What’s new in prostate cancer part 1, 2021

Questions about
Prostate Cancer
ASPEC Part 1 2021
Robert Miller MD

Do we know who gets prostate cancer and why?
Is it worth screening for this cancer? (and why is this
so controversial?)
Is the PSA blood test really the best way to protect
yourself from ever dying of prostate cancer?

PROSTATE
CANCER
FAKE NEWS ALERT
Prostate Cancer Does not look like this
picture

Bladder
Prostate
Urethra
Cancer
Picture of locally
advanced prostate
cancer, most men
have only scattered
cells in the gland and
no symptoms
If a man has urinary
frequency or a weak
stream it is almost
always due to benign
prostate enlargement

Because there are usually no symptoms from prostate
cancer it would be necessary to screen for it

Why is the management of prostate cancer still
controversial?
1. It’s very common but many cases are so indolent they
should not be treated if discovered
2. The PSA test does not perfectly predict the men who need a biopsy (but there are now better
tests to predict if a biopsy is necessary)
3. The path report may not perfectly predict who needs aggressive treatment (but there are now
better tests to predict that as well).

controversial?
1. It’s very common but many cases are so indolent they should not be treated if discovered
2. The PSA test does not perfectly predict the men who
need a biopsy (but there are now better tests to
predict if a biopsy is necessary) Overdiagnosis?
3. The path report may not perfectly predict who needs aggressive treatment (but there are now
better tests to predict that as well).

controversial?
1. It’s very common but many cases are so indolent they should not be treated if discovered
2. The PSA test does not perfectly predict the men who need a biopsy (but there are now better
tests to predict if a biopsy is necessary)
3. The path report may not perfectly predict who needs
aggressive treatment (but there are now better tests
to predict that as well). Overtreatment?

Topics to Consider
1.General Stats: how common and how serious
2.Do we know enough about the cause so we can prevent
it?
3.Screening: do we really benefit from diagnosing this
early?
4.If you are diagnosed what are the treatment options?
Part 2

Posted on YouTube about prostate cancer screening is here: https://youtu.be/mucbSbiQ1r4
and the one on treatment decisions is here: https://youtu.be/pX2j8FVWPTA
Go to my You Tube channel: www.youtube.com/c/RobertMillerMD

2021 US Cancer Stats for Men
#1 New Cases (26%) #2 Cancer Deaths (11%)

Site Cases Men Women Deaths Men Women
All 1,898,160 970,250 927,910 608,570 319,420 289,150
Breast 284,200 2,650 281,550 44,130 530 43,600
Colorectal 149,500 79,520 69,980 52,980 28,520 24,260
Lung 235,760 119,100 116,660 131,880 69,410 62,470
Prostate 248,530 248,530 34,130 34,130
2021 US Cancer Statistics
Prostate cancer causes 13% of all cancers but ‘only’ 5.6% of call cancer deaths
https://acsjournals.onlinelibrary.wiley.com/doi/full/10.3322/caac.21654

https://gis.cdc.gov/Cancer/USCS/DataViz.html
At 5 Years almost
everyone with
prostate cancer is still
alive
So no value in using 5
years stats to
compare treatments

Prostate
Stage Distribution of SEER Incidence Cases, 2009-
2018
Stage at Diagnosis Percent of cases
Localized 73.3
Regional 12.4
Distant 6.3
Prostate
Recent Trends in SEER Relative Survival Rates, 2000-
2018
All 96.5%
Localized 100%
Regional 99.6%
Distant 39.8%
https://seer.cancer.gov/explorer
Male By Race/Ethnicity, All Ages, 5 years
85% of cases are
diagnosed at local or
regional stage and
their relative 5-year
survival is close to
100%

Prostate
Stage Distribution of SEER Incidence Cases, 2009-
2018
Stage at Diagnosis Percent of cases
Localized 73.3
Regional 12.4
Distant 6.3
Prostate
Recent Trends in SEER Relative Survival Rates, 2000-
2018
All 96.5%
Localized 100%
Regional 99.6%
Distant 39.8%
Male By Race/Ethnicity, All Ages, 5 years
6% present with
metastases but even
in this group 40% are
alive at 5 years

12.5%
2.4%
6.1%
4.5%

Sites 0 – 49 50-59 60-69 70+ 0 to Death
All 3.5% 6.2% 13.6% 33.2% 40.5%
Colorectal 0.4% 0.7% 1.1% 3.2% 4.3%
Lung 0.1% 0.6% 1.7% 5.9% 6.6%
Prostate 0.2% 1.8% 5.0% 8.7% 12.1%
Probability (%) of Developing
Invasive Cancer Within Selected Age
Intervals for Men, United States, 2015
to 2017

Sites 0 – 49 50-59 60-69
70+ 0 to Death
All 3.5% 6.2% 13.6% 33.2% 40.5%
Colorectal 0.4% 0.7% 1.1% 3.2% 4.3%
Lung 0.1% 0.6% 1.7% 5.9% 6.6%
Prostate 0.2% 1.8% 5.0%
8.7% 12.1%
Probability (%) of Developing
Invasive Cancer Within Selected Age
Intervals for Men, United States, 2015
to 2017
Most of these cancers 8.7/12.1 (72%) aren’t diagnosed before 70
(the age where screening is supposed to stop!)

https://seer.cancer.gov/explorer/
12.5%
2.4%
60-70’s
80-90’s

Prostate Cancer…more
people die with it than
of it.

Autopsy studies conducted in multiple countries that found
occult cancer in the Prostate in Men
●20 to 30 years, 2 to 8 percent
Cancer Control. 2006;13(3):158.

Prostate Cancer…more people die with it than of it.
Autopsy on 100 random men of > 80y
2 died from prostate cancer
12 had been diagnosed with prostate
cancer
70 had cancer cells found in their
prostate

Prostate Cancer Incidence in the US.
PSA Approval in 1986
Peak 1992
USPTF opposed PSA
screening in 2012

Prostate cancer mortality rates have declined in the United States between 1992 and 2017,
decreasing from 39 to 19 per 100,000 persons.
Simulation models suggest that prostate-specific antigen (PSA) screening could account for 45 to 70
percent of the decline, mainly by decreasing the incidence of distant-stage disease. Other factors that
may explain the decline in mortality rates include advances in treatment.

Why is this more common in blacks?

12.0%
2.3%
White men

16.7%
3.8%
Black men

Incidence by Site White Black
All Cancers 501.4 534.0 (106%)
Prostate 97.7 171.8 (176%)
Mortality by Site White Black
All Cancers 190.2 227.2 (119%)
Prostate 17.9 38.3 (214%)
Incidence and Mortality Rates for Selected
Cancers by Race and Ethnicity, United States,
2013 to 2018
Rates are per
100,000 population
and age adjusted to
the 2000 US
standard population

JAMA Oncol. 2019;5(7):975-
983
May 23, 2019
Association of Black Race With
Prostate Cancer–Specific and Other-
Cause Mortality
Health equity : how
much is genetics
(biology) or socio-
economic (racism)?

Black men do worse nationally but not at the VA or in trials where they get
equal access to care

A 2021 studyTrusted Source into the heredity of prostate and generated a genetic
risk score (GRS)
We conducted a multi-ancestry meta-analysis of prostate cancer
genome-wide association studies (107,247 cases and 127,006 controls)
and identified 86 new genetic risk variants independently associated
with prostate cancer risk, bringing the total to 269 known risk variants.
Men of African ancestry were estimated to have a mean GRS that was
2.18-times higher and men of East Asian ancestry 0.73-times lower
than men of European ancestry.
https://pubmed.ncbi.nlm.nih.gov/33398198/

About 50% of prostate tumors harbor a fusion between the ERG gene and the promoter region of TMPRSS2 gene. This chromosomal
rearrangement leads to abnormal production of ERG and promotes tumor progression. EZH2 is a partner-in-crime of ERG in prostate cancer
progression

Cancer Facts & Figures for African Americans 2019-2021

BM/WM cancer death rate 228/190 (120%) total death rate 1088/880 (123%)

https://www.pnas.org/content/118/5/e2014746118

Cause and Prevention of Prostate Cancer
Clearly related to presence of
testosterone and some role for
genetics

Prostate Cancer Prevention (PDQ®)–Health
Professional Version
www.cancer.gov/types/prostate/hp/prostate-prevention-pdq
Risk factors include age, hormones, race, diet and vitamins and minerals
Results of studies: small benefit with side effects from drugs that lower testosterone like
Finasteride (Proscar or Propecia) or Dutasteride (Avodart) but not enough to recommend
them, and no benefit from selenium and vitamin E trials (cancer went up with vitamin E)

When to consider genetic testing?
- High risk or metastatic prostate cancer
- Ashkenazi Jewish ancestry
- Strong family history (first degree relative diagnosed age
<60y or die of prostate cancer
The prevalence of a germ line mutation in high-risk patients is
6% and for those with metastases 11.8%
NCCN.org

https://www.facingourrisk.org/

“Prostate cancer represents a spectrum of disease that
ranges from nonaggressive, slow growing disease that
may not require treatment to aggressive, fast growing
disease that does.
…need to develop a strategy to maximize the detection
of cases that are effectively treatable and that if left
undetected represents a risk to the patient”
NCCN.org
Screening…Is it worth getting my PSA level tested?

uspreventiveservicestaskforce.org/webview

Final Recommendation Statement
Prostate Cancer: Screening
2018

Age 55 – 69: Discuss it
70 or older: Don’t

Evidence Summary
Prostate Cancer: Screening
May 08, 2018
Sixty-three studies in 104 publications were included (N = 1,904,950).
Randomization to PSA screening was not associated with reduced risk of prostate cancer mortality in either a
US trial with substantial control group contamination (n = 76,683) or a UK trial with low adherence to a single
PSA screen (n = 408,825)
But was associated with significantly reduced prostate cancer mortality in a European trial (relative risk, 0.79);
absolute risk reduction, 1.1 deaths per 10,000 person-years.
Conclusions and Relevance: PSA screening may reduce prostate cancer mortality risk but is associated with
false-positive results, biopsy complications, and overdiagnosis.
Compared with conservative approaches, active treatments for screen-detected prostate cancer have unclear
effects on long-term survival but are associated with sexual and urinary difficulties.

The number of prostate cancer deaths in the UK has overtaken the number of
breast cancer deaths (approximately 12,000 compared with 11,000), with the
national breast screening programme credited with saving an estimated 1,300 lives
a year.
Last year, Prostate Cancer published research showing it is the most commonly
diagnosed cancer in the UK, with 57,192 new cases in 2018.
PSA tests are not recommended for screening because they are unreliable and can
yield false positive results, while digital rectal examinations (DREs) are invasive,
which can put men off being tested, and also have issues with reliability.
What happens if the national health system (in the UK)
decides to screen for breast cancer but not for prostate
cancer?

General advice to stop screening once life expectancy is less
than 10 years.
Life Expectancy in Men by Age and
Health Status

https://www.ssa.gov/oact/STATS/table4c6_2016.html
+ or –
by 50%
based
on
health
status

PSA (Prostate Specific Antigen) glycoprotein made by the prostate
to lyse the clotted ejaculate to increase sperm mobility
PSA Level Risk of Cancer
< 4 15%
4- 10 18%
> 10 67%
Cancer cells release more PSA into the blood than normal cells

Median for man 40 -49y (0.7) and 50-59y (0.9)
a rise of > 0.75 in one year is worrisome ,
Men up to 60 with PSA < 1 rarely have serious cancer and
men 75 with 3 or less rarely serious.
Drugs (avodart, proscar, flomax , saw palmetto, may lower the PSA by as much as 50%)

PSA alone is probably not good enough to decide on biopsy unless
it’s very high (> 10 – 15).
1. Consider getting an MRI to help determine if cancer is likely and
where to do the biopsy
2. Consider more modern biomarkers
- Free PSA
- Prostate Health Index (PHI)
- SelectMDx
- 4K score
- ExoDx Prostate Test

MRI of BPH = benign prostatic hypertrophy
Huge central or
transition zone
Very small peripheral zone
Normal size of
the peripheral
zone
Cancer is usually
found in the
peripheral zone

T2 Images on MRI
Central
zone
Peripheral zone Cancer
Prostate MRI Showing Early Cancer

MRI-Targeted or Standard Biopsy in Prostate Cancer
Screening
NEJM July 9, 2021
Randomized Swedish trial with PSA of 3 or higher, half had biopsy and
the other half had an MRI and then biopsy only if lesion noted
Result Standard Biopsy MRI then Biopsy
Low risk cancer 12% 4%
High risk 18% 21%
https://www.nejm.org/doi/10.1056/NEJMoa2100852

PSA Cancer
0.5 6.60%
.6-1 10%
1.1-2 17%
2.1-3 24%
3.1-4 27%
4-10 25-30%
>10 42-64%
% Free PSA Age 50 - 64y Age 65 - 75y
0 - 10% 56% 55%
10.1 - 15% 24% 35%
15.1 - 20% 17% 23%
20.1 - 25% 10% 20%
> 25% 5% 9%
Specificity of PSA Specificity of free- PSA when
PSA is 4 to 10

A urine test to help
decide on a biopsy

A negative MDx will rule out the chance of a more serious Gleason
7 cancer with 95% accuracy and rule out dangerous Gleason 8 with
99% certainty

Purification techniques are used to isolate exosomes and RNA
from urine specimens without the need for a prior digital rectal
exam (DRE).
The EPI gene signature and score incorporates levels of:
PCA3 (PCa antigen 3) Prostate Cancer Antigen 3],
ERG (v-ets erythroblastosis virus E26 oncogene homologs)
and
SPDEF (SAM-pointed domain-containing Ets transcription
factor)

The ExoDx™ Prostate Test (EPI) analyzes prostate gene expression in very small extracellular
vesicles called exosomes.
These vesicles contain DNA, RNA and proteins, and are produced and secreted in large
quantities from every cell in the body and can be found in urine and other bodily fluids. The
ExoDx Prostate test is a risk assessment tool that assesses the risk of aggressive prostate
cancer, with a result between 0 and 100

1. Because prostate cancer is so common and so often indolent, we need to
avoid overdiagnosis and overtreatment
2. Checking a PSA as a baseline (in your 40’s 0.7 and 50’s 0.9) may give you a
sense of risk
3. If a man is in his 60’s and PSA < 1 the long-term risk is very low
4. If a man is 75 and PSA is less than 3 the long-term risk is very low
5. Depending on perceived risk and life expectancy should guide how often
to consider checking the PSA
6. If the PSA is elevated special tests should be considered before
proceeding to a biopsy
7. If a biopsy shows cancer, then special tests and life expectancy should
guide decisions on treatment which can range from observation only to
more aggressive options (including surgery, radiation, hormones,
immunotherapy or other new innovative treatments)
How to think about prostate cancer in 2021

www.youtube.com/c/RobertMillerMD
tinyurl.com/robertmillermd

What’s new in prostate cancer part 1, 2021

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What’s new in prostate cancer part 1, 2021