This document discusses factors to consider when determining treatment for prostate cancer, including the biology and extent of the cancer, patient health status and life expectancy. It outlines prostate cancer risk groups based on staging and tumor characteristics, and how newer genomic testing can better classify risk. Combining clinical and genomic data separates risk groups and more accurately predicts outcomes like metastasis and mortality risks over 10 years. Genomics may reclassify some patients originally in intermediate risk groups to lower or higher risk, influencing treatment decisions.

1. *
www.aboutcancer.com Robert Miller MD

2. Are we over-treating or under-treating men with prostate cancer?
How do you balance the aggressiveness of the cancer versus the patient’s
age and other medical problems?

3. Things that might effect the decision to
treat
• Biology and extent of the cancer (how
aggressive and how advanced)
• Health status of the patient (general
state of health, other disease
problems, life expectancy, personal
goals)

4. Biology: The more mutated the cancer cells the lower the cure rate
88% if well differentiated cells
70% if moderate differentiated cells
50% if poorly differentiated cells

5. Risk Stratification and Staging
By 2018
there are
at least 8
risk groups

6. Stages of Prostate Cancer

7. Tumor (T, N, M) Stage

9. Stage groups now
include the degree of
spread but also the
level of the tumor
marker (PSA) and the
degree of cancer cell
mutation (Gleason)

10. Gleason Scoring System
From the biopsy, the pathologist grades
the appearance of the cells. From least serious
(slow growing or Grade 1 to the fastest
growing and most dangerous or grade 5). The
first number is the most common pattern seen
and the second number the next most common.
So a 4+3 is more serious than 3+4 even though
they both are Gleason 7.
So the slowest is a score of 2 and the fastest is
a 10.

11. Gleason Scoring
System and
Graded Group

12. The higher the PSA the lower the Cure
Rate

13. The higher the PSA the lower the Cure
Rate
PSA Level
Relapsed after
Radiation
0.1 to 4 4%
4 to 10 7%
10 to 20 22%
20 - 50 48%
over 50 67%

14. Average Life Expectancy for a
Man in the US 2015 Data
Current Age Average Years Left
50 – 54 30.2
55 – 59 26
60 – 64 22.1
65 – 69 18.3
70 – 74 14.8
75 – 79 11.6
80 – 84 8.7
85 + 6.2
WHO Data apps.who.int/gho/data/view.main.61780?lang=en
Life expectancy can be
adjusted using the physician’s
assessment of over all health
Top quartile : add 50%
Lowest quartile: subtract 50%

15. Social Security Data
ssa.gov/OACT/STATS/table4
c6.html
Age Life Expectancy Age Life
Expectancy
Life expectancy can be
adjusted using the physician’s
assessment of over all health
Top quartile : add 50%
Lowest quartile: subtract 50%

16. Life Expectancy for Men By QuartilesYears
Age

17. Median survival (half will liver
shorter and half will live longer)

18. Treatment Recommendations
O (Observation)
AS (Active Surveillance)
Radiation (EBRT external beam or Brachytherapy
seeds)
RP (radical prostatectomy, i.e. surgery)

19. Definition of Non Treatment from the NCCN
Observation: monitor until symptoms develop or are imminent (ie. PSA
> 10) and then start palliative hormone therapy
Active Surveillance: check every 6 months and if disease progression
consider curative treatment
Monitor: PSA every 6 to 12 months, DRE every 12 months, MRI-US fusion
may improve accuracy of biopsy
Consider repeat biopsy: if DRE progression, MRI more aggressive
disease, rising PSA
Used to be called ‘Watchful Waiting’

20. Selected Active Surveillance Experience
in North America
Center Toronto Hopkins UCSF UCSF
(newer)
Number 993 1298 321 810
Median Age 68 66 63 62
Median Follow Up 77 mos 60 mos 43 mos 60 mos
Overall Survival 80% (10y) 93% (10y) 98% (10y) 98% (5y)
Cancer Spec Surv 98% (10y) 99.9% (10y) 100% (5y)
Convert to Treat 36.5% (10y) 50% (10y) 24% (3y) 40% (5y)
NCCN 2018 Review

21. Selected Active Surveillance Experience
in North America
Center Toronto Hopkins UCSF UCSF
(newer)
Number 993 1298 321 810
Median Age 68 66 63 62
Median Follow Up 77 mos 60 mos 43 mos 60 mos
Overall Survival 80% (10y) 93% (10y) 98% (10y) 98% (5y)
Cancer Spec Sur 98% (10y) 99.9% (10y) 100% (5y)
Convert to Treat 36.5% (10y) 50% (10y) 24% (3y) 40% (5y)
NCCN 2018 Review

22. Selected Active Surveillance Experience
in North America
Center Toronto Hopkins UCSF UCSF
(newer)
Number 993 1298 321 810
Median Age 68 66 63 62
Median Follow Up 77 mos 60 mos 43 mos 60 mos
Overall Survival 80% (10y) 93% (10y) 98% (10y) 98% (5y)
Cancer Spec Sur 98% (10y) 99.9% (10y) 100% (5y)
Convert to Treat 36.5% (10y) 50% (10y) 24% (3y) 40% (5y)
NCCN 2018 Review

23. Risk Groups from the NCCN
Very Low
Stage T1c and
Gleason Group 1
PSA < 10
Volume less than 3 biopsy fragments
+ and < 50% cancer per fragment
PSA density < 0.15

24. Very Low Risk
Short Life Expectancy (less than 10 years, older than
76) then just observation
Younger (> 10 years life expectancy) then active
surveillance
Really young (20 years expectancy, 62 or younger) then
along with surveillance you can consider surgery or
radiation

25. Risk Groups from the NCCN
Low
Stage T1 – T2a and
Gleason Group 1 (volume higher)
PSA < 10
Consider genomic testing

26. Low Risk
Older (< 10 year life expectancy, over 76)
observation
Younger (10+ years , less than 76 )
consider active surveillance or surgery or
radiation

27. Risk Groups from the NCCN
Favorable Intermediate
Stage T2b – T2c or
Gleason Group 2
PSA < 10
Consider genomic testing

28. Favorable Intermediate Risk
Older (< 10 y, over 76) observation or
radiation
Younger (10+ y, less than 76) then active
surveillance or surgery or radiation

29. Risk Groups from the NCCN
Unfavorable Intermediate
Stage T2b – T2c or
Gleason Group 2 or 3 or
PSA 10 - 20

30. Unfavorable Intermediate Risk
Older (< 10 y, over 76) observation or
radiation + hormones (4-6 mos)
Younger (10+ y, less than 76) then active
surveillance or surgery or radiation +
hormones

31. Risk Groups from the NCCN
High
Stage T3a or
Gleason Group 4 or 5 or
PSA > 20

32. Risk Groups from the NCCN
Very High
Stage T3b – T4 or
Gleason Pattern 5 or
Volume > 4 cores with Gleason group 4 or 5

33. High Risk or Very High
Old (less than 5 years, or 87) then
observation
Younger (less than 87y) then surgery or
radiation + hormones (2 – 3 years)

34. In 2018 the NCCN Included Genomics in the
Decision Process

35. Risk Stratification and Staging

36. Genomic test evaluates the activity of genes in
the tumor that are shown to be involved in the
development and progression of prostate cancer.

37. Decipher Biopsy

40. The 46-gene expression signature includes
cell cycle progression genes selected
based upon correlation with prostate
tumor cell proliferation:
low gene expression associated with a low
risk of disease progression
high gene expression associated with
disease progression

41. Genomics Risk Score from Prolaris

44. Development and
Validation of a Novel
Integrated Clinical-
Genomic Risk Group
Classification for Localized
Prostate Cancer
New scoring system
that combined the
NNCN with Decipher
Score
Spratt Journal of Clinical
Oncology 36, no. 6, 2018

45. Which is more Predictive of Outcome, the
NCCN grouping or Genomics?
Group NCCN Decipher
low 7.3% 3.5%
intermediate 29.4%
favorable intermed. 9.2%
Unfavorable intermed. 38.0%
high 39.5% 54.6%
10 Year Metastatic Risk Probability
Spratt Journal of Clinical Oncology 36, no. 6 (February 2018)

46. Risk of Metastases using Combined
System
Spratt Journal of Clinical
Oncology 36, no. 6, 2018
Clear separation
between risk
groups and
outcome

47. Risk of Metastases using Combined
System
Most of the
problems
don’t show
up until after
5 years

48. Risk of Metastases using Combined
System
10 Year Risk of Mets
Very-low 3.1%
Low 3.7%
Favor Intermed 25.9%
Unfav Intermed 31.7%
High 49.7%
Very High 61.9%
Spratt Journal of Clinical
Oncology 36, no. 6, 2018

49. 10 Year Risk of Metastases
Very-low 3.1%
Low 3.7%
Favor Intermed 25.9%
Unfav Intermed 31.7%
High 49.7%
Very High 61.9%
How is this Helpful?
Do Less Therapy
Do More Therapy
Do A lot More Therapy
Bone mets

50. Risk of Prostate Specific Mortality
using Combined System
10 Year Risk of Mortality
Low Risk 2%
Intermediate 10.7%
High Risk 27.3%
Spratt Journal of Clinical
Oncology 36, no. 6, 2018

51. Risk of Prostate Specific Mortality
using Combined System
Most of the
deaths don’t
show up
until 10 to
15 years
later

52. 66.6% of patients
classified by the NCCN
six-tier system would
be reclassified using
the new six-tier
clinical-genomic risk
groups
Spratt Journal of Clinical
Oncology 36, no. 6, 2018

53. After Genomics
44% Low Risk (? Over treating)
28% Favorable Intermediate
27% Unfavorable Intermediate
(? Undertreating)
Favorable Intermediate / Based on NCCN

54. Prostate Calculators Prostate Cancer Nomograms
mskcc.org/nomograms/prostate
Male Life Expectancy and Watchful Waiting

55. urology.jhu.edu/prostate/

56. aboutcancer.com/prostate_calc_main_page
Go to this site for
more prostate
cancer calculators

57. For more information go to aboutcancer.com
or the video site at:
aboutcancer.com/you_tube_videos.htm
or the YouTube site at:
youtube.com/user/robertmillermd/videos