Prostate Cancer Update 2017

Transcription

1 Prostate Cancer Update 2017 Arthur L. Burnett, MD, MBA, FACS Patrick C. Walsh Distinguished Professor of Urology The James Buchanan Brady Urological Institute The Johns Hopkins Medical Institutions Baltimore, Maryland

2 Objectives Review basic epidemiologic statistics Emphasis on rates in minority populations Review role of screening in African American populations Key on benefits vs limitations controversy Review advances in the management of localized disease Perspectives on shared decision making Review advances in the management of advanced disease Role for increased interdisciplinary interactions Consider unmet needs in diagnosis and management Attention to racial disparities

3 Problem of Prostate Cancer Most commonly diagnosed cancer among men New cases in US in 2016: 180,890; deaths: 26,120 3% of men older than 50 years will die Effects on quality of life Controversies Natural history Need for early detection Benefits of treatment

4 Estimated New Cancer Cases and Deaths in the US Siegel RL, et al. CA Cancer J Clin. 2016; 66(1):7-30.

5 Cancer Death Rates* for US Men, 1930 to 2003 *Age-adjusted to the 2000 US standard population US Mortality Public Use Data Tapes and US Mortality Volumes Accessed July 20, National Center for Health Statistics, Centers for Disease Control and Prevention. Accessed July 20, 2017.

6 Risk Associations Age and disease probability 70 years or older: 1 in years: 1 in years: 1 in 39 Race/ethnicity and disease prevalence Black men: per 100,000 American Indian: 68.2 per 100,000 Family history 40% to 50% of all prostate cancers result from heritable susceptibility gene Men with a first-degree male relative (father or brother) have 2-fold risk Risk may be increased with a family history of cancer of the ovary, bladder, or kidney Genetics of Prostate Cancer, NCI Accessed July 12, Jemal A, et al. CA Cancer J Clin. 2008;58(2): Negri E, et al. Int J Cancer. 2005;114(4):

7 Problem of Prostate Cancer: Racial Variation A racial variation exists with respect to the incidence and outcomes of prostate cancer The incidence of prostate cancer among white American men is per 100,000 population, compared with for black Americans, producing a rate-ratio of 1.62 for black men The mortality of prostate cancer among white American men is 22.4 per 100,000 population, compared with 54.9 for black Americans, producing a rate-ratio of 2.45 for black men Siegel R, et al. CA Cancer J Clin. 2012;62(1):10-29.

8 Multiple Factors Associated With Racial Variation in Prostate Cancer Outcomes Disease Factors Grade Stage Volume PSA Patient Factors Values/beliefs/preferences Demographics Comorbidities Education Access to care Provider Factors Experience Specialty Case volume Practice setting Geographic location PSA, prostate-specific antigen Zeliadt SB, et al. Cancer. 2006;106(9):

9 Why Prostate Cancer? More aggressive disease Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) database: Black men presented at younger mean age (64.6 years vs 66.8 years), had higher median PSA (9.8 ng/ml vs 6.7 ng/ml), higher clinical Gleason Score (43% Gleason Score 7 vs 33%), higher stage at presentation (stage T3a, or N+ or M+ 10% vs 4%), all P<.01 1 Poorer early detection Surveillance, Epidemiology, and End Results (SEER) database (NCI): Most striking differences in racial and ethnic variation among all cancers were in cancers that are most amenable to early detection and/or treatment, such as prostate cancer 2 Poorer aggressive treatment After adjusting for individual factors such as stage, grade, socioeconomic status, and comorbidity, differences in treatment patterns persist Latini DM, et al. Cancer. 2006;106(4): Tehranifar P, et al. Cancer Epidemiol Biomarkers Prev. 2009;18(10): Zeliadt SB, et al. Urology. 2004;64(6): Lyratzopoulos G, et al. BMJ. 2010;340: c Du XL, et al. Cancer. 2011;117(14):

10 Putative Factors Associated With Decreased Utilization of Definitive Care in Ethnic Populations Treatment selection bias Watchful waiting was administered an increased 1.4 x odds ratio in African Americans 1 Shared decision making occurred very often in 26% of African Americans vs 52% of Caucasian Americans 2 Treatment delays Proposed but may not be an issue in equal-access centers 3 Lack of treatment access Lack of health insurance Lack of available medical facilities Systemic barriers Low volume urologists 4 Hospital racial composition (high proportion of black patients) 5 1. Shavers VL, et al. Gen Intern Med. 2004;19(2): Rim SH, et al. Int J Gen Med. 2011;4: Banez LL, et al. Cancer Epidemiol Biomarkers Prev. 2009;18(4): Pollack CE, et al. Med Care. 2011;49(11): Pollack CE, et al. Cancer. 2011;117(24):

11 Screening Recommendations: Common Historical Practice Combination of PSA and DRE was associated with 92% rate of detection of localized prostate cancers 1 Screening at age 50 years if life expectancy is at least 10 years and at 40 years to 45 years of age if high risk 2 Process to include discussion of benefits, harms and limitations of screening; consideration of patient preferences; informed decision-making DRE, digital rectal examination 1. Mistry K, et al. J Am Board Fam Pract. 2003;16(2): Smith RA, et al. CA Cancer J Clin. 2006;56(1):11-25.

12 Moyer VA. Ann Intern Med. 2012;157(2):

13 Consequences and Implications of the D Recommendation by the USPSTF Age-adjusted prostate cancer incidence rates are at their lowest level since the 1980s Prostate cancer mortality rates are no longer declining USPSTF, US Preventive Services Task Force USPSTF Prostate Cancer Screening Accessed July 21, 2017.

14 New Draft Guideline by USPSTF: C Recommendation Men aged 55 years to 69 years: Should be informed about the benefits and harms of screening and offered PSA testing if they choose it Men aged 70 years: Do not screen ( D recommendation) USPSTF Draft Recommendation Statement Accessed July 21, 2017.

15 The Problem for African American Men (or High Risk Men) The Guidelines cite no screening research outside the European Randomized Study of Screening for Prostate Cancer (ERSPC) and the US Prostate, Lung, Colorectal, and Ovarian (PLCO) trials, which are limited by screening violations and lack of diversity/ethnic representation The Guidelines miss the point that higher risk cancers can be risk-stratified with approximately 80% accuracy using clinical parameters Absence of evidence does not mean evidence of absence Cooperberg MR, et al. J Natl Cancer Inst. 2009;101(12):

16 Diagnostic Evaluation Digital Rectal Examination T 1a, b, c T 2a, b, c T 3a, b, c T 4 Serum Markers PSA PAP? Advanced Disease vs Localized Disease??? Gleason Grade Gleason grade 1-5 Gleason score 2-10 Radiologic Scans TRUS Bone scan MRI CT PAP, prostate acid phosphatase; TRUS, transrectal ultrasound scan

17 Combination of PSA, DRE, and Gleason Scores as Prognostic Indicators Exemplative Nomogram for Prediction of Organ-Confined Disease at PSA Values of 0.0 ng/ml to 4.0 ng/ml Gleason Clinical Stage by DRE Score T 1a T 1b T 1c T 2a T 2b T 2c T 3a Makarov DC, et al. Urology. 2007;69(6): Augustin H, et al. J Urol. 2004;171(1):

18 Combination of PSA, DRE, and Gleason Scores as Prognostic Indicators Clinical Example A 55-year-old male Clinical stage T 1c PSA 6.5 ng/ml Gleason score 6 Prognosis P[OC] = 59% P[LN+] = 2% Clinical Example B 62-year-old male Clinical stage T 2b PSA 10.7 ng/ml Gleason score 8 Prognosis P[OC] = 14% P[LN+] = 40%

19 Patient Assessment Health status Life expectancy

20 Management Options for Localized Disease Expectant management Radiation therapy Surgery

21 Expectant Management Also termed active surveillance Appropriate strategy when life expectancy is less than 10 years, and for healthy men 65 years of age or older who have low-volume, low grade prostate cancer Management usually consists of PSA and DRE every 6 months and prostate biopsies annually

22 Radiation Therapy Current treatment commonly consists of conformal, externally applied techniques Brachytherapy involves implantation of radioactive iodine-125 or palladium-103 seeds into the prostate Advantages Noninvasive/minimally invasive Lower likelihood (than RP) of certain complications such as severe urinary incontinence Role in men with locally extensive disease Potential complications Intermittent rectal bleeding (1.5% to 18%) Erectile dysfunction (40% to 60%) RP, radical prostatectomy

23 Surgery Radical prostatectomy usually with bilateral pelvic lymphnode dissection (anatomical technique) Approaches: Open incisional, laparoscopic, robot-assisted Advantages Potential for cure because of total surgical removal Prominent role for perceived organ-confined disease Potential complications Clinically significant urinary incontinence (3% to 74%) Erectile dysfunction (30% to 90%) Thompson I, et al. J Urol. 2007;177(6): Burnett AL, et al. J Urol. 2007;178(2):

24 Guidelines for Management of Localized Prostate Cancer Risk Option Low (PSA 10 ng/ml, Gleason score <7, and clinical stage T1c or T2a) Intermediate (PSA ng/ml, or Gleason score 7, or clinical stage T2b) High (PSA >20 ng/ml, or Gleason score 8-10, or clinical stage T2c) Active surveillance, brachytherapy, external-beam radiotherapy, radical prostatectomy Active surveillance, brachytherapy, external-beam radiotherapy, radical prostatectomy Active surveillance, brachytherapy, external-beam radiotherapy, and radical prostatectomy are options; prostate-cancer recurrence rates are high with all of these options Thompson I, et al. J Urol. 2007;177(6):

25 The Landscape in Prostate Cancer 2017 Clinical Metastases Noncastrate Clinical Localized Prostate Cancer Rising PSA Clinical Metastasis CRPC Chemotherapy Naïve Clinical Metastasis CRPC POD on Chemotherapy Rising PSA Noncastrate Bicalutamide LhRH agonists LhRH antagonists Bicalutamide Ketoconazole Docetaxel Flutamide Nilutamide LhRH agonists LhRH antagonists Enzalutamide Abiraterone Radium-223 Sipuleucel-T Zoledronic Acid Denosumab Docetaxel Estramustine Enzalutamide Abiraterone Cabazitaxel Radium-223 Samarium Mitoxantrone Zoledronic Acid Denosumab CRPC, castrate-resistant prostate cancer

26 Treatment Options for mcrpc (NCCN Guidelines) Maintain castrate level of testosterone Consider bone anti-resorptive therapies (denosumab or zoledronic acid) Asymptomatic/minimally symptomatic: Consider sipuleucel-t mcrpc, metastatic castrate-resistant prostate cancer; NCCN, National Comprehensive Cancer Network National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Prostate Cancer. V Accessed July 21, 2017.

27 Treatment Options for mcrpc (NCCN Guidelines) Symptomatic patients: Palliative RT to site of bone disease No visceral metastases: RT, radiation therapy Enzalutamide (category 1) Abiraterone (1) Docetaxel with prednisone (1) Radium-223 (1) Secondary hormonal manipulation Corticosteroids National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Prostate Cancer. V Accessed July 21, 2017.

28 Treatment Options for mcrpc (NCCN Guidelines) Symptomatic patients: Positive visceral metastases: Docetaxel with prednisone (category 1) Enzalutamide (1) Abiraterone with prednisone (1) Clinical trial Alternative chemotherapy (mitoxantrone) Consider biopsy to evaluate for small cell/neuroendocrine tumor National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Prostate Cancer. V Available at:

29 Multidisciplinary Team Approach Growing awareness of utility of collaborative approaches earlier in disease CHAARTED study and docetaxel data highlight role of cytotoxic chemotherapy for mcrpc Urologists not typically comfortable or capable with chemotherapy Increased opportunities for clinical trial enrollment Sartor O, et al. BJU Int. 2012;110(3):

30 Racial Disparity After Radical Prostatectomy: Yes or No? Survival outcomes equivalence - If localized prostate cancer is treated adequately and appropriately across all grades and stages 1-3 Survival outcomes nonequivalence - Black men had significantly shorter overall and cancer-specific survival times, regardless of treatment and after adjustment for multiple covariates 4,5 1. Klein JB, et al. J Natl Med Assoc. 2010;102(2): Merrill RM, et al. Urology. 2000;55(5): Resnick MJ, et al. Urology. 2009;73(3): Cohen JH, et al. Cancer Causes Control. 2006;17(6): Godley PA, et al. J Natl Cancer Inst. 2003;95(22):

31 Take-Action Considerations Pattern of care improvements - Early detection, diagnosis, and treatment - Access: Health insurance, healthcare administration Quality of care improvements - Adherence to quality indicators across structure, process, and outcome domains Research endeavors - Elucidation of risk factors for disparities (biological, genetic, social, environmental, dietary, lifestyle) - Discrimination between high vs low risk disease - Discovery of biomarkers, technologies, etc

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