By: Dr. Richard F. Sanchez-Ortiz

1. Localized Prostate Cancer in
Puerto Rico
Ricardo F. Sánchez-Ortiz, MD
Assistant Professor of Urology
University of Puerto Rico School of Medicine
Adjunct Assistant Professor of Urology
The University of Texas M. D. Anderson Cancer Center
Partnership in Cancer Research

2. Disclosures
• Intuitive Surgical
– Robotic surgery proctor
– Robotic surgery course faculty
• No stock ownership

4. Early Detection
• Who should be screened?
• Who should be biopsied?
–At what PSA?
• How should we biopsy?

6. PLCO trial. NEJM 2009
• 76,693 men
• Screening vs. no screening
– Ages 55 to 75 yrs.
• Followed with PSA for 6 yrs
• No difference in survival
• Problem:
– Screening vs. “partial
screening”

7. PLCO: 80% of Control Group Participants
had at least 1 PSA during the trial
Shoag et al. NEJM 2016

8. European Randomized Study for Screening
for Prostate Cancer (ERSPC)
• 182,160 men
• Screening versus
no screening
– Ages 55 to 69
• F/U: 16 years
• 21% lower mortality
– 29% after adjusting
non-compliance
Shroder et al, N Engl J Med. 2012

9. Goteborg Trial
• 20,000 men
• Randomized 1:1
– PSA Screening vs. no
screening every 2 yrs
• Ages 50 to 69 yrs
• Risk reduction of
prostate cancer death
by almost 50%
Hugosson et al, Lancet Oncol, 2010

10. AUA guidelines 2013
• Every two years between 55 and 70
• Except African American or first degree
family history

11. What is a “normal” PSA?

12. Normal
3.67 ng/ml 0.00 – 4.00 ng/ml
Juan del Pueblo

14. NCCN: biopsy if > 3 ng/ml

15. PSA Between Median and 2.5 ng/ml
Age range Median Prostate cancer risk
40 – 49 0.7 ng/ml 14.6-fold
50 – 59 0.9 ng/ml 7.6-fold
• Higher Gleason scores
• Higher rate of biochemical progression
Urology: 67(2): 316-20, 2006

16. Prostate Cancer Gene 3
PCA3
• Gene that expresses non-
coding RNA in human prostate
tissue
• Highly over-expressed in PCa
• Post-DRE first voided urine
specimen
• Lower sensitivity, higher
specificity than PSA

17. Prostate Health Index (phi)
• NCCN
• Combination of:
– Free PSA
– Total PSA
– p2PSA

18. PHI Performance Characteristics
X3 more specific
than serum PSA
-may help with
active surveillance
-more likely to
predict higher
grade tumors

20. • NCCN
• Four Kallikreins
– Total PSA
– Free PSA
– Intact PSA
– Human Kallikrein 2
(hk2)

21. Prostate biopsy
• Transrectal ultrasound
• Local anesthesia or
sedation
• NCCN guidelines
– 12 or more cores
– Now standard of care

22. Multiparametric MRI
• MRI-Ultrasound fusion
• Visual estimation

23. Multiparametric Prostate MRI
• PIRADS 1
• PIRADS 2
• PIRADS 3
• PIRADS 4
• PIRADS 5

24. Diffusion
Axial

26. Diffusion
Axial

27. MRI-guided biopsy with Visual Estimation
Overall Detection Rate
71.8%
56.3% 50.0%
6.2%
9.4%
25.0%
37.5% 40.6%
0.0%
10.0%
20.0%
30.0%
40.0%
50.0%
60.0%
70.0%
80.0%
90.0%
100.0%
Standard 12- core only MRI guided nodule
biopsy only
Standard 12-core and
MR guided nodule biopsy
Negative ASAP or HGPIN Positive
n=80

28. MRI-guided biopsy with Visual Estimation
Detection rate by Gleason Score
46.8%
56.3% 50.0%
6.2%
9.4%
15.6%
9.4%
9.4%
31.2% 31.2%
0.0%
10.0%
20.0%
30.0%
40.0%
50.0%
60.0%
70.0%
80.0%
90.0%
100.0%
Standard 12- core only MRI guided nodule
biopsy only
Standard 12-core and
MR guided nodule biopsy
Negative ASAP or HGPIN
Grade group 1 (gleason 6) Grade group 2 or higher
6.3%
n=80

29. ISUP/WHO New Grading
System
• Grade 1: Gleason score 6 (3+3)
• Grade 2: Gleason score 7 (3+4)
• Grade 3: Gleason score 7 (4+3)
• Grade 4: Gleason score 8
• Grade 5: Gleason score 9 - 10.

30. Increase in PCa Aggressiveness
• Patients divided into three groups to compare
clinical and pathological variables over time
• SPSS was used for statistical analysis
A
2007-2009
B
2010-2012
C
2013-2015
119 323 277

31. PSA and Clinical Stage over Time
5.2
5.9
6.57
0
1
2
3
4
5
6
7
8
9
10
2007-20092010-20122013-2015
serum PSA (ng/dL)
16.0%
26.6%
36.5%
0.0%
5.0%
10.0%
15.0%
20.0%
25.0%
30.0%
35.0%
40.0%
Clinical Stage > T1c (%)
P<0.05 P<0.0001
N=791

32. Gleason Score over Time
37.0%
37.0%
65.7%
12.6% 13.0%
20.2%
0.0%
10.0%
20.0%
30.0%
40.0%
50.0%
60.0%
70.0%
80.0%
90.0%
100.0%
2007-2009 2010-2012 2013-2015
GS ≥7 on Biopsy
Primary Gleason Grade 4 on Biopsy
N=791
P<0.05

33. Cancer Volume on Biopsy over Time
5.2
8.4
9.6
3.6 4
4.9
0
2
4
6
8
10
12
14
2007-2009 2010-2012 2013-2015
Total Sum of Cancer Cores per Lobe (mm)
Largest Positive Tumor Core per Lobe (mm)
N=791
P<0.01
P<0.01

34. Use of Robotic RP over Time
51.3%
93.2%
100.0%
0.0%
20.0%
40.0%
60.0%
80.0%
100.0%
2007-2009 2010-2012 2013-2015
N=791P<0.001
A
2007-2009
B
2010-2012
C
2013-2015
119 323 277

35. Prostate Cancer Mortality in PR
Puerto Rico
2006 – 2010
27.3 per 100,000

36. Average African
Ancestry: 20.2%

37. High BMI increases Risk of High Risk
CaP on Biopsy
• Liang et al, J Urol 2014
– CCF
• 3,258 SELECT trial participants
– 29.3% obese
• Without FHx: obesity ñrisk of Gleason ≥ 7 (OR 2.31)
• With FHx: obesity ñ overall risk (3.73) and ñrisk of
Gleason ≥7 (7.95)

38. BMI Cohort Characteristics
Puerto Rican Prostate Cancer
35.4%
(20% higher than SELECT trial)

39. Risk of Gleason Score ≥ 7 or
Extraprostatic Disease
*p < 0.05
N=791

40. Biopsy is positive…Now what?
Staging studies rarely needed

41. Staging
• Bone scan
– PSA > 20
– Abnormal DRE
and PSA > 10
– Gleason score >7
– T3/T4
– Symptoms
• MRI
– T3, T4
– LN involvement
probability > 10%
CT scan for local staging not as useful

42. Organ-confined Prostate Cancer
• Active surveillance/watchful waiting
• Surgery
– Open
– Robotic
– Cryoablation
• Radiation therapy
– External beam
– Radioactive Seeds

43. Scandinavian Prostatic Cancer
Group Randomized Trial
• 695 men
– watchful waiting or radical prostatectomy
• After 8 years:
–50% ↓ cancer-specific mortality
• 7% versus 14%
–50% ↓ distant metastasis
• 13% versus 27%
Holmberg N Engl J Med. 2002

44. < 65 y/o observation

45. PIVOT trial
• VA Hospital study. NEJM 2012
– 700 pts. 10 year follow-up
• Surgery vs. Observation
• Surgery only benefitted:
– Gleason 7 or PSA > 10
• Conclusions:
– Men > 60 with low grade, PSA < 10 should
be observed

46. PIVOT trial
• Problems:
• Elderly, infirmed cohort: mean age 67
yrs
• 40% were dead at 10 years of all
causes
• Only 10% below age 60 yrs.

47. Organ-confined Prostate Cancer
• Active surveillance/watchful waiting
• Surgery
– Open
– Robotic
– Cryoablation
• Radiation therapy
– External beam
– Radioactive Seeds

48. Low risk
prostate cancer
Less than 65
Surgical
candidate?
No
Not surgical
candidate or not
accepting risks
Brachytherapy
or EBRT
Cryoablation
Active
surveillance
Yes Surgery
65 or older
Active
surveillance (1st
choice)
Others
Surgery (not
willing to accept
risks)
Radiation
Brachytherapy
External
Radiation
Cryoablation

49. Ideal Candidate
• Age > 65
• ≤ 2 positive cores
• Gleason 6 only
• Less than 50% core
length involved
• Normal volume-adjusted
PSA
• PSA velocity before
diagnosis < 2 ng/ml/yr
• No perineural invasion
• Free PSA > 15%
• NORMAL mMRI
• Low genomic score

51. Low risk
prostate cancer
Less than 65
Surgical
candidate?
No
Not surgical
candidate or not
accepting risks
Active
surveillance
Brachytherapy
or EBRT
CryoablationYes Surgery
65 or older
Active
surveillance (1st
choice)
Others
Surgery (not
willing to accept
risks)
Radiation
Brachytherapy
External
Radiation
Cryoablation

52. Intermediate to
High risk prostate
cancer
Less than 70
Surgical
candidate?
No
Not surgical
candidate or not
accepting risks
External radiation
and Androgen
Deprivation
Yes Surgery
70 to 80 yrs
Life expectancy >
10 years?
Yes
External radiation
and Androgen
Deprivation
UC, Crohn’s, prior
RT
Surgery or
Cryoablation
No Watchful waiting
> 80 years Watchful waiting

53. Intermediate to
High risk prostate
cancer
Less than 70
Surgical
candidate?
No
Not surgical
candidate or not
accepting risks
External radiation
and Androgen
Deprivation
Yes Surgery
70 to 80 yrs
Life expectancy >
10 years?
Yes
External radiation
and Androgen
Deprivation
UC, Crohn’s, prior
RT
Surgery or
Cryoablation
No Watchful waiting
> 80 years Watchful waiting

54. Organ-confined Prostate Cancer
• Active surveillance/watchful waiting
• Surgery
– Open
– Laparoscopic/Robotic
– Cryoablation
• Radiation therapy
– IGRT
– Proton therapy
– Brachytherapy

56. Open
(n=154)
Robotic
(n= 930)
P value
Days with catheter Median 11.7
(8 to 21)
Median 8.1
(5 to 15)
0.0001
OR time 176 min
Median: 175
167 min
Median: 170
no difference
Blood loss 566
(150 to 1300)
143
(20 – 700)
< 0.0001
Blood transfusions 2.5%
(4 pt)
0.004%
(4 pt)
<0.0001
Open Conversion 2/930

57. Early Complications
• Rectal injury
– Robotic: 0/930
– Open: 2/154
• Ileus:
– Robotic: 2.7% (25/930)
– Open: 3.2% (5/154)
• P = 0.09.
• Prolonged urine leak:
– Robotic: 0.8% (8/930)
– Open: 2.6% (4/154)
• DVT
– Robotic: 0.004% (4/930)
– Open: 1.2% (2/154)
• Stroke
– 1 robotic

58. Late Complications
0
2
4
6
8
10
12
14
16
18
20
4 3.9%
Robotic
Open
• Hernia
– Robotic: 2.7% (25/930)
– Open: 0.06% (1/154)
• P= 0.06
• Robotic
– Orchitis
• Bladder neck
contracture/Stricture
– Robotic: 1.2% (11/930)
– Open: 7.7% (12/154)
• P = 0.0001
p = 0.54
N =306 N =154

59. Positive surgical margins
0
5
10
15
20
25
9.0 6.8
p = 0.13
National average ~ 15.7%
Patel et al. J Urol, 186(2):511-6, 2011

60. Urinary Continence
Free of pads
> 12 months follow-up
89.1% 92.1%
0
10
20
30
40
50
60
70
80
90
100
Open Robotic
*p = 0.04107/120N= 69/72

62. Posterior Reconstruction

63. Posterior Reconstruction

64. Double Layer Anterior Anastomosis

65. Double Layer Anterior Anastomosis

66. Incontinence by BMI
N= 300

67. Incontinence vs. Age
N= 300

68. Incontinence vs. Diabetes
N=45N=255

69. Bilateral Nerve Sparing
Having Intercourse with or without PDE5I
(If fully potent preoperatively)
*p = 0.51
N= 75 N= 101
Median f/u 35 mo 10 mo

70. Risk of ED after 1 year
Multivariate Analysis
P<0.001
OR: 3.30
95% CI: 1.54 to 7.11
P<0.001
OR: 5.02 (if ≥60g)
95% CI 1.88 to 13.4
P<0.02
OR: 3.34
95% CI: 1.25 to 8.89

71. Adjuvant vs. Salvage Radiation
• Criteria: T3a/T3b or +SM, N0
• EORTC 22911 trial
– 1005 patients. 5 year median follow-up
– 60 Gy
• SWOG 8764 trial, 2009
– 473 men T3 disease. 10 year median follow-up
– 60 to 64 Gy

72. SWOG 8764
Salvage vs. Adjuvant Radiation
Radiation No radiation
Risk of recurrence 35% 65%
Risk of metastasis
at 10 years
8% 17%

73. EORTC 22911
– 5-yr PSA-free survival
• 74% versus 52%
– Grade 3 -4 toxicity
• 4.2% vs. 2.6% at 5 years

74. SWOG 8764’
Salvage vs. Adjuvant Radiation
Improved metastasis-free and overall survival
Thompson et al, J Urol March 2009
Metastasis-free survival Overall survival

75. Radiation therapy
Secondary Malignancies
• Overall risk: 1/290
• After 10 years:
– Risk: 1/70

76. customersupport@genomedx.com | www.genomedx.com
Patient Details
Patient Name: Pedro Saade Llorens
Medical Record Number: not provided
Date of Birth: 06/12/1945
Date of Prostatectomy: 01/23/2016
Pathology Laboratory: San Pablo PathologyGroup
Pathologist: Juan Serrano-Olmo, MD, FCAP
Address: 68 CII Santa Cruz Torre San
Pablo Suite 403-404, Bayamon,
PR 00957, USA
Order Information
Order Date: 10/03/2016
Specimen Received Date: 11/04/2016
GenomeDx Accession ID: MC-014608
Specimen ID: 16SP824-B
Ordering Physician: Sanchez Ortiz, Ricardo F
Clinic/Hospital Name: Robotic Urology& Oncology
Institute
Clinic/Hospital Address: 400 FD Roosevelt Suite 306, San
Juan, PR 00918-0000, USA
Clinical Details: Preoperative PSA (ng/mL): N/A Gleason Score: 4+3
SM+ EPE SVI LNI BCR Tertiary Gleason 5
Other: Lymphovascular Invasion
9.4%
8.0%
Your Decipher Result - Genomic High Risk
Decipher Score 0.60
Risk - Percent Likelihood
5-Year Metastasis
10-Year Prostate Cancer Specific Mortality
Interpretation
Clinical studies concluded that Decipher high risk men with adverse pathology have a
poor prognosis overall. These men may benefit from adjuvant or early salvage
radiotherapy and consideration for clinical trials.
Relevant findings from published clinical studies: Patients with Decipher high risk had
77% 5-year metastasis free survival and 70% 10-year cause specific survival. For
these patients there was improved metastasis-free survival favoring adjuvant and early
salvage postoperative radiotherapy.
In patients with PSA rise or biochemical recurrence after surgery that received salvage
radiotherapy, only 66.5% remained metastasis free after 5 years.
Decipher Post-Operative Report
*Average clinical risk refers to the average cohort risk of metastasis at 5 years post radical prostatectomy. The average cumulative incidence of metastasis was 6.0%at 5 years post radicalprostatectomy, as
reported by Karnes et al., 2013 from analysis of a cohort of 1,010 men with intermediate and high risk clinical features who received radical prostatectomy as first line treatment at the Mayo Clinic between 2000
and 2006.
Five-year probability of metastasis endpoint: Decipher uses the genomic risk score to predict the 5-year probability of metastasis from the time of radical prostatectomy. Probabilities were generated from a
Cox proportional hazards model based upon a cohort of 1,010 men with intermediate and high risk clinical features with a median 6.9 years of followup. Decipher had an AUC of 0.76-0.85 in multiple clinical
validation studies for prediction of metastasis. Percent likelihood for this endpoint ranges from 0.3-67%.
Ten-year probability of prostate cancer specific mortality (PCSM) endpoint: Decipher uses the genomic risk score to predict the 10-year probability of PCSMfrom the time of radical prostatectomy.
Probabilities are generated from a logistic regression analysis based upon a cohort of 557 patients with 112 prostate cancer deaths within 10 years post radical prostatectomy. These probabilities are adjusted for
a PCSMcumulative incidence of 5%at 10 years post radical prostatectomy. All non-PCSMpatients in the study had at least 10 years of follow-up. Decipher had an AUC of 0.72 in predicting PCSM. Percent
likelihood for this endpoint ranges from 0.7-30.5%.
POST OP
DecipherScore
1.00
High
Risk
0.60
Avg.*
Risk
0.45
Low
Risk
0.00
1-3
4-6
1,2
4-6
4
References on reverse
1
1
1-8
9 2,7,8
Your
Decipher
Score
GenomeDx Biosciences Laboratory
10355 Science Center Dr. Suite 240, San Diego, CA92121
Tel: 1-888-792-1601 | Fax: 1-855-324-2768
customersupport@genomedx.com | www.genomedx.com
Patient Details
Patient Name: Pedro Saade Llorens
Medical Record Number: not provided
Date of Birth: 06/12/1945
Date of Prostatectomy: 01/23/2016
Pathology Laboratory: San Pablo PathologyGroup
Pathologist: Juan Serrano-Olmo, MD, FCAP
Address: 68 CII Santa Cruz Torre San
Pablo Suite 403-404, Bayamon,
PR 00957, USA
Order Information
Order Date: 10/03/2016
Specimen Received Date: 11/04/2016
GenomeDx Accession ID: MC-014608
Specimen ID: 16SP824-B
Ordering Physician: Sanchez Ortiz, Ricardo F
Clinic/Hospital Name: Robotic Urology& Oncology
Institute
Clinic/Hospital Address: 400 FD Roosevelt Suite 306, San
Juan, PR 00918-0000, USA
Clinical Details: Preoperative PSA (ng/mL): N/A Gleason Score: 4+3
SM+ EPE SVI LNI BCR Tertiary Gleason 5
Other: Lymphovascular Invasion
9.4%
8.0%
Your Decipher Result - Genomic High Risk
Decipher Score 0.60
Risk - Percent Likelihood
5-Year Metastasis
10-Year Prostate Cancer Specific Mortality
Interpretation
Clinical studies concluded that Decipher high risk men with adverse pathology have a
poor prognosis overall. These men may benefit from adjuvant or early salvage
radiotherapy and consideration for clinical trials.
Relevant findings from published clinical studies: Patients with Decipher high risk had
77% 5-year metastasis free survival and 70% 10-year cause specific survival. For
these patients there was improved metastasis-free survival favoring adjuvant and early
salvage postoperative radiotherapy.
Decipher Post-Operative Report
POST OP
DecipherScore
1.00
High
Risk
0.60
Avg.*
Risk
0.45
Low
Risk
1-3
4-6
1,2
4-6
Your
Decipher
Score
DocuSign Envelope ID: BC1F6A69-5EFD-4C0D-822E-0779A9BCF451

77. Organ-confined Prostate Cancer
• Active surveillance/watchful waiting
• Surgery
– Open
– Laparoscopic/Robotic
– Cryoablation
• Radiation therapy
– IGRT
– Proton therapy
– Brachytherapy

78. Brachytherapy

79. Brachytherapy
• Gleason 6, PSA <10, T1c
• Less than 50% of cores positive
• No perineural invasion
• PSA before diagnosis < 2 ng/ml/yr.
• Feasibility:
– Volume < 70 cc , > 25 cc
– No voiding symptoms
– No previous TURP

80. External Beam Radiotherapy
IMRT - IGRT
75.6 Gy
conform to PTV
c Effect of Organ
ariability
Original Plan on New CT

81. Fiducial Markers
• Electromagnetic
transponders
• 4D localization system
• Motion shifts
continuously monitored
• No extra radiation used
Calypso ©

82. Case: C.R.
• 53 y/o
• PSA: 3.5 ng/ml
• DRE: Bilateral SV
and R extraprostatic
(T3a, T3b)
• Prostate: 50 grams
• Patient weight: 310
pounds
IMRT plus androgen deprivation

83. Randomized Trial
RT vs. RT+ADT
D’Amico. JAMA 2008

84. Clínica Las Américas Suite 306, Hato Rey
787-756-5200