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Introducing the Next Generation of
Prostate Cancer Staging –
Working with The AJCC Cancer
Staging Manual, Seventh Edition
Sam S. Chang, MD
Associate Professor
Department of Urologic Surgery
Vanderbilt University School of Medicine
Nashville, Tennessee
The American Cancer Society has provided financial support for the
development and presentation of this webinar.
The information provided does not necessarily represent the views of the
American Cancer Society, Society staff or its Board of Directors.
ACCREDITATION
The American College of Surgeons is accredited by the
Accreditation Council for Continuing Medical Education (ACCME)
to provide continuing medical education for physicians.
CME CREDIT
The American College of Surgeons designates this educational
activity for a maximum of 1 AMA PRA Category 1 Credits™.
Physicians should only claim credit commensurate with
the extent of their participation in the activity.
FACULTY DISCLOSURE
The presenter of this activity has nothing to disclose.
Overview
• Identify the changes to the prostate chapter
• Discuss the reasons for the changes
• Recognize the new criteria for Anatomic Stage /
Prognostic Groups
• Identify the prognostic factors
Introducing the Next Generation of Prostate Cancer Staging –
Working with The AJCC Cancer Staging Manual Seventh Edition
No materials in this presentation may be repurposed
without the express written permission of the American Joint Committee on Cancer.
Permission requests may be submitted at CancerStaging.net.
1
Summary of Changes – Bladder Neck
Invasion
• Microscopic bladder neck invasion now T3a
• Not an independent prognostic factor
• Clinical outcome is better than cases with
seminal vesicle invasion
• Necessary to reclassify from T4 to T3a
Summary of Changes - Grade
• Grading system of choice is Gleason Score
• Histologic grade is important for prognosis
• Grading is complex
– Morphologic heterogeneity
– Inherent tendency to be multifocal
• Gleason Score
– Highest reproducibility
– Best validation in relation to outcome
Summary of Changes – Anatomic
Stage / Prognostic Groups
• PSA and Gleason Score added to T N M to
assign group
• More definitive grouping of wide variety of
patients in heterogenous disease process
• If not available, use PSA X and Gleason X
designation
Introducing the Next Generation of Prostate Cancer Staging –
Working with The AJCC Cancer Staging Manual Seventh Edition
No materials in this presentation may be repurposed
without the express written permission of the American Joint Committee on Cancer.
Permission requests may be submitted at CancerStaging.net.
2
Introduction
• Prostate cancer
– Most common non-cutaneous cancer in men
– Increasing incidence in older age groups
• Incidence of clinical and latent ca increases with age
• Rarely diagnosed clinically in men under 40 yrs of age
– Tendency to metastasize to bone
– Early detection possible with PSA
– Dx generally made with TRUS guided bx
Introduction
• Limitations of DRE and TRUS
– Cannot precisely define size or local extent of ca
• DRE most common modality to define local stage
• Heterogeneity in T1c category
– From inherent limitations of DRE and imaging
– Balanced by inclusion of prognostic factors
• Histologic grade
• PSA
• Extent on needle bx
Primary Site
• Peripheral zone
– 80-85% of cancers
– Detected by DRE
• Transition zone – anteriomedial prostate
– 10-15% of cancers
– Common site for benign nodular hyperplasia
• Central zone – mainly the base of prostate
– 5-10% of cancers
– Seldom the origin but often invaded by spread of
large cancers
Introducing the Next Generation of Prostate Cancer Staging –
Working with The AJCC Cancer Staging Manual Seventh Edition
No materials in this presentation may be repurposed
without the express written permission of the American Joint Committee on Cancer.
Permission requests may be submitted at CancerStaging.net.
3
Regional Nodes
• Nodes of the true pelvis
– Pelvic nodes below the bifurcation of the common
iliac arteries
– Include:
•
•
•
•
•
Pelvic NOS
Hypogastric
Obturator
Iliac (internal, external, or NOS)
Sacral (lateral, presacral, promontory (Gerota’s) or NOS)
• Laterality does not affect the N classification
Distant Nodes
• Nodes outside the confines of the true pelvis
• Clinical evaluation
– US, CT, MRI, lymphangiography
– Fewer patients initially dx on imaging
– Not helpful in low risk patients
• Evaluation
– Risk tables may be used in place of imaging
Distant Nodes
• Distant Nodes are M1a
• Include
–
–
–
–
–
–
–
–
Aortic (para-aortic lumbar)
Common iliac
Inguinal, deep
Superficial inguinal (femoral)
Supraclavicular
Cervical
Scalene
Retroperitoneal, NOS
Introducing the Next Generation of Prostate Cancer Staging –
Working with The AJCC Cancer Staging Manual Seventh Edition
No materials in this presentation may be repurposed
without the express written permission of the American Joint Committee on Cancer.
Permission requests may be submitted at CancerStaging.net.
4
Metastatic Sites
• Common metastatic sites
– Osteoblastic mets are most common non-nodal
– Distant nodes
– Lung and liver are identified late in the disease course
Clinical Staging
• All information prior to first definitive treatment
• Primary tumor assessment includes
– Digital rectal exam
– Histologic or cytologic confirmation of ca
– Imaging techniques valuable in some cases
• Need Gleason score and PSA value
Clinical Staging – Imaging Studies
• TRUS is most common imaging tool
– Poor ability to identify tumor location and extent
• T1c – tumor found in one/both lobes by biopsy
but not palpable or visible by imaging
• Specify how T1c identified
– DRE only
– DRE plus TRUS
• Imaging studies should not be used
– Gleason scores <7 and PSA <20
Introducing the Next Generation of Prostate Cancer Staging –
Working with The AJCC Cancer Staging Manual Seventh Edition
No materials in this presentation may be repurposed
without the express written permission of the American Joint Committee on Cancer.
Permission requests may be submitted at CancerStaging.net.
5
Clinical Staging – T1c and T2a
• Few clinical differences in outcome
• Value of T1c category
– Defines clinical circumstances resulting in dx
(screening)
– Lack of palpable disease
• Distinction between T1c by palpation and T2a
based on imaging is problematic
– Inconsistent use of imaging as staging tool
– Interobserver variability of imaging modalities
– Lack of sensitivity and specificity of imaging
Clinical Staging - Workup
• DRE is gold standard
– Insensitive for detecting extracapsular tumor
• Imaging has limited utility
– Reproducibility
– Patient selection
– Contradictory results
Clinical Staging - Workup
• TRUS
– Can predict extracapsular extension
• Doppler
– Doesn’t improve staging accuracy
• MRI
–
–
–
–
T2 weighted MRI
MRSI
DCE-MRI
None are consistently helpful in staging
Introducing the Next Generation of Prostate Cancer Staging –
Working with The AJCC Cancer Staging Manual Seventh Edition
No materials in this presentation may be repurposed
without the express written permission of the American Joint Committee on Cancer.
Permission requests may be submitted at CancerStaging.net.
6
Pathologic Staging
• Information from total prostatectomy and node
dissection
• Bx for pT can be used in certain circumstances
– Rectum bx is pT4
– Extraprostatic soft tissue or seminal vesicles bx is pT3
• Need Gleason score and PSA value
Pathologic Staging - pT2
• Subdivisions of a, b, and c
– Broad surrogate to describe cancer volume
– Correlate to risk of clinical relapse
• 7th edition
– Retrospective outcome data challenged these subgroups
– Insufficient evidence to collapse pT2a and pT2b
– No data available to correlate subgroups to survival
• Due to indolent and prolonged clinical course
– Continued follow-up and analysis to resolve for future
versions
Pathologic Staging - pT3
• Subdivisions into a and b
– Extracapsular invasion (unilateral or bilateral)
– Seminal vesicles
• Retrospective studies have challenged
– 6th edition eliminating the division of
unilateral/bilateral
– 5th edition had this distinction
• 7th edition
– Definitive data of subgroups and survival do not exist
– Reversal of previous subgroups was not made
– Data will be gathered to decide for future versions
Introducing the Next Generation of Prostate Cancer Staging –
Working with The AJCC Cancer Staging Manual Seventh Edition
No materials in this presentation may be repurposed
without the express written permission of the American Joint Committee on Cancer.
Permission requests may be submitted at CancerStaging.net.
7
Pathologic Staging - pT4
• 6th edition T4
– Included microscopic finding of bladder invasion
• 4 large retrospective analyses revealed
– Micro bladder neck did NOT independently predict a
worse prognosis than extracapsular extension
• Microscopic bladder neck
– Moved to pT3a
– Based on the study results
Pathologic Staging - Surgical Margin
Status
• Controversy regarding surgical margins
– Parameters or elements for positive margins
• Prognostic importance of margins
– Impact on further postsurgical treatment
– Impact on outcome
• Important to document margin status
– Positive surgical margin
– R1 – residual microscopic disease
Prognostic Features
• Predicting stage and outcomes
– Algorithms and nomograms
– Proposed molecular markers
– Clinical features
• AJCC 7th
– T, N, M
– Serum prostate-specific antigen
– Gleason score
Introducing the Next Generation of Prostate Cancer Staging –
Working with The AJCC Cancer Staging Manual Seventh Edition
No materials in this presentation may be repurposed
without the express written permission of the American Joint Committee on Cancer.
Permission requests may be submitted at CancerStaging.net.
8
Prognostic Features – Gleason
• Gleason Score recent studies
– Single most important predictor of death
– Combined with AJCC stage subgroups identified
– These could predict disease-specific survival at 5, 10
and 15 yrs
Prognostic Features – PSA
• Pre-rx PSA >20 recent studies
– Predicts greater chance of distant failure and
– Greater need for hormonal therapy
– Associated with greater risk of death
Prognostic Features
• Gleason & PSA adds prognostic info
– Aids in treatment decisions
• Reduce the number of cases in Stage I
• Stratify clinically localized (T1 and T2) by these
prognostic indicators
Introducing the Next Generation of Prostate Cancer Staging –
Working with The AJCC Cancer Staging Manual Seventh Edition
No materials in this presentation may be repurposed
without the express written permission of the American Joint Committee on Cancer.
Permission requests may be submitted at CancerStaging.net.
9
Prognostic Features
• Beyond the AJCC Stage/Prognostic Groups
– Use other clinical features
• Percentage of positive bx
• Margin status
– Allows more accurate prognosis for individual patient
• Data will show impact of variables on prognosis
Outcomes by Stage, Grade, and PSA
• Multiple endpoints to assess disease outcomes
following therapy
• Clinically localized disease
– Vast majority of patients
– Multiple predictive models for outcome
• Cancer-specific survival and overall survival
– Key endpoints not evaluated
– Due to length of follow-up required
Outcomes by Stage, Grade, and PSA
• Biochemical (PSA)-free recurrence indicates
– Chance free of recurrence as manifested by rising
PSA
• Biochemical failure
– Useful surrogate endpoint
– Predict risk of death with prolonged expected survival
• Natural history of biochemical failure
– Progression to clinical disease recurrence is variable
Introducing the Next Generation of Prostate Cancer Staging –
Working with The AJCC Cancer Staging Manual Seventh Edition
No materials in this presentation may be repurposed
without the express written permission of the American Joint Committee on Cancer.
Permission requests may be submitted at CancerStaging.net.
10
Outcomes by Stage, Grade, and PSA
• Multiple variables include
–
–
–
–
–
TNM characteristics
PSA and PSA kinetics
Gleason sum
Treatment modality
Timing of biochemical recurrence
• Studies continue to evaluate
– Predictors of ultimate outcome
– Based on different therapies
Primary Tumor (T) - Clinical
• TX Primary tumor cannot be assessed
• T0 No evidence of primary tumor
• T1 Clinically inapparent tumor neither palpable
nor visible by imaging
Primary Tumor (T) - Clinical
• T1a Tumor incidental histologic finding in 5% or
less of tissue resected
• T1b Tumor incidental histologic finding in more
than 5% of tissue resected
• T1c Tumor identified by needle biopsy (e.g.,
because of elevated PSA)
Introducing the Next Generation of Prostate Cancer Staging –
Working with The AJCC Cancer Staging Manual Seventh Edition
No materials in this presentation may be repurposed
without the express written permission of the American Joint Committee on Cancer.
Permission requests may be submitted at CancerStaging.net.
11
Primary Tumor (T) - Clinical
• T2
Tumor confined within prostate*
• T2a Tumor involves one-half of one lobe or
less
• T2b Tumor involves more than one-half of one
lobe but not both lobes
• T2c Tumor involves both lobes
Primary Tumor (T) - Clinical
• T3
Tumor extends through the prostate
capsule**
• T3a Extracapsular extension (unilateral or
bilateral)
• T3b Tumor invades seminal vesicle(s)
Primary Tumor (T) - Clinical
• T4 Tumor is fixed or invades adjacent
structures other than seminal vesicles such
as external sphincter, rectum, bladder,
levator muscles, and/or pelvic wall (Figure
41.1 on next slide)
Introducing the Next Generation of Prostate Cancer Staging –
Working with The AJCC Cancer Staging Manual Seventh Edition
No materials in this presentation may be repurposed
without the express written permission of the American Joint Committee on Cancer.
Permission requests may be submitted at CancerStaging.net.
12
T4
FIGURE 41.1.
T4 tumor invading
adjacent structures
other than
seminal vesicles, such
as bladder, rectum,
levator muscles, and/
or pelvic wall.
Primary Tumor (T) - Clinical
• * Note: Tumor found in one or both lobes by
needle biopsy, but not palpable or reliably visible
by imaging, is classified as T1c.
• ** Note: Invasion into the prostatic apex or into
(but not beyond) the prostatic capsule is
classified not as T3 but as T2.
Primary Tumor – Pathologic (pT)
• pT2
Organ confined
• pT2a Unilateral, one-half of one side or less
• pT2b Unilateral, involving more than one-half of
side but not both sides
• pT2c Bilateral disease
Introducing the Next Generation of Prostate Cancer Staging –
Working with The AJCC Cancer Staging Manual Seventh Edition
No materials in this presentation may be repurposed
without the express written permission of the American Joint Committee on Cancer.
Permission requests may be submitted at CancerStaging.net.
13
Primary Tumor – Pathologic (pT)
• pT3
Extraprostatic extension
• pT3a Extraprostatic extension or microscopic
invasion of bladder neck**
• pT3b Seminal vesicle invasion
• pT4
Invasion of rectum, levator muscles, and
/or pelvic wall
Primary Tumor – Pathologic (pT)
• * Note: There is no pathologic T1 classification.
• ** Note: Positive surgical margin should be
indicated by an R1 descriptor (residual
microscopic disease).
Regional Lymph Nodes (N)
Clinical
• NX Regional lymph nodes were not assessed
• N0 No regional lymph node metastasis
• N1 Metastasis in regional lymph node(s)
Introducing the Next Generation of Prostate Cancer Staging –
Working with The AJCC Cancer Staging Manual Seventh Edition
No materials in this presentation may be repurposed
without the express written permission of the American Joint Committee on Cancer.
Permission requests may be submitted at CancerStaging.net.
14
Regional Lymph Nodes (N)
Pathologic
• pNX Regional nodes not sampled
• pN0 No positive regional nodes
• pN1 Metastases in regional node(s)
Distant Metastasis (M)
• M0
No distant metastasis
• M1
Distant metastasis
• M1a Nonregional lymph node(s)
• M1b Bone(s)
• M1c Other site(s) with or without bone disease
Distant Metastasis (M)
• * Note: When more than one site of metastasis
is present, the most advanced category is used.
pM1c is most advanced.
Introducing the Next Generation of Prostate Cancer Staging –
Working with The AJCC Cancer Staging Manual Seventh Edition
No materials in this presentation may be repurposed
without the express written permission of the American Joint Committee on Cancer.
Permission requests may be submitted at CancerStaging.net.
15
Anatomic Stage/Prognostic Groups*
Group T
N
M
PSA
Gleason
I
T1a – c
N0
M0
PSA < 10
Gleason ≤
6
T2a
N0
M0
PSA < 10
Gleason ≤
6
T1 – 2a
N0
M0
PSA X
Gleason X
Anatomic Stage/Prognostic Groups*
Group T
IIA
M
PSA
Gleason
T1a – c N0
N
M0
PSA < 20
Gleason 7
T1a – c N0
M0
PSA ≥ 10 < 20 Gleason ≤ 6
T2a
M0
PSA ≥ 10 < 20 Gleason ≤ 6
N0
T2a
N0
M0
PSA < 20
Gleason 7
T2b
N0
M0
PSA < 20
Gleason ≤ 7
T2b
N0
M0
PSA X
Gleason X
Anatomic Stage/Prognostic Groups*
Group T
N
M
PSA
Gleason
IIB
T2c
N0
M0
Any PSA
Any Gleason
T1 – 2
N0
M0
PSA ≥ 20
Any Gleason
T1 – 2
N0
M0
Any PSA
Gleason ≥ 8
T3a – b N0
M0
Any PSA
Any Gleason
III
Introducing the Next Generation of Prostate Cancer Staging –
Working with The AJCC Cancer Staging Manual Seventh Edition
No materials in this presentation may be repurposed
without the express written permission of the American Joint Committee on Cancer.
Permission requests may be submitted at CancerStaging.net.
16
Anatomic Stage/Prognostic Groups*
Group T
N
M
PSA
Gleason
IV
T4
N0
M0
Any PSA Any Gleason
Any T
N1
M0
Any PSA Any Gleason
Any T
Any N
M1
Any PSA Any Gleason
• * When either PSA or Gleason is not available, grouping
should be determined by T stage and/or either PSA or
Gleason as available.
Anatomic Stage/Prognostic Groups
• Choosing the appropriate category
– Must meet all the criteria in that line
– If PSA and Gleason are unknown
• Grouping is determined by T
• Use the PSA X and Gleason X line if available
• More than one Stage Group applies
– Choose the higher stage
– Important for patients to NOT be undertreated
Prognostic Factors – Required for
Staging
• Prostate-specific antigen (PSA)
• Gleason Score
– Will be recorded twice by registrars
– Biopsy or TURP Gleason
– Prostatectomy Gleason
Introducing the Next Generation of Prostate Cancer Staging –
Working with The AJCC Cancer Staging Manual Seventh Edition
No materials in this presentation may be repurposed
without the express written permission of the American Joint Committee on Cancer.
Permission requests may be submitted at CancerStaging.net.
17
Prognostic Factors – Clinically
Significant
• Gleason primary and secondary patterns
• Gleason tertiary pattern
• Clinical staging procedures performed
• Number of biopsy cores examined
• Number of biopsy cores positive for ca
Histologic Grade
• Gleason score is recommended grading system
– Accounts for inherent morphologic heterogeneity
– Studies clearly established its prognostic value
• Gleason score
– Primary and secondary pattern assigned
– Summed to yield a total score
• Vast majority of newly dx needle bx
– Graded Gleason score 6 or above
Histologic Grade
• Tertiary pattern
– Radical prostatectomy
– Reported but not added to score
• Prostatectomy specimen processing
– Determine dominant nodule or separate tumor
nodules
• Dominant nodule in prostatectomy
– Gleason score separately mentioned
– Often the focus with highest grade/stage
Introducing the Next Generation of Prostate Cancer Staging –
Working with The AJCC Cancer Staging Manual Seventh Edition
No materials in this presentation may be repurposed
without the express written permission of the American Joint Committee on Cancer.
Permission requests may be submitted at CancerStaging.net.
18
Histologic Grade
• Gleason X
Gleason score cannot be
processed
Well differentiated (slight
• Gleason <6
anaplasia)
• Gleason 7
Moderately differentiated
(moderate anaplasia)
• Gleason 8-10 Poorly differentiated/
undifferentiated (marked
anaplasia)
Histopathologic Type
• Classification applies to
– Adenocarcinoma
– Squamous cell carcinoma
• Adenocarcinoma variants include
–
–
–
–
Mucinous
Signet ring cell
Ductal
Neuroendocrine (including small cell)
Histopathologic Type
• Does not apply to
– Sarcoma
– Transitional cell (urothelial) carcinoma
• Transitional cell (ureothelial) ca of prostate
– Classified as urethral tumor (see chapter 46)
Introducing the Next Generation of Prostate Cancer Staging –
Working with The AJCC Cancer Staging Manual Seventh Edition
No materials in this presentation may be repurposed
without the express written permission of the American Joint Committee on Cancer.
Permission requests may be submitted at CancerStaging.net.
19
Summary
• Limitations in defining clinical stage
– Size and local extent
• Balanced by addition of prognostic factors
– Histologic grade
– PSA level
– Percentage of biopsy cores positive
• Goal
– Assess different treatment therapies
– Predict outcomes
Conclusions
• Anatomic Stage/Prognostic Groups includes
–
–
–
–
–
T
N
M
PSA
Gleason
• Documentation
– Provide data for analysis
– Evidence for possible changes in AJCC 8th Edition
American Joint Committee on Cancer
Contact Information
AJCC Web Site: www.cancerstaging.org
Karen A. Pollitt – Manager
email: [email protected]
phone: 312-202-5313
Donna M. Gress, RHIT, CTR – Technical Specialist
email: [email protected]
phone: 312-202-5410
Introducing the Next Generation of Prostate Cancer Staging –
Working with The AJCC Cancer Staging Manual Seventh Edition
No materials in this presentation may be repurposed
without the express written permission of the American Joint Committee on Cancer.
Permission requests may be submitted at CancerStaging.net.
20
American Joint Committee on Cancer
Contact Information
Marty Madera – Education Administrator
email: [email protected]
phone: 312-202-5287
Judy Janes – AJCC Coordinator
email: [email protected]
phone: 312-202-5205
General Inquiries can be directed to
[email protected]
Questions
Future AJCC 2010 Webinars
• February 24 – Colorectal
• March 5 – Breast
• March 15 – Head & Neck
• March 29 – Lung
• April 13 – Esophagus & Stomach
Introducing the Next Generation of Prostate Cancer Staging –
Working with The AJCC Cancer Staging Manual Seventh Edition
No materials in this presentation may be repurposed
without the express written permission of the American Joint Committee on Cancer.
Permission requests may be submitted at CancerStaging.net.
21