Lung cancer staging

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Lung cancer staging

• DR. KOMALDEEP
• JUNIOR RESIDENT
• PULMONARY MED
• TBHP

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Causes and Risk factors of Lung Cancer
3
diagnosis
4
Definition of Clinical Stage

• The extent of disease that can be determined from
• history and physical examination,
• biopsy procedure,
• imaging studies,
• endoscopy, and
• exploration prior to initial treatment.

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Importance Why do we need Clinical Staging?

• To aid the clinician in the planning of
  treatment.
• To give some indication of prognosis.
• To assist in evaluation of the results of
  treatment.
• To facilitate the exchange of information between
  treatment centres.
• To contribute to the continuing investigation of
  human cancer.

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• CLINICAL STAGING
• Pre-treatment

• PATHOLOGICAL
• Post-treatment

• based on findings gathered by the doctor by
  non-invasive or minimally invasive techniques
  like physical exam, radiological exam, endoscopic
  ultrasound, bronchoscopy, mediastinoscopy and
  thoracoscopy.
• used to plan the initial therapy
• may be modified by additional information found
  during pathological examination

• Based on the examination of the tissue samples
  obtained from the primary tumor, nodes or
  metastasis
• Helpful in planning additional treatment and
  follow-up

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CLASSIFICATION DATA SOURCE
Clinical (pretreatment) (cTNM) symptoms, physical examination, imaging, endoscopy biopsy surgical exploration without resection etc
Pathologic (pTNM) surgical resection and pathology
Post therapy (ycTNM or ypTNM) after systemic or radiation before surgery or as primary therapy denoted with a yc (clinical) or yp (pathologic)
Retreatment (rTNM) at time of retreatment for recurrence or progression
Autopsy (aTNM) as determined at autopsy
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Staging and grading

• grade

• stage

• Cancer stage refers to the size and/or extent
  (reach) of the original (primary) tumor and
  whether or not cancer cells have spread in the
  body.

• Tumor grade is the description of a tumor based
  on how abnormal the tumor cells and the tumor
  tissue look under a microscope. It is an
  indicator of how quickly a tumor is likely to
  grow and spread.

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1 1977 19781983
2 1983 19841988
3 1988 19891992
4 1992 19931997
5 1997 19982002
6 2002 20032009
7 20o9 2010-

• Dr. Pierre Denoix, a surgical oncologist
  (Institut Gustave-Roussy in Paris) analyzed a
  series of papers published between 1943 and 1952.
• Published by the International Union Against
  Cancer (UICC) in 1968
• The second international recommendation came in
  1974 with the support of the American Joint
  Committee on Cancer (AJCC).
• 6th edition in 1997 5,319 casesUSA, published
  in 2002.
• 7the edition 100,869 patients 46 sources in 19
  countries-, 81,015 were eligible for inclusion.
• 7th edition took effect on january 1st , 2010.

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History of staging of sclc

• According to veterans administration lung study
  group 2 stages of SCLC.
• Limited stage disease LD SCLC Confined to the
  hemithorax of origin, the mediastinum, or the
  supraclavicular nodes.
• Extensive stage disease ED-SCLC Any disease not
  meeting limited stage criteria and with Distant
  metastasis
• The international association for the study of
  lung cancer (IASLC) revised the VALG
  classification in accordance with the TNM system.
• LD definition is consistent with stages I to IIIb
• ED is limited to patients with distant
  metastasis.

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TNM Staging system for Lung Cancer

• T Tumor size or contiguous extension of the
  primary tumor
• N Node the absence, or presence and extent of
  cancer in the regional draining lymph nodes.
• M Metastasis the absence or presence of
  distant spread or metastases involvement in
  organs and tissues
• Were all in the same game just different
  levels,
• Dealing with the same hell just different
  devils.

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Descriptor Definition subgroups
T0 No evidence of primary tumour
T1 Tumour lt3cm, in the greatest dimension surrounded by lung or visceral pleura, not proximal than the lobar bronchus Tumour lt/ 2cm in greatest dimension Tumour gt2cm but lt/3cm in the greatest dimension T1a T1b
T2 Tumor gt3cm but lt7cm or Tumor with any of the following features Involves main bronchus gt2cm distal to carina Invades visceral pleura Associated with atelectasis or obstructive pneumonitis that extends to the hilar region but does not involve the entire lung. T2a gt3 but lt5cm T2b gt5 but lt7cm T2a T2b
T3 Tumour gt7cm or directly invading chest wall, diaphragm, phrenic nerve, mediastinal pleura or patietal pericardium Tumour in the main bronchus lt2cm distal to carina Atelectasis/obstructive pneumonitis of the entire lung Separate tumour nodules in the same lobe
T4 Tumour of any size with invasion of heart, great vessels, trachea, recurrent laryngeal nerve, esophagus, vertebral body Or carina Or separate tumour nodules in a different ipsilateral lobe
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T1 tumor

• Tumor lt3cm diameter
• Surrounded by lung or visceral pleura
• Without invasion of more proximal than lobar
  bronchus.
• T1a lt2cm
• T1b gt2cm but lt3cm

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T2 Tumor

• Tumor gt3cm but lt7cm or
• Tumor with any of the following features
• Involves main bronchus gt2cm distal to carina
• Invades visceral pleura
• Associated with atelectasis or obstructive
  pneumonitis that extends to the hilar region but
  does not involve the entire lung.
• T2a gt3 but lt5cm
• T2b gt5 but lt7cm

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T3 tumor

• Tumour gt7cm with
• directly invading chest wall, diaphragm, phrenic
  nerve, mediastinal pleura or patietal pericardium
• Tumour in the main bronchus lt2cm distal to
  carina without involvement of carina.
• Atelectasis/obstructive pneumonitis of the entire
  lung
• Separate tumour nodules in the same lobe

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T4 tumor

• Tumour of any size with invasion of
• Heart, great vessels, trachea, recurrent
  laryngeal nerve, esophagus, vertebral body
• Or carina
• Or separate tumour nodules in a different
  ipsilateral lobe

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Regional lymph nodes (N)
descriptor definition
N0 No regional lymph node metastasis
N1 Metastasis in ipsilateral peribronchial and/or perihilar lymph nodes and intrapulmonary nodes, including involvement by direct extension
N2 Metastasis in ipsilateral mediastinal and/or subcarinal lymph nodes
N3 Metastasis in contralateral mediastinal, contralateral hilar, ipsilateral or contralateral scalene or supraclavicular lymph nodes
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N0 n1

• Metastasis in ipsilateral peribronchial and/or
  perihilar lymph nodes and intrapulmonary nodes,
  including involvement by direct extension
• N1 means at least stage IIa

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n2

• Metastasis in ipsilateral mediastinal and/or
  subcarinal lymph nodes
• N2 means at least stage IIIa

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n3

• Metastasis in contralateral mediastinal,
  contralateral hilar, ipsilateral or contralateral
  scalene or supraclavicular lymph nodes
• N3 means at least stage IIIb
• N3-nodes are clearly unresectable. 

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Distant metastasis
descriptor definition subgroups
M0 No distant metastasis
M1a M1b Separate tumour nodules in a contralateral lobe or tumour with pleural nodules or malignant pleural effusion Distant metastasis in extrathoracic organs M1a contr nod M1a pl dissem M1b
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m1

• M1a Separate tumour nodules in a contralateral
  lobe
• Or
• Tumour with pleural nodules or malignant pleural
  effusion.
• M1b Distant metastasis in extrathoracic organs

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Special situations
descriptor definition subgroups
Tx, Nx, Mx T, N or M status cannot be assessed
Tis Focus of in situ cancer Tis
T1 Superficial spreading of tumour of any size but confined to the wall of the trachea or main stem bronchus T1ss
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GENERAL RULES

• All cases should be confirmed microscopically.
• Two classifications are described for each site
  Clinical classification AND Pathological
  classification
• After assigning T, N and M and/or pT, pN and pM
  categories, these may be grouped into stages.
• The TNM classification and stage grouping, once
  established, must remain unchanged in the medical
  records.
• If there is doubt concerning the correct T, N or
  M category to which a particular case should be
  allotted, then the lower (i.e., less advanced)
  category should be chosen.
• In the case of multiple simultaneous tumours in
  one organ, the tumour with the highest T category
  should be classified and the multiplicity or the
  number of tumours should be indicated in
  parentheses.

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TNM Groupings

• A tumour with four degrees of T, three degrees of
  N, and two degrees of M will have 24 TNM
  categories
• T, N, and M are grouped into so-called anatomic
  stage/prognostic groups , commonly referred to as
  stage groups.
• Groups are classified by Roman numerals from I to
  IV with increasing severity of disease.
• Stage I generally denotes cancers that are
  smaller or less deeply invasive with negative
  nodes
• Stage II and III define cases with increasing
  tumor or nodal extent
• Stage IV identifies those who present with
  distant metastases (M1) at diagnosis.
• In addition, the term Stage 0 is used to denote
  carcinoma in situ with no metastatic potential.
  Stage 0 is almost always determined by pathologic
  examination.

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 stage grouping "shorthand notation"
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Stage I Non-Small Cell Lung Cancer

• Cancer is found only in the lung
• Surgical removal recommended
• Radiation therapy and/or chemotherapy may also
• be used
• If you dont look at the lymph nodes, everyone
  has stage 1 disease

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Stage II Non-Small Cell Lung Cancer

• The cancer has spread to lymph nodes in the lung
• Treatment is surgery to remove the tumor and
  nearby lymph nodes
• Chemotherapy recommended radiation therapy
  sometimes given after chemotherapy

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Stage III Non-Small Cell Lung Cancer

• The cancer has spread to the lymph nodes located
  in the center of the chest, outside the lung
• Stage IIIA cancer has spread to lymph nodes in
  the chest, on the same side where the cancer
  originated
• Stage IIIB cancer has spread to lymph nodes on
  the opposite side of the chest, under the
  collarbone, or the pleura (lining of the chest
  cavity)
• Surgery or radiation therapy with chemotherapy
  recommended for stage IIIA
• Chemotherapy and sometimes radiation therapy
  recommended for stage IIIB

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Stage IV Non-Small Cell Lung Cancer

• The cancer has spread to different lobes of the
  lung or to other organs, such as the brain,
  bones, and liver
• Stage IV non-small cell lung cancer is treated
  with chemotherapy

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Limitations of new classification

• No data at all being included from Africa, South
  America or the Indian subcontinent.
• Russia, China, and Indonesia are not represented
  or only poorly represented.
• The database used for the 7th edition predates
  the widespread and routine use of PET which has
  had an enormous impact on clinical staging
  algorithms.
• Lympahngitis carcinomatosis is believed to be
  associated with worse prognosis in lung cancer
  patients. However, there is no evidence to
  support this. The new TNM classification does not
  specifically take account of lymphangitis.

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OTHER CLASSIFICATIONAnn Arbour ?
lymphomasDukes classification ? colon cancer
Breslow scale and Clarks level ? melanoma
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MEDIASTINAL STAGING

• Determining the involvement of the mediastinal
  lymph nodes.
• Mediastinal lymph nodes status and the presence
  or absence of direct tumor mediastinal invasion
  will determine the eligibility of the patient to
  treatment with intention to cure (surgical
  treatment) or a palliative care intending to
  prolong life and better quality of life.

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A Brief History

• Naruke et al proposed the 1st lymph node map in
  the 1960s
• The Next 30 years Mountain system proposed in
  1973(2,155 patients) The Mountain Era
• Revised in 1997(5,319 patients)
• The IASLC Staging System Performed by the
  International Association for the Study of Lung
  Cancer

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IASLC lymph node map 2009

• Supraclavicular nodes 1 
• Superior Mediastinal Nodes 2-4
• 2r 2l right and left upper paratracheal
• 3a 3p prevascular and prevertebral
• 4r 4l right and left lower paratracheal
• Aortic Nodes 5-6
• 5 subaortic
• 6 paraaortic
• Inferior Mediastinal Nodes 7-9
• 7 subcarinal
• 8 paraesophageal
• 9 pulmonary ligament
• Hilar, Lobar and (sub)segmental Nodes 10-14
• 10 hilar
• 11 interlobar
• 12 lobar
• 13 segmental
• 14 subsegmental

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American Thoracic Society mapping scheme.

• Supraclavicular zone (1)
• Superior Mediastinal Nodes (2-4)
• 2. Upper Paratracheal
• 3A. Pre-vascular
• 3P. Pre-vertebral
• 4. Lower Paratracheal 
• Aortic Nodes (5-6)
• 5. Subaortic
• 6. Para-aortic
• Inferior Mediastinal Nodes (7-9)
• 7. Subcarinal.
• 8. Paraesophageal (below carina).
• 9. Pulmonary Ligament
• Hilar, Interlobar, Lobar, Segmental and
  Subsegmental Nodes (10-14)

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Non- invasive invasive
Chest radiography Mediastinoscopy GOLD STANDARD
Computed tomography Video Assisted Thoracic Surgery
PET scan Anterior Mediastinotomy (Chamberlain procedure
MRI Endobronchial Ultrasound with Fine Needle Aspiration (EBUS-FNA)
Endoscopic Ultrasound with Fine Needle Aspiration(EUS-FNA)
Transbronchial Fine Needle Aspiration (TBNA-FNA)
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CHEST RADIOGRAPHY

• In certain situations, the plain film may be
  sufficient to detect spread to the mediastinum.
• For example, the presence of bulky
  lymphadenopathy in the superior or contralateral
  mediastinal areas may be considered adequate
  evidence of metastatic disease.
• Can detect pleural effusions that obliterate
  costophrenic recesses and lung nodules larger
  than 7 mm.
• Every patient suspected of having lung neoplasm
  must have a posterior-anterior and lateral chest
  radiograph
• Still, most patients should undergo CT scan of
  the chest unless they are so debilitated that no
  further evaluation or treatment is planned.

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COMPUTED TOMOGRAPHY OF THE CHEST

• The lung lesion itself is more specifically
  evaluated by CT scan, characteristics of the
  primary mass (i.e., smooth bordered, spiculated,
  calcified, etc.), the limits of the lesion are
  better assessed and the rest of lung parenchyma
  may be screened for additional lesions.
• Routine chest CT may also evaluate the presence
  of distant metastasis to the liver, adrenals or
  bones, which are some of the commonest sites of
  metastatic disease.
• The bony structures of the thoracic cavity can
  also be evaluated by chest CT.

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POSITRON EMISSION TOMOGRAPHY

• This imaging modality is based on the biologic
  activity of neoplastic cells.
• PET is better used in conjunction to CT (PET-CT)
  in which single machine incorporates CT and PET
  during the same scan.
• LIMITATIONS
• Brain metastasis
• Inflammation TB, fungal etc.
• Slow growing neoplasms BAC,
• 
  carcinoid tumour
• Size smaller than 7mm

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MRI

• There are very few circumstances in which
  magnetic resonance imaging (MRI) is a useful tool
  in staging lung cancer.
• Helps in evaluating limits and possible invasion
  in soft tissue, bone and vascular structures but,
  with new generations of multislice CT scans that
  are capable to perform three-dimensional
  angiotomography, MRI has diminished one of its
  main indications, which is to evaluate vascular
  and neural invasion in superior sulcus tumor.
• Its main use is to image the brain when
  suspecting of metastasis at this organ.

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THE SEARCH FOR METASTATIC DISEASE

• To detect metastatic disease at common
  metastatic sites, such as the adrenal glands,
  liver, brain, and skeletal system, thereby
  sparing the patient fruitless surgical
  intervention.
• Computed tomography of the chest, CT or MRI with
  contrast of the brain, and 99mTc nuclear imaging
  of the skeletal system, whole-body PET scans for
  extrathoracic staging.
• False-positive scans- Adrenal adenomas (present
  in 2 to 9 of the general population), hepatic
  cysts, degenerative joint disease, old fractures,
  and a variety of nonmetastatic space-occupying
  brain lesions are present in the general
  population.
• False-negative scansthat is, metastases are
  present but not picked up by current scanning
  techniques

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Invasive Mediastinal Staging of Lung Cancer

• After distant metastasis has been ruled out, the
  mediastinal staging is the most important aspect
  to focus in these patients.
• The main purpose of the IMS is to differentiate
• a) patients that will benefit from straight
  surgical resection
• b) patients that will benefit from neoadjuvant
  therapy, followed by surgical resection
• c) patients who will not benefit from surgical
  resection, and should receive only chemo and/or
  radiotherapy.
• In general, patients with lung cancer may be
  divided in four categories, according to
  tomographic characteristics of the primary tumor
  and the mediastinum, regarding to size, location
  and extension of the disease
• (proposed by Dr. Frank Detterbeck and adopted by
  the American College of Chest Physicians
  Guidelines for Diagnosis and Management of Lung
  Cancer)

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• Group A extensive mediastinal infiltration by
  the primary tumor.
• Group B enlarged paratracheal lymph nodes.
• Group C central tumor with normal-sized
  mediastinal lymph nodes.
• Group D peripheral small tumor with
  normal-sized mediastinal lymph nodes .

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Mediastinoscopy

• The procedure is done through a transverse
  cervical incision, with pretracheal dissection
  until the mediastinum and introduction of the
  mediastinoscope.
• It is possible to perform biopsies of the
  following lymph nodes
• Pretracheal(1), Right and left high and low
  paratracheal (3,2R, 2L, 4R, 4L),Subcarinal(7)
• The procedure may also be done with the
  videomediastinoscope, allowing a magnification of
  the operative field.
• Mediastinoscopy is the gold standard method to
  the invasive mediastinal staging, with which the
  other methods should be compared.

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Video assisted thoracic surgery

• Better staging regarding the T descriptor, given
  we have the wide approach to the pleural cavity,
  making possible a better evaluation of pleural
  effusion, pleural metastatic disease, chest wall,
  diaphragm and vascular structures invasion.
• At the right side, paratracheal lymph nodes are
  relatively easily accessed, but left paratracheal
  lymph nodes are extremely difficult to be
  accessed by this method, due to the great
  vessels anatomy.
• VATS not a substitution but is a complementary
  procedure to the mediastinoscopy, especially when
  there is a left upper lobe tumor with enlarged
  lymph node station 5 and 6.
• Allows simultaneous resection of the tumour.
• Limitation unilateral approach.

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Anterior mediastinotomy (chamberlain procedure)

• A horizontal incision is done through second
  left intercostal space, and the aortic arch and
  left pulmonary artery are identified by
  palpation.
• Regarding to lung cancer staging, anterior
  mediastinotomy is used exclusively in selected
  patients with left upper lobe (LUL) tumor, aiming
  to evaluate lymph nodes at the aortopulmonary
  window (station 5) and preaortic (station 6).
• When there is cancer spread only to these
  stations, usually patients have a better
  prognosis and, if patients are fit, there are two
  possible treatements 1) neoadjuvant therapy
  aiming to posterior pulmonary resection intending
  to cure 2)surgical resection followed by
  adjuvant chemotherapy.

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Endobronchial ultrasound with fine needle
aspiration

• Accessible lymph nodes by this method are
  pretracheal (1), high and down right and left
  paratracheal (2R, 2L, 4R. 4L), and subcarinal(7).
• It may be used in substitution to
  mediastinoscopy, but, if the results are negative
  with the EBUS, the mediastinoscopy should be
  performed.
• There are many false negatives with EBUS, thus,
  if a high index of suspicion exists, a
  mediastinoscopy should be performed when EBUS was
  negative.
• Doppler feature allows for identification of
  vessels and landmarks for nodal stations.

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Endoscopic ultrasound with fine
needleaspiration (EUSFNA)

• EUS is performed using an ultrasound transducer
  coupled with the flexible esophagoscope.
• This device guides the needle through the
  esophageal wall and allows the approach of lymph
  nodes in pulmonary ligament(9),
  paraesophageal(8), subcarinal(7) and
  aortopulmonary window(5).
• Additionally, EUS may be able to detect
  metastatic disease in sites as left adrenal
  gland, celiac lymph nodes and liver and also
  direct invasion to some mediastinal structures
  (T4).
• The ideal procedure is when both (EUS EBUS)
  methods are performed at the same session, with
  the patient under general anesthesia or sedation.

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Transbronchial needle aspiration (TBNA)

• TBNA utilizes a standard flexible bronchoscope
  and a needle, known as Wang Needle through the
  scope.
• Its main indication is to evaluate enlarged
  subcarinal lymph nodes (station 7).
• Negativity of this test should prompt the
  mediastinal evaluation by other method, such as
  mediastinoscopy.
• Operator dependent.
• TBNA is safe and performed in an outpatient basis.

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Thoracocentesis

• Aspiration and cytological examination of
  pleural fluid in
• patients presenting with suspected malignant
  pleural effusion
• provides a diagnostic yield of approximately
  60
• the addition of needle pleural biopsy may
  raise the possibility
• of detecting cancer to 75.
• The presence of neoplastic cells in the fluid
  excludes surgical treatment.
• Will be of help only if there is pleural
  involvement by the tumor.
• When there is no diagnosis of pleural fluid after
  thoracocentesis and the effusion is recurrent,
  one should perform a videothoracoscopy, which
  have a sensibility of 95 in detecting pleural
  metastasis (by pleural biopsy and fluid
  analysis), and also has the advantage of allowing
  to perform the pleurodesis at the same surgical
  procedure.

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TTNA

• Transthoracic needle aspiration, usually under CT
  or fluoroscopic guidance, is an expedient and
  relatively safe way to diagnose the primary tumor
  mass and establish a diagnosis of lung cancer.
• As a general rule, if a lesion is less than 3 cm
  in size and lateral to the mid-clavicular line,
  bronchoscopy would not be the diagnostic
  procedure of choice. Transthoracic needle
  aspiration should be considered under such
  circumstances if tissue diagnosis is necessary.

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Special Situations1.Left upper lobe tumors

• Patients with left upper lobe (LUL) tumors
  deserve a special mention, because the lymphatic
  system drains preferentially to lymph nodes in
  the aortopulmonary window (station 5) and
  preaortic location (station 6).
• These nodes are rarely involved by tumors
  originating from other pulmonary lobes.
• The approach to station 5 and 6 must be done by
  anterior mediastinoscopy or videothoracoscopy,
  and choosing between these two methods must be
  individualized according to each patient

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2.Pancoast tumor

• A Pancoast tumor is a tumor of the superior
  pulmonary sulcus
• characterized by pain due to invasion of the
  brachial plexus,
• Horner's syndrome and destruction of bone due to
  chest wall invasion.
• Pancoast tumors are staged at least as T3,
  because there is almost
• always chest wall invasion. 
• When there is ingrowth into a vertebral body or
  vital mediastinal structures, the tumor is staged
  as T4.
• Ipsilateral supraclavicular nodes (N3)
  (peritumoral lymph nodes) are potentially
  resectable with en bloc resection, while
  mediastinal nodes (N2) are not.
• After histological diagnosis, if noninvasive
  staging points to the possibility of a pulmonary
  resection, the mediastinum must obligatory be
  invasive staged.

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3.Invasive re-staging after neoadjuvant treatment

• If previous IMS was positive, it is obligatory to
  repeat it, more commonly with the
  mediastinoscopy
• If previous IMS was negative and the new CT and
  PET-CT show neither enlargement nor augmentation
  in the SUV when compared to the CT and PET-CT
  performed before the neoadjuvant therapy, it is
  not necessary to repeat the IMS
• If previous IMS was negative, but the new CT and
  PETCT reveal mediastinal node enlargement and/or
  augmentation in SUV comparing to the CT and
  PET-CT performed before the neoadjuvant therapy,
  the IMS must be performed again, usually by
  mediastinoscopy.
• Finally, after neoadjuvant therapy, if N2 or N3
  disease is detected in this second IMS, the
  patient will not benefit from surgical resection
  if there is no N2 or N3 disease, the patient
  should have a pulmonary resection.

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Conclusion Staging matters!!!

• Lung cancer staging must have a simple and
  logical sequence.
• The only possible method to cure this neoplasm is
  by surgical resection, therefore a correct
  staging should be offered to every patient facing
  this disease.
• The most important point when evaluating a
  patient suspected of having lung cancer, refers
  to the oncological status of mediastinal lymph
  nodes, and its evaluation, by means of
  radiological examinations or invasive procedures,
  is the critical part for every patient.
• Every patient should start the investigation with
  a chest radiograph and chest CT with intravenous
  contrast.
• The clinician must be wary of abnormal scans
  that may falsely suggest metastatic disease to
  the mediastinum and distant sites

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Conclusion Staging matters!!!

• After this initial evaluation, the mediastinal
  evaluation should be complemented based on the
  size of mediastinal lymph nodes, the location and
  size of the lung lesion. Recently, PET-CT has
  been added to the investigation of every patient
  who is a potential candidate for pulmonary
  surgical resection.
• Tissue confirmation by whatever means necessary
  is the rule rather than the exception prior to
  deciding on correct stage and the most
  appropriate treatment.
• A detailed preoperative workup is essential to
  choose the most appropriate therapeutic plan to
  each patient, with best results regarding to
  possible cure, improvement of quality of life,
  rational use of medical resources and less
  morbidity and mortality.

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