have clinical symptoms in their lifetime. New England J Medicine 2009; 360:1320

Goteborg Study Goteborg Randomized Population-Based Prostate Cancer Screening Trial Time:1994-Dec 31 st,2008 Population: 20,000 randomized Age: 50-64 yr Intervention:(9,952)PSA screening every 2 years Control: (9952)Not invited for screening Median follow-up 14 years Lancet Oncol 2010, 11:725

Goteborg Study Men with raised PSA were offered DRE or biopsies Results: 7578 continued on in the intervention group 1046 (12.7%) diagnosed with PCA vs 718 (8.2%) control group 27 deaths intervention group vs 78 deaths control group Decreased mortality rate by 44% in intervention group Lancet Oncol 2010, 11:725

USPSTF Their Conclusion: Any Decrease in prostate-specific mortality amounted to too few lives saved and did not outweigh the harms of screening and diagnosis/and the harms of treatment PSA causes more harm than good!!

Additional Flaws Acknowledge strong evidence that treatment of localized prostate cancer reduced mortality compared to observation. Overlooked the fact that the unscreened population had higher stage prostate cancersresulted in more significant complications

Additional Flaws Unscreened group had a 40% higher incidence of locally advanced and metastatic prostate cancer. Focused on mortality, and did not weigh in on the substantial illness associated with living advanced prostate cancer. (No comparisons made!) Lack focus on high risk groups. Lack focus on the epidemiology data re: 30% reduction in PCA deaths since early 1990 s and 75% reduction in presentation with advanced cancer.

To justify screening, one must demonstrate that treatment of the disease is beneficial A randomized trial comparing radical prostatectomy with watchful waiting in early prostate cancer Holmberg et al., NEJM 352/2005

Scandinavian study After PCA Dx 10.8 years 12.8 years Radical Prostatectomy 47 deaths from PCA/347 men Watchful Waiting 68 deaths from PCA/348 men 55 deaths from PCA/347men 81 deaths from PCA/348men % Deaths Radical Prostatectomy vs Watchful Waiting 12.5% vs 17.9% 14.6% vs 20.7% JNCI 2008;100;1144-1154:;N Engl j Med 2011;364 1708-17.

A Different Conclusion! PSA-based screening for prostate cancer is USEFUL in helping to save lives! Per SEER Cancer Statistic Review prostate cancer mortality has decreased 30% AUA Prostate Specific Antigen Best Practice Guidelines 2009 Update

Prostate Cancer Screening Need to continue to modify our screening criteria to aim for the best good and the least harm PSA is TOO GOOD at finding early stage prostate cancer!! Start screening efforts at younger ages look at number trend over time

Prostate Cancer Screening Need to continue to improve our treatments for prostate cancer- radiation and surgery LESS side-effects when treating EARLY stage prostate cancer!! Continue efforts in molecular biology to identify patients who really need treatment vs those that can be safely watched.

The Dilemma Once diagnosed, cannot know with certainty whether the prostate cancer is going to affect life expectancy. Therefore, treatment is a dilemma, (and the treatment options can affect quality of life).

USPSTF Transparency and Accountability Act 2012 Publish a draft research plan to guide the systematic evidence review process Make the evidence review available for public comment Consider findings and research by federal agencies and departments Coordinate activity with Federal agencies Consult with external subject matter experts, i Ensure greater transparency in appointing members through a notice and comment process Disclose potential conflicts of interest. AUAnet:2012

Critics of Prostate Screening Screening is too $$$ Side effects from the prostate biopsy Abnormal PSA only (normal rectal exam) results in high rate of cancer detection. Nonsignificant cancers are found, therefore many men are over treated. No significant evidence that PCA screening results in a decrease in mortality.

Insignificant tumors No definitive test on significance of tumor Reliable criteria PSA velocity grade (Gleason score) number cores involved rectal exam

Insignificant tumors Responsibility of urologist to discuss and educate patient on treatment or nontreatment options Future key: genetic markers (blood, urine, skin)

Is there a mortality benefit? Implied benefit Since 1990, significant stage migration of prostate cancer (earlier stages!, less metastatic disease at time of diagnosis). Prostate cancer mortality has been decreasing

The Facts Pre-PSA era 35% of men who underwent prostatectomy were found to have positive lymph nodes at surgery and 75% were found to have advanced prostate cancer Vs. Since PSA testing 48% of patients diagnosed with prostate cancer have organ and capsule contained disease and 85% are clinically localized. AUA PSA Best Practice Statement 2009: SEER Cancer Statistics Review

Studies are less than 10 years Contaminated groups PSA absolute values The answer still remains UNCLEAR

Traditional screening-starts at age 50, studies out to less than 10 years. Death from prostate cancer High risk.need earlier screening efforts Moderate risk.need studies out to 15 years

The Challenge... is not to reduce the rate of prostate cancer detection, but to identify men whose disease may be life-threatening.

While Prostate cancer screening is SAFE, and EASY... Future -better diagnostic tools (imaging MRI). -better screening tools (other tumor markers in blood, urine or skin). -genetic markers to identify patients with clinically relevant prostate cancer.

Prostate Cancer Prevention Selenium (Vit E) Soy Lycopenes Green Tea Folic Acid Hops (xanthohumol) Proscar (finasteride)

Selenium An essential component of our diet forms parts of many proteins throughout the body antioxidant promotes immune function provokes cancer cells to programmed cell death 200 micrograms/day (seafood, lean meats, grains, eggs, garlic)

pizza??? Lycopenes A powerful antioxidant, found abundant in tomato products

Obesity and risk of prostate cancer progression and recurrence Body mass index (weight to height index) Obesity has been shown to be a statistically significant predictor of both biochemical failure and disease recurrence. Especially in younger men As the severity of the obesity worsened, the risk of these negative outcomes increased.

Obesity and Prostate Cancer?less likely to be detected difficult rectal exams fat makes estrogen-like compounds, which can lower circulating PSA Less likely to eat right

The bottom L-I-N-E Moderate exercise and a healthy diet consisting mostly of food from plant sources, (fruits, vegetables, bread cereals, rice and beans)

Treatment for PCA Watchful Waiting Radiation External Beam 3-D conformal intensity modulated radiotherapy (IMRT) Proton beam Brachytherapy Cryotherapy Surgery open retropubic (pelvic lymph nodes) open perineal laparoscopic/robotic HIFU Hormone Therapy

da VINCI: 2002 (Talamini, M., et al: JLAST 12: 225, 2002)

Radiation Treatment Intensity-Modulated Radiation Therapy (IMRT). Uses computers to deliver radiation precisely to the cancer. It also reduces damage to the healthy tissue nearby, such as the rectum and bladder. Proton beam therapy Uses protons rather than x-rays. The use of protons may allow a very high dose of radiation to reach the prostate while reducing the amount of normal tissue that is affected. 3-D conformal is a type of external beam radiation that is often used to treat prostate cancer. It allows doctors to carefully plan the shape of the radiation beam http://www.cancer.gov/cancertopics/treatment/prostate/understanding-prostatecancer-treatment/page3

References Andriole, G.L., Grubb, R.L., Buys, S.S., et al. Mortality results from a randomized prostate cancer screening trial. N Engl J Med, 360: 1310-19, 2009 Andriole, G.L., Crawford, D., Grubb, R.L., Buys, S.S., Chia, D., Church, T., et al.,prostate cancer screening in the radomized prostate, lung, colorectal and ovarian cancer screening trial: Mortality results after 13 years of follow- up. J Natl Cancer Inst;104:125-132,2012 Hugosson, J.,Carlsson, S., Aus, G., Bergdahl, S., Khatami, A., Lodding, P., et al. Prostate specific antigen based biennial screening issufficient to detect almost all prostate cancers while still curable. J Urol, 169: 1720, 2003 Prostate-Specific Antigen Best Practice Statement:2009 Update. Retrieved from http://www.auanet.org/content/guidelines-and-quality-care/clinical-guidelines/mainreports/psa09.pdf Schroder, F.H., Hugosson, J., Roobol, M.J., et al. Screening and prostate-cancer mortality in a randomized European study. N Engl J Med, 360: 11320-8, 2009

American Cancer Society Prostate Cancer (reviewed 2012). Retrieved from http://www.cancer.org/acs/groups/cid/documents/webcontent/003134-pdf.pdf Chou, R., Croswell, J.M., Dana, T., Bougatsos,C.,Blazina, I., Fu, R.,Gleitsmann, K., Koenig, H.C.,Lam, C., Maltz, A.,Rugge, J.,B., Lin, K., (2011)Screening for Prostate Cancer A Review of the Evidence for the U.S. Preventive Services Task Force Retrieved fromhttp://www.uspreventiveservicestaskforce.org/prostatecancerscreening/prostate art.htm Obek, C., Onal, B., Ozkan, B., et al: Is periprostatic local anesthesia for transrectal ultrasound guided prostate biopsy associated with increased infectious or hemorrhagic complications? A prospective randomized trial. J Urol, 168: 558, 2002 Virginia A. Moyer, MD, PhD, on behalf of the U.S. Preventive Services Task Force* (2012) Screening for Prostate Cancer: U.S. Preventive Services Task Force Recommendation Statement. Retrieved from http://www.uspreventiveservicestaskforce.org/prostatecancerscreening/prostatefinalr s.pdf

References Bill-Axelson, A., Holmberg, L., Ruutu, M., et al: Radical prostatectomy versus watchful waiting in localized prostate cancer:the scandinavian prostate cancer group-4 randomized trial. J Natl Cancer Inst 2008;100:1144-1154. Bill-Axelson, A., Holmberg, L., Ruutu, M., et al: Radical prostatectomy versus watchful waiting in early prostate cancer. N Engl J Med, 364:1708-1717 National Cancer Insitute: Treamtnet chlices for men with early stage prostate cancer(2011) retrieved from http://www.cancer.gov/cancertopics/treatment/prostate/understanding-prostatecancer-treatment/page3 Ragavan, N., Philip, J., Balasubramanian, S.P., et al: A randomized, controlled trial omparing lidocaine periprostatic nerve block, diclofenac suppository and both for transrectal ultrasound guided biopsy of prostate. J Urol, 174: 510, 2005 The essential resource for your practice USPSTF Transparency and Accountability Act of 2012:July 3 2012 (vol XXI. 7)retreived from http://www.auanet.org/eforms/hpbrief/view.cfm?i=1129&a=2695