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NCCN Clinical Practice Guidelines in Oncology™
Prostate Cancer
Early Detection
V.2.2010
www.nccn.org
Version 2.2010, 08/07/09 © 2009 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.
NCCN
® Practice Guidelines
in Oncology – v.2.2010
Guidelines Index
Prostate Early Detection TOC
Discussion, ReferencesProstate Cancer Early Detection
NCCN Prostate Cancer Early Detection Panel Members
Mark H. Kawachi, MD/Chair
City of Hope Comprehensive Cancer
Center
Richard J. Babaian, MD
The University of Texas M.D. Anderson
Cancer Center
Robert R. Bahnson, MD
Arthur G. James Cancer Hospital & Richard
J. Solove Research Institute at The Ohio
State University
Michael Barry, MD
Dana-Farber/Brigham and Women’s Cancer
Center | Massachusetts General Hospital
Cancer Center
J. Erik Busby, MD
University of Alabama at Birmingham
Comprehensive Cancer Center
Peter R. Carroll, MD
UCSF Comprehensive Cancer Center
H. Ballentine Carter, MD
The Sidney Kimmel Comprehensive Cancer
Center at Johns Hopkins
William J. Catalona, MD
Robert H. Lurie Comprehensive Cancer
Center of Northwestern University
Michael S. Cookson, MD
Vanderbilt-Ingram Cancer Center
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Jonathan I. Epstein, MD
The Sidney Kimmel Comprehensive Cancer
Center at Johns Hopkins
Ruth B. Etzioni, PhD
Fred Hutchinson Cancer Research
Center/Seattle Cancer Care Alliance
Veda N. Giri, MD
Fox Chase Cancer Center
George P. Hemstreet, III, MD, PhD
UNMC Eppley Cancer Center at The
Nebraska Medical Center
Richard J. Howe, PhD
Consultant
Paul H. Lange, MD
Fred Hutchinson Cancer Research
Center/Seattle Cancer Care Alliance
Hans Lilja, MD, PhD
Memorial Sloan-Kettering Cancer Center
Kevin R. Loughlin, MD
Dana-Farber/Brigham and Women’s Cancer
Center | Massachusetts General Hospital
Cancer Center
James Mohler, MD
Roswell Park Cancer Institute
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††
†
†
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Judd Moul, MD
Duke Comprehensive Cancer Center
Robert B. Nadler, MD
Robert H. Lurie Comprehensive Cancer
Center of Northwestern University
Stephen G. Patterson, MD
H. Lee Moffitt Cancer Center and Research
Institute at the University of South Florida
Joseph C. Presti, MD
Stanford Comprehensive Cancer Center
Antoinette M. Stroup, PhD &
Huntsman Cancer Institute at the
University of Utah
Robert Wake, MD
St. Jude Children’s Research
Hospital/University of Tennessee Cancer
Institute
John T. Wei, MD, MS
University of Michigan Comprehensive
Cancer Center
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† Medical oncology
§ Radiotherapy/Radiation oncology
* Writing committee member
� Urology
Þ Internal Medicine
Pathology
& Epidemiology
†† Biostatistician
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¥ Patient advocacy
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NCCN Guidelines Panel Disclosures
Version 2.2010, 08/07/09 © 2009 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.
NCCN
® Practice Guidelines
in Oncology – v.2.2010
Guidelines Index
Prostate Early Detection TOC
Discussion, ReferencesProstate Cancer Early Detection
Table of Contents
NCCN Prostate Cancer Early Detection Panel Members
Summary of Guidelines Updates (UPDATES)
Introduction (PROSD-1)
Baseline Evaluation (PROSD-2)
Diagnostic Evaluation, Screening Results (PROSD-3)
DRE Positive (PROSD-4)
DRE Negative, PSA Performed (PROSD-5)
Screening Results; PSA 4-10 ng/mL (PROSD-6)
Screening Results; PSA > 10 ng/mL (PROSD-7)
Guidelines Index
Print the Prostate Cancer Early Detection Guidelines
TRUS-Guided Biopsy Results (PROSD-8)
Talking Points About the Pros and Cons of PSA Testing (PROSD-A)
These guidelines are a statement of evidence and consensus of the authors regarding their views of currently accepted approaches to treatment.
Any clinician seeking to apply or consult these guidelines is expected to use independent medical judgment in the context of individual clinical
circumstances to determine any patient's care or treatment. The National Comprehensive Cancer Network makes no representations nor warranties
of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way. These
guidelines are copyrighted by National Comprehensive Cancer Network. All rights reserved. These guidelines and the illustrations herein may not
be reproduced in any form without the express written permission of NCCN. ©2009.
Clinical Trials:
Categories of Evidence and
Consensus:
NCCN
The
believes that the best management
for any cancer patient is in a clinical
trial. Participation in clinical trials is
especially encouraged.
To find clinical trials online at NCCN
member institutions,
All recommendations
are Category 2A unless otherwise
specified.
See
NCCN
click here:
nccn.org/clinical_trials/physician.html
NCCN Categories of Evidence
and Consensus
This discussion is being
updated to correspond
with the newly updated
algorithm.
For help using these
documents, please click here
Discussion
References
Version 2.2010, 08/07/09 © 2009 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.
NCCN
® Practice Guidelines
in Oncology – v.2.2010
Guidelines Index
Prostate Early Detection TOC
Discussion, ReferencesProstate Cancer Early Detection
Note: All recommendations are category 2A unless otherwise indicated.
Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged. UPDATES
Summary of changes in the 1.2010 version of the Prostate Cancer Early Detection Guidelines include:
)
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�
�
The Guidelines are specifically for men opting to participate in an early detection program (after receiving the appropriate counseling on
the pros and cons of early detection).
Under Screening and Follow-Up, the PSA value was changed from 0.6 ng/mL to 1.0 ng/mL with the addition of a footnote. Footnote “e”
states “The PSA value of 1.0 ng/mL selects for the upper range of PSA values for 40-49 year-old men.”
Footnote “g” is new to the page. “Less frequent PSA/DRE follow-up in the older patient may be appropriate based on their individual risk
stratification.”
Level 1 evidence for PSA screening is now available through a European study released in 2009. The European Randomized Study of
Screening for Prostate Cancer (ERSPC) was initiated in the early 1990's to evaluate the effect of prostate-specific antigen (PSA) testing
on death rates from prostate cancer. The trial involved 182,000 men between the ages of 50 and 74 in 7 European countries, randomly
assigned to a group that was offered PSA screening at an average of once every 4 years or to a control group that did not receive such
screening. The predefined core group included 162,243 men of ages of 55-69 years. Death from prostate cancer was the primary
outcome. During a median follow-up of 9 years, the cumulative incidence of prostate cancer was 8.2% in the screening group and 4.8% in
the control group. There were 214 prostate cancer deaths in the screening group, and 326 in the control group. The rate ratio for death
from prostate cancer in the screening group, compared to the control group, was 0.80 (95% confidence interval [CI], 0.65-0.98; adjusted
P=0.04). The researchers concluded that PSA-based screening reduced the rate of death from prostate cancer by 20%. However, they
also concluded that this was associated with a high risk of over-diagnosis. Statistically, 1,410 men would need to be screened and 48
men would need to be treated to prevent one death from prostate cancer
Footnote “a” has been modified. “Screening in men over 75 y should be considered individually.” Previously recommended
individualized screening in men over 80 y.
PROSD-1
PROSD-2
PROSD-A (page 2 of 3
Summary of changes in the 2.2010 version of the Prostate Cancer Early Detection Guidelines include:
� The addition of the updated .Discussion section
Version 2.2010, 08/07/09 © 2009 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.
NCCN
® Practice Guidelines
in Oncology – v.2.2010
Guidelines Index
Prostate Early Detection TOC
Discussion, ReferencesProstate Cancer Early Detection
It is neither the intent nor the suggestion of the panel that all men diagnosed with prostate cancer require treatment. It is
inhe
The guidelines are continuously in a state of evolution and the panel will incorporate changes based on new evidence and
expert opinion and provide a rating of consensus with respect to each recommendation.
rent that as we maximize the detection of early prostate cancer we will increase the detection of both non-aggressive (slow
growing) and aggressive (faster growing) prostate cancers. The challenge is to identify the biology of the cancer that is detected
and thus identify cancers that, if treated effectively, will result in a significant decrease in morbidity and mortality.
This variability in prostate tumor behavior is unlike any other cancer and, consequently, causes major concern with the problem
of over treatment resulting in potentially significant adverse implications on quality of life issues (eg, urinary, bowel and erectile
dysfunction). The natural history of prostate cancer is that it will progress over time, but the unanswerable question is over
what period of time.
The Prostate Cancer Early Detection guidelines do not address the treatment of prostate cancer. The guidelines are specifically
for men opting to participate in an early detection program (after receiving the appropriate counseling on the pros and cons). It
is the majority opinion of the Prostate Cancer Early Detection panel members that there is a growing population of men currently
being diagnosed with prostate cancer who can, and should, be monitored for their disease as presented in the Prostate Cancer
Treatment Guidelines. The guidelines for a baseline PSA and lowering the PSA thresholds for biopsy were recommended by
most panel members, but a consensus was not reached.
See Suggested “talking points” to cover in a discussion with a potential screenee about the pros and cons of PSA testing
(PROSD-A).
INTRODUCTION
PROSD-1
See Baseline Evaluation
(PROSD-2)Note: All recommendations are category 2A unless otherwise indicated.
Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.
Version 2.2010, 08/07/09 © 2009 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.
NCCN
® Practice Guidelines
in Oncology – v.2.2010
Guidelines Index
Prostate Early Detection TOC
Discussion, ReferencesProstate Cancer Early Detection
Return to Prostate
Cancer Early Detection
Table of Contents
PROSD-2
BASELINE
EVALUATION
SCREENING
EVALUATION
FOLLOW-UP
Start risk and
benefit
discussion
and
Offer baseline
DRE and PSA
at age 40
(category 2B)
PSA
1.0 ng/mL
�
e
or
African
American
or
Family history
PSA < 1.0 ng/mLe
Repeat at
age 45
PSA ng/mL� 1.0
PSA 1.0 ng/mL>
Annual follow-up
(category 2B):
�
�
DRE
PSA
Annual follow-up
(category 2B):f
�
�
DRE
PSA
Offer regular
screening at
age 50g
See
Screening
Results
(PROSD-3)
See
Screening
Results
(PROSD-3)
See
Diagnostic
Evaluation
(PROSD-3)
a
c
d
e
g
Screening in men over 75 y should be considered individually.
PSA Velocity: For men with PSA < 4 ng/mL, data suggest that a PSA velocity of 0.35 ng/mL/y is suspicious for the presence of cancer (Carter HB, Ferrucci L,
Kettermann A at el. Detection of Life-Threatening Prostate Cancer With Prostate-Specific Antigen Velocity During a Window of Curability. J Natl Cancer Inst
2006;98(21):1521-1527); for men with PSA 4-10 ng/mL, a PSA velocity of 0.75 ng/mL/y is suspicious for cancer. PSA velocity in men with PSA > 10 ng/mL has not
been determined useful. Measurement should be made on at least three consecutive specimens drawn over at least an 18-24 mo interval. There is variability. Longer
time periods increase reliability, but, as calculation of PSA velocity over longer prior time intervals usually decreases the PSA velocity estimate, it might decrease
predictive power. It is also important to remember that biologic variability and/or prostatitis may be confounding factors in determining PSA velocity; therefore, antibiotic
therapy and repeated PSA measurements may be considered to minimize these sources of confusion.
The PSA value of 1.0 ng/ml selects for the upper range of PSA values for 40-49 year-old men.
There is no evidence in the literature to support the follow-up recommendations listed; they represent the consensus-based opinions of the panel based upon their
clinical experience.
Less frequent PSA/DRE follow-up in the older patient may be appropriate based on their individual risk stratification.
bFamily history may affect a decision to biopsy. The closer the relative, the earlier the onset and the more affected family members, the higher the risk.
�
�
f
See Introduction (PROSD-1)
RISK
ASSESSMENTd
�H&P including:a
�
�
�
�
Family history
Medications
History of
prostate disease
and screening,
including prior
PSA and/or
isoforms, exams
and biopsies
PSA velocity, if
available
b
c
Note: All recommendations are category 2A unless otherwise indicated.
Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.
PSA
1.0 ng/mL�
Repeat at
age 45
PSA
1.0 ng/mL>
Annual follow-up
(category 2B):
�
�
DRE
PSA
If PSA
,
offer screening
at age 50
� 1.0 ng/mL
g
See
Diagnostic
Evaluation
(PROSD-3)
Version 2.2010, 08/07/09 © 2009 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.
NCCN
® Practice Guidelines
in Oncology – v.2.2010
Guidelines Index
Prostate Early Detection TOC
Discussion, ReferencesProstate Cancer Early Detection
PROSD-3
DIAGNOSTIC
EVALUATION
hIn patients using finasteride or dutasteride, failure to have a substantial decrease (approximately 50%) in PSA or an increase while on medication can be associated
with an increased risk of prostate cancer.
DRE
Offer total PSA
See Screening
Results and Follow-
up (PROSD-5)
See Follow-up
(PROSD-4)
DRE positive
regardless of
PSA results
TRUS-guided
biopsy
(See PROSD-8)
SCREENING
RESULTS
FOLLOW-UP
DRE negative
PSA performed
Note: All recommendations are category 2A unless otherwise indicated.
Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.
Version 2.2010, 08/07/09 © 2009 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.
NCCN
® Practice Guidelines
in Oncology – v.2.2010
Guidelines Index
Prostate Early Detection TOC
Discussion, ReferencesProstate Cancer Early Detection
Note: All recommendations are category 2A unless otherwise indicated.
Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.
PROSD-4
See NCCN Prostate Cancer Treatment Guidelines
Benign See Screening
Results (PROSD-5)
FOLLOW-UP
DRE positive
Regardless of
PSA result:
Findings from
TRUS-guided
biopsy
(See PROSD-8)
hIn patients using finasteride or dutasteride, failure to have a substantial decrease (approximately 50%)
in PSA or an increase while on medication can be associated with an increased risk of prostate cancer.
Cancer
Atypia,
suspicious for
cancer or
High-grade PIN
See Follow-up for TRUS-
guided biopsy (PROSD-8)
PSA
�
�
�
�
�
�
h
h
Ejaculation:
Results are more reliable if patient has
abstained from ejaculation for 48 hr. If this
condition is not met, repeat after 48 hr
abstention, if the original sample was
marginally elevated.
Medicines that affect PSA:
Finasteride
Androgen receptor blockers
Dutasteride
Version 2.2010, 08/07/09 © 2009 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.
NCCN
® Practice Guidelines
in Oncology – v.2.2010
Guidelines Index
Prostate Early Detection TOC
Discussion, ReferencesProstate Cancer Early Detection
Note: All recommendations are category 2A unless otherwise indicated.
Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.
PROSD-5
SCREENING RESULTS FOLLOW-UP
DRE
negative
PSA
performed
PSA Velocity
< ng/mL/y0.35 c
Continue follow-up
PSA Velocity
ng/mL/y� 0.35 c
Consider initial TRUS-
guided biopsy
(See PROSD-8)
TRUS-guided
biopsy performed
(See PROSD-8)
PSA 4-10 ng/mL
PSA > 10 ng/mL
See NCCN Prostate Cancer
Treatment Guidelines
Benign
�
�
�
PSA 2.6-4 ng/mL
or
PSA velocity
0.35 ng/mL/yc
when PSA 2.5
ng/mL
�
�
�
PSA 2.5 ng/mL
and
PSA velocity
< 0.35 ng/mL/y if
available
�
See PSA 4 to 10 ng/mL (PROSD-6)
See PSA > 10 ng/mL (PROSD-7)
6-12 mo follow-up with DRE
Consider percent free PSA
c
cPSA Velocity: For men with PSA < 4 ng/mL, data suggest that a PSA velocity of 0.35 ng/mL/y is suspicious for the presence of cancer (Carter HB, Ferrucci L,
Kettermann A at el. Detection of Life-Threatening Prostate Cancer With Prostate-Specific Antigen Velocity During a Window of Curability. J Natl Cancer Inst
2006;98(21):1521-1527) and biopsy is recommended; for men with PSA 4-10 ng/mL, a PSA velocity of 0.75 ng/mL/y is suspicious for cancer. PSA velocity in men
with PSA > 10 ng/mL is not available. Measurement should be made on at least three consecutive specimens drawn over at least an 18-24 mo interval. There is
variability. Longer time periods increase reliability, but, as calculation of PSA velocity over longer prior time intervals usually decreases the PSA velocity estimate, it
might decrease predictive power. It is also important to remember that biologic variability and/or prostatitis may be confounding factors in determining PSA velocity;
therefore, antibiotic therapy and repeated PSA measurements should be used to minimize these sources of confusion.
Factors to consider: age (men over 75 y should be considered individually), comorbid conditions, percent free PSA, prostate exam/size, strength of family history,
African American.
�
�
j
kFree PSA is not generally used in deciding whether or not to perform an initial biopsy. However, in selected circumstances, it may be considered employing the
following recommendations: > 25%, no biopsy; 10% biopsy; > 10% 25% indeterminate, consider biopsy.� �
Consider
biopsyj
TRUS-guided biopsy
not performed
Use of free PSA in considering initial
biopsy:
10% Biopsy
> 10 25% Consider biopsy
> 25% Consider deferring biopsy
k
�
�
�
�
�
Annual DRE
and PSA
Cancer
Atypia,
suspicious for
cancer or
High-grade PIN
See Follow-up for TRUS-
guided biopsy (PROSD-8)
Version 2.2010, 08/07/09 © 2009 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in