Download Updates in TNM Staging of Prostate Cancer

Updates in TNM Staging
of Prostate Cancer
Samson W. Fine, MD
Memorial Sloan Kettering Cancer Center
AJCC 8TH EDITION – PROSTATE TEAM
• Multidisciplinary effort
•
•
•
•
•
Radiation Oncology
Urologic Surgery
Urologic Oncology
Biostatistics
Pathology
Updates in TNM Staging of Prostate Cancer
• National Cancer Data Base
(NCDB)
• Recent publications since
2008 (7th edition)
– Focus on quality of manuscripts
• Literature watch from UICC
• Levels of evidence (and
Guiding Principles)
• Guidance of local & national
leaders
AJCC Levels of Evidence
I. Includes consistent results from multiple large, well-designed and wellconducted national/international studies in appropriate patient populations
with appropriate end points and treatments. Prospective/retrospective
population-based registry studies acceptable.
II. Is obtained from at least one large, well-designed and well-conducted
study in appropriate patient populations with appropriate end points and
with external validation
III. Somewhat problematic because of one or more factors: number, size
or quality of individual studies; inconsistency of results across individual
studies; appropriateness of patient population or outcomes
IV. Insufficient because appropriate studies have not yet been performed
Updates in TNM Staging of Prostate Cancer
How elements were excluded
• Based on available data
• Critical review of level of evidence
• Examples of topics that fell below acceptable level:
• Imaging (e.g. MRI)
• Molecular markers
• Imaging (does have a new section):
• “…inter-observer reproducibility, issues with patient selection and
contradictory results have limited the utility of imaging in clinical
staging.”
Updates in TNM Staging of Prostate Cancer
Summary of changes:
Comparison of 7th & 8th editions
7th EDITION
• Extraprostatic extension in the
form of microscopic bladder
neck invasion changed from
pT4 to pT3a
• Gleason score recognized as
the preferred grading system
• Prognostic factors incorporated
into the Prognostic Stage
Groups (GS; PSA)
Updates in TNM Staging of Prostate Cancer
8TH EDITION
• Definition of Primary Tumor:
pathologically organ-confined
disease = pT2; no longer subclassified by extent of involvement
or laterality
• Histologic Grade: GS (2014
criteria) and Grade Group [GrdGrp]
should both be reported
• AJCC Prognostic Stage Groups:
Stage III includes select OC
tumors based on PSA and/or
GS/GrdGrp
Organ-confined disease
• 1992: pT2a, b, c
• 1997: pT2a, b
• 2002: pT2a, b, c
• 2010: pT2a, b, c
Updates in TNM Staging of Prostate Cancer
Evidence to change pT2 classification
• Substaging does not convey prognostic
information
• Correlation between cT & pT substaging
poor
• Unilateral large tumor would be assigned
lower pT stage than 2 small b/l cancers
• Poor reproducibility: <1/2 v. >1/2 lobe
Stephenson et al. Cancer 2004;100:1646-1649
Updates in TNM Staging of Prostate Cancer
Summary of Changes #1:
Definition of Primary Tumor
• Pathologically organ-confined
disease is considered pT2 and no
longer sub-classified by extent of
involvement or laterality (III)
Updates in TNM Staging of Prostate Cancer
PROGNOSTIC GRADE
GROUPS
BJU Int 2013; 111:753-760
Updates in TNM Staging of Prostate Cancer
• 5 institutions
• 21K patients: RP
• 16K patients: NB
• 5.5K patients: RT
• GrdGrp 1 v. GS 6
• discrimination
GS7:
• GrdGrp 2 v. 3
Eur Urol 2016;69:428-435
Updates in TNM Staging of Prostate Cancer
Br J Cancer 2016;114:1078-1083
Updates in TNM Staging of Prostate Cancer
Eur Urol 2016;69:1135-1141
Summary of Changes #2: Histologic Grade
• Gleason
score (2014
criteria) &
Grade Group
should both
be reported
(II)
Grade Group
1
2
3
4
5
Updates in TNM Staging of Prostate Cancer
Gleason Score
≤6
7
7
8
9 or 10
Gleason Pattern(s)
≤3+3
3+4
4+3
4+4 (3+5/5+3)
4+5, 5+4, or 5+5
2016 WHO GU Classification
Table 3.03
Grade group 1: Gleason score < 6
Only individual discrete well-formed glands
Grade group 2: Gleason score 3+4=7
Predominantly well-formed glands with lesser component of
poorly formed / fused / cribriform glands
Grade group 3: Gleason score 4+3=7
Predominantly poorly formed / fused / cribriform glands with lesser component
of well-formed glands
Grade group 4: Gleason score 4+4=8; 3+5=8; 5+3=8
Only poorly formed / fused / cribriform glands
Predominantly well-formed glands and lesser component lacking glands
Predominantly lacking glands and lesser component of well-formed glands
Grade group 5: Gleason scores 9-10
Lack gland formation (or with necrosis) with or without poorly formed / fused /
cribriform glands
Updates in TNM Staging of Prostate Cancer
Updates in TNM Staging of Prostate Cancer
Revisions to CAP Protocols
• In addition to Primary/Secondary/Tertiary
Gleason patterns and Total Gleason Score
• Grade Group
___ Grade group 1
___ Grade group 2
___ Grade group 3
___ Grade group 4
___ Grade group 5
Updates in TNM Staging of Prostate Cancer
AJCC Prognostic Stage Groups
Prognostic Stage
Group
I
IIA
IIB
IIC
IIIA
IIIB
IIIC
IVA
IVB
T
N
M
PSA
Grade Group
cT1a-c, cT2a
pT2
cT1a-c, cT2a
cT2b-c
T1-2
T1-2
T1-2
T1-2
T3-4
Any T
Any T
Any T
N0
N0
N0
N0
N0
N0
N0
N0
N0
N0
N1
N0
M0
M0
M0
M0
M0
M0
M0
M0
M0
M0
M0
M1
< 10
< 10
≥ 10 < 20
< 20
< 20
< 20
< 20
≥ 20
Any
Any
Any
Any
1
1
1
1
2
3
4
1–4
1–4
5
Any
Any
Updates in TNM Staging of Prostate Cancer
Am J Surg Pathol 2012;36:1346-1352
Stage I includes a pT staged tumor
Updates in TNM Staging of Prostate Cancer
AJCC Prognostic Stage Groups
Prognostic Stage
Group
I
IIA
IIB
IIC
IIIA
IIIB
IIIC
IVA
IVB
T
N
M
PSA
Grade Group
cT1a-c, cT2a
pT2
cT1a-c, cT2a
cT2b-c
T1-2
T1-2
T1-2
T1-2
T3-4
Any T
Any T
Any T
N0
N0
N0
N0
N0
N0
N0
N0
N0
N0
N1
N0
M0
M0
M0
M0
M0
M0
M0
M0
M0
M0
M0
M1
< 10
< 10
≥ 10 < 20
< 20
< 20
< 20
< 20
≥ 20
Any
Any
Any
Any
1
1
1
1
2
3
4
1–4
1–4
5
Any
Any
Updates in TNM Staging of Prostate Cancer
Summary of Changes #3:
AJCC Prognostic Stage Groups
• Stage II further subdivided by Gleason
Score/Grade Group
•Stage III includes select organ-confined
tumors based on PSA and Gleason
Score/Grade Group (II)
Updates in TNM Staging of Prostate Cancer
AJCC-Prostate
Registry Data Collection Variables
• Tertiary/Limited Gleason patterns (prostatectomy)
• Number of cores positive / # of cores examined
• For + cores: u/l, b/l, beyond prostate
• Metastatic sites
Updates in TNM Staging of Prostate Cancer
Evaluation of Risk Assessment Tools
• 15 available prognostic models evaluated = multivariable model
where factors predict a clinical outcome in the future
• 13 models rejected, including all 8 for localized disease
• 2 models met all of the criteria – both based on data from large
phase III trials in metastatic pts. that were externally validated
Approved Prognostic Tool
Reference
Metastatic castration-resistant prostate cancer
Halabi et al. J Clin Oncol 2014;32:671-677
Metastatic castration-resistant prostate cancer
treated with second-line therapy
Halabi et al. J Natl Cancer Inst 2013;105:17291737
Updates in TNM Staging of Prostate Cancer
Precision Medicine Core
Inclusion/Exclusion Criteria
• Inclusion Criteria:
• Inclusion Criteria:
• OS/DSS/DSM
• Calibration assessed & provided
• Model addresses clinically relevant Q
• Model validated over time frame / in practice setting
relevant to contemporary pts.
• Model includes relevant predictors
• Validation study: which pts. used to evaluate & data
sets I/E criteria
• Generalizability & external validation
• What treatment(s) were applied if any and with what
frequency
• Development +/- validation of prediction model appears
as peer-reviewed journal article
• Well-defined prognostic time zero
• All predictors known at time zero and clearly defined
• Sufficient detail to implement model (i.e. equation)
or free access to it
• Measure of discrimination must be reported (usually
as CI) on the validation data sets (VDS)
Updates in TNM Staging of Prostate Cancer
• Exclusion Criteria:
• Substantial proportion of pts. with no follow-up in VDS
• No info on # of pts. w/ missing values in VDS
• # of events in VDS is small
What’s Not Included
• Tumor Volume
• Extent of extraprostatic extension (EPE)
• Subclassification of (+) Surgical Margins
Updates in TNM Staging of Prostate Cancer
Tumor Volume/Size
• Well-established correlation with grade, stage,
tumor progression
• Visual estimate quantitation and/or maximum
diameter
• Fail to show IPV
• No accepted standard for measurement of
tumor volume
• Needs to be appropriate for routine clinical practice
• Even “objective” measures subject to issues of:
• Total v. subtotal embedding
• Processing effects: shrinkage; irregular sectioning
• Dominant/index tumor v. overall volume/size
Tumor Quantitation
Intraglandular extent (%)
Maximum size of dominant nodule (mm)
International Collaboration on
Cancer Reporting
Tumor Quantitation
% of prostate involved by tumor
Tumor size (dominant nodule, if present):
Greatest dimension:
+ Additional dimensions:
CAP Protocols
Updates in TNM Staging of Prostate Cancer
mm
x
mm
PROSTATIC ADENOCARCINOMA
Prostatic Capsule
• Not a true “capsule”
• Condensation of fibromuscular
stroma
• Covers most of the posterolateral
prostate
• Anterior / Apex / Bladder neck
• Indistinct
• Not present
The Prostatic “Capsule”: Does It Exist?
Ayala AG, et al. Am J Surg Pathol 1989
Updates in TNM Staging of Prostate Cancer
PROSTATIC ADENOCARCINOMA
Prognostic Factors for PSA Progression
• Prognostic Factor
P
Risk Ratio
• Preop PSA
.001
1.02
• Gleason sum
.001
2.01
• Tumor volume
.704
1.01
• Level of PCI
.001
• Level 3F vs 0-2
.019
2.03
• Level 3E vs 0-2
.001
3.88
• SVI
.002
2.00
Wheeler TM et al.
Hum Pathol
• +LN
.001
2.55
1998; 29:856-862
Updates in TNM Staging of Prostate Cancer
• 10,750 RP pts.
• No EPE: 7843 (73%)
• F-EPE: 1258 (12%)
• NF-EPE: 1649 (15%)
Extent of Extaprostatic Extension
Updates in TNM Staging of Prostate Cancer
Urology 2015;85:161-164
Surgical Margin Positivity
pT2, +SM
Tumor at inked margin in an area
of capsular incision
Updates in TNM Staging of Prostate Cancer
pT3a, +SM
Tumor at inked margin in an area
of extraprostatic extension
Positive Surgical Margins: Meta-Analysis
J Urol 2009; 182:1357-1363
pT2
pT3a
pT3b
GS6
GS7
GS>8
Number and extent of M+ correlated with BCR
Did not improve predictive accuracy v. +/- margin alone
Updates in TNM Staging of Prostate Cancer
Further Subclassification
of +SM
Margin status
• Independent Predictive Value for BCR
Gleason score at margin [if >1 +SM,
record highest score]: REC
• Location
• Extent
• One v. multiple
• Length in mm
• Grade at +SM (GG, GS)
• Limited follow up
• Limited # of events
**Lack of randomized study to see if early
adjuvant RT = decreased risk of BCR
Location(s): REQ
Extent (total) [if >1 +SM, record
cumulative length]: REC
International Collaboration on
Cancer Reporting
Margins
Margin involved by invasive carcinoma:
Focal (<3mm)
REQ
Nonfocal (>3mm)
Linear length of +SM:
mm REC
Location of +SM: REQ
Gleason PATTERN at +SM:
Pattern 3
REC
Pattern 4 or 5
CAP Protocols
Updates in TNM Staging of Prostate Cancer
Disclosure of Relevant
Financial Relationships
USCAP requires that all faculty in a position to
influence or control the content of CME disclose any relevant financial
relationship WITH COMMERCIAL INTERESTS which they or their
spouse/partner have, or have had, within the past 12 months, which relates to
the content of this educational activity and creates a conflict of interest.
Dr. Samson W. Fine declares he has no conflict(s) of interest to disclose.
Updates in TNM Staging of Prostate Cancer
Updates in TNM Staging of Prostate Cancer: References
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