Prostate Cancer 2013  Still an
Cancer Cases in 2013
Cancer Deaths in 2013
Life time risk of developing cancer             2007 - 2009 Site         Men      Women All sites    44%      38% Breast  ...
Life time risk of dying ofcancer  Site        Men     Women  All sites   23.5%   19.9%  Breast              2.9%  Colorect...
Prostate CancerIncidence PeakedDuring the ClintonYears
Male Cancer           Incidence Rates 1975           to 2009Prostate           Peak year 1992
Male Cancer Mortality Rates 1930 to 2009                               lung   stomach                              prostat...
Median Age at Diagnosis and Death
Median Age at Diagnosis and Death 80                Diagnosis 78                Death 76                                  ...
Leading Cause of Cancer     Death in 2009
Trends in Relative 5 Year     Survival RateTime Period    Survival Rate1975-1977          68%1987-1989          83%2002-20...
Prostate Cancer…more men die with it than of it 80%    found at autopsy 16% diagnosed during their  lifetime 3% will di...
Risk Factors for Prostate CancerAgeFamily HistoryHormonesRaceDietary FatMultivitamin useDairy and Calcium IntakeCadmium Ex...
Can you PreventProstate Cancer?Based on solid evidence, chemoprevention withfinasteride and dutasteride reduces the incide...
Prostate Cancer                              Prevention                              Trials•(PCPT) Prostate Cancer Prevent...
Vitamins E and C in the Prevention of Prostate and Total Cancer in Men ThePhysicians Health Study II Randomized           ...
Should you screen for  prostate cancer?
Age Distribution of Men Diagnosed with      Prostate Cancer 2000-2010                      39%40%35%                      ...
The evidence is insufficient to determinewhether screening for prostate cancerwith prostate-specific antigen (PSA) ordigit...
Men who have at least a 10-y life expectancyshould have an opportunity to make aninformed decision with their health carep...
Median Life Expectancy in Men by Health     (poor, average or excellent)
? Proven Benefit from                    PSA Screening ERSPCEuropean Randomized Screening for Prostate Cancer (ERSPC)Trial...
Mortality results from the Göteborgrandomized population-basedprostate-cancer screening trial.University of Göteborg, Swed...
? Proven Benefit from PSA              Screening PLCO StudyProstate, Lung, Colorectal, Ovary US Study, n =  76,693 , annua...
Prostate, Lung, Colorectal, and Ovarian (PLCO) CancerScreening Trial on prostate-cancer mortality. NEJM.org March 18, 2009...
Long Term PLCO Trial• Those who had 2 or more early PSA screenings had 25% lower  prostate cancer mortality• Those with mi...
Prostate Cancer ScreeningMata-analysis of 6 trials ( n = 387,286)• Odds of diagnosing prostate cancer  = increased by 46%•...
Prostate Cancer ScreeningMata-analysis of 6 trials ( n = 387,286)                         Favor Screening   Favor Control ...
Check for a baseline PSA at age 40 and if 1 orover go to annual (if less than 1 start screeningat 50) Median PSA for Men a...
• If PSA is > 2.5 or higher or velocity is 0.35/y  consider biopsy or check Free-PSA• If PSA 4-10 get biopsy or at least f...
Probability of finding cancer in men withclinically normal prostate glands but PSAbetween 4 – 10 using Free PSAPSA     Can...
Prostate Cancer Biopsy Predictor     http://www.aboutcancer.com/prostate_calc_main_page.htm
Prostate Cancer Biopsy Predictor
Prostate Cancer Biopsy Predictor
Positive Biopsy based on PSA andFamily History
Positive Biopsy by Age, Race andPSA   80%   70%   60%   50%                               W55   40%                       ...
Positive High Grade Biopsy by Age, Race               and PSA80%70%60%50%                                  W5540%         ...
Radical Prostatectomy versus     Observation for Localized Prostate                  CancerProstate Cancer Intervention ve...
Death from Any Cause         During the median follow-                             up of 10.0 years, 47.0%                ...
NEJM 2012; 367:203
Incidence of death from prostate cancer in a randomized trial thatcompared radical prostatectomy with watchful waiting.Onl...
Patient Reported Dysfunction          at 2 YearsDysfunction      Surgery            ObservationUrinary           17.1%    ...
Treating prostate cancer                         Surgery?    Radiation?Or Watchful Waiting?
Prostate Cancer Treatment120       in 2008 from NCDB100 80                              Surgery 60                        ...
Choices with Prostate Cancer1. Depending on the man’s life expectancy   and the nature of the specific cancer   (Gleason s...
Watchful Waiting or Active Surveillance                NCCN appropriate for:                1. Very low risk cancers      ...
Very Low Recurrence Risk1. Stage T1c2. Gleason 6 or lower3. Less than 3 cores positive and   none over 50%4. PSA density <...
Low Recurrence Risk 1. Stage T1 – T2a 2. Gleason 6 or lower 3. PSA < 10
Median Life Expectancy in Men by Health     (poor, average or excellent)
Life Tables for Men in the US (2007 data)       Age           Expectancy        50               29        55             ...
Watchful Waiting?        Mortality if UntreatedGleason Score       Death by 15 Years       2–4                  4 – 7%    ...
Mortality with No Active Therapy
Watchful Waiting, the odds that untreated prostatecancer would cause death related to the age and the GleasonScore
Active Surveillance• Limited to men with low risk cancer and shorter life  expectancy• PSA every 3 to 6 months• DRE every ...
Partin Tables: calculate the risk that thecancer is already outside the capsuleprior to therapy
Laparoscopic Prostate Surgery                       The surgeon                       tries to dissect                    ...
Radiation Fields with Prostate CancerA Low Dose Large Area (Phase 1)                           With radiation it is       ...
Radiation Fields with Prostate CancerA High Dose Large Area (Phase 2)                          The final, high            ...
NCCN.org
Prostate Cancer Risk Groups  combine all 3 things, thestage, the PSA level and the       Gleason score•Low risk: (T1c, T2a...
Cure Rates with Radiation versus Surgery forEarly Stage Prostate Cancer are the same           from the Cleveland Clinic. ...
10 Year Cure Rates for Patients with High Risk              Prostate Cancer       (PSA >20 or Gleason 8-10 or T3)Treatment...
Long-Term Functional Outcomes after   Treatment for Localized Prostate Cancer The Prostate Cancer Outcomes Study (PCOS), c...
Sexual Function afterRadiotherapy orSurgery   N Engl J Med 2013; 368:436-445
Quality of Life / Medicare Survey     Prostate Cancer PatientsSymptom                           Surgery             Radiat...
Potency Rates after Prostate             Cancer TreatmentTreatment                        Probability    RangeSeeds       ...
Potency Rates after Surgery  can range from 2% to70%) Did they have a ‘nerve sparing’  prostatectomy? Hold old is the ma...
Potency Results after ExternalRadiation can range from 16% to 92% Did they get hormone therapy along  with the radiation?...
Responded to                       ViagraSurgery:               43%Radiation:          70 – 91%General Population:   80%  ...
Choosing Treatment Prostate Cancer                    Urologist with                    experience and a good             ...
The experience of the surgeon is a criticalfactor associated with a successful outcomeOpen prostatectomy the learning curv...
Minimally invasive prostatectomy – In aseries of 4,702 men who were managed withlaparoscopic prostatectomy by one of 29sur...
Evolving RadiationTechnology
Using the proper dose of        radiation   “It may be a bit over-exposed”
Prostate Cures Rates by Treatment,The Radiation Dose is Critical                 External beam > 72Gy                   Su...
Cure Rate (PSA cure) in 2991      Men By Therapy                   Best results with                   high dose external
Prostate Cancer Relapse Rate by         Radiation Dose                    < 72Gy                      72 - 82Gy           ...
Goal = radiation zone precisely around      the prostate cancer with small margin       bladder                      prost...
IMRT (intensitymodulatedradiation therapy) using 7 different beamsto target the prostateThe computer candetermine the opti...
After IMRT was established then IGRT(image guided) was introduced
Lower Risk of Side Effects with ImageGuided IMRT compared to IMRT
Better Cure Rates with Image Guided IMRT     compared to IMRT for Prostate  Intermediate Risk      High Risk
The most sophisticated technique for  image guided IMRT is Tomotherapy.Combine a CT scan and linear accelerator to ultimat...
There is significant movement of the prostate gland based on daily gas in rectum      Planned      target                 ...
Cyberknife Radiosurgery
Non Isocentric Delivery with CK            Beams
SBRT Prostate Cancer / Naples-Tampa            Experience   Feb 2005 – Apr 2008 (Naples, FL)    • 164 monotherapy, 35 Gy ...
PSA Response to CyberKnife                  Mean PSAi 6.8ng/ml                  Mean PSAp 0.78ng/ml97% biochemical control...
Cure Rate after Cyberknife   N = 515, Alan Katz in New York
PSA Response after Cyberknife Follow-up median 54 months (range, 7 -  78) Median PSA     7                              ...
New MedicalTreatmentsfor Prostate  Cancer
Clinical development of novel therapeuticsfor castration‐resistant prostate cancer
New Drugs for Prostate     Cancer
New Drugs for Advanced       Prostate CancerDrug                            FDA Approval           CostProvenge (sipuleuca...
Expose the patient’s                             activated T cells to                             cancer antigen          ...
FDA Approval 4.29.10median OS of 25.8 months compared to 21.7months for patients who received the controltreatment There w...
Phase 3 TROPIC clinical study involving 755 patients with mHRPC previously treated with a docetaxel-containingMedian overa...
Xgeva the first and only RANK Ligand inhibitor toprevent SRE (skeletal related events in cancer)FDA Approval 11.19.10
Xgeva RANK Ligand inhibitor
Recent advances have demonstrated thatandrogen-based pathways continue to have aclinically significant role in the progres...
ZYTIGA is an oral androgen        biosynthesis inhibitor that works        by inhibiting the CYP17 enzyme        complex, ...
Zytiga and prednisone combination had a median overall survival of 14.8 months compared to 10.9 months for patients receiv...
August 2012In clinical trials, men who received the drug, which waspreviously known as MDV3100, lived a median of 18.4mont...
Enzalutamide (marketed as Xtandi and formerly known as MDV3100) is asecond generation androgen receptor antagonist drug fo...
www.aboutcancer.com            Cancer Information            Cancer Videos            Tomotherapy            Cyberknife   ...
www.aboutcancer.comCancer Information  •Basic Cancer Information  •General Cancer Statistics  •Most Common Cancers  * brai...
Robert Miller MD Medical Channelbone metastasesbrain metastasesbreast cancer:  understanding the disease, treatment decisi...
Prostate Cancer 2013
Prostate Cancer 2013
Prostate Cancer 2013
Prostate Cancer 2013
Prostate Cancer 2013
Prostate Cancer 2013
Prostate Cancer 2013
Prostate Cancer 2013
Prostate Cancer 2013
Prostate Cancer 2013
Prostate Cancer 2013
Prostate Cancer 2013
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Prostate Cancer 2013

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an update on prostate

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  • Library of 1200 BeamletsPaints Multiple Points of the target rather than one fixed point, improved Conformality.
  • 400 Naples150 Tampa
  • 1st 155 pts treated in Naples
  • Prostate Cancer 2013

    1. 1. Prostate Cancer 2013 Still an
    2. 2. Cancer Cases in 2013
    3. 3. Cancer Deaths in 2013
    4. 4. Life time risk of developing cancer 2007 - 2009 Site Men Women All sites 44% 38% Breast 12.4% Colorectal 5.17% 4.78% Lung 7.8% 6.4% Melanoma 2.9% 1.9% Prostate 16.2%
    5. 5. Life time risk of dying ofcancer Site Men Women All sites 23.5% 19.9% Breast 2.9% Colorectal 2.3% 2.2% Lung 7.8% 4.9% Melanoma 0.35% 0.20% Prostate 2.97%
    6. 6. Prostate CancerIncidence PeakedDuring the ClintonYears
    7. 7. Male Cancer Incidence Rates 1975 to 2009Prostate Peak year 1992
    8. 8. Male Cancer Mortality Rates 1930 to 2009 lung stomach prostate colorectal
    9. 9. Median Age at Diagnosis and Death
    10. 10. Median Age at Diagnosis and Death 80 Diagnosis 78 Death 76 13 74 year 72 age 70 gap 68 66 64 62 60 Lung Colon All Breast Prostate
    11. 11. Leading Cause of Cancer Death in 2009
    12. 12. Trends in Relative 5 Year Survival RateTime Period Survival Rate1975-1977 68%1987-1989 83%2002-2008 100%
    13. 13. Prostate Cancer…more men die with it than of it 80% found at autopsy 16% diagnosed during their lifetime 3% will die of it
    14. 14. Risk Factors for Prostate CancerAgeFamily HistoryHormonesRaceDietary FatMultivitamin useDairy and Calcium IntakeCadmium Exposure (-)Dioxin Exposure (-)
    15. 15. Can you PreventProstate Cancer?Based on solid evidence, chemoprevention withfinasteride and dutasteride reduces the incidenceof prostate cancer, but the evidence is inadequateto determine whether chemoprevention withreduces mortality from prostate cancer.
    16. 16. Prostate Cancer Prevention Trials•(PCPT) Prostate Cancer Prevention Trial the 24.8% reduction ofprostate cancer prevalence over a 7-year period in those mentaking the 5alpha-reductase inhibitor, finasteride (Proscar 5mg perday)•REDUCE study using dutasteride (Avodart) (-23%)•CombAT Trial (Avodart + Tamsulosin (Flomax) (-40% and noincrease in high grade cancers)•SELECT study using vitamin E and selenium (worse, Viy Eincreased prostate cancer by 17%)•Physicians Health Study (PHSII) beta-carotene, Vit E, C ormultivitamins (no benefit)
    17. 17. Vitamins E and C in the Prevention of Prostate and Total Cancer in Men ThePhysicians Health Study II Randomized Controlled Trial JAMA. 2009;301(1):52-62
    18. 18. Should you screen for prostate cancer?
    19. 19. Age Distribution of Men Diagnosed with Prostate Cancer 2000-2010 39%40%35% 28%30% 22%25%20%15% 7%10% 3%5% 1%0% 30 40 50 60 70 80 90 Age
    20. 20. The evidence is insufficient to determinewhether screening for prostate cancerwith prostate-specific antigen (PSA) ordigital rectal exam (DRE) reducesmortality from prostate cancer.
    21. 21. Men who have at least a 10-y life expectancyshould have an opportunity to make aninformed decision with their health careprovider about whether to be screened forprostate cancer. Asymptomatic men whohave less than a 10-year life expectancybased on age and health status should not beoffered prostate cancer screening.
    22. 22. Median Life Expectancy in Men by Health (poor, average or excellent)
    23. 23. ? Proven Benefit from PSA Screening ERSPCEuropean Randomized Screening for Prostate Cancer (ERSPC)Trial, 182,000 men age 50-74y, PSA yearly for 4 yearsMedian follow up of 11 years Screen No ScreenDiagnosis of prostate cancer 7.4% 5.1%Deaths from prostate cancer 299 462Death risk prostate cancer 0.79 1.00Conclusion: screen lowers the death rate by 21%, butyou would need to screen 1,055 men and treat 37 toprevent one death
    24. 24. Mortality results from the Göteborgrandomized population-basedprostate-cancer screening trial.University of Göteborg, Sweden.Lancet Oncol. 2010 Aug;11(8):725-32. Epub 2010 Jul 2. 20,000 men, age 50 to 64, half PSA every 2 years 14 year follow up Screen Control prostate cancer 12.7% (1.64) 8.2%Screening had 44% lower 0.5% (0.56X) rate so had prostate death prostate death 0.9%to screen 293 and treat an additional 12 to save 1
    25. 25. ? Proven Benefit from PSA Screening PLCO StudyProstate, Lung, Colorectal, Ovary US Study, n = 76,693 , annual PSA for 6 years and DRE 4 years, with 13 years follow up Screen No ScreenIncidence cancer 1.22 1prostate cancer death 50 44mortality rate/100,000 2 1.7
    26. 26. Prostate, Lung, Colorectal, and Ovarian (PLCO) CancerScreening Trial on prostate-cancer mortality. NEJM.org March 18, 200976,693 men at 10 U.S. study centers, Men in the screening group wereoffered annual PSA testing for 6 years and digital rectal examination for 4years.Incidence 22% higher Mortality was 13% higher (not lower)
    27. 27. Long Term PLCO Trial• Those who had 2 or more early PSA screenings had 25% lower prostate cancer mortality• Those with minimal comorbidities had a 44% reduction in prostate cancer mortality. Treat an additional 5 to save 1 Prostate Cancer Mortality No screen screen JCO February 1, 2011 vol. 29no. 4 355-361
    28. 28. Prostate Cancer ScreeningMata-analysis of 6 trials ( n = 387,286)• Odds of diagnosing prostate cancer = increased by 46%• Odds of being in stage I = increased by 95%• Impact on prostate cancer mortality = none• Impact on overall survival = none BMJ. 2010 Sep 14;341:c4543
    29. 29. Prostate Cancer ScreeningMata-analysis of 6 trials ( n = 387,286) Favor Screening Favor Control BMJ. 2010 Sep 14;341:c4543
    30. 30. Check for a baseline PSA at age 40 and if 1 orover go to annual (if less than 1 start screeningat 50) Median PSA for Men age 40 – 49 median 0.5 to 0.7 75th percentile is 0.7 to 0.9
    31. 31. • If PSA is > 2.5 or higher or velocity is 0.35/y consider biopsy or check Free-PSA• If PSA 4-10 get biopsy or at least free-PSA• If over 10 get biopsy
    32. 32. Probability of finding cancer in men withclinically normal prostate glands but PSAbetween 4 – 10 using Free PSAPSA Cancer % Free PSA Age 50 - 64y Age 65 - 75y0.5 6.60% 0 - 10% 56% 55%.6-1 10% 10.1 - 15% 24% 35%1.1-2 17% 15.1 - 20% 17% 23%2.1-3 24% 20.1 - 25% 10% 20%3.1-4 27% > 25% 5% 9%4-10 25-30%>10 42-64%
    33. 33. Prostate Cancer Biopsy Predictor http://www.aboutcancer.com/prostate_calc_main_page.htm
    34. 34. Prostate Cancer Biopsy Predictor
    35. 35. Prostate Cancer Biopsy Predictor
    36. 36. Positive Biopsy based on PSA andFamily History
    37. 37. Positive Biopsy by Age, Race andPSA 80% 70% 60% 50% W55 40% W70 30% B55 B70 20% 10% 0% 2.5 4 10 20 50
    38. 38. Positive High Grade Biopsy by Age, Race and PSA80%70%60%50% W5540% W7030% B55 B7020%10%0% 2.5 4 10 20 50
    39. 39. Radical Prostatectomy versus Observation for Localized Prostate CancerProstate Cancer Intervention versus Observation Trial (PIVOT).From November 1994 through January 2002, we randomly assigned 731men with localized prostate cancer (mean age, 67 years; median PSAvalue, 7.8 ng per milliliter) to radical prostatectomy or observation andfollowed them through January 2010.Patients had to be medically fit for radical prostatectomy and to havehistologically confirmed, clinically localized prostate cancer (stage T1-T2NxM0) of any grade diagnosed within the previous 12 months.Patients also had to have a PSA value of less than 50 ng per milliliter, anage of 75 years or less, negative results on a bone scan for metastaticdisease, and a life expectancy of at least 10 years from the time ofrandomization. NEJM 2012; 367:203
    40. 40. Death from Any Cause During the median follow- up of 10.0 years, 47.0% assigned to radical prostatectomy died, as compared with 49.9% assigned to observation absolute risk reduction, 2.9 percentage points). Among men assigned toDeath from Prostate Cancer radical prostatectomy, 5.8% died from prostate cancer or treatment, as compared with 8.4% assigned to observation absolute risk reduction, 2.6 percentage points NEJM 2012; 367:203
    41. 41. NEJM 2012; 367:203
    42. 42. Incidence of death from prostate cancer in a randomized trial thatcompared radical prostatectomy with watchful waiting.Only the young men (< 65 years) did poorly without activetreatment Death from Prostate Cancer
    43. 43. Patient Reported Dysfunction at 2 YearsDysfunction Surgery ObservationUrinary 17.1% 6.3%IncontinenceErectile 81.1% 44.1%DysfunctionBowel 12.2% 11.3%Dysfunction NEJM 2012; 367:203
    44. 44. Treating prostate cancer Surgery? Radiation?Or Watchful Waiting?
    45. 45. Prostate Cancer Treatment120 in 2008 from NCDB100 80 Surgery 60 Radiation Watchful Waiting 40 20 0 18-64 65-74 75-85
    46. 46. Choices with Prostate Cancer1. Depending on the man’s life expectancy and the nature of the specific cancer (Gleason score) is treatment necessary?2. If treatment is appropriate how to choose between surgery or radiation?
    47. 47. Watchful Waiting or Active Surveillance NCCN appropriate for: 1. Very low risk cancers and life expectancy < 20 y 2. Low Risk and life expectancy < 10 y
    48. 48. Very Low Recurrence Risk1. Stage T1c2. Gleason 6 or lower3. Less than 3 cores positive and none over 50%4. PSA density < 0.15 (so PSA was 5 and volume 35g then density would be 0.14 or 5/35)
    49. 49. Low Recurrence Risk 1. Stage T1 – T2a 2. Gleason 6 or lower 3. PSA < 10
    50. 50. Median Life Expectancy in Men by Health (poor, average or excellent)
    51. 51. Life Tables for Men in the US (2007 data) Age Expectancy 50 29 55 25 60 21 65 17 70 14 75 11 80 7.9 85 5.7
    52. 52. Watchful Waiting? Mortality if UntreatedGleason Score Death by 15 Years 2–4 4 – 7% 5 6 – 11% 6 18 – 30% 7 42 – 70% 8 – 10 60 – 87%
    53. 53. Mortality with No Active Therapy
    54. 54. Watchful Waiting, the odds that untreated prostatecancer would cause death related to the age and the GleasonScore
    55. 55. Active Surveillance• Limited to men with low risk cancer and shorter life expectancy• PSA every 3 to 6 months• DRE every 6 to12 months• Repeat biopsy may be considered every 12 months up to the age of 75• Repeat biopsy if increased PSA or PSA velocity Considered Disease Progression and Reason to Initiate Therapy • If Gleason Grade 4 or 5 is found on repeat biopsy • If prostate volume increase (number of + biopsies or the extent of the cancer)
    56. 56. Partin Tables: calculate the risk that thecancer is already outside the capsuleprior to therapy
    57. 57. Laparoscopic Prostate Surgery The surgeon tries to dissect the prostate away from the rectum, bladde r, the neurovascular bundle (nerves) and penile urethra
    58. 58. Radiation Fields with Prostate CancerA Low Dose Large Area (Phase 1) With radiation it is possible to include a wider area around the prostate to cover any cells that may have escaped After the highest safe dose is reached, the radiation target will be made smaller
    59. 59. Radiation Fields with Prostate CancerA High Dose Large Area (Phase 2) The final, high dose radiation target will be focused very precisely only on the prostate gland
    60. 60. NCCN.org
    61. 61. Prostate Cancer Risk Groups combine all 3 things, thestage, the PSA level and the Gleason score•Low risk: (T1c, T2a Gleason 6, PSA <10)•Intermediate risk: (T2b, T2c, Gleason 7, PSA 10-20)•High risk: (T3, Gleason 8-10 or PSA > 20)
    62. 62. Cure Rates with Radiation versus Surgery forEarly Stage Prostate Cancer are the same from the Cleveland Clinic. Kupelian. JCO Aug 15 2002: 3376-3385
    63. 63. 10 Year Cure Rates for Patients with High Risk Prostate Cancer (PSA >20 or Gleason 8-10 or T3)Treatment Number Cure RateRadical Prostatectomy 1,238 92%Radiation/Hormones 344 92%Radiation 265 88% Mayo Clinic Study (Cancer Jan 10, 2011)
    64. 64. Long-Term Functional Outcomes after Treatment for Localized Prostate Cancer The Prostate Cancer Outcomes Study (PCOS), comprised 1655 men in whom localized prostate cancer had been diagnosed between the ages of 55 and 74 years and who had undergone either surgery (1164 men) or radiotherapy (491 men). Functional status was assessed at baseline and at 2, 5, and 15 years after diagnosis• Urinary Incontinence: worse with surgery at 2 and 5 years but the same by 15 years• Erectile Dysfunction: worse with surgery at 2 and 5 years but the same by 15 years• Bowel Urgency: worse with radiation at 2 and 5 years but by 15 years the same N Engl J Med 2013; 368:436-445
    65. 65. Sexual Function afterRadiotherapy orSurgery N Engl J Med 2013; 368:436-445
    66. 66. Quality of Life / Medicare Survey Prostate Cancer PatientsSymptom Surgery RadiationWear Pads 30% 7%Potent (< 70y) 11% 33%Potent (>70y) 12% 27%More frequent bowel 3% 10%movements J Clin Oncol 14 (8): 2258-65, 1996
    67. 67. Potency Rates after Prostate Cancer TreatmentTreatment Probability RangeSeeds 80% 64 – 96%Seeds + External 69% 51 – 86%External 68% 51 – 95%Radical Prostatectomy Nerve Sparing 22% 0 – 53% Standard 16% 0 – 37%Cryotherapy 11% 0 - 53% IJROBP 2002:54:1063
    68. 68. Potency Rates after Surgery can range from 2% to70%) Did they have a ‘nerve sparing’ prostatectomy? Hold old is the man? How high was the PSA? How good was their sexual function before? JAMA. 2011;306(11):1205-1214
    69. 69. Potency Results after ExternalRadiation can range from 16% to 92% Did they get hormone therapy along with the radiation? How high was the PSA prior to radiation? How good was their sexual function before?
    70. 70. Responded to ViagraSurgery: 43%Radiation: 70 – 91%General Population: 80% from other studies in the literature
    71. 71. Choosing Treatment Prostate Cancer Urologist with experience and a good outcome with the procedureExperienced RadiationOncologist withModern Technology(IGIMRT) and goodoutcome data
    72. 72. The experience of the surgeon is a criticalfactor associated with a successful outcomeOpen prostatectomy the learning curve did notplateau until a surgeon had performed at least250 retropubic radical prostatectomies Theprobability of biochemical recurrence at fiveyears was significantly lower (10.7 versus 17.9percent)
    73. 73. Minimally invasive prostatectomy – In aseries of 4,702 men who were managed withlaparoscopic prostatectomy by one of 29surgeons at seven centers,the five-year risk of recurrence progressivelydecreased with increasing experience (17, 16,and 9 percent with 10, 250, and 750 priorlaparoscopic procedures)
    74. 74. Evolving RadiationTechnology
    75. 75. Using the proper dose of radiation “It may be a bit over-exposed”
    76. 76. Prostate Cures Rates by Treatment,The Radiation Dose is Critical External beam > 72Gy Surgery or Seeds External beam < 72Gy IJROBP 2004; 58:25 Months
    77. 77. Cure Rate (PSA cure) in 2991 Men By Therapy Best results with high dose external
    78. 78. Prostate Cancer Relapse Rate by Radiation Dose < 72Gy 72 - 82Gy 82Gy Years Kupelian. IJROBP 2008:71:16
    79. 79. Goal = radiation zone precisely around the prostate cancer with small margin bladder prostateRadiation zone rectum
    80. 80. IMRT (intensitymodulatedradiation therapy) using 7 different beamsto target the prostateThe computer candetermine the optimalnumber of beams todeliver the radiationdose to hit the target andavoid other structures
    81. 81. After IMRT was established then IGRT(image guided) was introduced
    82. 82. Lower Risk of Side Effects with ImageGuided IMRT compared to IMRT
    83. 83. Better Cure Rates with Image Guided IMRT compared to IMRT for Prostate Intermediate Risk High Risk
    84. 84. The most sophisticated technique for image guided IMRT is Tomotherapy.Combine a CT scan and linear accelerator to ultimate intargeting (IGRT) and ultimate in delivery (dynamic, helicalIMRT) ability to daily adjust the beam (ART or adaptiveradiotherapy)
    85. 85. There is significant movement of the prostate gland based on daily gas in rectum Planned target No Rectal gasPlanned target,missed badly ifrectal gas pushesthe prostate Rectal gasforward
    86. 86. Cyberknife Radiosurgery
    87. 87. Non Isocentric Delivery with CK Beams
    88. 88. SBRT Prostate Cancer / Naples-Tampa Experience Feb 2005 – Apr 2008 (Naples, FL) • 164 monotherapy, 35 Gy • 168 monotherapy, 36.25 Gy • 59 EBRT + CK boost Jul 2008 – Dec 2011 (Tampa, FL) • 121 monotherapy, 36.25 Gy • 10 monotherapy, 38 GY • 12 EBRT + CK boost
    89. 89. PSA Response to CyberKnife Mean PSAi 6.8ng/ml Mean PSAp 0.78ng/ml97% biochemical control at 30 months median follow-up
    90. 90. Cure Rate after Cyberknife N = 515, Alan Katz in New York
    91. 91. PSA Response after Cyberknife Follow-up median 54 months (range, 7 - 78) Median PSA 7 35 Gy ◦ 36 m 0.20 ng/ml 6 36.25 Gy 5 ◦ 60 m 0.10 ng/ml PSA ng/ml 4 By 48 months 3 ◦ 290 of 329 pts 2 1 PSA < 0.5 0 0 12 24 36 48 60 72 Months
    92. 92. New MedicalTreatmentsfor Prostate Cancer
    93. 93. Clinical development of novel therapeuticsfor castration‐resistant prostate cancer
    94. 94. New Drugs for Prostate Cancer
    95. 95. New Drugs for Advanced Prostate CancerDrug FDA Approval CostProvenge (sipuleucal) immunoRx 4/2010 $93,000Jevtana(cabazitaxel) chemoRx 6/2010 $8.000 q3wXgeva (denosumab) skeletal 11/201$1,600 doseZytiga (abiraterone) hormone Lupron (1985) LHRH agonist 4/2011 $5,000/mos Bicalutamide (Casodex, 1995) anti-androgenXtandi (enzalutamide) hormone 8/2012 Degarelix/ Firmagon(2008) GnRH antagonist $7,450/mos Abiraterone androgen synthesis inhibitor Enzalutamide androgen receptor blocker
    96. 96. Expose the patient’s activated T cells to cancer antigen targetsThen re-infuse thepatient’s activated cells(atc’s) back into themwhich will attack prostatecancer cells
    97. 97. FDA Approval 4.29.10median OS of 25.8 months compared to 21.7months for patients who received the controltreatment There was no difference in time-to-progression.The total cost for three courses of treatmentwith Sipuleucel-T is $93,297.60
    98. 98. Phase 3 TROPIC clinical study involving 755 patients with mHRPC previously treated with a docetaxel-containingMedian overall survival in the patients receiving JEVANA + prednisone was 15.1 months compared to 12.7 monthstumor response rates were 14.4% and 4.4% for cabazitaxel-treated and mitoxantrone-treated patients respectively, FDA Approval 6.18.10
    99. 99. Xgeva the first and only RANK Ligand inhibitor toprevent SRE (skeletal related events in cancer)FDA Approval 11.19.10
    100. 100. Xgeva RANK Ligand inhibitor
    101. 101. Recent advances have demonstrated thatandrogen-based pathways continue to have aclinically significant role in the progression ofcastrate-resistant prostate cancer. In addition to androgen production by theadrenal gland and testis, several of the enzymesinvolved in the synthesis of testosterone anddihydrotestosterone, including CYP17, are highlyexpressed in tumor tissue
    102. 102. ZYTIGA is an oral androgen biosynthesis inhibitor that works by inhibiting the CYP17 enzyme complex, which is required for the production of androgens at these three sources.FDA Approval 4.28.11
    103. 103. Zytiga and prednisone combination had a median overall survival of 14.8 months compared to 10.9 months for patients receiving the placebo and prednisone combination.
    104. 104. August 2012In clinical trials, men who received the drug, which waspreviously known as MDV3100, lived a median of 18.4months, nearly five months longer than the median of13.6 months for those who received a placebo. Before2004, the only drug shown to prolong the survival of menwith advanced prostate cancer wasthe chemotherapy drug docetaxel. Now there are fourothers on the market — Jevtana, Provenge, Zytiga and
    105. 105. Enzalutamide (marketed as Xtandi and formerly known as MDV3100) is asecond generation androgen receptor antagonist drug for the treatment ofmetastatic castration-resistant prostate cancer.Enzalutamide has approximately fivefold higher binding affinity for theandrogen receptor (AR) compared to the antiandrogen bicalutamide(Casodex)
    106. 106. www.aboutcancer.com Cancer Information Cancer Videos Tomotherapy Cyberknife Other Topics Dr. Miller
    107. 107. www.aboutcancer.comCancer Information •Basic Cancer Information •General Cancer Statistics •Most Common Cancers * brain * breast * colon/rectum * gynecologic * lung * prostate •Other Specific Cancers Radiation or Chemotherapy •All Other Cancer Topics •Other Topics •Best Web Sites
    108. 108. Robert Miller MD Medical Channelbone metastasesbrain metastasesbreast cancer: understanding the disease, treatment decisionshead and neck cancer (mouth, throat, larynx understanding the disease, radiation treatmentlung cancer: understanding lung cancer, radiation treatmentsprostate cancer: understanding the disease, treatmentdecisions, radiation therapyskin canceruterine (endometrial cancer) aboutcancer.com/you_tube_videos
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