Principles of Diagnosis,

Staging and Management

of Cancer Patients
Dennis L. Sacdalan, MD
primum non nocere

first do no harm
primum succerrere

hasten to help
 INCREASED EFFICACY

ACTIVITY SAFETY

Different mechanisms of action Compatible side effects

Different mechanisms of resistance
Source: http://www.livercancer.com/cancer_carcinogenesis.html
 Diagnosis of Cancer

Pathological examination
= definitive diagnosis
 Diagnosis of Cancer
Pathologic examination obtained from:
cluster of cells from body fluids or from organs
tissue samples obtained by biopsy
(endoscopic / surgical / fine needle aspiration)
Choice of procedure depends on how
much tissue is needed to allow evaluation
of the tumor
Diagnosis of Cancer
 Essential Elements
in a Pathologic Report

Anatomic origin
Tissue of origin (histology)
Degree of differentiation (grade)
Molecular diagnostic information
Expression of cell surface
markers/intracellular proteins
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 Tumor Markers
Useful in certain tumors when monitoring
response to treatment (if elevated upon
diagnosis of cancer)
Can be measured in serum, urine or
tissues
Not specific; NOT used to diagnose
cancer
 Imaging Studies

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 Ancillary tests
Complete blood count
Blood chemistry
BUN, Creatinine
AST, ALT, alk phos, bilirubins
Electrolytes
2D echo - performed on patients who will
receive anthracyclines
 Cancer Staging
Determination of the extent of tumor
involvement
Determination of optimal treatment plan
Evaluation of prognosis
Standardized description of disease
extent
 Cancer Staging
Clinical staging
Based on physical examination and imaging
studies

Pathologic staging
Based on information obtained from surgical
procedure
 Cancer Staging
Pathologic staging takes into account
the following information:
Histopathologic examination of the specimen
Intraoperative inspection and palpation
Resection of lymph nodes and/or tissues
adjacent to the tumor
 Cancer Staging
TNM
Most widely used system codified by the
AJCC
Anatomically based
Dukes classification (colorectal cancers)
FIGO (gynecologic cancers)
Ann Arbor (lymphoma)
 TNM Staging
T: primary tumor
T0 = No evidence of tumor
T1-4 = Ascending degrees of increase in
tumor size and involvement
 TNM Staging
N: regional lymph nodes
N0 = No evidence of disease in lymph nodes
N1-3 = Ascending degrees of nodal
involvement
 TNM Staging
M: distant metastasis
M0 = No evidence of distant metastasis
M1 = Presence of distant metastasis
Goals of Cancer Therapy
Goals of Cancer Therapy
 Modalities
Local treatment

Surgery

Radiation Therapy
 Modalities
Systemic treatment

Cytotoxic chemotherapy

Hormonal therapy

Biologic/Immunologic therapy
 Surgery
Cancer prevention
Diagnosis
Staging
Treatment
Palliation
Rehabilitation
Radiation Therapy
 Radiation Therapy
Uses:
Adjuvant treatment after surgery
Curative treatment
Palliative treatment for pain and
obstruction/compression
Total body irradiation prior to bone marrow
transplant
Radiation Therapy
Radiation Therapy
 Systemic Therapy

Cytotoxic chemotherapy

Hormonal therapy

Biologic/Immunologic therapy
 Cytotoxic Chemotherapy

The use of drugs in

the management of
the cancer patient.

Effects are usually

systemic in nature.
Cytotoxic Chemotherapy

Primary chemotherapy
Adjuvant chemotherapy
Neoadjuvant (Induction)
chemotherapy
Concurrent chemoradiotherapy
Palliative chemotherapy
Principles of Chemotherapy
Mechanisms: act on DNA, RNA, or proteins
of signal transduction
Combinations preferred over single agents
Given in several schedules depending on
pharmacokinetics and effect on cancer cells
(e.g. cytotoxic versus cytostatic)
The Cell Cycle
The Cell Cycle and
Chemotherapy

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Principles of Chemotherapy

Mode of administration depends on drug

pharmacology
 Combination Chemotherapy

Indications:
Prevention of resistant clones
Cytotoxicity to resting and dividing cells
Biochemical enhancement or effect
Rescue
 Aim of Combination
Chemotherapy
INCREASED EFFICACY

ACTIVITY SAFETY

Different mechanisms of action Compatible side effects

Different mechanisms of resistance
 CONTRAINDICATIONS TO
SYSTEMIC THERAPY
Infection
Previous chemotherapy given < 2 weeks
Leukopenia and thrombocytopenia
Severely debilitated patients
Pregnancy (1st trimester)
Major surgery < 2 weeks
Poor patient follow-up
Psychological problems
 Hormonal Therapy
Additive hormonal therapy:
Corticosteroids
Estrogen, Progesterone QuickTime and a
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Androgens

Ablative hormonal therapy:

Anti-estrogens
Anti-androgens
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Gonadotrophin analogues
Oophorectomy, Orchiectomy
 Hormonal Therapy
Targets tissues whose growth and
function are under hormonal control
Breast (tamoxifen, aromatase inhibitors)
Prostate (GnRH analogs, antiandrogens)
Uterus (megestrol acetate)
Lymphocytotoxic (corticosteroids)
Used in lymphoma
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 Hormonal Therapy
Features:
Relatively little toxicities
Act by modifying expression of genes
responsible for cell growth and proliferation
Mostly used only for hormonally responsive
tumors
Slower response compared to chemotherapy
 Biologic/Immunologic
Therapy
Classical
Interferon and other cytokines
Molecularly targeted
Monoclonal Antibodies
Small Molecules/TKI
Gene therapy
Measures of Efficacy
of Treatment
 Complete Remission

Primary
Tumor

Nodes
Treatment
Treatment
Metastases

Disappearance of all clinical, radiologic, and biologic signs of tumor.

WHO, 1980.
 Partial Remission

Treatment
Treatment

a
a
b
b

Decrease of the multiple of two tumor diameters by at least 50%

(ab)<(ab)/2
WHO, 1980.
 Stable Disease

Treatment
Treatment

a a
b b

Regression in tumor size less than 50% or no change in size from baseline.

WHO, 1980.
 Progression

Treatment
Treatment

a
b
b

Increase of the multiple of two tumor diameters by at least 25%

(ab) > 1.25 (ab)
WHO, 1980.
 Quality of Life Parameters
Cognitive functioning
Social functioning
Sleep disorders
Pain
Fatigue
Nutrition
Sexuality
Exercise
Performance Status Scales
ECOG KARNOFSKY

Grade Criteria (simplified) % Functional status

0 Normal activity 100 Able to carry on normal activity;
no special care is needed
90

1 Symptoms but ambulatory 80

70 Unable to work; able to live at home;

cares for most personal needs;
a varying amount of assistance is needed
2 In bed <50% of time 60
50
3 In bed >50% of time 40 Unable to care for self; requires
equivalent of institutional or hospital
30 care; disease may be progressing rapidly
4 100% bedridden 20
10
5 Dead 0 Dead
 SIDE EFFECTS

Mucositis Alopecia

Nausea/vomiting Pulmonary fibrosis

Diarrhea Cardiotoxicity
Cystitis
Local reaction
Sterility
Myalgia Renal failure
Neuropathy
Myelosuppression

Phlebitis
Significance of Assessment
of Treatment Response
Guides oncologist in deciding on what to
do with treatment
Continue?
Stop?
Change drugs/treatment modality?
Provides information on prognosis
 Supportive Care
Pain control
Nausea/vomiting
Nutrition
Management of effusions
Psychosocial support
Counseling
Death and dying issues
End of life issues
 Management of Cancer
Multidisciplinary
team approach
Medical oncologist Psychiatrist
Surgical oncologist Pain specialist
Radiation oncologist Oncology nurse
Rehab medicine Pharmacist
specialist Social worker
Dentist etc.
Steps in the Evaluation of a
Patient with Malignancy

Establish the pathologic diagnosis

Determine the extent of tumor spread
Determine the effects of the tumor on
health and performance of the patient
Select the appropriate cancer therapy
 Cancer Patient
Management
Extent of
Cancer disease
Biopsy
diagnosis evaluation

Grading Staging
metastatic/localized

Therapeutic
decision
 Summary
Histopathologic assessment is
essential in confirming the diagnosis.

Staging is needed to determine extent of

disease, to determine the optimal
treatment plan and to evaluate
prognosis.
 Summary
One of the greatest challenges is to
balance effectiveness of treatment
with adverse reactions.

A multidisciplinary team approach

should be undertaken to determine the
optimal treatment.