Update on Prostate Cancer Current Controversies Lucas Jacomides, M.D.

Transcription

1 Update on Prostate Cancer Current Controversies Lucas Jacomides, M.D. Assistant Professor of Surgery, Texas A&M Health Science Center College of Medicine Director of Urology, Scott & White-Round Rock

2 The proposed revision of the prostate cancer screening recommendations has generated considerable controversy

3 What all providers should know about PSA testing

4 Lifetime Probability of Developing Cancer, by Site, Men Site Risk All sites 1 in 2 Prostate 1 in 6 Lung and bronchus 1 in 13 Colon and rectum 1 in 17 Urinary bladder 1 in 28 Non-Hodgkin lymphoma 1 in 46 Melanoma 1 in 52 Kidney 1 in 64 Leukemia 1 in 67 Oral Cavity 1 in 73 Stomach 1 in 82 * For those free of cancer at beginning of age interval. Based on cancer cases diagnosed during 2000 to All Sites exclude basal and squamous cell skin cancers and in situ cancers except bladder. Includes invasive and in situ cancer cases

5 2006 Estimated US Cancer Cases* Prostate ( K) 33% Men 720,280 Women 679,510 Breast 31% Lung & bronchus 13% Colon & rectum 10% Urinary bladder 6% Melanoma of skin 5% Non-Hodgkin 4% lymphoma Kidney 3% Oral cavity 3% Leukemia 3% Pancreas 2% Lung & bronchus 12% Colon & rectum 11% Uterine corpus 6% Non-Hodgkin lymphoma 4% Melanoma of skin 4% Thyroid 3% Ovary 3% Urinary bladder 2% Pancreas 2% All Other Sites 18% All Other Sites 22% *Excludes basal and squamous cell skin cancers and in situ carcinomas except urinary bladder. Source: American Cancer Society, 2006.

6 2006 Estimated US Cancer Deaths* Lung & bronchus 31% Colon & rectum 10% Prostate (26-33K) 9% Pancreas 6% Leukemia 4% Liver & intrahepatic 4% bile duct Esophagus 4% Non-Hodgkin 3% lymphoma Urinary bladder 3% Kidney 3% All other sites 23% Men 291,270 Women 273,560 Lung & bronchus 26% Breast 15% Colon & rectum 10% Pancreas 6% Ovary 6% Leukemia 4% Non-Hodgkin lymphoma 3% Uterine corpus 3% Multiple myeloma 2% Brain/ONS 2% All other sites 23% ONS=Other nervous system. Source: American Cancer Society, 2006.

7 2012 Estimates 241,740 American men diagnosed in % of Americans diagnosed have African heritage (41,095) 28,170 American men will die of prostate cancer in 2012

8 Change in the US Death Rates* by Cause, 1950 & 2007 Rate Per 100, Heart Diseases 45.1 Cerebrovascular Diseases 48.1 * Age-adjusted to 2000 US standard population. Sources: 1950 Mortality Data - CDC/NCHS, NVSS, Mortality Revised Mortality Data: US Mortality Public Use Data Tape, 2003, NCHS, Centers for Disease Control and Prevention, Pneumonia/ Influenza Cancer

9 American Cancer Society Breaking News Feb fewer deaths

10 Cancer Screening Well designed clinical studies have demonstrated the mortality reduction through: Mammography and CBE for Breast Cancer Stool Blood Testing, Sigmoidoscopy and Colonoscopy for Colorectal Cancer Pap and Visual Screening for Cervical Cancer Low Dose Spiral CT for Lung Cancer

11 Death rate due to cancer from in men From Jemal, A. et al. CA Cancer J Clin 2007;57: Copyright 2007 American Cancer Society

12 Introduction of PSA

13 Cannot Completely Link PSA Screening To Mortality Declines PSA Screening Patterns Prostate Cancer Deaths?

14 Mortality Trends Suggest a Clear Role for PSA Screening No treatment Treatment Treatment and screening Cases diagnosed since 1975 ERSPC benefit

15 About Prostate Cancer Some prostate cancers are aggressive, advancing quickly and threaten the life of the patient. Some are indolent, slow growing and may never become life threatening in the man s lifetime. The only way to know if either exists is to be tested.

16 Before the PSA Era Prostate cancers were most commonly found following the onset of symptoms from advanced disease, or as a nodule found on DRE. Symptomatic tumors were of a higher grade, more advanced and often deadly.

17 Primary Treatment Changed Before and During the PSA Era Conservative management RP RT+ADT RT Data from SEER and CaPSURE

18 The most effective way to prevent advanced (metastatic) prostate cancer is to detect it early.

19 The goal of prostate cancer testing is not only to prevent mortality, but even more so to prevent the attendant morbidity that comes with metastatic prostate cancer. Urinary tract obstruction Fractures Significant bone pain

20 About the PSA Test The PSA test is the most widely available test to identify changes in the prostate. PSA is prostate-specific, not cancerspecific. Currently, there is no other widely available blood test for prostate cancer.

21 About the PSA Test When used appropriately, the PSA test provides clinicians with valuable information to aid in the diagnosis and treatment of prostate cancer.

22 Screening Decreases Prostate Cancer Mortality 11-Year Follow-Up of the 1988 Quebec Prospective Randomized Controlled Trial (Labrie et al Prostate 59:311, 2004)

23 SEER Database 75% reduction in metastases at time of diagnosis 42% reduction in prostate-cancer specific mortality over the most recent 20 years fewer men died of prostate cancer in 2007, compared to 1992 Models have suggested that 40-70% percent of this reduction is due to early detection.

24 PSA Screening Guidelines Annual PSA/DRE, beginning at age 50 Exceptions- begin at age 40 Well-informed men interested in early detection First-degree family members diagnosed before 65 African Americans Stop when less than 10-year life expectancy (USPSTF: age 75?)

25 So with all these positive reports, what s with all the recent controversy regarding PSA screening?

26 Critics of Prostate Cancer Screening There are cancers that do not need to be cured but can be cured. There are cancers that need to be cured but cannot be cured. (Our patients and friends who die). We do not know if we cure any disease that needs to be cured. ( Do we save lives? is an open question).

27 Prostate Cancer Incidence and Mortality ( ) Age-Adjusted Rate Per 100, Black Incidence 200 White Incidence 150 Black Mortality White Mortality

28 Critics of Prostate Cancer Screening Several studies have shown PSA screening finds a lot of cancer, but have failed to convincingly show that prostate cancer screening saves lives.

29 Most of the studies analyzed by the USPSTF demonstrate benefits from PSA testing.

30 Results from the PLCO and ERSPC Prostate Cancer Screening Trials were Published in NEJM, March 2009

31 PLCO 73,000 men aged 55 to 74 randomized to screening annually vs routine follow-up Began in 1993, ten U.S. Centers Median follow-up about ten years

32 Argument against PSA Screening: Results from NCI Randomized Prostate-Cancer Screening Trial (PLCO) (Andriole et al, N Engl J Med 2009;360:1310-9) Results: In the screening group, rates of compliance were 85% for PSA testing and 86% for digital rectal examination. Rates of screening in the control group increased from 40% in the first year to 52% in the sixth year for PSA testing and ranged from 41 to 46% for digital rectal examination. After 7 years of follow-up, the incidence of prostate cancer per 10,000 person-years was 116 (2820 cancers) in the screening group and 95 (2322 cancers) in the control group (rate ratio, 1.22; 95% confidence interval [CI], 1.16 to 1.29). The incidence of death per 10,000 person-years was 2.0 (50 deaths) in the screening group and 1.7 (44 deaths) in the control group (rate ratio, 1.13; 95% CI, 0.75 to 1.70). The data at 10 years were 67% complete and consistent with these overall findings. Conclusions: After 7 to 10 years of follow-up, the rate of death from prostate cancer was very low and did not differ significantly between the two study groups.

33 PLCO Randomized Trial Outcomes: Prostate Cancer Deaths

34 ERSPC 162,000 men aged 50 to 69 randomized to screening vs routine follow-up (there was no standardized protocol) Began in 1991, seven countries Median follow-up about nine years For men 55 to 69, death rate 20% difference favoring screening P=.04 (minimally statistically significant) NNT 48 to 1 (overtreatment) Overall death rate not reported Treatment differences did exist

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36 Over 14 years These men didn t die from CaP These men benefitted These men still died of CaP

37 If We Stick With the Observed Data ERSPC 2009 Publication 20% Reduction In Prostate Cancer Deaths Lives saved Deaths Without screening 1,000 men screened: 0.7 lives saved Significant Short-term Relative Benefit Insignificant Short-term Absolute Benefit

38 Issues with ERSPC Positive finding 20% risk reduction of prostate cancer death. Those in the screened arms had different treatment patterns than those in the control arms To prevent one prostate cancer death: - Screen 1410 men - Treat 48 men This is a pre-specified subset analysis. The actually trial was men 50 to 69 Is the study negative or positive?

39 Screening and Prostate-Cancer Mortality in a Randomized European Study (ERSPC) Schröder et al, N Engl J Med 2009;360: Background The European Randomized Study of Screening for Prostate Cancer was initiated in the early 1990s to evaluate the effect of screening with prostate-specific antigen (PSA) testing on death rates from prostate cancer. Methods We identified 182,000 men between the ages of 50 and 74 years through registries in seven European countries for inclusion in our study. The men were randomly assigned to a group that was offered PSA screening at an average of once every 4 years or to a control group that did not receive such screening. The predefined core age group for this study included 162,243 men between the ages of 55 and 69 years. The primary outcome was the rate of death from prostate cancer. Mortality follow-up was identical for the two study groups and ended on December 31, 2006.

40 Screening and Prostate-Cancer Mortality in a Randomized European Study (ERSPC) Schröder et al, N Engl J Med 2009;360: Results In the screening group, 82% of men accepted at least one offer of screening. During a median follow-up of 9 years, the cumulative incidence of prostate cancer was 8.2% in the screening group and 4.8% in the control group. The rate ratio for death from prostate cancer in the screening group, as compared with the control group, was 0.80 (95% confidence interval [CI], 0.65 to 0.98; adjusted P = 0.04). The absolute risk difference was 0.71 death per 1000 men. This means that 1410 men would need to be screened and 48 additional cases of prostate cancer would need to be treated to prevent one death from prostate cancer. The analysis of men who were actually screened during the first round (excluding subjects with noncompliance) provided a rate ratio for death from prostate cancer of 0.73 (95% CI, 0.56 to 0.90). Conclusions PSA-based screening reduced the rate of death from prostate cancer by 20% but was associated with a high risk of overdiagnosis. (Current Controlled Trials number, ISRCTN )

41 Relative Risk of Death for Screened vs Unscreened by Country

42 Surgical Treatment of Localized Cancer (Scandinavian Study, SPCG-4) years years years

43 Study Overview A total of 695 men with early prostate cancer were randomly assigned to radical prostatectomy or watchful waiting from

44 Surgical Treatment of Localized Cancer The Swedish prospectively randomized study of radical prostatectomy vs observation in a largely non screen detected cohort with T1b, T1c or T2 disease was the first study to show only a slight advantage to radical prostatectomy. 2% difference in mortality at 5 yrs follow-up 5.3% difference in mortality at 10 yrs follow-up Number needed to treat (NNT) was 20 treated to save one life

45 VA, NCI, AHRQ Cooperative Study #407: Prostate cancer Intervention Versus Observation Trial (PIVOT) PIVOT First randomized trial of radical prostatectomy versus observation for treatment of localized prostate cancer during PSA era

46 The PIVOT (Prostatectomy vs Observation Trial) Began in 1994, randomized to radical prostatectomy or supportive care Clinically localized PSA < 50 ng/ml Age <75 Mean PSA 10.2 ng/ml and Median 7.8 Wilt et al, AUA 2011

47 PIVOT 731 men (more than 9000 invited) 43% low risk 36% intermediate 21% high risk Median 12 years follow-up 354 of 731 dead (48.4%) Insignificant differences in all cause and prostate specific mortality A subset analysis showed slight benefit for high risk Wilt et al, AUA 2011

48 PIVOT Conclusions Compared to observation, radical prostatectomy produced small absolute differences (<3%) in all-cause and prostate cancer mortality that were not significant in men with clinically localized primarily PSA detected cancer. While a larger effect may occur in men with higher PSA or risk disease, surgery was not more effective than observation in men with low PSA or low risk prostate cancer.

49 Discussion Among men with localized prostate cancer detected in the early PSA era, prostate cancer mortality through 12 years was <10% Varied little by race, age, health status Varied considerably by tumor factors Low PSA, low stage and low risk disease: < 6% Higher PSA/risk disease: 10-20%

50 How does this fit into existing information? For most men with early stage PSA detected prostate cancer, surgery does not improve longterm overall or prostate cancer survival compared to observation and has harms The vast majority of men with PSA detected early stage prostate cancer do not die of their disease even if not treated with surgery or radiation Men treated with observation have similar longterm physical and mental health outcomes but fewer harms due to urinary, sexual and erectile dysfunction compared to men treated with surgery

51 What are the implications for prostate cancer care? PIVOT results support the role of observation in most men with PSA detected early stage prostate cancer. Men can be informed that observation provides similar survival, especially for those with low PSA, low risk disease, as well as mental and physical function compared to surgery and can avoid surgery related harms that include urinary and erectile dysfunction. Men can be informed that any survival benefit exists due to surgery may be limited to the minority of men with higher PSA and higher risk prostate cancer.

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53 an independent panel of non-federal experts in prevention and evidence-based medicine and is composed of primary care providers (such as internists, pediatricians, family physicians, OB/Gyns, nurses, and health behavior specialists). Did not include a prostate cancer expert (urologist or oncologist) in the development of recommendations for PSA testing.

54 USPSTF and the Affordable Care Act The ACA broadened the scope of the USPSTF, mandating that the group must assess, develop and update clinical preventive recommendations. The ACA requires that Medicare and qualified commercial plans cover those preventive services graded A and B by the USPSTF at 100 percent. Services with grades of C or D will require a co-pay.

55 In October, 2011, the USPSTF released a draft recommendation statement updating the 2008 Prostate Cancer Screening Recommendations. The new statement downgrades prostate cancer screening from an I to a D

56 The USPSTF organized their recommendation statement as follows: Importance - statement related to the disease burden and natural history Detection - performance of DRE, PSA, but also the evidence for distribution of aggressive vs. slow growing cancers, and overdiagnosis Benefits of detection and early intervention For men aged 50 to 69 years, the evidence is convincing that the reduction in prostate cancer mortality 10 years after screening is small to none Harms of detection and early intervention The USPSTF considered the magnitude of these screening-associated harms to be at least small The USPSTF considered the magnitude of these treatmentassociated harms to be at least moderate. USPSTF Assessment The USPSTF concludes that there is moderate certainty that the harms of PSA-based screening for prostate cancer outweigh the benefits.

57 Why not Grade C? Grade C would have meant that the USPSTF has concluded that there is at least moderate certainty that the overall net benefit of the service is small. The USPSTF felt they could not assign a grade C recommendation for PSA screening because it did not conclude that the benefits outweigh the harms.

58 The USPSTF Prostate Screening Statement The decision to initiate or continue PSA screening should reflect an explicit understanding of the possible benefits and harms and respect the patient s preferences. Physicians should not offer or order PSA screening unless they are prepared to engage in shared decision making that enables an informed choice by the patient.

59 The USPSTF Prostate Screening Statement Similarly, patients requesting PSA screening should be provided the opportunity to make an informed choice to be screened that reflects their values regarding specific benefits and harms. However, community- and employer-based screening should be discontinued.

60 The USPSTF Prostate Screening Statement The USPSTF has clarified in the Implementation section that a D recommendation does NOT preclude discussions between clinicians and patients to promote informed decision making that supports individual values and preferences. While the USPSTF discourages the use of screening tests for which the benefits do not outweigh the harms in the target population, it recognizes the common use of PSA screening in practice today and understands that some men will continue to request screening and some physicians will continue to offer it.

61 The USPSTF Prostate Screening Statement The USPSTF recognizes that clinical decisions involve more considerations than evidence alone. Clinicians should understand the evidence but individualize decision making to the specific patient or situation. Similarly, the USPSTF notes that policy and coverage decisions involve considerations in addition to the evidence of clinical benefits and harms.

62 In May 2012, following the release of the USPSTF s recommendations, the Obama Administration told the Associated Press that Medicare would continue to pay for the PSA test ( for now).

63 Organizations Recommending Against Routine Prostate Cancer Screening U.S. Preventive Services Taskforce Canadian Taskforce on the Periodic Health Examination American College of Preventive Medicine American College of Physicians

64 National Comprehensive Cancer Network There are advantages and disadvantages to having a PSA test, and there is no right answer about PSA testing for everyone. Each man should make an informed decision about whether the PSA test is right for him.

65 European Association of Urology Recommend for informed decision making within the physician-patient relationship. Recommends against mass screening. Men should obtain information on the risks and potential benefits of screening and make an individual decision European Urology 56(2), 2009

66 2009 Best Practice Statement on Prostate-Specific Antigen Early detection and risk assessment of prostate cancer should be offered to asymptomatic men 40 years of age or older who wish to be screened with an estimated life expectancy of more than 10 years. Men who wish to be screened for prostate cancer should have both a PSA test and a DRE. The decision to use PSA for the early detection of prostate cancer should be individualized. Patients should be informed of the known risks and the potential benefits.

67 2009 Best Practice Statement on Prostate-Specific Antigen Given the uncertainty that PSA testing results in more benefit than harm, a thoughtful and broad approach to PSA is critical. Patients need to be informed of the risks and benefits of testing before it is undertaken. The risks of overdetection and overtreatment should be included in this discussion.

68 2009 Best Practice Statement on Prostate-Specific Antigen The AUA strongly supports that men be INFORMED OF THE RISKS AND BENEFITS of prostate cancer screening before biopsy and the option of ACTIVE SURVEILLANCE IN LIEU OF IMMEDIATE TREATMENT FOR CERTAIN MEN newly diagnosed with prostate cancer.

69 The American Cancer Society 2010 Prostate Cancer Screening Guideline Men should have an opportunity to make an informed decision with their health care provider about whether to be screened for prostate cancer, after receiving information about the uncertainties, risks, and potential benefits associated with prostate cancer screening.

70 ACS Response to the Draft USPSTF Prostate Cancer Screening Recommendation Statement The ACS-PCAC agreed with the Task Force that there are significant limitations and risks associated with prostate cancer screening The ACS-PCAC concluded,..based on our interpretation of the current evidence related to benefits and harms, we recommend that the Task Force reconsider their interpretation of the data and upgrade prostate cancer screening to a C recommendation. Issuing a C recommendation would provide men with the opportunity to integrate their personal values into the screening decision.

71 ACS Response to the Draft USPSTF Prostate Cancer Screening Recommendation Statement The ACS Prostate Cancer Advisory Committee ACS-PCAC has submitted a comment on the draft screening recommendation to AHRQ, recommending that they upgrade the recommendation to a C grade. Specifically, the ACS-PCAC concluded that: the overdiagnosis associated with screening is significant the evidence from the European trials is more supportive of a possible benefit than has been interpreted by the Task Force. the estimate of the number needed to invite to prevent one prostate cancer death may be overstated.

72 Study Flaws of PLCO and ERSPC Contamination Selection Bias Length of followup

73 Contamination At least 52% concurrent PSA testing in PLCO control group and 40% or more had PSA testing before enrolling. Centers conducting PLCO were concurrently advertising mass PSA testing like Prostate Cancer Awareness Week! Is it then surprising that if you screen a lot and compare with screening a little bit more that you ll see no difference?

74 Contamination The likely consequence of the high rate of PSA testing in the control population is that contamination rates in the trials would be approximately 20% to 50%, and this appears to be having a major impact on the effective sample size, and the statistical power, of the studies.

75 Another Criticism of PLCO Screening Trial Prostate cancer detection rate was 12 % higher in the screening arm.

76 ERSPC Trial Selection Bias Influence of selection bias in countries where control group men were unaware they were in a study Were men in the control group with prostate cancer pre-randomization identified through the registries? Were men in the screened group with prostate cancer pre-randomization not allowed to opt out of the study? Differential availability of treatment in the screened vs. control group

77 Length of Followup Updated data demonstrates a 21 percent risk reduction in prostate cancer-related death (up to 29 percent after accounting for non compliance). Benefits observed primarily in men younger than 70 years Number of cancers that would need to be detected to prevent one death has dropped to 37.

78 Recent results from the Göteborg arm of the ERSPC 20,000 men born between Randomized 1:1, 10,000 in each arm PSA screening every 2 years, up to ~ age 70 vs. usual care Endpoint: Prostate cancer specific mortality

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80 Göteborg Randomized Population-Based Prostate Cancer Screening Trial Population-based trial of 20,000 men ages Demonstrated a 41 percent decrease in advanced disease. Showed a 44 % relative risk reduction in prostate cancer mortality in men ages after a median of 14 years.

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82 2011 Update (AUA National Meeting) Extending ERSPC to 11 years of followup Decreased NNS to 500 Decreased NNT to 18 Goteborg, Sweden Trial: 14 year followup NNS = 293 NNT = 12 44% reduction in prostate cancer-specific mortality (Mammography for breast cancer: NNT = 10)

83 Scandinavian Study (SPCG-4) years years years

84 Conclusions from 2002 (> 6 year followup) In this randomized trial, radical prostatectomy significantly reduced disease-specific mortality, but there was no significant difference between surgery and watchful waiting in terms of overall survival After a median follow-up of more than six years, more deaths due to prostate cancer had occurred in the watchful-waiting group, but overall survival in the two groups was essentially the same

85 2005: Argument for radical prostatectomy (> 8 year followup) Radical prostatectomy reduces disease-specific mortality, overall mortality, and the risks of metastasis and local progression The absolute reduction in the risk of death after 10 years is small, but the reductions in the risks of metastasis and local tumor progression are substantial Men <65 years of age with prostate cancer diagnosed on the basis of obstructive urinary symptoms (rather than elevated prostate-specific antigen levels) and assigned to radical prostatectomy, as compared with watchful waiting, have improved survival.

86 Conclusions from 2011 (nearly 13 year followup) Radical prostatectomy was associated with a reduction in the rate of death from prostate cancer. Men with extracapsular tumor growth may benefit from adjuvant local or systemic treatment (7x more likely to die of cancer). NNT=15 NNT = 7 for younger men

87 The argument for prostate cancer treatment Significant reduction in risk of prostate cancer death in Scandinavian RCT.

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89 The only problem: compare it with the outcome seen with contemporary surveillance

90 49% fall in prostate cancer mortality. Continues to increase

91 We can t predict the future outcomes of our screening trials. However, there are very strong data to suggest that screening is currently preventing tens of thousands of deaths each year. I would not personally want to be in the position 5-6 years from now after PSA testing is stopped in the US, we learn that the ERSPC is showing what we ve seen in the US, and then I have to face the wife of a man who was denied a PSA test and died of the disease.

92 My take on all this Early on (<10 year followup), it seemingly doesn t matter what you do- you ll be fine After years, there may be significant differences in patient outcomes, depending on low or high-risk disease Key is early detection & risk-stratification Aggressively treat the bad ones Potentially observe the slow-growing ones

93 Who is at highest risk for prostate cancer & may derive greater benefit from screening? African-americans 1.6 x more likely to be diagnosed 2.5 x more likely to die Family history of prostate cancer Abnormal DRE PSA > 1 ng/ml at age 40

94 Variables associated with prostate cancer risk Digital rectal examination Age Race/ethnicity Family history Prior negative biopsy

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97 PSA testing isn t a black and white issue.

98 Elevated PSA Scores A rise in PSA does NOT automatically: mean a man needs a BIOPSY. result in a CANCER diagnosis.

99 A prostate cancer DIAGNOSIS does not automatically mean a man needs immediate TREATMENT.

100 The current community standard is that active surveillance should be offered to appropriate patients. Low risk disease Limited life expectancy (<10 yrs) Patients who do not wish to pursue aggressive interventions

101 But the BOTTOM LINE is that a patient cannot make an informed decision about prostate cancer if he doesn t even know he has it.

102 Take-away Points Not all prostate cancers are life threatening and not all require active treatment immediately; however, we cannot do anything if we do not know a cancer exists. The decision to test for prostate cancer should be individualized to the patient (what is good for one man may not be best for another). Men should understand the pros and cons of testing (including next steps if cancer is suspected) and be allowed to make their own personal decision. Prostate cancer testing is necessary in order to provide patients the most options (including active surveillance) as early as possible in the progression of their disease.

103 Prostate cancer screening: yes or no? Mortality due to prostate cancer has and is decreasing Whether or not this is due to screening or aggressive disease findings is not clear Effective treatments for localized disease stages are part of the reasons While screening of entire populations may not show benefit, discuss with your patients the use of PSA in managing his prostate health

104 Questions in Prostate Cancer Medicine Risk factors including race Effectiveness of screening Effectiveness of treatments Localized disease Early metastatic disease Predicting biologic behavior of disease* *Perhaps most imperative

105 What steps urologists can take? 1. Biopsy only men with consequential cancer. 2. Consider surveillance in low-risk men. - 5-year DSS 99.6%; 10-year DSS > 97% My expectation is that it will become (or is) the standard of care.

106 What steps can we take after diagnosis 1. Consider surveillance in low-risk men. - 5-year DSS 99.6%; 10-year DSS > 97% My expectation is that it will become (or is) the standard of care. (For the NCCN, it is.) 2. Explore, especially in older men, expanding the definition of low-risk disease. 3. For high-risk disease, focus on multidisciplinary care.

107 We are approaching our ideal goal 1. Preferentially biopsy men with aggressive cancer. 2. In them, offer aggressive, multi-modal therapy. 3. In men in whom we detect low-grade, lowvolume disease, monitor it. These men may actually have a lower risk of death from prostate cancer than the man we re not currently offering a biopsy. 4. In men at risk of cancer, prevent it in the first place.

108 The Future of Prostate Cancer Better chemopreventative agents Better screening tests than PSA Better imaging to detect extra-prostatic disease More ablative treatment options Cyberknife? HIFU? Better options for metastatic disease Zytiga, Xgeva, Provenge, MDV3100

109 Conclusions Despite controversies surrounding prostate cancer prevention, detection, and treatment, fewer patients are dying of the disease in 2012 PSA remains the mainstay of prostate cancer detection (for now) Important to inform patients and involve them in decision-making regarding treatment options Need for risk-stratification

110 Thank you for coming! Questions & Answers