The misuse of tumour markers and other tests: What it means to you, the patient and the Health Care System Elizabeth MacNamara 64th McGill Family Medicine Refresher Course December 4th 2013 Disclosure of Commercial Support  This Jewish General Hospital Laboratory has received financial support from Roche Diagnostics of $10,000 per annum for five years as an unrestricted educational grant.  I have received no monies, or in kind support, from any commercial company in any capacity apart form the above Goals  Understand that the excessive use of laboratory tests results in a waste of resources, unnecessary follow up tests and possible harm to the patient. Workload Controlling unnecessary tests 1. Urine microscopy Savings – $280,000 per year 2. Folic acid Savings $50,000 per year Controlling unnecessary tests 3. Anticipation of exponential growth Ex: Vitamin D 4. Accepting the limitations of a new test Ex: BNP 3. Multidiciplinary approach for complex algorithms Ex: hs Troponin Réduction de 14% des tests hs Troponin Family Physicians and the lab  Many physicians do not follow guidelines for testing  Physicians can easily overcome any restriction  Most physicians do not see the negative impacts of over testing  How can we work together to decrease unnecessary tests such as tumour markers? Uses of tumour markers  Screening  Diagnosis  Monitoring  Prognosis The ideal tumour marker Characteristics Highly specific Detectable only in one tumor type Highly Sensitive Non-detectable in physiological or benign disease states Long lead time Sufficient time for alteration of natural course of disease Levels correlate with tumour Prognostic and predictive utility of the tumour marker Short half-life Frequent serial monitoring of the marker levels after 5-6 half lives Simple/inexpensive/ easily attainable Applicability as screening test & acceptability by target population Tumour Markers for Screening  Not recommended in healthy population  No tumour marker is 100% specific  Often elevated with non-malignant conditions  Most not elevated in early stages of malignancy Non-Malignant Conditions associated with elevated tumour markers  AFP: viral hepatitis, liver injury, IBD, pregnancy  B-HCG: testicular failure, marijauna smokers, pregnancy  CEA: smokers, IBD, hepatitis, Cirrhosis, Pancreatitis, Gastritis  Ca 15-3: G-CSF use, cirrhosis, benign breast disease  Ca-125: peritoneal irritation, endometriosis, PID, Hepatitis, pregnancy  Ca: 19-9: biliary disease, pancreatitis, jaundice, IBD, cirrhosis  PSA: prostatitis, BPH, DRE, ejaculation, urinary retention THE CASE OF PSA  PSA is one of the few tumour markers routinely recommended for screening, diagnosis, prognosis and monitoring Canadian Urology Association 2011  Offer to men > 50 with at least 10 years life expectancy  Offer to men > 40 if high risk (family hx, African American)  May benefit from offering baseline PSA in men 40-49  If bx indicated (PSA >4 +/- abnormal DRE), 10-12 core TRUS peripheral zone  Consider treatment (surgery, radiation or androgen deprivation) according to tumour volume, grade, DRE, PSA Controversy  k Controversy “…final guideline says there’s little if any evidence that PSA testing saves lives – while too many men suffer impotence, incontinence, heart attacks, occasionally even death from treatment of tiny tumours that never would have killed them.” New York Times, July 2012 Reasoning for USPTF for not recommending PSA screening  Lifetime risk for diagnosis 15.9%  Lifetime risk for dying of prostate cancer is 2.8%  Most cases have good prognosis even without treatment but some cases are aggressive  Rare before age 50  70% of deaths occur after age 75 (as with all causes of death) Harms of Screening  The reduction in prostate cancer mortality after PSA based screening is very small (0-1/1000)  33% of those screened suffer significant harmful side effects  Pain, fever, bleeding, infection, and transient urinary difficulties associated with prostate biopsy, psychological harm of false-positive results  90% of positive biopsies go on to active treatment Harms of Treatment  Harms of treatment  Erectile dysfunction (29/1000)  Urinary incontinence (18/1000)  DVT or PE (1/1000)  Cardiovascular event (2/1000)  Death (<1/1000)  Bowel dysfunction  Psychological harm Reaction in the US; which do you think is correct?  American Urological Association:  “Outraged”  Recommendations are “inappropriate and irresponsible”  Sited significant methodological flaws, and inadequate follow up to make a judgment  Annals of Internal Medicine:  The task force is “ideally suited to provide an objective, unbiased assessment” because it’s members, unlike many of it’s critics “have no emotional, ideological or financial conflicts of interest” So… how is PSA used at the JGH? How is PSA used at the JGH How is PSA used at Herzl HERZL requisition changed to include PSA – increase from ~150 to 560 per yr What was the greatest # of PSAs requested for one patient in 2012? What was the greatest # of PSAs requested for one patient in 2012? 27 PSAs  Dr. Melnychuk??  Requisitions under his name but…  He did not order all of them!!  So who did?  ? Phelbotomist  ? Nurse  ? Secretary  ? Patient Patient Pressure  How many of you have been asked to order tests that you were not convinced were indicated by patients? American Urological Association  No PSA screening if     <40 >70 < 15 year life expectancy Average risk of prostatic cancer and >40 <54 yr.  55 to 69yr weigh the benefits of preventing prostate cancer mortality in (1 man for every 1,000 men screened in 10 years) against the known potential harms associated with screening and treatment.  If screening every two or more years preferable to annual Vitamin D: Is routine measurement necessary? Increase in Testing 2004 to 2010  Ontario increase X 24 ($66,000,000/yr)  Quebec increase X 5  France increase X 3  US increase X 12  UK increase X 6 Exponential increase in requests for serum vitamin D at JGH 7000 6000 y = 8E-232e0.2688x Number of assays performed 5000 4000 3000 2000 1000 0 2007 2008 2009 2010 Year 2011 2012 2013 Vitamin D: Is routine measurement necessary? Increase in Vitamin D testing  2004 to 2010  Ontario increase X 24  Quebec increase X 5  France increase X 3  US increase X 12  UK increase X 6 2 4 6 (Months) 8 10 12 14 16 Modified from Am J Clin Nutr 96(5) 1152-3 Physiological (sun exposure)  Vitamin D intakes of 2,000 IU/day are safe  IOM 4,000 IU/day  10,000 IU/day from UV  Lifeguards in the United States and in Israel, farmers in the Caribbean all >100 nmol/L  Regular sun-tan parlor users >80 nmol/L  The highest 25(OH)D concentrations up to 235 nmol/L from UV  No hypercalcemia JGH lab policy  Toxicity in normal adults requires intake of more than 40,000 IU/day  <50 nmol/L supplement and repeat after 6 months  50 – 75 nmol/L supplement and repeat after 1 year  >75 nmol/L no repeat  Decrease of 30% of assays performed Summary  High prevalence of insufficiency - 85%  Target is likely > 75 nmol/L  Likely need 1500 – 2000 IU/day  6-8 months to reach a plateau Patient harm from excessive testing Summary  Consider whether there is truly an indication for the blood test  Ask, will the results alter patient management and if so how  Ask if the result can harm the patient if wrong  Wasting Health Care money damages our Health Care System Thank you  Questions? Canadian Urology Association 2011  Watchful waiting: no therapy until the patient develops symptoms secondary to advanced prostate ca  PSA Q 6-12 months  Active Surveillance: close follow up on patients dx with early stage, low risk prostate ca  PSA Q 3-6 months, bx 1x/year  Therapy recommended when cure deemed possible and disease progression occurs (rapid PSA doubling time, progression on DRE, grade progression or tumour volume progression on repeat Bx) Cut-off: 50 or 75 nmol/L Best Practice & Research Clinical Endocrinology & Metabolism 25 (2011) 681 - 691 Cut-off: 50 or 75 nmol/L Best Practice & Research Clinical Endocrinology & Metabolism 25 (2011) 681 - 691 Cut-off: 50 or 75 nmol/L Best Practice & Research Clinical Endocrinology & Metabolism 25 (2011) 681 - 691 Prevalence  50% <50 nmol/L European countries  25% <25 nmol/L in some groups  JGH  85% <75 nmol/L  55% <50 nmol/L  6% <25 nmol/L Dosing  600 IU/day probably insufficient  1000 IU/day will increase 25 Vitamin D by 20-25 nmol/L  Increase to mean from 50 to 75  Osteoporosis Canda  800 - 2000 IU/day