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Staging in Cancer: Order out of Chaos
Lily L. Lai, MD, FACS
Chair, Clinical Cancer Committee
City of Hope
Life
The one thing that (scientists) do not and
must not tolerate is disorder. The whole
aim of theoretical science is to carry to
the highest possible and conscious
degree the perceptual reduction of chaos
that began in so lowly and (in all
probability) unconscious a way with the
origin of life.
George Gaylord Simpson (Principles of Animal Taxonomy, 1961)
Cancer
Outline
•
•
•
•
•
History
Rationale
Application
Types of Staging
Future
History
Frederic Greene
Cuthbert Dukes
Pierre Denoix
Mahul Amin
Dukes
1932
A
B
C
+LNs
Astler & Collier
1954
A
B1 B2
C1
C2
+ LNs
TNM
1968
Tis T1 T2 T3 T4
Staging: why?
• Cancer care expectations
– To aid the clinician in planning treatment
– To give some indication of prognosis
– To assist in evaluating the results of treatment
– To facilitate the exchange of information between
treatment centers
– To contribute to continuing investigations of human
malignancies
UICC, 1958
AJCC Cancer Staging Manual (v. 7),
2010
Staging: Why?
• Institutional requirements
– American College of Surgeons, Commission on
Cancer, Clinical Cancer Program
• Standards for evaluation of cancer clinics since 1931
• Accreditation of institution as providing quality cancer care
• Surveys of programs conducted every 3 years
– Standards of the ACoS, CoC specific to Staging
• 90% of cases are correctly staged
• Clinical staging occurs preoperatively, pre-treatment
• Completed staging (Collaborative Stage) within 4 months of
initiating treatment
The three axes of cancer classification
Topographic site
Location can change
progression
Rectal v. colon
Head and neck v. lung
Histology
Topographic site
Histologic type
(disease site)
Kind of cell responds to
treatments
Nonsmall cell lung ca v.
lung cancer
Melanoma v. basal cell
skin
Anatomic extent
(Staging)
Degree of local and
involvement
Patient’s
Disease
Anatomic extent
(TNM)
Anatomic Staging
• Based on three components
T
The extent of the primary tumor
N
The absence or presence and extent of
node metastasis
M
The absence or presence of distant
Primary Tumor
(T)
Regional Lymph
nodes (N)
Distant Metastases (M)
Cannot be assessed Tx
Nx
Mx
No evidence
T0
N0
M0
In situ
Tis
Increasing
involvement
T1 - 4
N1-3
M1
Tumor (T)
• cT can be based on palpation or imaging
• pT requires adequate resection of tumor
• If tumor is removed in pieces, an effort at reconstruction is
needed to approximate the native size prior to manipulation
(add the pieces together)
• In cases with > 1 tumor in the same site, the tumor that is
the highest T category is used and a parenthesis after T is
used to designate multiplicity: T1 (m) or T1 (3)
• In cases with simultaneous bilateral tumors, each tumor is
staged
– as independent tumors (breast)
– as metastasis (lung)
• Unknown primary is based on clinical suspicion of primary
origin and is designated T0 (not Tx)
Tumor (T): Breast Cancer
T1
T2
T3
>5 cm
tumor
T4
Tumor (T): Colorectal Cancer
Tumor (T): Lung Cancer
T1
T2
T4
T3
Accurate T-staging predicts outcome
Staging outcomes
AJCC v. 6
Staging outcomes
AJCC v. 7
Regional Lymph Nodes (N)
• pN entails removal of a sufficient number of LNs to
ensure appropriate staging
– Colon (>12)
– Gastric (>16)
• If number of LNs reveals negative nodes but the total
< suggested LN dissection, then N = pN0
– May affect treatment
• Sentinel lymph node assessment is appropriate in
some sites (breast, melanoma)
• Isolated tumor cell clusters (ITC) (< 0.2mm, less than
200 cells) are staged as N0(i+)
• Micrometastases (> 0.2 mm, <2 mm, more than 200
cells) are staged as N1mi
– Breast T0-1,N1mi = St. 1B
Nodes (N)
Absolute number of positive LNs predict
survival
T1, 2, N1
T3, 4, N1
any T, N2
Greene, CA Cancer J Clin 2008; 58:180-90
Total number of LNs removed predicts survival
Greene, CA Cancer J Clin 2008; 58:180-90
Location of lymph nodes removed predicts
survival
NX
Regional node cannot be
addressed
N0
No regional lymph node
metastases
N1
Metastasis in ipsilateral
peribronchial +/- ipsilateral hilar
and intrapulmonary nodes,
including direct extension
N2
Metastasis in ipsilateral
mediastinal +/- subcarinal nodes
N3
Metastases in contralateral
mediastinal, contralateral hilar,
ipsilateral or contralateral scalene,
or supraclavicular nodes
Metastasis (M)
• Metastasis can be staged clinically (cM) or
pathologically (pM)
• cM is adequate if T and N have meet pathologic
staging
– Biopsy of metastasis not absolutely needed
• If metastasis has tissue diagnosis, then pM
• If metastasis identified, any T and any N is
acceptable including TX, NX, M1
Metastases
Stage Grouping
STAGE
T
N
M
0
I
is
+
-
-
II
+
+/-
-
III
+/-
+
-
IV
+/-
+/-
+
Descriptors
Indication
Suffix
m
Presence of multiple primary T
pT(m)NM
Prefix
y
Post initial treatment (staging after ycTNM or
preop treatment)
ypTNM
r
Recurrent tumor after a disease
free interval
rTNM
a
Autopsy
aTNM
Other factors
• Histopathologic subtype
– Adenocarcinoma, SCCA
• Histology/Grade
– Poor, mod, well differentiated
– Undifferentiated
• Lymphovascular invasion
• Residual tumor
– RX, R0 – 2 resections
• Site-specific factors
– Breast: ER, PR, Her2-neu
– Thyroid: Age
– CRC: Microsatellite instability, MMR, K-ras status
– Prostate: PSA, Gleason’s Score
Site specific factors: Prostate Cancer
STAGE
T
N
M
PSA
Gleason
I
T1a-c
T2a
T1-2a
N0
N0
N0
M0
M0
M0
< 10
< 10
X
<6
<6
X
IIA
T1a-c
T1a-c
T2a
T2b
T2b
N0
N0
N0
N0
N0
M0
M0
M0
M0
M0
<20
< 10, <20
<20
<20
X
7
<6
<7
<7
X
IIB
T2c
T1-2
T1-2
N0
N0
N0
M0
M0
M0
Any
>20
Any
Any
Any
>8
III
T3a-b
N0
M0
Any
Any
IV
T4
Any T
Any T
NO
N1
Any
M0
M0
M1
Any
Any
Any
Any
Any
Any
Clinical, Pathologic, Collaborative Staging
• Clinical (cT, cN, cM)
– Before initiation of primary treatment
– Important in deciding primary treatment
• Pathologic (pT, pN, pM)
– From resected tissues
• Collaborative (CS)
– Clinical, pathologic staging AND nonanatomic (site• Implemented by the cancer registries
• Stage derived through computer algorithms
Collaborative staging: example
• 65 yo male with cT3, cN0 colon cancer
• Preoperative imaging does not demonstrate
metastasis, cM0
• Patient undergoes resection
• Pathology is pT3N1
– Pathology cannot really decide if M0, especially when no
specimen was sent for evaluation of metastases
• Collaborative stage is: T3N1M0 – Stage IIIA
• The “STAGE” is a combination of pathologic
and clinical findings
NCCN Guidelines Version 3.2012
Colon Cancer
PATHOLOGIC STAGE
T1-3, N1-2, M0
Or T4, N1-2, MO
ADJUVANT THERAPY
FOLFOX (category 1) preferred
Other options include:
FLOX (category 1)
Or
CapeOx (category 1)
Or
Capecitabine
Or
5FU/Leucovorin
SURVEILLANCE
History and PE every 3 – 6m for 2 y, then every
6 m for a total of 5y
CEA every 3 – 6m for 2 y, then every 6 m for a
total of 5y
Chest/abdominal/pelvic CT annually x 3 -5y
Colonoscopy in 1y except if no preoperative
colonoscopy due to obstructing lesion,
colonoscopy in 3-6m; if advanced adenoma,
repeat in 1y; if no advanced polyp, repeat in 3y,
then every 5 y
PET-CT scan is not reoutinely recommended
See Principles of Survivorship
COL-4
Changes in 2010
• Revision cycle = 6 – 8 years
– AJCC Cancer Staging Manual (Version 7), published Nov 2009
• Applied to cancer cases from January 2010
– AJCC Cancer Staging Manual (Version 8), published in late
• Applied to cancer cases from January 2016
• Lung
– T subcategories (T(n) a,b)
– Nodes by zones (not specific nodal stations)
– Contralateral disease = M1a
• Colon
– N subcategories (N1a – c; N2a - b)
– M subcategories (M1a – single site, M1b – multiple sites)
• Breast
– Stage I subcategories (IA, 1B – includes LN with
Limitations of Staging
• Not used in hematologic malignancies
– Ann Arbor Staging System
• Not used in pediatric cancer
• Not useful in rare diseases
– Not enough cases to stratify T, N, M
• Merkel Cell Cancer
– Lumping different histopathologic subtypes
• Soft tissue sarcoma: multiple histologies
• Dominated by anatomic pathology and
histology (size, nodes, histopathology,
grade)
– Gradually incorporating other prognostic variables
Future of staging
• Refined clinically
– Number of lymph nodes in CRC
– Ulceration in melanoma
• Molecular markers
– Microarray research to determine prognosis based on
– Oncotype DX in breast cancer, in CRC
• Post treatment staging vs. pretreatment staging
– Rectal cancer – does pretreatment staging matter if
pathological response to chemoradiation?
Staging in the future?
Essential Factors
TNM categories
Histologic grade
Extramural venous invasion
Obstruction
Quality of surgery
Additional Factors
Grade
Tumor perforation
Perineural invasion
Invasion pattern
Peritumoral lymphoid reaction
Medullary type
CEA serum level
Number of lymph nodes
Resected
New and Promising Factors
Microsatellite instability
LOH 18q status
P53
DNA ploidy
VEGF, Kras expression
20q copy number
Greene, CA Cancer J Clin 2008; 58:180-90
Responsibilities
• Completion of forms
– Accurate
– Timely
• Completed staging within 4 months of initial treatment
• Clinical staging before patient receives initial treatment
– Attendings must sign and are ultimately responsible – in
• Use of patient stage in notes, presentations
• Use of Stage in multidisciplinary conferences
– References to NCCN guidelines in treatment
Never wonder. By means of addition, subtraction,
multiplication, and division, settle everything
somehow.
Charles Dickens, Hard Times, 1853
Acknowledgements
Ina Ervin, Registrar (Emeritus)
Kelli Olsen, Registrar
COH Tumor Registry
ACS, Commission on Cancer
National Comprehensive Cancer Network
References
•
Gunderson LL et.al. Revised Tumor and Node Categorization for
Rectal Cancer Based on Surveillance, Epidemiology, and End Results
and Rectal Pooled Analysis Outcomes, JCO Jan 10, 2010:256-263;
published online on November 30, 2009
•
Kligerman, S. and G. Abbott (2010). "A Radiologic Review of the New
TNM Classification for Lung Cancer." Am. J. Roentgenol. 194(3): 562573.
•
AJCC Committee, AJCC Staging Manual, Version 7, Springer-Verlag,
2009.
•
Greene FL. The Staging of Cancer: A Retrospective and Prospective
Appraisal, CA Cancer J Clin 2008;58;180-190
•
http://www.nccn.org/professionals/physician_gls/f_guidelines.asp