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Prostate Cancer. John W. Ragsdale, III M.D. Associate Professor Duke Family Medicine and Community Health Sea Pines July 2019. Disclosures. CDC: consultant – Prostate Cancer Decision tool Merck: consultant – Nexplanon instructor. A Big Topic: Goals & Objectives.
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Prostate Cancer John W. Ragsdale, III M.D. Associate Professor Duke Family Medicine and Community Health Sea Pines July 2019
Disclosures • CDC: consultant – Prostate Cancer Decision tool • Merck: consultant – Nexplanon instructor
A Big Topic: Goals & Objectives • The scope of the problem – prostate cancer by the numbers • Screening updates: Where do we stand? • Cancer treatments – Family Medicine’s role in supportive care • Survivorship: a growing need for engagement across the care continuum
By The Numbers • Second common cause of cancer death in American men • 1 in 9 will be diagnosed • 1 in 41 will die from prostate cancer • 174,650est diagnosis for 2019 • 31,620 est deaths for 2019 • 2.9 million men still alive with prostate cancer
Survival Rates Percent Total # 79% 12% 5% American Cancer Society.org/cancer/prostate-cancer/detection
Cancer Death Rate 1999-2015 from the CDC CDC Mortality Data 1999 -2015
PSA Screening: Lessons learned Merenstein D. Winners and Losers. JAMA. 2004;291(1):15–16. doi:10.1001/jama.291.1.15
??? Evolving Clinical Guidelines Community Standard of Care Personal preference Medical / Legal Doctor patient relationship
To screen or not to screen • Guidelines: • United States Preventative Task Force: • American Urology Association • American Cancer Society • External pressure: Performance Standards (HM reminders), payment schemes, peer pressure (Choosing Wisely) • Teaching environment: • Community Standard of care : what is everyone else doing ?
To screen or not to screen: USPTF • 2008 – insufficient evidence to come out for or against screening in men younger than 75 Grade I • Not done at all in men older than that • 2012: Prostate cancer screening should not be done at all! Grade D • More “conservative” than ACS, and AUA • 2018: For Ages 55-69, the decision to screen should be an individual one after discussion of risk and benefits in the context of an individual patient Grade C
The Other Major Players • American Urology Association:A little more positive… • Screening is recommended for all men ages 55 to 70 years old on an every other year. • Screening for men 40-55 is recommended for men with high risk for prostate cancer (family history or African American race). • Screening for men in good health over the age of 70 is recommended • American Cancer Society: • Age 50 for men who are at average risk of prostate cancerand are expected to live at least 10 more years. • Age 45 for men at high risk of developing prostate cancer. This includes African Americans and men who have a first-degree relative (father, brother, or son) diagnosed with prostate cancer at an early age (younger than age 65). • Age 40 for men at even higher risk (those with more than one first-degree relative who had prostate cancer at an early age).
Commonalities: AUA, ACS & USPTF • Does it really save lives? • Sharing known risks and the potential for benefit • Men should be offered and should be able to get it if they wish • All who want screening should get it…
Digital Rectal Exam • Limitations: • Only lesions laterally and posteriorly are palpated • Identifies only a fraction of cancers (35%) • Many (up to 50%) recent graduates do not know how to do it correctly Ann Fam Med 2018;16:149-154. https://doi.org/10.1370/afm.2205
Digital Rectal Exam • Roughly 50% physicians know how to do it correctly out of residency • Meta –Analysis • 7 studies with 9241 patients… All had DRE and biopsy • DRE: Failed to meet standard for routine screening • Definitely if symptomatic • ACS: “may also be done be a part of screening” • AUA: “recommends DRE as a part of screening “ • Community Standard… Ann Fam Med 2018;16:149-154. https://doi.org/10.1370/afm.2205
To screen or not to screen • Why all of this confusion? • The nature of the disease…. • Long slow growing – not known which cancers will progress • Two major studies that created all this • ERSCP: 162K men • 73k • PLCO
Prostate, Lung, Cervical and Ovarian Trial • 76 K men at 10 U.S. Study Centers • 38K annual screening • Offered PSA x 6 years • Offered DRE x 4 years • 38K “usual care” • At 13 years – NO BENEFIT in fact pointed towards harm • BUT: not a real RCT trial • Lots of Screening vs. less screening
Prostate, Lung, Cervical and Ovarian Trial • Did not show a mortality benefit • Attributable to high % of screening in control group
European Randomized Study of Screening for Prostate Cancer Cancer(ERSPC) • Seven European Countries 1990s – early 2000s • 162,000 ages 50-69 • 73K Screening group • 90K: • Protocols varied • More of a meta-analysis of Seven “smaller” trials • There WAS a benefit: NNT: 27 over 11 years
ERSCP Results • At 13 years: • Prostate Cancer Mortality was 21% lower • Absolute rates of death were • .43 vs. .54 per 1000 person years (.11 fewer deaths per 1000 person years) • 781 men need to be invited to be screened to prevent one death over 13 years • All cause mortality not reduced
Screening initiative What Happened?
Patients meeting criteria for screening increased with initiative
Shared Decision Making One idea: Information giving Second Idea: give the patient a choice: A or B Third Idea …
Decision Aids • Critical given evidence on Prevention, genetic testing, screening and potential treatments • Identifies the value the patients give on outcomes (which varies significantly) • Addresses barriers about literacy and incite around disease process • Tend to lower decisional conflict • Quality of decision by patient improved and lead to more informed and engaged patients
Links to Shared Decision making Guides American Cancer Society: • http://www.cancer.org/prostatemd • Foundation For Informed Decision Making • http://www.healthdialog.com/ • CDC: • http://www.cdc.gov/cancer/prostate/pdf/aaprosguide.pdf • Mayo Clinic: • http://www.mayoclinic.com/health/prostate-cancer/HQ01273
New Screening Tools in the Works • PSA velocity • Percent Free PSA: (Free/Bound PSA): > greater than 25% is good • [-2]ProPSA: PSA isoform • PHI : “Prostate Health index – integrated metric of -2ProPSA and %Free • 4K(Four kallikrein): Total PSA, free PSA, intact PSA, and human kallikrein-related peptidase 2
The Bottom Line There is no consensus on using any of the PSA modifications None of them has been shown in clinical trials to reduce the number of unnecessary biopsies or improve clinical outcomes. The total PSA cutoff of 4.0 ng/mL has been the most accepted standard because It balances the tradeoff between missing important cancers at a curable stage and avoiding both detection of clinically insignificant disease and subjecting men to unnecessary prostate biopsies
The Bottom Line… • The is a small but real survivor benefit to screening • There are real and significant harms to screening • Bleeding infection (< 1%) • Hospital admission (0.6-4.1 % • PSA and DRE are currently the best tools we have (for now) for screening but expect that answer to evolve AUA/SUNA white paper on the incidence, prevention and treatment of complications related to prostate needle biopsy. www.auanet.org/content/health-policy/quality/pdf/AUA-SUNA-PNBWhitePaper.pdf (Accessed on November 30, 2012).
Risk Stratification • Very low risk: local not palpable, one side of prostate (Gleason score ≤6), • PSA <10 ng/mL, • Low risk: Both sides of prostate(Gleason score ≤6), PSA <10 ng/mL. • Intermediate risk: (Gleason score 7), or PSA ≥10 to 20 ng/mL. • High risk: Gleason score 8 to 10, or PSA >20 ng/mL. • Very high risk: T3b to T4 tumor (Gleason score 8 to 10) known metastasis
Treatments • Active Surveillance • Chemotherapy • Hormone therapy (ADT) • Immunotherapy • Radiation therapy/brachytherapy
Active Surveillance: • Patient Factors • Age (significant risk) • Race ? (probably) • Conflicting evidence on • BMI • Family History • Biopsy Factors • Clinical Stage • Prostate Volume • Number of positive cores • Gleason’s Stage • Genetics • PCA3 (prostate cancer Ag 3) • TMIRSS2:ERG(Transmembrane protease)
Active Surveillance • A conservative management approach, conducted for those patients with “low-risk” or “favorable-risk” disease, • Avoids long-term adverse effects on the patient’s quality of life. • Routine protocol of close monitoring with digital rectal examination, periodic biopsy, and serial PSA testing
Active Surveillance • Gleason score of 6 • PSA level of less than 10 ng/mL
Active Surveillance: • Patient Factors • Age • Race • Conflicting evidence on • BMI • Family History • Biopsy Factors • Clinical Stage • Prostate Volume • Number of positive cores • Gleason’s Stage • Genetics • PCA3 (Prostate Cancer Antigen 3):
Active Surveillance • Efficacy: it works • cancer-specific mortality rate of 3% at 10 to 15 years Oncology (Williston Park). 31(5):333-340, 345. 2017
Androgen Deprivation Therapy • For palliation for metastatic cancer • Improved bone pain, pathological fracture, spinal cord compression • For Adjuvant to radiation therapy or prostatectomy for locally invasive or node positive disease • Mortality 62% vs. 78% at five years • Disease free 40% vs. 74% at five years
Androgen Deprivation Therapy • Lupron and it’s effects: • Statin therapy to lower low-density lipoprotein cholesterol levels to <70 to 100 mg/dL (based on baseline cardiovascular history and risk) • Antihypertensive therapies to lower blood pressure to <130 to 140/80 to 90 mmHg if needed • Glucose-lowering therapies to recommended levels in patients with a history of diabetes mellitus • Aspirin (generally 81 mg/day) for patients with known cardiovascular disease • Smoking cessation programs for men who continue to smoke (which remains a relevant recommendation for all prostate cancer survivors)
Provenge • A "Vaccine” • Pooled collection of engineered white blood cells from patient • For Castration resistant prostate cancer “CRPC” • May carry slight increase risk of stroke • 50% more patients alive after receiving at 3 years (31.7% vs. 21.7%)
Risk-based health care of cancer survivors • Monitor for recurrence of cancer • Surveillance for second cancers and late effects • Early diagnosis and intervention • Prevention • Tobacco use, physical activity, calcium intake • Counseling and targeted education Oeffinger KC. Institute of Medicine, 2003 Oeffinger KC, Hudson MM. CA Cancer J Clin 54:208-236, 2004
Survivorship • Risk of dying from prostate cancer is quite low unless there is distant metastasis • Focus on tight chronic disease control • Address underlying psycho social illness • Team-based care
Survivorship • Diet: low fat diet association but not yet causal • Relationship between high fat and obesity • Statistically lower intervention on plant based low fat diet • 27% versus 5% • Physical Activity: • 46% lower all cause mortality in men who walked “moderate to brisk” pace