Active Surveillance in Prostate Cancer: Risks and

Controversies

Behfar Ehdaie, MD, MPH

Assistant A4ending

Urology Service,
Department of Surgery
Department of Epidemiology
and Biosta@s@cs

Memorial Sloan Ke4ering
New York, NY

Disclosures: NONE

This talk will outline paradigm changes in the

management of localized prostate cancer
Epidemiology of prostate cancer and defining
controversies with prostate cancer screening
Advances in imaging to select patients
with low risk tumors
Observational studies with long-term
outcomes using active surveillance
Barriers to acceptance of active
surveillance as a viable option

Trends in Cancer Incidence and Death Rates

Among Males, United States, 1930 to 2008

[Jemal, 2012]

Cumulative hazard of
prostate cancer mortality

Significant reduction in prostate-cancer specific mortality

benefiting PSA screening; however, 27 men are required to
be detected (treated) to prevent 1 death

No PSA screening

PSA screening

Years following randomization (PSA screening)

[Schroder, 2014]

The greatest risk of screening is over-detection of indolent

disease and subsequent risk of unnecessary treatment
Age

% Alive

Years following prostate cancer detection

In the era of PSA-based screening, the percentage of prostate cancers

over-diagnosed is es9mated to be as high as 23% to 67%1,2
[Welch, 2010; Gula@, 2011]

Whitmore Dilemma

For a patient with prostate cancer

If treatment for cure is necessary, is
it possible?
If possible, is it necessary?

Active
Surveillance for localized prostate cancer

Paradigm shift: deferment of treatment

Men are observed carefully with serial examinations
and at the first signs of higher-risk disease,
the cancer can be treated within the window of
opportunity for cure

Enrollment: establish eligibility criteria based on clinical

and pathological factors to select low-risk prostate cancer
patients.
Observation: schedule regular visits to monitor serum
PSA and clinical exams, including follow-up prostate
biopsies.
Deferred treatment: patient will undergo curative
treatment based on progression of prostate cancer to
higher risk using clinical and pathological factors.

Eligibility criteria vary widely among physicians,

hospitals, and countries
Memorial Sloan Kettering Cancer Center
Gleason grade 3+3 (low volume 3+4)
Clinical stage T2b
Johns Hopkins Medical Center
Gleason grade 3+3
% core 60%
# cores <3
PSA density 0.15

Biopsy techniques have relied on random sampling of the

prostate gland
SV

SV
Base

Mid

PZ

Base

CZ

TZ

Mid

TZ

Apex

Apex

Sextant
Sextant

PZ

CZ

Urethra

Urethra

12-core
12-core
extended

SV
Base

Mid

Figure 1

PZ

CZ
TZ

Apex
Urethra

Saturation
Saturation

Some clinically significant cancers are missed because of

sampling error of the biopsy, and many men are diagnosed
with clinically insignificant disease.

A confirmatory biopsy reclassifies 28% of men who

were initially eligible for active surveillance
Repeat biopsy pathological results

[Berglund, 2008]

The sensitivity of MRI to detect prostate cancer is

improved with larger tumor volumes and higher
Gleason scores


Overall
PPV:
98%

Sensi@vity:
Gleason 7 (0.69-0.80)
<7 (0.27-0.47)
Volume >5mm (0.53-0.68)
5mm (0.13-0.37)

[Turkbey, 2012]

MR-targeted prostate biopsies improves detection of

clinically significant cancer compared to standard biopsy
MRI T2-weighted/
ADC sequences

Observation compared to surgery results in similar longterm prostate cancer survival

[Wilt, 2012]

However, the incidence rate of bone metastases was

increased in patients in the observation cohort

[Wilt, 2012]

Benefit of treatment is dependent on prostate cancer risk

Low risk: PSA<10,
Gleason 6,
Stage <T2a

Cancer-specic Survival

Overall Survival

Intermediate risk:
PSA 10-20, Gleason 7,
stage T2B

High risk:
PSA>20 or
Gleason >7 or
stage >T2B

[Wilt, 2012]

Long-term observational studies demonstrate that active

surveillance is safe for men with low risk prostate cancer

[Klotz, 2015]

Men on active surveillance have a several fold increased

risk of dying from something other than prostate cancer

[Tosoian, 2015]

Although significant variation exists in identifying patients

eligible for active surveillance, detecting disease
progression is equally challenging
Tools to detect prostate cancer disease progression:
Digital rectal exam
Serial prostate biopsy
Serum PSA changes
Adverse findings on MRI

The risk of prostate cancer progression increases with

time thereby necessitating long-term surveillance.

[Klotz, 2015]

Significant cost variation exists between treatments for

low risk prostate cancer and active surveillance is cheaper
than surgery and radiation therapy

[Laviana, 2015]

The number of men being managed with active

surveillance is rising across clinics in the US

[Silberstein, 2011]

Implementing a nurse-led active surveillance

program is feasible and provides quality of care
100% of nurses and 51% of urologists strongly agreed
that nurse-led care provided benefits to patients
compared to standard physician clinics
In patient surveys, 3 key themes emerged in support of
nurse-led care:
1. Efficient use of resources
2. Quality of care
3. Convenience of care
[Wade, 2015]

The majority of men diagnosed with prostate

cancer in the PSA-screening era are eligible for
active surveillance

Very Low Risk

High Risk
Low-Intermediate
Risk

[Homan, 2014]

Despite rising trends in active surveillance use,

<40% of patients choose active surveillance

[Cooperberg, 2015]

Barriers to Active Surveillance

80% of physicians believe active surveillance is underutilized

71% of physicians report their patients are not interested in
active surveillance

[Kim, 2014]

My early experience

Conceptual Framework of Barriers to Active Surveillance

Seek
treatment.
Early
aggressive
treatment
improves
survival
Influence.
Partner/spouse
and family
member
preferences

Fear.
Cancer will
spread
without
detection

Education.
Lack of
knowledge
about AS

Attitudes and
beliefs.
AS is for older
men who are
not surgical
candidates

Solutions?

Multi-disciplinary clinics

Genomic tests

60% adherence to AS

$$$

Communication

Nomenclature

Focus on interests as opposed to positions

Sex

Surgery

Urinary
symptoms

Active
Surveillance
Quality
of Life

Life

Death

Costs

Survival

Not what you say but learning how to

effectively say it.

Mr Jones, we will monitor your cancer by checking a PSA every 6

months and repeating a biopsy every 2 years.

Vs.
Mr Jones, we believe that the PSA test has enabled us to find
your cancer 4-6 years early and changes to your tumor is not
expected until the second decade after diagnosis. Therefore, we
can see you again in 5 years; however, we will monitor your
cancer closely and check a PSA every 6 months and repeat the
biopsy every 2 years.

N=897 consecutive men with low risk prostate

cancer during the study period
Interven@on Cohort

In conclusion, active surveillance is a safe and

effective management strategy for men with low
risk prostate cancer
Interven@on Cohort
1

There is no evidence to suggest immediate

.6

.8

treatment for low risk prostate cancer

.4

confers a survival advantage

.2

Despite advances in technology to support

better patient selection, majority of men do

Aug 1, 2012 Feb 1, 2013 Aug 1, 2013 Feb 1, 2014 Aug 1, 2014 Feb 1, 2015
New Visit Date

QUESTIONS?

not choose active surveillance

Novel approaches targeting the patientphysician relationship may decrease
overtreatment and its consequent harms