Download LUNG CANCER. III. SCREENING, DIAGNOSIS AND STAGING

Corso Integrato di Clinica Medica
ONCOLOGIA MEDICA
AA 2010 - 2011
LUNG CANCER. III.
SCREENING, DIAGNOSIS
AND STAGING
Prof. Alberto Riccardi
SCREENING
LUNG CARCINOMA
Screening. I. Sputum cytology and chest X - ray
* screening people at high risk (men > 50 yrs; current
or former smokers ≥ 40 cigarettes / day; women not
studied) by sputum cytology and chest X - ray: no ↑
survival (= despite 90% of pts with LC detected by
screening were asymptomatic, no # in survival rates
between screened and non screened groups, probably
due to presence of metastases in most screened pts);
- false+ (4 - 15%) → overdiagnosis and overtreatment
LUNG CARCINOMA
Screening. II. Computed tomography
* low dose spiral computed tomography (CT) lung
scanning (only pulmonary parenchyma examined,
no use of intravenous contrast and no necessity of
physician present at exam, quick, within one breath)
and involving low doses of radiation) > sensitive
(especially for peripheral lesions)
LUNG CARCINOMA. Screening. III. Computed tomography
3 - D images of nodule
comparing results of baseline
and 2nd study 3 mos later =
tumor growth, consistent with
diagnosis of lung cancer (pt
diagnosed adenocarcinoma)
LUNG CARCINOMA
Screening. IV. Computed tomography
* survival from diagnosis longer (predicted 10 - yr
survival = 92% in screening - detected stage I
NSCLC pts);
- however, no decline in no. of advanced LC cases
or deaths from LC in screened group;
- overall, spiral CT diagnoses more early LC
without improving overall LC mortality;
- moreover, high false+ rate (abnormal tests in 25 50% of screened pts, with LC in only 10% of them)
LUNG CARCINOMA
Screening. V. Computed tomography
no. of
lung
cancers Stage I,
(%)
%
Name or institution
no.
no. of positive
results (%)
ELCAP, US
1184
40 (3.4)
7 (0.6)
83
I - ELCAP, International
27,45
6
NR
74 (0.3)
86
University of Munster
1735
89 (5.1)
10 (0.6)
70
Mayo Clinic, US
5365
NR
31 (0.6)
61
Hitachi Health Care
Center, Japan
5568
148 (2.7)
4 (0.07)
100
PALCAD, Ireland
826
NR
3 (0.4)
100
University of Milano,
Italy
996
34 (3.4)
11 (1.1)
100
NY - ELCAP, USA
6014
361 (6.0)
20 (0.3)
85
LSS, USA
1398
360 (25.8)
8 (0.6)
40
LUNG CARCINOMA
Screening. VI. Computed tomography
* high false+ rate (abnormal tests in 25 - 50% of
screened pts, with LC in only 10% of them)
LUNG CARCINOMA
Screening. VII. Computed tomography
* survival from
diagnosis longer
(predicted 10 - yr
survival = 92%) in
screening detected stage I
NSCLC pts
LUNG CARCINOMA
Screening. VIII. Computed tomography (combined results)
* however, no decline in no. of advanced LC cases or deaths from
LC in screened group;
* from Istituto Tumori
(Milan, Italy), Mayo Clinic
(Rochester, Minn) and Moffitt
Cancer Center (Tampa, Fla);
- left axis = actual and
predicted no. of individuals
with different LC outcomes;
- right axis = no. at risk
(blue tinted area);
- P values for # between
observed and predicted no.
of events over study
LUNG CARCINOMA
Screening. IX. Computed tomography
* concerns include influence of:
- lead - time bias,
- length - time bias, and
- over - diagnosis (slow - growing cancers unlikely to
cause death)
LUNG CARCINOMA
Screening. X. Lead time bias
* diagnosis of disease made earlier in screened group,
resulting in apparent ↑ in survival (time of death = same)
LUNG CARCINOMA
Screening. XI. Lenght time bias
* probability of detecting disease related to growth rate of tumor;
* aggressive, rapidly growing tumors → short potential screening period (= short
interval between possible detection and symptoms) → unless screening repeated
frequently, pts more likely to present with symptoms;
* slow growing tumors → longer potential screening period (= more likely to be
detected when asymptomatic) → higher proportion of indolent tumors found in
screened group, wth apparent improvement in survival
LUNG CARCINOMA
Screening. XII. Overdiagnosis bias
* extreme form of length time bias;
* detection of very
indolent tumors in screened
group → apparent increase
in no. of cases of cancer (3
in screened group and one
in control group) and in
survival [2 / 3 pts in
screened group treated and
died of natural causes,
without evidence of disease
(= 66% survival) and one pt
* 2 pts in control group died with
in control group did not
undiagnosed LC not affecting natural life span
survive (0% survival]), with
no effect on mortality (one
death from LC in each
group)
LUNG CARCINOMA
Screening. XIII. Computed tomography
* over - diagnosis = well - established problem in prostate
cancer screening, but also some lung cancers not fatal;
- e.g., many of small adenocarcinomas found as "ground
glass" opacities on screening CT have such long doubling
times (> 400 days) never harming pt
LUNG CARCINOMA
Screening. XIV. Computed tomography
* while CT screening detects LC in 1 - 4% of screened pts over
5 - yr period, it also detects substantial no. of false+ lung
lesions (25 to 75%) needing follow - up and evaluation;
* appropriate management of these small lesions undefined;
- unnecessary treatment including thoracotomy and lung
resection → adding cost, mortality and morbidity
LUNG CARCINOMA
Screening. XV. Computed tomography
* a large, randomized trial of CT screening for LC (National
Lung Cancer Screening Trial) involving ~ 55,000 individuals
completed accrual and will provide definitive data in next
several yrs on whether screening ↓ mortality;
- until these results available, routine CT screening not be
recommended for any risk group;
* for pts pts who want be screened, physicians need to
discuss possible benefits and risks of screening, including risk
of false+ scans that could result in multiple follow - up CTs and
possible biopsies for malignancy not life - threatening
PREVENTION
LUNG CARCINOMA
LC prevention
* deterring children from taking up smoking and
helping young adults stop smoking likely most
effective LC prevention;
- smoking cessation programs successful in 5 20% of volunteers (poor efficacy due to nicotine
addiction, as strong as heroin addiction);
* chemo - prevention = experimental approach to ↓
LC risk (at present, no benefit for chemo prevention, with two putative chemo - preventive
agents, vitamin E and β - carotene, actually ↑ risk of
LC in heavy smokers)
GUIDELINES FOR EVALUATION
LUNG CARCINOMA
Giudelines for evaluation
* data to be obtained once signs, symptoms or
screening suggest LC:
- tissue diagnosis of malignancy;
- histologic cell type, and
- stage of pt (for appropriate treatment)
DIAGNOSIS
LUNG CARCINOMA
Diagnosis. I. Tumor tissue
* tumor tissue for diagnosis when signs,
symptoms or screening data suggest LC:
* pathologist required for definite diagnosis of
epithelial malignancy and crucial differentiation
between SCLC and NSCLC (difficult with
cytology)
LUNG CARCINOMA.
Diagnosis. II. Obtaining tumor tissue
* bronchial or transbronchial biopsy (fiberoptic
bronchoscopy);
- node biopsy during mediastinoscopy;
- fine - needle percutaneous aspiration of thoracic or
extrathoracic (enlarged nodes, soft tissue mass, lytic bone
lesion, bone marrow or adequate cell block from malignant
pleural effusions) tumor masses using CT guidance;
- operative specimen at surgical resection;
- in most cases, pathologist able for definite diagnosis of
epithelial malignancy and distinguish SCLC from NSCLC;
[* cytologic diagnoses from washings or needle aspirates only
for very high risk or relapsing pts after initial treatment]
BRONCHIAL OR TRANSBRONCHIAL BIOPSY
BRONCHIAL OR
TRANSBRONCHIAL
BIOPSY
FINE - NEEDLE
PERCUTANEOUS
ASPIRATION
OF THORACIC
MASS
STAGING
LUNG CARCINOMA
STAGING
* “anatomic staging” = location of tumor, and
* “physiologic staging” = pt's ability to withstand
antitumor treatments;
* e.g. in NSCLC:
- resectability (= tumor can be entirely removed
by standard surgical procedure?, e.g., lobectomy
or pneumonectomy) depends on anatomic stage,
and
- operability (= can pt tolerate such a surgical
procedure?) mainly depends on cardio pulmonary function
STAGING
NON SMALL CELL LUNG CANCER
LUNG CARCINOMA
NSCLC
* from TNM, especially in evaluating pts for
curative surgery (or radiotherapy);
* T (tumor size), N (regional node involvement),
and M (presence or absence of distant
metastases) factors combined to form different
stage groups (with prognostic information)
LUNG CARCINOMA. II.
Distribution by localization at diagnosis
* 30% = local disease
(curative attempt with
surgery or radiotherapy =
pts with stage I or II and
some with stage IIIA
disease);
- 30% = involved regional
lymph nodes (regional
disease amenable or not for
curative attempt = some pts
with stage IIIA and others
with stage IIIB disease);
- 40% = metastases
STAGING
1997
International System for Staging
Lung Cancer adopted by
American Joint Committee on Cancer
(AJCC)
and
Union Internationale Contre le Cancer
(UICC)
STAGING NSCLC. I.
STAGING NSCLC. II.
LYMPH NODE (N) INVOLVEMENT DESCRIPTOR
NX
= regional lymph nodes cannot be assessed
N0
= no regional lymph node metastasis;
N1
= metastasis to ipsilateral peribronchial and / or
ipsilateral hilar lymph nodes, and
intrapulmonary nodes
involved by direct extension of
primary tumor
N2
= metastasis to ipsilateral mediastinal and / or subcarinal
lymph nodes(s)
N3
= metastasis to contralateral mediastinal, contralateral
hilar, ipsilateral or contralateral scalene, or
supraclavicular lymph node(s)
NSCLC STAGING
LYMPH NODE MAP
N1 = HILAR LOBAR
NODES
N2 = MEDIASTINAL
NODES
NSCLC STAGING
LYMPH NODE MAP
N1 = HILAR LOBAR NODES
N2 = MEDIASTINAL NODES
* Mountain - Dresler lymph
node map (modified from
original of American
Thoracic Society, 1997);
- N2 nodes include: superior
and inferior mediastinal
nodes and aortic nodes
NSCLC STAGING
LYMPH NODE MAP
N1 = HILAR LOBAR NODES
N2 = MEDIASTINAL NODES
Naruke lymph node map for staging
lung cancers (Japan Lung Cancer
Society, 2000)
STAGING NSCLC. III.
Staging NSCLC. IV.
surgery
no surgery
NON SMALL LUNG CANCER STAGES
surgery
no
surgery
LUNG CARCINOMA
Staging. III. NSCLC stages at diagnosis
* ~ 1 / 3 of pts = localized disease possibly
treatable with surgery or radiotherapy (stage I or II
pts and some stage IIIA pts);
* ~ 1 / 3 of pts = local or regional disease
amenable or not to curative attempt with
combined modality therapy (some stage IIIA pts
and all stage IIIB pts), and
* ~ 1 / 3 of pts = distant metastases (stage IV)
NSCLC
Survival by stage
STAGING
INTERNATIONAL ASSOCIATION
FOR THE STUDY OF LUNG CANCER
(IASLC, 2010)
STAGING
INTERNATIONAL ASSOCIATION FOR THE STUDY OF LUNG CANCER
(IASLC, 2010). I.
* revised International System for Staging Lung Cancer (based
on information from clinical database of > 5,000 pts) adopted in
2010 by American Joint Committee on Cancer (AJCC) and
Union Internationale Contre le Cancer;
- revisions provide greater prognostic specificity for pt groups
(however, the correlation between stage and prognosis
predates the widespread availability of PET imaging)
STAGING
INTERNATIONAL ASSOCIATION FOR THE STUDY OF LUNG CANCER
(IASLC, 2010). II.
* recommended for classification of both NSCLC and SCLC:
* T (primary tumor) redefined:
- T1 subclassified into T1a (≤ 2 cm in size) and T1b (≥ 2 - 3 cm in
size).
- T2 subclassified into T2a (≥ 3 - 5 cm in size) and T2b (≥ 5 - 7 cm in
size);
- T2 > 7 cm in size reclassified as T3;
* multiple tumor nodules in same lobe reclassified from T4 to T3;
- multiple tumor nodules in same lung but a different lobe
reclassified from M1 to T4;
STAGING
INTERNATIONAL ASSOCIATION FOR THE STUDY OF LUNG CANCER
(IASLC, 2010). III.
* no changes for N (regional lymph nodes) classification, but
developed new international lymph node map defining “anatomical
boundaries for lymph node stations” (“zones”);
* M (distant metastases) redefined, with M1 subdivided into M1a and
M1b:
- malignant pleural and pericardial effusions reclassified from T4 to
M1a;
- separate tumor nodules in contralateral lung considered M1a;
- distant metastases = M1b
TUMOR (T) STATUS DESCRIPTOR. I.
TX
primary tumor cannot be assessed, or tumor proven by presence of
malignant cells in sputum or bronchial washings but not visualized by imaging
or bronchoscopy;
T0
no evidence of primary tumor;
Tis
carcinoma in situ;
T1
tumor ≤ 3 cm in greatest dimension, surrounded by lung or visceral
pleura, without bronchoscopic evidence of invasion more proximal
than lobar bronchus (i.e., not in main bronchus)a;
T1a
tumor ≤ 2 cm in greatest dimension;
T1b
tumor > 2 cm but ≤ 3 in greatest dimension
from AJCC: Lung. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed.
New York, NY: Springer, 2010, pp 253 - 70.
bThe uncommon superficial spreading tumor of any size with its invasive component limited to the
bronchial wall, which may extend proximally to main bronchus, also classified as T1a
TUMOR (T) STATUS DESCRIPTOR BY TUMOR SIZE
* T1 < 3 cm:
T1a ≤ 2 cm;
T1b = 2 - 3 cm;
* T2 < 7 cm:
T2a ≤ 3 - 5 cm;
T2b = 5 - 7 cm;
* T3 > 7 cm
TUMOR (T) STATUS DESCRIPTOR. II.
T2
T2a
T2b
tumor > 3 cm but ≤7 cm or tumor with any of following
features:
- involves main bronchus;
- ≥ 2 cm distal to carina;
- invades visceral pleura (PL1 or PL2);
- associated with atelectasis or obstructive pneumonitis extended
to hilar region but not involving entire lung;
> 3 cm but ≤ 5 cm in greatest dimension;
> 5 cm but ≤ 7 cm in greatest dimension
from AJCC: Lung. In: Edge SB, Byrd DR,
Compton CC, et al., eds.: AJCC Cancer Staging
Manual. 7th ed. New York, NY: Springer, 2010, pp
253 - 70
TUMOR (T) STATUS DESCRIPTOR BY TUMOR SIZE
BY LOCAL EXTENT. T2a CANCER
* invasion of visceral
pleura (purple) or main
airway ≥ 2 cm from
carina (red) or atelectasis
or obstructive
pneumonia extending to
hilum, but not involving
entire lung (yellow)
TUMOR (T) STATUS DESCRIPTOR. III.
T3
- tumor > 7 cm or directly invading any of following:
parietal pleural (PL3), chest wall (including superior sulcus
tumors), diaphragm, phrenic nerve, mediastinal pleura or
parietal pericardium;
- tumor in main bronchus < 2 cm from carina but without
involvement of carina;
- associated atelectasis or obstructive pneumonitis of entire
lung or separate tumor nodule(s) in same lobe;
T4
- tumor of any size invading any of following:
- mediastinum, heart, great vessels, trachea, recurrent
laryngeal nerve, esophagus, vertebral body, carina or
- separate tumor nodule(s) in different ipsilateral lobe
from AJCC: Lung. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed.
New York, NY: Springer, 2010, pp 253 - 70.
TUMOR (T) STATUS DESCRIPTOR BY TUMOR SIZE
BY LOCAL EXTENT. T3 CANCER
- invasion of parietal pleura or
pericardium, chest wall,
diaphragm, phrenic nerve or
mediastinal pleura (purple) or
main airway < 2 cm from carina
(red), without carinal
involvement;
- atelectasis or obstructive
pneumonia of entire lung
(yellow), and
- satellite nodule in same lobe
(blue)
TUMOR (T) STATUS DESCRIPTOR
BY SATELLITE NODULES (SN)
* T3 = SN in same lobe;
* T4 = SN in different
ipsilateral lobe;
* M1a = SN in contralateral
lung
TUMOR (T) STATUS DESCRIPTOR BY TUMOR SIZE
BY LOCAL EXTENT. T4 CANCER
* invasion of mediastinum,
heart, great vessels, trachea,
recurrent laryngeal nerve,
esophagus, vertebral body, or
carina (red):
- satellite nodule(s) in different
ipsilateral lobe (orange)
* a new international lymph node map defining anatomical
boundaries for lymph node stations developed
LYMPH NODE ZONES. I.
(International Association for the Study
of Lung Cancer, IASLC). I.
Rusch VW et al
J Thorac Oncol 2009; 4: 568 - 77
* includes proposed grouping of
lymph node stations into “zones”
for purposes of prognostic
analyses;
- exploratory analyses of overall survival
in relationship to various levels of lymph
node involvement previously grouped
together in certain lymph node stations
into “zones”;
- zone concept proposed for future
survival analyses, not for current standard
nomenclature, with hope be of value to
oncologists and radiologists when dealing
with large nodal masses that transgress
individual nodal stations)
Lymph node zones. II.
* lymph node zones are
supraclavicular (green), upper
mediastinal (blue),
aortopulmonary (gray),
subcarinal (yellow), lower
mediastinal (orange), hilar /
interlobar (pink) and peripheral
(aqua) (N2 nodes include:
superior and inferior mediastinal
nodes and aortic nodes)
Lymph node zones. III.
* supraclavicular zone (green) (1 = low
cervical, supraclavicular and sternal
notch nodes)
- upper mediastinal zone (blue) (2R =
right upper paratracheal; 2L = left upper
paratracheal; 3a = prevascular; 3b =
retrotracheal; 4R = right lower
paratracheal; 4L = left lower paratracheal);
- aortopulmonary zone(gray) (5 =
subaortic; 6 = para - aortic);
- subcarinal zone (yellow) (7 =
subcarinal)
- lower mediastinal zone (orange) (8 =
paraesophageal; 9 = pulmonary ligament
hilar)
- interlobar zone (pink) (10 = hilar; 11 =
interlobar);
- peripheral zone (aqua) (12 = lobar; 13 =
segmental; 14 = subsegmental)
LYMPH NODE ZONES. IV.
(International Association for
the Study of Lung Cancer,
IASLC). II.
Rusch VW et al
J Thorac Oncol 2009; 4: 568 - 77
* how IASLC lymph node map
can be applied to clinical staging
by computed tomography scan in
axial (A - C), coronal (D) and
sagittal (E, F) views (order
between right and left
paratracheal region shown in A
and B) Ao, aorta; AV, azygos vein;
Br, bronchus; IA, innominate
artery; IV, innominate vein; LA,
ligamentum arteriosum; LIV, left
innominate vein; LSA, left
subclavian artery; PA, pulmonary
artery; PV, pulmonary vein; RIV,
right innominate vein; SVC,
superior vena cava.
DISTANT METASTASIS (M) DESCRIPTOR. III.
M0
M1
no distant metastasis;
distant metastasis;
M1a = separate tumor nodule(s) in a contralateral lobe or
tumor with pleural nodules or malignant pleural (or pericardial)
effusion*;
M1b = distant metastasis
from AJCC: Lung. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed.
New York, NY: Springer, 2010, pp 253 - 70
most pleural (and pericardial) effusions with lung cancer due to tumor;
- in a no. of pts, however, multiple cytopathologic examinations of pleural (pericardial) fluid
negative for tumor, fluid nonbloody and not an exudate;
- where these elements and clinical judgment dictate that effusion is not related to tumor,
effusion should be excluded as staging element and pt be classified as M0
*
M1a cancer
* associated with
malignant pleural or
pericardial effusion,
malignant pleural nodules,
or with satellite nodules in
contralateral lung (green)
Descriptors, proposed T and M categories and stage groupings
Goldstraw P et al J Thorac Oncol 2: 706, 2007
T = primary tumor; M =
distant metastasis; N0 =
no regional lymph node
metastases; N1 =
metastasis in ipsilateral
peribronchial and/or
ipsilateral hilar lymph
nodes and intrapulmonary
nodes, including
involvement by direct
extension; N2 =
metastasis in ipsilateral
mediastinal and/or
subcarinal lymph node(s);
N3 = metastasis in
contralateral mediastinal,
contralateral hilar,
ipsilateral or contralateral
scalene, or supra clavicular lymph node(s)
Proposed TNM Stage Groups
Goldstraw P et al J Thorac Oncol 2: 706, 2007
T = primary tumor; M = distant metastasis; N0 = no regional lymph node metastases; N1 =
metastasis in ipsilateral peribronchial and / or ipsilateral hilar lymph nodes and
intrapulmonary nodes, including involvement by direct extension; N2 = metastasis in
ipsilateral mediastinal and/or subcarinal lymph node(s); N3 = metastasis in contralateral
mediastinal, contralateral hilar, ipsilateral or contralateral scalene or supraclavicular lymph
node(s)
Proposed TNM Stage Groups
Goldstraw P et al J Thorac Oncol 2: 706, 2007
T = primary tumor; M = distant metastasis; N0 = no regional lymph node
metastases; N1 = metastasis in ipsilateral peribronchial and / or ipsilateral hilar
lymph nodes and intrapulmonary nodes, including involvement by direct
extension; N2 = metastasis in ipsilateral mediastinal and/or subcarinal lymph
node(s); N3 = metastasis in contralateral mediastinal, contralateral hilar, ipsilateral
or contralateral scalene or supraclavicular lymph node(s)
NSCLC
Survival by stage
* overall survival [as Median
Survival Time (MST), mos]
and 5 - yr survival (%), by
“clinical stage” using 6th
edition of TNM (A) and
proposed International
Association of Study of Lung
Cancer recommendations (B)
NSCLC
Survival by stage
* overall survival [as median
survival time (MST), mos] and 5 yr survival (%), by “pathologic
stage” using 6th edition of TNM
(A) and proposed International
Association of Study of Lung
Cancer recommendations (B)
LUNG CARCINOMA
STAGING
* pathological staging requires:
- examination of tumor;
- resection margins;
- lymph nodes status;
* prognostic and treatment decisions based on some of following:
- knowledge of histologic type;
- tumor size and location;
- involvement of pleura;
- surgical margins;
- status and location of lymph nodes by station;
- tumor grade;
- lymphovascular invasion
STAGING
SMALL CELL LUNG CANCER
LUNG CARCINOMA
Staging. III. SCLC. I
* two - stage system (from physical examination,
X - ray, CT and bone scans, and BM examination):
- “limited - stage disease” (~ 30% of pts) =
disease confined to one hemithorax and regional
lymph nodes (including mediastinal, contralateral
hilar, and usually ipsilateral supraclavicular
nodes), and
- “extensive - stage disease” (~ 70% of pts) =
disease exceeding these boundaries
LUNG CARCINOMA
Staging. IV. SCLC. II
* limited - stage disease = tumor encompassed
within a tolerable radiation therapy port (including
contralateral supraclavicular nodes, recurrent
laryngeal nerve involvement, and superior vena cava
obstruction);
- extensive - stage disease (including cardiac
tamponade, malignant pleural effusion, and bilateral
pulmonary parenchymal involvement) = organs
cannot safely tolerate curative radiation doses within
curative radiation therapy port
PRETREATMENT
STAGING PROCEDURES
FOR ALL PTS
PRETREATMENT STAGING PROCEDURES FOR PTS WITH LUNG CANCER
ALL PTS
* complete history and physical (including performance status and weight loss) and
laboratory (including blood count, serum electrolytes, glucose, calcium, and
phosphorus; renal and liver function tests) examination;
* electrocardiogram:
* skin test for tuberculosis;
* chest x - ray;
* CT or MRI scan of chest and abdomen;
* CT scan of brain and radionuclide scan of bone (if any finding suggests metastasis
in these organs);
* fiberoptic bronchoscopy with washings, brushings, and biopsy of suspicious
lesions unless medically contraindicated or if it would not alter therapy (e.g., very late
stage pt);
* X - rays of suspicious bony lesions detected by scan or symptom;
* barium- swallow radiographic examination (if esophageal symptoms exist);
* pulmonary function studies and arterial blood gas measurements (with signs or
symptoms of respiratory insufficiency);
* biopsy of accessible lesions suspicious for cancer if histologic diagnosis is not yet
made or if treatment or staging decisions would be based on whether or not a non pulmonary lesion contains cancer
PRETREATMENT
STAGING PROCEDURES
FOR ALL PTS
LUNG CARCINOMA
General staging procedures. I.
* complete history and physical and laboratory
examination (all medical problems, with prognostic
value of performace status and weight loss; tumor
markers);
- ear, nose, and throat examination (possible second
cancer in this area);
- electrocardiogram:
- skin test for tuberculosis
LUNG CARCINOMA
General staging procedures. II.
* chest X - ray and contrast CT scan (old radiographs
useful for comparison):
- to detect mediastinal nodes, pleural extension and occult
abdominal disease (e.g., of liver and adrenal glands), and
- to plan curative radiation therapy (= design of fields
encompassing all known tumor with avoiding as much
normal tissue as possible);
[- after treatment: for tumor recurrence (surgery or RT
make difficult interpretation of chest X - rays);
* positron emission tomography (PET) scan sensitive in
detecting both intratoracic and metastatic disease]
LUNG CARCINOMA
General staging procedures. III.
* fiberoptic bronchoscopy:
- for pathologic examination, and
- information on tumor size, location, degree of
bronchial obstruction (= assesses resecability) and
recurrence
LUNG CARCINOMA
General staging procedures. IV. Abdomen
* histology of suspicious abdominal lesions to be
confirmed by fine - needle aspiration if pt
candidate for curative surgery (unless
unequivocally CT - detected abnormalities);
- as a rule, a radiographic finding of isolated
lesion (e.g., enlarged adrenal gland) confirmed as
cancer by fine - needle aspiration before rejecting
curative attempt (as decision based on whether or
not lesion contains cancer)
LUNG CARCINOMA
General staging procedures. V. Skeleton and brain
* X - rays + radionuclide scans if sign or
symptoms suggest bone involvement (not
routinely: high % of false+ and false- findings);
* pts suspected for brain metastases be staged
with CT or MRI scans
LUNG CARCINOMA
General staging procedures. VI. Brain
“pts at risk for brain metastases”;
- in a study, 332 pts with potentially operable NSCLC but without
neurological symptoms randomly assigned to brain CT or MRI
imaging to detect occult brain metastasis before lung surgery;
- MRI → trend (p = .06) toward ↑ preoperative detection rate than CT,
with overall detection rate of ~ 7% from pretreatment to 12 mos after
surgery;
- pts with stage I - II disease: detection rate = 4%;
- pts with stage III disease: detection rate = 11.4%;
* still unknown whether ↑ early detection rate of MRI translates into
↑ outcome (not all pts able to tolerate MRI, and contrast - enhanced
CT scan is reasonable substitute)
LUNG CARCINOMA
General staging procedures. VII. Other tests
* as indicated to evaluate specific symptoms in
pts with disease confined to chest but not
resectable (or candidates for curative neoadjuvant
chemotherapy → surgery or curative radiotherapy
± chemotherapy), e.g.:
- fiberoptic bronchoscopy for evaluating
hemoptysis, obstruction, or pneumonitis;
- thoracentesis with cytologic examination (+
chest tube drainage as indicated if fluid is
present)
LUNG CARCINOMA
General staging procedures. VIII. Mediastinum
* usually, mediastinal nodal involvement crucial in
considering a curative surgical approach;
- to be documented histologically for ± N2 or N3
nodes for pts with clinical stage I, II or IIIA using
different approaches:
- CT scan → mediastinoscopy (right - sided tumors)
or lateral mediastinotomy (left - sided lesions);
- direct thoracotomy (with staging at this time)
LUNG CARCINOMA
General staging procedures. IX. Mediastinum
* wider availability and use of fluorodeoxyglucose positron emission tomography (FDG - PET) partially
modified this approach to staging mediastinal lymph
nodes (and distant metastases)?
LUNG CARCINOMA
MEDIASTINAL LYMPH
NODE STAGING. I.
CT SCANNING
* from systematic
reviews of literature
relating on accuracy of
CT scanning for
noninvasive staging of
mediastinum, median
prevalence of mediastinal
metastasis (= presence of
≥ 1 lymph node > 1 cm in
) = 28%;
- sensitivity and
specficity = 51 - 64% and
74 - 86%, respectively
metanalysis, Gould MK et al Ann Intern Med 139: 879, 2003
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MEDIASTINAL LYMPH NODE STAGING. II. FDG - PET
* from systematic FDG - PET reviews of literature with
evaluating mediastinal lymph nodes using surgery (i.e.,
mediastinoscopy and / or thoracotomy) as gold standard of
comparison:
- median prevalence of mediastinal metastases = 29 (5 64)%;
- sensitivity and specificity = 74 and 85%, respectively →
PET scanning more accurate than CT scanning for staging
mediastinum;
LUNG CARCINOMA
MEDIASTINAL LYMPH NODE
STAGING. III. FDG - PET
* from meta - analysis (Gould MK et
al Ann Intern Med 139: 879, 2003)
evaluating conditional test
performance of FDG - PET and CT
scanning, median sensitivity and
specificity of PET scans:
= 100 and 78%, respectively, in pts
with enlarged lymph nodes → PET
scanning falsely identifies
malignancy in ~ 25% of pts with
nodes enlarged for other reasons
(usually inflammation or infection);
= 82 and 93%, respectively, in pts
with normal - sized lymph nodes →
falsely negative PET scan in ~ 20%
of pts with normal - sized nodes with
malignant involvement
LUNG CARCINOMA
18 - FDG - PET FOR METASTASES. I.
* higher than CT sensitivity and reasonable specificity for
# benign from malignant lesions < 1 cm;
- PET ↑ results of early - stage lung cancer by identifying
pts with metastatic disease (beyond scope of surgical
resection, but not evident by other preoperative staging
procedures)
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18 - FDG - PET FOR METASTASES. II.
* despite ?FDG - PET offer diagnostic advantages over
conventional imaging in detecting distant metastatic
disease, limitations for standard FDG - PET scan include:
- not extends below pelvis = may not detect bone
metastases in long bones of lower extremities;
- not reliable for detection of metastases in brain and
urinary tract, because metabolic tracer used in FDG - PET
scanning accumulates in these sites
LUNG CARCINOMA
General staging procedures. X. Mediastinum
Mediastinal lymph node staging with FDG - PET. I.
* overall, PET superior to CT imaging for mediastinal staging;
→ PET scanning accurate in identifying malignant nodal
involvement with enlarged nodes (with standardized uptake value,
SUV, > 2.5 highly suspicious for malignancy);
- however, PET scanning falsely identifies malignancy in ~ 25% of
pts with nodes enlarged for other reasons (inflammation, infection,
granulomatous diseases, diabetes, slow - growing tumors as BAC)
and falsely negative in ~ 20% of pts with normal - sized nodes with
malignant involvement;
→ PET never be used alone to diagnose LC, mediastinal
involvement or metastases;
* instead, primary function = to help guide mediastinal biopsy for
staging purposes [and to help ?identify sites of metastatic disease]
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General staging procedures. XI. Mediastinum
Mediastinal lymph node staging with FDG - PET. II.
* FDG - PET may ↓ overall costs of medical care by
identifying pts with falsely negative CT scans in
mediastinum or otherwise undetected sites of metastases;
- however, money saved by avoiding mediastinoscopy in
FDG PET+ mediastinal nodes not justified because of
unacceptably high no. of false+ and false- results
LUNG CARCINOMA
General staging procedures. XII. Mediastinum
Mediastinal lymph node staging with FDG - PET. III.
* randomized trials on utility of PET in potentially resectable NSCLC
→ conflicting results for reduction in no. of noncurative (exploratory)
thoracotomies:
- e.g., in a randomized trial, addition of FDG - PET to conventional
staging → significantly fewer thoracotomies (van Tinteren H et al
Lancet 2002), but
- another randomized trial → PET provides additional information on
appropriate stage without leading to fewer thoracotomies (Viney RC
et al JCO 2004)
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MEDIASTINAL LYMPH NODE STAGING. IV.
INTEGRATED CT - FDG - PET
* with no evidence of distant metastatic
disease on CT scan, combination of CT
scanning and PET scanning → greater
sensitivity and specificity than CT
scanning alone for mediastinum;
Figure: true+ mediastinal lymph node
metastasis at integrated PET / CT in 46 - yr old man with lung adenocarcinoma:
(a) lung window view of transverse CT
scan → 28 - mm nodule (arrow) with
lobulated margin in right lower lobe;
(b) mediastinal window view of transverse
unenhanced CT scan at level of right
bronchus intermedius → 3.8 - mm lymph
node (arrow) in subcarinal area;
(c) PET and (d) integrated PET / CT scan →
node with markedly ↑ FDG uptake (arrow)
strongly suggesting malignant node, proved
to contain metastatic adenocarcinoma cells
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General staging procedures. XIII. Mediastinum
Surgical mediastinal lymph node staging. I.
* overall, as mediastinal nodal involvement crucial in
considering a curative surgical approach, for pts with
clinical stage I, II or IIIA to be documented
histologically for ± N2 or N3 nodes (regardless of
whether PET or integrated CT - FDG - PET is positive or
negative) using different approaches:
- mediastinoscopy (right - sided tumors) or lateral
mediastinotomy (left - sided lesions);
- direct thoracotomy (with staging at this time)
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General staging procedures. XIV. Mediastinum
Surgical mediastinal lymph node staging. II.
* especially, for “pts with clinically operable NSCLC”,
recommendation for biopsy of mediastinal lymph nodes
found on chest CT scan > 1 cm in shortest transverse axis
or positive on FDG - PET scanning (negative FDG - PET
scanning does not preclude biopsy of radiographically
enlarged mediastinal lymph nodes);
- mediastinoscopy also necessary for detection of cancer
in nodes when results of CT scan and FDG - PET do not
corroborate each other
MEDIASTINOSCOPY
(right - sided tumors)
MEDIASTINOTOMY
(left - sided tumors)
MEDIASTINOSCOPY AND MEDIASTINOTOMY
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General staging procedures. XV. Mediastinum
Surgical mediastinal lymph node staging. III.
* possibly, preoperative mediastinoscopy not needed in
pts with both normal - size nodes (by CT) and PET negative (as discovery of micrometastases unlikely to
change preoperative management of disease, although
lymph node sampling be done intraoperatively)
ENDOSCOPIC ULTRASOUND - GUIDED
FINE - NEEDLE ASPIRATION BIOPSY
* an endoscope with ultrasound
probe and biopsy needle inserted
through mouth and into
esophagus;
- probe bounces sound waves off
body tissues to make echoes that
form sonogram (computer picture)
of lymph nodes near esophagus;
- sonogram helps to place biopsy
needle to remove tissue from
lymph nodes
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General staging procedures. XVI. Mediastinum
* accurate staging of mediastinal
nodes → prognostic information;
- association between survival and no.
of examined nodes during surgery for
pts with stage I NSCLC treated with
definitive surgical resection;
- from population - based Surveillance,
Epidemiology and End Results database
(1990 - 2000, 16,800 pts, ± radiation
therapy) (Ludwig MS et al Chest 2005);
- in pts with 5 - 8 nodes examined
during surgery → modest but significant
↑ in survival vs pts with 1 - 4 nodes
examined;
- for pts with 9 - 12 and 13 - 16 nodes
examined, modest ↑ in survival with
maximum in 13 - 16 node group → no
incremental improvement after
evaluating > 16 nodes
.
* because most likely result from
reduction of staging error, namely, a
decreased likelihood of missing positive
lymph nodes with increasing number of
lymph nodes sampled, evaluation of
nodal status do include between 13 - 16
lymph nodes
PTS WITH NSCLC
WITH NO CONTRAINDICATION
TO CURATIVE SURGERY
OR RADIOTHERAPY ± CHEMOTHERAPY
LUNG CARCINOMA
Pts with NSCLC with no contraindicationa to curative surgery or
radiotherapy ± chemotherapy
* all above procedures, with focus on (especially if surgical resection
planned):
- CT and / or PET scan to evaluate mediastinum and detect metastatic
disease + surgical evaluation of mediastinum at mediastinoscopy or at
thoracotomy;
- CT or MRI scan of brain if symptoms suggestive;
- pulmonary function tests and arterial blood gas measurements;
- cardiopulmonary exercise testing if performance status or pulmonary
function tests are borderline;
- coagulation tests;
- if pt is poor surgical risk or candidate for curative radiotherapy:
transthoracic fine - needle aspiration biopsy or transbronchial forceps
biopsy of peripheral lesions (if material from routine fiberoptic
bronchoscopy negative)
pts with NSCLC and extrathoracic metastatic disease, malignant pleural effusion or intrathoracic
disease beyond bounds of tolerable radiotherapy port
a
PTS WITH ADVANCED NSCLC
OR CANCER OF UNKNOWN PRIMARY
LUNG CARCINOMA
PTS WITH ADVANCED NSCLC
OR CANCER OF UNKNOWN PRIMARY
* all procedures under “all pts," plus following:
* fiberoptic bronchoscopy if indicated (by hemoptysis,
obstruction, pneumonitis, or by no histologic diagnosis of
cancer);
* diagnostic and therapeutic thoracentesis (if pleural
effusion present);
* biopsy of accessible suspicious lesions (in attempt of
obtaining histologic diagnosis or if therapy altered by finding
of tumor)
- e.g., fine - needle aspiration biopsy of peripheral lesions,
especially single (e.g.,from radiographic finding of isolated
enlarged adrenal gland)
STAGING SMALL CELL LUNG
CANCER
PRETREATMENT
STAGING PROCEDURES
FOR SCLC
LUNG CARCINOMA
Staging SCLC. I.
* initial general LC evaluation (with chest and
abdominal CT scans, due to high frequency of
hepatic and adrenal involvement);
* fiberoptic bronchoscopy with washings and
biopsies (for tumor extent before therapy);
* brain CT scan (metastases in 10% of pts);
* BM biopsy and aspiration (BM infiltration in 20 30% of pts), and
* bone radionuclide scans (with symptoms or
other findings suggesting bone involvement)
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Staging SCLC. II.
* spinal CT or magnetic resonance (MRI) scan
and examination of cerebrospinal fluid cytology
(rachicentesis) if signs or symptoms of:
- spinal cord compression (→ local radiotherapy
to site of compression), or
- leptomeningitis (→ radiation therapy and
intrathecal CT, usually methotrexate);
* brain CT or MRI scan performed with spinal
cord or leptomeningeal metastases (frequently
associated brain metastases)
RESECABILITY AND OPERABILITY
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Resecability and operability. I.
* assessment of tumor location (anatomic
staging = determination of “resectability”), and
- assessment of pt's ability to withstand
antitumor treatments (physiologic staging =
determination of "operability”);
* e.g., a NSCLC pt can be resected by standard
surgical procedure, i.e., lobectomy or
pneumonectomy (= resectable, from anatomic
stage) and tolerate surgical procedure (=
operable, from cardio - pulmonary condition)
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Resectability. I. Contraindications to standard curative
surgery or radiotherapy in NSCLC. I.
* extrathoracic metastases;
* superior vena cava syndrome;
* vocal cord and (usually) phrenic nerve paralysis;
* pleural effusion (generally considered malignant
regardless cytologically positive, especially when
exudative, bloody and with no other probable etiology);
* cardiac tamponade;
* tumor < 2 cm from carina;
* bilateral endobronchial tumor (potentially curable by
radiotherapy)
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Resectability. II.
Contraindications to standard curative surgery or
radiotherapy in NSCLC. II.
* metastasis to supraclavicular lymph nodes;
* lymph node metastasis in contralateral
mediastinum (potentially curable by
radiotherapy);
* involvement of main stem pulmonary artery
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Resecability in SCLC. III.
* most pts with SCLC have unresectable disease;
- however, resection be considered if clinical
findings suggest potential for resection (most
common with peripheral lesions)
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Operability. I.
* frequent cardiopulmonary and other problems
(mainly related to chronic obstructive pulmonary
disease) in pts with LC;
- addressing correctable problems (e.g., anemia,
electrolyte and fluid disorders, infections and
arrhytmias), stopping smoke and instituting
appropriate chest therapy;
* not always possible to predict whether lobectomy
or pneumonectomy required until surgery →
conservative approach = to restrict resectional
surgery to pts potentially tolerating pneumonectomy
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Operability. II.
Contraindications to thoracic surgery in NSCLC. I.
* non - ambulatory performance status;
* myocardial infarction < 3 mos (= absolute
contraindication: 20% of pts die of reinfarction)
and between 3 - 6 mos (relative contraindication);
* uncontrolled major arrhytmias
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Operability. III.
Contraindications to thoracic surgery in NSCLC. II.
* maximum breathing capacitiy < 40% of predicted;
* FEV1 (forced expiratory volume in 1 second) < 1 L (with
FEV1 = 1.1 - 2.4 L = careful judgment; FEV1 > 2.5 L =
usually allows pneumonectomy);
- CO2 resting retention (more serious than hypoxemia),
- DLCO (= Diffusing capacity of Lung fo Carbon
Monoxide) < 40%, and
* severe pulmonary hypertension
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Operability. IV.
Contraindications to thoracic surgery in NSCLC. III.
* in pts with borderline lung function and
resectable tumor, cardiopulmonary exercise
testing performed as part of physiologic
evaluation;
- test allows an estimate of maximal oxygen
consumption (VmaxO2 → VmaxO2 < 15 mL / kg /
min predicts high risk of postoperative
complications)