PANTGQ#@E 108 C

Approach
A p p r o a c h to
t o ._
Patient with
Patient with
Cancer
Cancer
 This is a slide title

The application
The application ofof current
current treatment
treatment
techniques :
techniques
* Surger
✘ Surgery
* radiation
✘ radiation therap
therapy
* Chemotherap
✘ Chemotherapy
* biologic
✘ biologic therap
therapy
>
! results in
results in the
the cure
cure ofof nearly
nearly two
two of
of three
three
patients diagnosed
patients diagnosed with with cancer.
cancer.

2
y

The most
The most significant
significant risk
risk factor
factor for
for cancer
cancer
overall is
overall is age;
age; two-thirds
two-thirds ofof all
all cases
cases were
were
in those
in those aged
aged >65
>65 year
years

Cancer is
Cancer is the
the second
second leading
leading cause
cause of
of death
death
behind heart
behind heart disease.
disease.

3
s

 The eight
The eight most
most common
common forms
forms of of cance
cancer
x lung
✘ lung
breast
✘ breast more
more common
common inin
more developed
more developed
prostate
✘ prostate countries
countries

✘ Colorecta
Colorectal

✘ liver
liver
✘ cervical more
more common
common inin less
less
cervical
developed
developed countries
countries
esophageal.
✘ esophageal.

 The nine
The nine modifiable
modifiable riskrisk factors
factors are
are responsible
responsible for
for more
more than
than one-
one-
third of
third of cancers
cancers worldwide.
worldwide. These
These includ
include
Ti
1. Smoking
Smokin
2.
2. alcohol consumptio
alcohol consumption
3.
3. Obesity
Obesit
4.
4. physical inactivity
physical inactivity
Si
5. low fruit
low fruit and
and vegetable
vegetable consumptio
consumption
6.
6. unsafe se
unsafe sex
ti
7. air pollutio
air pollution
8.
8. indoor smoke
indoor smoke from
from household
household fuel
fuels
a,
9. contaminated injections
contaminated injections

5
y

 Patient
Patient
Management
Management
History and
History and physical
physical examination
examination ! >
Important information
Important information is
is obtained
obtained

7
Diagnosis
Diagnosis
The diagnosis
The diagnosis ofof cancer
cancer relies
relies most
most heavily
heavily on
on invasive
invasive
tissue biopsy
tissue biopsy and
and should
should never
never be
be made
made without
without
obtaining tissue;
obtaining tissue; nono noninvasive
noninvasive diagnostic
diagnostic test
test is
is
sufficient to
sufficient to define
define aa disease
disease process
process asas cancer.
cancer.

9
Once the
Once the diagnosis
diagnosis of of cancer
cancer is is made,
made, thethe management
management of of
the patient
the patient is
is best
best undertaken
undertaken as as aa multidisciplinary
multidisciplinary
collaboration among
collaboration among
the primary
the primary care
care physician,
physician, medical
medical oncologists,
oncologists, surgical
surgical
oncologists, radiation
oncologists, radiation oncologists,
oncologists, oncology
oncology nurse
nurse
specialists, pharmacists,
specialists, pharmacists, social
social workers,
workers, rehabilitation
rehabilitation
medicine specialists,
medicine specialists, andand a a number
number of of other
other consulting
consulting
professionals working
professionals working closely
closely with
with each
each other
other and
and with
with
the patient
the patient and
and family.
family.

10

 EeEDEFINING THE
■■DEFINING THE 4&
EXTENT OF
EXTENT OF DISEASE
DISEASE
AND THE
AND THE PROGNOSIS
PROGNOSIS
The first
The first priority
priority in
in patient
patient management
management afterafter
the diagnosis
the diagnosis of of cancer
cancer is
is established
established and
and
shared with
shared with the
the patient
patient is
is to
to determine
determine the
the
extent of
extent of disease.
disease.

12
The curability
The curability of
of a
a tumor
tumor usually
usually is
is inversely
inversely
proportional to
proportional to the
the tumor
tumor burden.
burden.

The tumor
The tumor will
will be
be diagnosed
diagnosed before
before symptoms
symptoms
develop or
develop or as
as aa consequence
consequence ofof screening
screening
efforts.
efforts.

13

* The
✘ The extent
extent of
of disease
disease is
is evaluated
evaluated by
by a
a
variety of
variety of noninvasive
noninvasive and
and invasive
invasive
diagnostic tests
diagnostic tests and
and procedures
procedures ! >
STAGING
STAGING

14
 T wo
T wo types
types of
of staging
staging
1. Clinical
1. Clinical ——> Pathologic
Pathologic
Clinical stagingstaging
staging
is based takes
on into
takes into
account
account
physical information
information
examination,
2. Pathologic
2. Pathologic —— obtained
radiographs, during
during a
obtained isotopic surgical
a scans,
surgical
procedure,
procedure,
computed which (CT)
which
tomography might
might
scans,include
include intraoperative
intraoperative
and other imaging
palpation,
palpation,
proceduresresection
resection of
of
regional lymph
regional lymph nodes
nodes and/or
and/or
tissue
tissue adjacent
adjacent to to the
the tumor,
tumor,
and inspection
and inspection and
and biopsy
biopsy of of
organs
organs commonly
commonly involved
involved
in
in disease
disease spread.
spread.

15

The most widely used system of staging is the

tumor, The node,
The TNM metastasis
TNM classification
classification is an(TNM)
is an system
anatomically
anatomically based
basedcodified
bysystem
system that
that categorizes the
the tumor
categorizes Union
the International tumor on
on the
Againstthe basis
basis
Cancer of
of the
theand
size
size of
of the
the primary
primary tumor
tumor lesion
lesion (T1–4,
(T1—4, where
where a a higher
higher
the American
number
number indicatesJoint
indicates a Committee
a tumor
tumor of
of larger on the
larger size),
size), Cancer
the presence
presence
of
of nodal
nodal involvement
involvement (usually
(usually N0NO and
and N1N1 for
for the
the
TNMabsence
then
absence and
broken into
and presence,
stages,
presence, respectively,
usually
respectively, of
designated
of involved
involved nodes,
nodes,
by
although
although
the roman some
some tumors have
tumors
numerals have more elaborate
more
I through elaborate systems of
IV systems of
nodal grading),
nodal grading), and
and the
the presence
presence ofof metastatic
metastatic disease
disease
(MO and
(M0 and M1
M1 for
for the
the absence
absence andand presence,
presence,
respectively,
respectively, ofof metastases).
metastases).

16

Tumor burden
Tumor burden increases
increases and
and curability
curability
decreases with
decreases with increasing
increasing stage.
stage.
Other anatomic
Other anatomic staging
staging systems
systems are are used
used for
for
some tumors
some tumors,
e.g., the
e.g., the Dukes
Dukes classification
classification for
for colorectal
colorectal
cancers, the
cancers, the International
International Federation
Federation of of
Gynecologists and
Gynecologists and Obstetricians
Obstetricians classification
classification
for gynecologic
for gynecologic cancers,
cancers, and
and the
the Ann
Ann Arbor
Arbor
classification for
classification for Hodgkin’s
Hodgkin’s disease.
disease.

17
,

 Second major
Second major determinant
determinant of of treatment
treatment
outcome is
outcome is the
the physiologic
physiologic reserve
reserve ofof the
the
patient.
patient
Physiologic reserve
Physiologic reserve is is a
a determinant
determinant of of how
how
a patient
a patient is is likely
likely to
to cope
cope with
with the
the
physiologic stresses
physiologic stresses imposed
imposed by by the
the cancer
cancer
and its
and its treatment.
treatment.

18
.

Patients who
Patients who are
are bedridden
bedridden before
before developing
developing
cancer are
cancer are likely
likely to
to fare
fare worse,
worse, stage
stage for
for
stage, than
stage, than fully
fully active
active patients.
patients.

19
Surrogate markers
Surrogate markers for
for physiologic
physiologic reserv
reserve
* patient’s
✘ patient’s agage
* Karnofsky
✘ Karnofsky performance
performance
* Eastern
✘ Eastern Cooperative
Cooperative Oncology
Oncology Group
Group
(ECOG) performance
(ECOG) performance status.
status.
“Older patients
“Older patients and
and those
those with
with aa Karnofsky
Karnofsky
performance status
performance status <70
<70 oror ECOG
ECOG
performance status
performance status ≥3=3 have
have a a poor
poor
prognosis”
prognosis”

20
e

é | Table 1. Karnofsky Performance Scale Index (KPS)

| Score (category) Karnofsky

Normal; no complaints; no evidence of
100
disease.
Able to carry on normal activity; minor
90
signs or symptoms.
Normal activity with effort; some signs or
80
symptoms of disease.
Care for self; unable to carry on normal
70
activity or to do active work.
Requires occasional assistance but is able
60
to care for most of his needs.
Requires considerable assistance and
50
frequent medical care.
Disabled; requires special care and
40
assistance.
Severely disabled; hospitalization
30 necessary; active supportive treatment is
necessary.
Very sick; hospitalization necessary;
active supportive treatment is necessary.
Moribund; fatal processes progressing
rapidly.
Dead.

21
Fully active, able to carry on all pre-disease performance
without restriction
Restricted in physically strenuous activity but ambulatory
and able to carry out work of a light or sedentary nature,
e.g., light house work, office work
Ambulatory and capable of all selfcare but unable to carry f
out any work activities. Up and about more than 50% iy
of waking hours
Capable of only limited selfcare, confined to bed or chair
more than 50% of waking hours
Completely disabled. Cannot carry on any selfcare. Totally
confined to bed or chair
Dead
22
Biologic features
Biologic features of of the
the tumor
tumor are
are being
being related
related
to prognosis.
to prognosis.
The expression
The expression of of particular
particular oncogenes,
oncogenes, drug-
drug-
resistance genes,
resistance genes, apoptosis-related
apoptosis-related genes,
genes,
and genes
and genes involved
involved in in metastasis
metastasis is is being
being
found to
found to influence
influence response
response to to therapy
therapy and
and
prognosis.
prognosis.
The presence
The presence of of selected
selected cytogenetic
cytogenetic
abnormalities may
abnormalities may influence
influence survival.
survival.

23

 MAKING A
MAKING A =
TREATMENT PLAN
TREATMENT PLAN
From information
From information onon the
the extent
extent of
of disease
disease and
and
the prognosis
the prognosis and
and in in conjunction
conjunction with
with the
the
patient’s wishes,
patient’s wishes, itit is
is determined
determined whether
whether
the treatment
the treatment approach
approach shouldshould be
be curative
curative
or palliative
or palliative in
in intent.
intent.

25
Cooperation among
Cooperation among the
the various
various professionals
professionals
involved in
involved in cancer
cancer treatment
treatment isis of
of the
the
utmost importance
utmost importance in in treatment
treatment planning.
planning.

26
Chemotherapy or
Chemotherapy or chemotherapy
chemotherapy plusplus radiation
radiation
therapy delivered
therapy delivered before
before the
the use
use ofof
definitive surgical
definitive surgical treatment.
treatment. !>
neoadjuvant therapy
neoadjuvant therapy

27
The chemotherapy
The chemotherapy andand radiation
radiation therapy
therapy need
need
to be
to be delivered
delivered sequentially,
sequentially, and
and other
other times
times
concurrently.
concurrently
Surgical procedures
Surgical procedures may
may precede
precede oror follow
follow
other treatment
other treatment approaches.
approaches.

28
.

 MANAGEMENT OF
MANAGEMENT OF a
DISEASE AND
DISEASE AND TREATMENT
TREATMENT
COMPLICATION
COMPLICATION
Patient management
Patient management involves
involves addressing
addressing
complications of
complications of both
both the
the disease
disease and
and its
its
treatment as
treatment as well
well as
as the
the complex
complex
psychosocial problems
psychosocial problems associated
associated with
with
cancer.
Cancer.

30
Treatment-induced toxicity
Treatment-induced toxicity is
is less
less acceptable
acceptable ifif
the goal
the goal of
of therapy
therapy isis palliation
palliation.

The most
The most common
common side
side effects
effects of
of treatmen
treatment
|. nausea
1. nausea andand vomiting
vomiting
2. febrile
2. febrile neutropenia
neutropenia
3. myelosuppression
3. myelosuppression

31

* Systemic
✘ Systemic infections,
infections, sometimes
sometimes with
with
unusual pathogens,
unusual pathogens, maymay be
be a
a consequence
consequence
of the
of the immunosuppression
immunosuppression associated
associated with
with
cancer therapy.
cancer therapy.

32
Assessing the
Assessing the response
response to to treatment
treatment -- A A critical
critical
component of
component of cancer
cancer management
management
“Response assessment
“Response assessment usually usually requires
requires
periodic repeating
periodic repeating of of imaging
imaging tests
tests that
that
were abnormal
were abnormal at at the
the time
time of
of staging
staging.
IfIf imaging
imaging tests
tests have
have become
become normal,
normal, repeat
repeat
biopsy of
biopsy of previously
previously involved
involved tissue
tissue isis
performed to
performed to document
document complete
complete response
response
by pathologic
by pathologic criteria.”
criteria.”

33

Complete response
Complete response isis defined
defined as
as disappearance
disappearance of
of all
all
evidence of
evidence of disease
disease.

Partial response
Partial response as as >50%
>50% reduction
reduction inin the
the sum
sum of of the
the
products of
products of the
the perpendicular
perpendicular diameters
diameters of of all
all
measurable lesions.
measurable lesions. The
The determination
determination of of partial
partial
response may
response may also
also be
be based
based on
on a a 30%
30% decrease
decrease in in the
the
sums of
sums of the
the longest
longest diameters
diameters ofof lesions
lesions (Response
(Response
Evaluation Criteria
Evaluation Criteria in
in Solid
Solid Tumors
Tumors [RECIST]).
[RECIST)).

34
.

Progressive disease
Progressive disease is is defined
defined asas the
the
appearance of
appearance of any
any new
new lesion
lesion or
or an
an
increase of
increase of >25%
>25% in in the
the sum
sum ofof the
the products
products
of the
of the perpendicular
perpendicular diameters
diameters of of all
all
measurable lesions
measurable lesions (or
(or an
an increase
increase of of 20%
20%
in the
in the sums
sums ofof the
the longest
longest diameters
diameters by by
RECIST)
RECIST)

35
 Tumor shrinkage
Tumor shrinkage oror growth
growth that
that does
does not
not meet
meet
any of
any of these
these criteria
criteria is
is considered
considered stable
stable
disease
diseas

Some sites
Some sites of
of involvement
involvement (e.g.,
(e.g., bone)
bone) oror
patterns of
patterns of involvement
involvement (e.g.,
(e.g., lymphangitic
lymphangitic
lung or
lung or diffuse
diffuse pulmonary
pulmonary infiltrates)
infiltrates) are
are
considered unmeasurable.
considered unmeasurable.

36
e

Tumor markers
Tumor markers may
may bebe useful
useful in
in patient
patient
management in
management in certain
certain tumors
tumors and
and
response to
response to treatment.
treatment.

37
 The recognition
The recognition and
and treatment
treatment ofof depression
depression are
are important
important
components of
components of management
management.
x Dysphoria
✘ Dysphoria -- depressed
depressed moomood
x Anhedonia
✘ Anhedonia -- loss
loss of
of interest
interest in
in pleasur
pleasure

In addition,
✘ In addition, three
three or
or more
more of
of the
the following
following symptoms
symptoms
are usually
are usually present:
present: appetite
appetite change,
change, sleep
sleep problems,
problems,
psychomotor retardation
psychomotor retardation or
or agitation,
agitation, fatigue,
fatigue, feelings
feelings
of guilt
of guilt or
or worthlessness,
worthlessness, inability
inability to
to concentrate,
concentrate, and
and
suicidal ideation
suicidal ideation

38

 seLONG-TERM
■■LONG-TERM
FOLLOW-UP/LATE
FOLLOW-UP/LATE
COMPLICATIONS
COMPLICATIONS
At the
At the completion
completion ofof treatment,
treatment, sites
sites originally
originally
involved with
involved with tumor
tumor areare reassessed,
reassessed, usually
usually
by radiography
by radiography or or imaging
imaging techniques,
techniques, andand
any persistent
any persistent abnormality
abnormality is is biopsied.
biopsied.

40
For many
For many years,
years, a a routine
routine practice
practice hashas been
been to to
follow the
follow the patient
patient monthly
monthly for for 6–12
6-12 months,
months,
then every
then every other
other month
month forfor a a year,
year, every
every 3 3
months for
months for a
a year,
year, every
every 4 4 months
months forfor aa
year, every
year, every 6 6 months
months forfor aa year,
year, and
and then
then
annually.
annually.

41
Important medical
Important medical problems
problems can
can occur
occur in
in
patients treated
patients treated for
for cancer
cancer and
and must
must bebe
examined.
examined.

some problems
Some problems emerge
emerge as
as a
a consequence
consequence of
of
the disease
the disease and
and some
some as
as a
a consequence
consequence ofof
the treatment.
the treatment.

42

SUPPORTIVE
SUPPORTIVE
CARE
CARE
The success
The success of
of cancer
cancer therapy
therapy depends
depends on
on the
the
success of
success of the
the supportive
supportive care
care.

Supportive care
Supportive care isis a
a major
major determinant
determinant of
of
quality of
quality of life.
life.

44
.

 Pain

25-50% of
✘ 25–50% of patients
patients present
present with
with pain
pain at
at
diagnosis, 33%
diagnosis, 33% have
have pain
pain associated
associated with
with
treatment, and
treatment, and 75%
75% have
have pain
pain with
with
progressive disease
progressive disease.
✘ In ~70%
In ~70% of of cases,
cases, painpain is
is caused
caused by by the
the tumor
tumor itself—by
itself—by invasion
invasion of
of
bone, nerves,
bone, nerves, blood
blood vessels,
vessels, or or mucous
mucous membranes
membranes or or obstruction
obstruction ofof a
a
hollow viscus
hollow viscus or or duct.
duct.
✘ In ~20%
In ~20% of of cases,
cases, painpain is
is related
related to
to aa surgical
surgical or or invasive
invasive medical
medical
procedure, to
procedure, to radiation
radiation injury
injury (mucositis,
(mucositis, enteritis,
enteritis, oror plexus,
plexus, or
or spinal
spinal
cord injury),
cord injury), oror to
to chemotherapy
chemotherapy injury injury (mucositis,
(mucositis, peripheral
peripheral neuropathy,
neuropathy,
phlebitis, steroid-induced
phlebitis, steroid-induced asepticaseptic necrosis
necrosis of of the
the femoral
femoral head)
head).
x
✘ In 10%
In 10% ofof cases,
cases, painpain is
is unrelated
unrelated to to cancer
cancer or or its
its treatment.
treatment.

45

About 85%
About 85% of
of patients
patients will
will have
have pain
pain relief
relief from
from
pharmacologic intervention.
pharmacologic intervention. other
other modalities,
modalities,

x
✗ antitumor therapy
antitumor therapy (such
(such as
as surgical
surgical relief
relief of
of
obstruction, radiation
obstruction, radiation therapy,
therapy, and
and strontium-89
strontium-89 or
or
samarium-153 treatment
samarium-153 treatment for
for bone
bone pain)
pain)
✗ neurostimulatory technique
neurostimulatory techniques
✗ regional analgesi
regional analgesia
✗ neuroablative procedures
neuroablative procedures

46
a

 Nausea

Emesis in
Emesis in the
the cancer
cancer patient
patient isis usuallyserotonin
serotonin receptor
caused receptor
by
chemotherapy.
chemotherapy. antagonists ondansetron
antagonists ondansetron
, and
and granisetron
granisetron are
are effective
effective
x
✘ Acute emesis
Acute emesis -- thethe most
most common
co see
variety,Peachy
occurs
drugs against highly within
24 h
24 h of
of treatment.
treatment. emetogenic agents,
emetogenic agents,
Delayed emesis
✘ Delayed emesis -- occurs
occurs 1–7 1 days after treatment; it7 is
rare, but,
rare, us
present, usually
when present,
but, when oral
oral dexamethasone
dexametha
follows sone and
cisplatin and
deninietrati oral
oral meto-
meto- clopramide,
clopramide, a a
administration.
a Ne ray. dopamine
dopamine receptor
receptor
Anticipatory emesis
✘ Anticipatory emesis -- occurs
occurs before administration
antagonist
antagonist of
chemotherapy and
chemotherapy and represents
represents a conditioned response
to visual
to visual andand olfactory
olfactory stimuli
stimuli previously
p associated
prophylactic
prophylactic
with chemotherapy
with chemotherapy delivery.delivery. antiemetics the
antiemetics the day
day
before
before treatment
treatment

47

 Effusions

Fluid may
Fluid may accumulate
accumulate abnormally
é in the
When the condition is
pleural cavity,
pleural cavity, pericardium,
perice Senne
or peritoneum
symptomatic,
Symptomatic
*
✘ Asymptomatic malignant
Asymptomatic malignant effusions
effu
thoracentesis is usually
nericardial
maypericardial
not require treatment
performed first. In most
*
✘ Symptomatic effusions
Symptomatic effusions occurring
occu effusions
in tumors
cases,
are
responsive
symptomatic to
systemic therapy
systemic therapy usually
usually do usually
do not require treated
local
improvement by but
treatment
occurs
creating a
respond to
respond to the
the treatment
treatment for for <1
for the underlying month.
Malignant
Malignant
tumor.Chest
ascites is
ascites is
pericardial
tube window
drainage is with to
✘ Symptomatic effusions
Symptomatic effusions occurring
occur inor usually
usually
tumors
by treated
treated
the with
unresponsive
stripping
required if repeated
symptoms
repeated
therapy may
systemic therapy
systemic require local treatment
may require pericardium.
in patients with a
parace2ntesis
recur within weeks.of
paracentesis of
life expectancy
life expectancy of of at
at least
least 66 months. small small volumes
volumes of of
fluid.
fluid.

48

 Nutrition

Cancer and its treatment may lead to a decrease in nutrient intake

of sufficient magnitude to cause weight loss and alteration of
intermediary metabolism
Tumor-derived factors contribute Effortstotothe
makealtered
the metabolism,
assessment and a
vicious cycl objective have included the use of
threshold
threshold for
for nutritional
nutritional intervention
intervention as as
✘ bombesin, a prognostic nutritional index based
<10% unexplained
<10% unexplained body
body weight
weight loss,
loss, serum
serum
✘ adrenocorticotropic on albumin
hormonmg/L levels, triceps skinfold
transferrin level
transferrin level <1500
<1500 mg/L (150
(150 mg/dL),
mg/dL),
thickness, transferrin levels, and
and serum
and
✘ host-derived serum albumin
albumin
factors <34
(e.g.,<34
tumorg/L (3.4Megestrol
g/L necrosis
(3.4 g/dL) acetate,
g/dL)factor, tate, aa
interleukins 1
delayed-type hypersensitivity
progestational agent, skin
and 6, growth hormone yent, has
has
testing
been advocated as a
dasa
pharmacologic intervention
‘ervention
Enteral nutrition provided orally or by tube feeding is preferred
to improve nutritional
-critional over
Parenteral supplementation. status.
eer ole

49

 Psychosocial Support

The psychosocial
The psychosocial needs
needs ofof patients
patients vary
vary with
with
their situation.
their situation. Patients
Patients undergoing
undergoing
treatment experience
treatment experience fear,
fear, anxiety,
anxiety, and
and
depression
depressio

Perhaps the
Perhaps the most
most pervasive
pervasive and
and threatening
threatening
concern is
concern is the
the ever-present
ever-present fear
fear of
of relapse
relapse
(the Damocles
(the Damocles syndrome).
syndrome).

50
n

 Death and Dying

The most
The most common
common causes
causes ofof death
death in
in patients
patients
with cancer
with cancer are
are infectio
infection

Preparation for
Preparation for the
the end
end of
of life
life and
and patient
patient with
with
cancer may
cancer may gogo through
through stages
stages of of
adjustment to
adjustment to the
the diagnosi
diagnosis
These stages
These stages include
include denial,
denial, isolation,
isolation, anger,
anger,
bargaining, depression,
bargaining, depression, acceptance,
acceptance, and and
hope.
hope.

51
n

 End-of-Life Decisions

* Treatment
✘ Treatment goals
goals from
from curative
curative toto palliative
palliative
may not
may not be
be possible
possible in in all
all cases
cases because
because of of
the occurrence
the occurrence ofof serious
serious treatment-related
treatment-related
complications or
complications or rapid
rapid disease
disease progression.
progression.

52
Thank You
Thank You
 Want big impact? Use big image.

a ort @fiek

54
Prevention and
Prevention and Early
Early
Detection of
Detection of Cancer
Cancer
Prevention concerns
Prevention concerns thethe identification
identification and
and
manipulation of
manipulation of the
the biologic,
biologic,
environmental, social,
environmental, social, and
and genetic
genetic
factors in
factors in the
the causal
causal pathway
pathway of of cancer.
cancer.

2
EDUCATION AND
EDUCATION AND
HEALTHFUL HABITS
"TI

=aml
Y)
Tl

~~
os
—

>a
—

> 3
Public education
Public education on on the
the avoidance
avoidance ofof
identified risk
identified risk factors
factors for
for cancer
cancer and
and
encouraging healthy
encouraging healthy habits
habits contributes
contributes
to cancer
to cancer prevention
prevention

4
 SMOKING CESSATION
SMOKING CESSATION

Tobacco smoking
Tobacco smokin is a strong, modifiable
} : Those
Those who
who stop
stop smoking
smoking have a
have lower
30-50% lower
a 30–50%
risk
risk factor
factor for
for cardiovascular
10-year
10-year lung
lung cancer disease,
cancer mortality
mortality rate
rate compared
compared to
smoking
to
ou | monary di those who
those continue smoking
who continue
pulmonary disease, and cance
Lung cancer
Lung cancer and
and cancers
cancers of of the
the larynx,
larynx,
| oropharynx, esophagus,
oropharynx, esophagus, kidney, kidney, bladder, bladder,
| colon, pancreas,
colon, pancreas, and and stomach
stomach are are all all
tobacco-related.
tobacco-related. 5
r

smokers who
Smokers who quit
quit completely
completely are
are more
more
likely to
likely to be
be successful
successful than
than those
those whowho
gradually reduce
gradually reduce the
the number
number of of
cigarettes smoked
cigarettes smoked oror change
change to to lower-
lower-
tar or
tar or lower-nicotine
lower-nicotine cigarettes.
cigarettes.

6
PHYSICAL ACTIVITY
PHYSICAL ACTIVITY
Physical activity
Physical activity is
is associated
associated with
with a
a
decreased risk
decreased risk of
of colon
colon and
and breast
breas
cancer.
cancer.

7
DIET MODIFICATION
DIET MODIFICATION
epidemiologic studies
International epidemiologic
International studies suggest suqaest
that diets
that diets high
high in | fat are associated with
fc Evidence does
.. Evidence does not currently
not currently
increased
increased riskrisk for cancers
establish the
establish
of the
the anticarcinogenic
breast,
anticarcinogenic value
value ofof
vitamin, mineral,
mineral, oror nutritional
nutritional
colon,
colon, prostate,
prostate, and endometrium.
vitamin,
supplements
supplements in in amounts
amounts greater
greater than
than
In observational st) even
those sie diet.
providedieby a balanced os
In observational studies, dietary fiber is
associated with
associated with a reduced risk of colonic
polyps and
polyps and invasive
invasive cancer cancer of O the colon. 8

ENERGY BALANCE
ENERGY BALANCE
© A
◈ Acohort study of
cohort study of >5
>5 million
million adults
adults
included in
included in the
the U.K.
U.K. Clinical
Clinical Practice
Practice
Research Datalink
Research Datalink (a (a primary
primary care
care
database) found
database) found that
that each
each 5 5 kg/m2
kg/m2
increase in
increase in BMI
BMI was
was linearly
linearly associated
associated
with cancers
with cancers of of the
the uterus,
uterus, gallbladder,
gallbladder,
kidney, cervix,
kidney, cervix, thyroid,
thyroid, andand leukemia.
leukemia.
9
SUN AVOIDANCE
SUN AVOIDANCE
◈
@ Nonmelanoma
Nonmelanoma skin skin cancers
cancers (basal
(basal cell
cell and
and squamous
squamous
cell) are
cell) are induced
induced by by cumulative
cumulative exposure
exposure to to ultraviolet
ultraviolet
(UV) radiation.
(UV) radiation. Intermittent
Intermittent acute
acute sunsun exposure
exposure and and sun sun
damage have
damage have been
been linked
linked to
to melanoma
melanoma.
@ Reduction
◈ Reduction of of sun
sun exposure
exposure through
through use use ofof protective
protective
clothing and
clothing and changing
changing patterns
patterns ofof outdoor
outdoor activities
activities cancan
reduce skin
reduce skin cancer
cancer risk.
risk. Sunscreens
Sunscreens decrease
decrease the the risk
risk
of actinic
of actinic keratoses,
keratoses, the the precursor
precursor to to squamous
Squamous cell Cell
skin cancer,
skin cancer, butbut melanoma
melanoma risk risk may
may notnot be
be reduced.
reduced.
10
.

CANCER
CANCER
CHEMOPREVENTION

=!
x
m
=
O
U
D
m
<
m

O
©

Zz

Zz
11
 © ItIt involves
◈ involves the
the use
use ofof specific
specific natural
natural or
or synthetic
synthetic
chemical agents
chemical agents toto reverse,
reverse, suppress,
suppress, or or prevent
prevent
carcinogenesis before
carcinogenesis before the
the development
development of of invasive
invasive
malignancy.
malignancy
◈
@ Cancer
Cancer develops
develops through
through anan accumulation
accumulation of of tissue
tissue
abnormalities associated
abnormalities associated with
with genetic
genetic and
and epigenetic
epigenetic
changes, and
changes, and growth
growth regulatory
regulatory pathways
pathways thatthat are
are
potential points
potential points of
of intervention
intervention toto prevent
prevent cancer.
cancer.
12
.

 ASSOCIATED CANCER OR
CARCINOGENS* NEOPLASM!
Alkylating agents Acute myeloid leukemia, bladder
cancer
Androgens Prostate cancer
Aromatic amines (ayes) Biadder cancer
Arsenic Cancer of the tung, skin
Asbestos Cancer of the tung. pleura, peritoneum
Benzene Acute myelocytic teukemia
Chromium Lung cancer
Diethy!Istilbestro!l (prenatal) Vaginal cancer (clear cell)
Epstein-Barr virus Burkitt's lympnomea, nasal T-cell
lymphoma
Estrogens Cancer of the endometrium, liver,
breast
Ethyl aliconol Cancer of the breast, liver, esophagus.
head and neck
Helicobacter pylori Gastric cancer, gastric MALT
lymphoma
Hepatitis B or C virus Liver cancer
Human immunodeficiency virus Non-Hodskin’s tympnoma, Kaposi's
sarcoma, squamous cell carcinomas
(especially of the urogenital tract)
Human papilloma virus Cancers of the cervix, anus,
oropharynx
Human T-cell tymphotropic virus Adult T-cell teukemia/lymphoma
type 1 (HTLV-1)
Immunosuppressive agents Non-Hodgkin's lymphoma
(azathioprine, cyclosporine,
Slucocorticoids)
lonizings radiation (therapeutic or Breast, bladder, thyroid. soft tissue,
diagnostic) bone, hematopoietic, and many more
Nitrogen mustard gas Cancer of the tung, head and neck,
nasal sinuses
Nickel Gust Cancer of the tung, nasal sinuses
Diesel exhaust Lungs camcer (miners)
Phenacetin Cancer of the renal pelvis and biadder
Polycyclic hydrocarbons Cancer of the tung, skin (especially
Squamous cell carcinoma of scrotal
skin)
Ragon gas Lung cancer
Schistosomiasis Bladder cancer (Squamous cell)
Sunlight (ultraviolet) Skin cancer (squamous cell and
melanoma)
Tobacco (including smokeless) Cancer of the upper aerodigestive
tract, bladder
Vinyl chioride Liver cancer (angiosarcoma) 13
“Agents that are thought to act as cancer initiators and/Yor promoters.
Initiation !
Initiation > initial changes
initial changes
The alteration
The alteration can
can be be inherited
inherited or
or acquired
acquired through
through the
the action
action of
of
physical, infectious,
physical, infectious, or or chemical
chemical carcinogens.
carcinogens.

Promoters !
Promoters > Influences that
Influences that cause
cause the
the initiated
initiated cell
cell and
and its
its
surrounding tissue
surrounding tissue micro-
micro- environment
environment to to progress
progress through
through
the carcinogenic
the carcinogenic process
process and
and change
change phenotypically
phenotypically are are
◈
@ Promoters
Promoters include
include hormones
hormones such
such asas androgens,
androgens, linked
linked toto
prostate cancer,
prostate cancer, and
and estrogen,
estrogen, linked
linked to
to breast
breast and
and
endometrial cancer.
endometrial cancer. 14

CHEMOPREVENTION OF
CHEMOPREVENTION OF CANCERS
CANCERS OF
OF THE
THE UPPER
UPPER
AERODIGESTIVE TRACT
AERODIGESTIVE TRACT
Smoking causes
Smoking causes diffuse
diffuse epithelial
epithelial injury
injury in
in the
the oral
oral cavity,
cavity, neck,
neck,
esophagus,
esophagus,and
andlung.
lung.
Patients cured
Patients cured of
of squamous
squamous cellcell cancers
cancers ofof the
the lung,
lung, esophagus,
esophagus, oral
oral
cavity, and
cavity, and neck
neck are
are at
at risk
risk (as
(as high
high as
as 5%
5% per
per year)
year) of
of developing
developing
second cancers
second cancers of
of the
the upper
upper aerodigestive
aerodigestive tract.
tract.
This “field
This “field carcinogenesis”
carcinogenesis” hypothesis
hypothesis for
for upper
upper aerodigestive
aerodigestive tract
tract
cancer has
cancer has made
made “cured”
“cured” patients
patients an
an important
important population
population for
for
chemoprevention of
chemoprevention of second
second malignancies.
malignancies.

15

◈ Persistent oral
Persistent oral human
human papilloma
papilloma virus
virus (HPV)
(HPV) infection,
infection, particularly
particularly HPV-16,
HPV-16,
increases the
increases the risk
risk for
for cancers
cancers of of the
the oropharynx.
oropharynx. This This association
association exists
exists
even in
even in the
the absence
absence of of other
other risk
risk factors
factors such
such asas smoking
smoking or or alcohol
alcohol use
use
(although the
(although the magnitude
magnitude of of increased
increased risk
risk appears
appears greater
greater than
than additive
additive
when HPV
when HPV infection
infection and
and smoking
smoking areare both
both present).
present).
◈ Oral HPV
Oral HPV infection
infection isis believed
believed to
to be
be largely
largely sexually
sexually acquired.
acquired. Although
Although the
the
evidence is
evidence is not
not definitive,
definitive, the
the introduction
introduction ofof the
the HPV
HPV vaccine
vaccine may
may
eventually reduce
eventually reduce oropharyngeal
oropharyngeal cancer
cancer rates.
rates.
◈ Oral leukoplakia,
Oral leukoplakia, a
a premalignant
premalignant lesion
lesion commonly
commonly found
found in
in smokers,
smokers, hashas
been used
been used as
as an
an intermediate
intermediate marker
marker ofof chemopreventive
chemopreventive activity
activity in
in smaller
smaller
shorter-duration, randomized,
shorter-duration, randomized, placebo-controlled
placebo-controlled trials.
trials.

16

 Several large-scale
Several large-scale trials
trials have
have assessed
assessed agents
agents in
in the
the chemoprevention
chemoprevention of
of lung
lung cancer
cancer in
in
patients at
patients at high
high risk.
risk.
◈
@ The α-tocopherol/
The a-tocopherol/ β-carotene
B-carotene (ATBC)
(ATBC) Lung
Lung Cancer
Cancer Prevention
Prevention Tria
Trial
◈
@ The β-Carotene
The B-Carotene and
and Retinol
Retinol Efficacy
Efficacy Trial
Trial (CARET
(CARET)

The ATBC
The ATBC and and CARET
CARET results
results demonstrate
demonstrate the the importance
importance ofof testing
testing chemoprevention
chemoprevention
hypotheses thoroughly
hypotheses thoroughly before
before widespread
widespread implementation
implementation because
because the
the results
results contradict
contradict
aa number
number of of observational
observational studies.
studies. The
The Physicians’
Physicians’ Health
Health Trial
Trial showed
showed no no change
change inin
the risk
the risk of
of lung
lung cancer
cancer for
for those
those taking
taking β-carotene;
B-carotene; however,
however, fewer
fewer of
of its
its partici-
partici- pants
pants
were smokers
were smokers thanthan those
those in
in the
the ATBC
ATBC andand CARET
CARET studies.
studies.

17

CHEMOPREVENTION OF
CHEMOPREVENTION OF COLON
COLON CANCER
CANCER
◈
@ Colon
Colon cancer
canes prevention trials are are based
based on
on
Based on
Based on aa systematic
systematic review
review of of
the premiseevidencethat from
evidence most
from colorectal
randomized
randomized trials for cancers
trials for
primary prevention
primary prevention of of cardiovascular
cardiovascular
develop from adenomatous
disease,
disease, the
the U.S.
U.S. Preventive
Preventive Services polyps
Services
Task
Task Force
Force concluded
concluded that that the
the balance
balance
◈ Early clinical
of trialand
of benefits
benefits results
and harms favored
harms suggest
favored initiating that
initiating
low-dose
low-dose aspirin
aspirin for
for colorectal
colorectal cancer
cancer
nonsteroidal anti-inflammatory
prevention in
prevention in adults
adults ageage 50–59 they drugs
50—59 ifif they
have
have a a 10%
10% or or greater
greater 10-year
10-year riskrisk ofof
(NSAIDs) may prevent
cardiovascular
adenoma
cardiovascular disease.
disease.
formation
or cause regression of adenomatous dtOUS polyps.
polyps.
18
18
.

◈ Epidemiologic studies suggest that that diets

diets
high in calcium lower colon cancer risk. ISk.
◆ CalciumTheThebinds
randomized
randomized bile andCalcium
controlled
controlled fattyPolyp
Calcium acids,
Polyp
Prevention Study
Prevention Study found
found that
that calcium
calcium
which cause proliferation
supplementation
supplementation decreased
decreased the
of colonic
the absolute
absolute
risk of
risk of adenomatous
adenomatous polyp polyp recurrence
recurrence byby
epithelium.
ea
7%
It is
at 4aLyears;
=t-ESF
hypothesized that
calcium reduces intraluminal
exposure to these compounds.
19

 @ Combined
◈ Combined_e¢estrogen plus progestin
The Women’s
The Women’s Health
Health Initiative
Initiative
therapy demonstrated
demonstrated thatthat postmenopausal
postmenopausal
women
women taking
taking estrogen
estrogen plus
plus progestin
progestin
◈ The positive effect
have a
have
colorectal
a 44%
colorectal cancer
on
44% lower
colon
lower relative
relative risk
cancer compared
compared to
cancer
risk of
to women
of
women
is
mitigated byOf the
Of >16,600
modest
taking
>16,600 women
placebo. increase in
taking placebo.
women randomized
randomized and and
cardiovascular
followed and
followed
invasive
for
for a
invasive colorectal
breast
a median
median
colorectal cancers
of
of 5.6 cancer
5.6 years,
years,
cancers occurred
occurred in
43
43
in
the hormone
the hormone group
group and
and 72
72 in
in the
the placebo
placebo
group.
group.

20
.

CHEMOPREVENTION OF
CHEMOPREVENTION OF BREAST
BREAST CANCER
CANCER
◈
@ Tamoxifen
Tamoxifen is is an
an antiestrogen
2 with partial Nartial
estrogen age
estrogen agonistic activity in some
: In a
In a randomized
randomized placebo-controlled
placebo-controlled
tissues,
tissues, such as endometrium
prevention trial
prevention trial involving
involving >13,000
>13,000 and bone.
pre- and
pre- and
One of postmenopausal women
postmenopausal women at at high
high risk,
risk,
One of its actions
tamoxifen is to
tamoxifen decreased
upregulate
decreased the the risk
risk of
of developing
developing
transfor breast cancer
breast cancer by by 49%
49% (from
(from 43.4
43.4 toto 22
22 per
per
transforming growth
1000 women)
1000
factor
women) after after a
β,
a median
which
median follow-up
follow-up of of
decreases breast cell nearly nearly 6 6 years.
proliferation.
21
◈
@ Tamoxifen
Tamoxifen also
also reduced
reduced bone
bone fractures;
fractures;
aa small
small increase
increase _ in
in risk
risk of
of endometrial
endometrial
cancer, stroke,
cancer, stroke, pulmonary
pulmonary emboli,
emboli, and
and
deep vein
deep vein thrombosis
thrombosis waswas noted.
noted.

22
 ◈ The International
The International Breast
Breast Cancer
Cancer Interven-
Interven- tion
tion Study
Study (IBIS-I)
(IBIS-l) and
and
the Italian
the Italian Randomized
Randomized Tamoxifen
Tamoxifen Prevention
Prevention Trial
Trial also
also
demonstrated a
demonstrated a reduction
reduction in
in breast
breast cancer
cancer incidence
incidence with
with
tamoxifen use
tamoxifen use.
◈ A trial
A trial comparing
comparing tamoxifen
tamoxifen with
with another
another selective
selective estrogen
estrogen
receptor modulator,
receptor modulator, raloxifene,
raloxifene, performed
performed in in postmenopausal
postmenopausal
women showed
women showed that
that raloxifene
raloxifene isis comparable
comparable to to tamoxifen
tamoxifen in
in
cancer prevention,
cancer prevention, but
but without
without the
the risk
risk of
of endometrial
endometrial cancer.
cancer.

23
.

@ Aromatase
◈ Aromatase inhibitors
inhibitors are
are even
even more
more effective
affective than
than
tamoxifen in adjuvant
tamoxifen in ad A
breast cancer therapy,trial
randomized, placebo-controlled
A randomized, placebo-controlled trial
it has
of
of
been
hypothesized
hypothesizes that they wouldreported
exemestane
exemestane be more
reported a 65%
a effective
65% relative in breast
relative
reduction (from
cancer prevention. reduction (from 5.5
5.5 to
to 1.9
1.9 per
per 1000
1000
women) in
women) in the
the incidence
incidence of of invasive
invasive
breast
breast cancer
cancer inin women
women at at elevated
elevated risk
risk
after a
after a median
median follow-up
follow-up ofof about
about 3 3 years.
years.
Common adverse
Common adverse effects
effects included
included
arthral- gias,
arthral- gias, hot
hot flashes,
flashes, fatigue,
fatigue, and
and
insomnia.
insomnia.

24
CHEMOPREVENTION OF
CHEMOPREVENTION OF PROSTATE
PROSTATE CANCER
CANCER
◈ Finasteride e and dutasteride
The Prostate
The Prostate Cancer
Cancer Prevention
Prevention Trial
are
Trial (PCPT)
(PCPT)
5-α- A

reductase randomlyinhibitors.
randomly
average
average risk
assigned
assigned men
risk of
men age
of prostate
age 55
prostate cancer
55 years
cancer to
years or or older
older at
to finasteride
finasteride or
at
or
◆ Theyscreened
inhibit
placebo.
placebo.
screened with
All conversion
All men
men in the
in the trial
with prostate-specific
trial were
prostate-specific antigen
of
were being
being
antigen (PSA)
regularly
regularly
(PSA) levels
levels
testosterone
and
and digital
the
digital rectal
the incidence
incidence of
to dihydrotestosterone
rectal examination.
examination.
of prostate
prostate cancer
After
After 7
cancer was
7 years
years of
was 18.4%
of therapy,
18.4% in
therapy,
in the
the
(DHT),
finasteride
finasteride
arm, a
arm,
a potent
arm, compared
arm,
a statistically
compared stimulator
Statistically significant
with 24.4%
with 24.4% in
significant difference.
of
in the
the
difference. However,
prostate
placebo
placebo
However, the the
cell proliferation.
finasteride
finasteride group group hadhad more
more patients
patients with
with tumors
tumors of of
Gleason
Gleason score
score 7
7 and
and higher
higher compared
compared with
with the
the placebo
placebo
arm
arm (6.4
(6.4 vs
vs 5.1%).
5.1%).
25

 The Reduction
The Reduction by by Dutasteride
Dutasteride of of Prostate
Prostate CancerCancer Events
Events
(REDUCE)
(REDUCE) trial trial was
was a a randomized
randomized double-blind
double-blind trial trial in
in which
which
◈ Dutasteride has also been evaluated as
~8200 men
∼8200 men with
50-60 years
50–60
with an
years and
an elevated
and 3–10
elevated PSA
3-10 ng/mL
PSA (2.5–10
ng/mL forfor men
(2.5—10 ng/mL
men age age 60
ng/mL for
60 years
for men
years or
men age age
or older)
older)
and
and negative
negative prostate
prostate biopsy
biopsy on on enrollment
enrollment received received dailydaily 0.50.5
a preventive agent for prostate cancer.
mg of
mg of dutasteride
dutasteride or or placebo.
placebo. The The trialtrial found
found a a statistically
statistically
significant 23%
significant 23% relative
relative riskrisk reduction
reduction in in the
the incidence
incidence of of
biopsy-detected
biopsy-detected prostate prostate cancer
cancer in in the
the dutasteride
dutasteride arm arm at at 4 4
years of
years of treatment
treatment (659 (659 cases
cases vs vs 858858 cases,
cases, respectively).
respectively).
Overall,
Overall, across
across yearsyears 1 1 through
through 4, 4, there
there was was no no difference
difference
between
between the the arms
arms in in the
the number
number of of tumors
tumors with with a a Gleason
Gleason
score
score of of 77 to
to 10;
10; however,
however, during during years
years 3 3 and
and 4,4, there
there waswas a a
statistically
statistically significant
significant difference
difference in in tumors
tumors with with Gleason
Gleason scorescore
of 8
of 8 toto 10
10 inin the
the dutasteride
dutasteride arm arm (12 (12 tumors
tumors vs vs 11 tumor,
tumor,
respectively).
respectively).
26
◈
® Selenium
Selenium and
ANOS α-tocopherol
The Selenium
The Selenium and (vitamin
and Vitamin
Vitamin Cancer E)
E Cancer
E
' Prevention Trial
Prevention Trial (SELECT)
(SELECT) assigned
assigned
as potential
as potenti / prostate cancer
35,533 men
35,533 men toto receivepreventives.
receive 200
200 µg/d
yg/d
selenium, 400
selenium, 400 IU/d
IU/d α-tocopherol,
a-tocopherol,
selenium plus
selenium plus vitamin
vitamin E, E, or
or placebo.
placebo. After
After
a median
a median follow-up
follow-up ofof 77 years,
years, a a trend
trend
toward an
toward an increased
increased risk
risk of
of developing
developing
prostate
prostate cancer
cancer was
was observed
observed for for those
those
men taking
men taking vitamin
vitamin E E alone
alone as as compared
compared
to the
to the placebo
placebo arm
arm (hazard
(hazard ratioratio 1.17;
1.17;
95% confi-
95% confi- dence
dence interval,
interval, 1.004–1.36).
1.004—1.36).

27
VACCINES AND
VACCINES AND CANCER
CANCER PREVENTION
PREVENTION
◈
@ Vaccines to
Vaccines to protect
protect against
against these
these agents
agents may
may therefore
therefore reduce
reduce the
the
risk of
risk of their
their associated
associated cancers.
cancers.
◈
@ The hepatitis
The hepatitis BB vaccine
vaccine isis effective
effective in
in preventing
preventing hepatitis
hepatitis and
and
hepatomas due
hepatomas due to
to chronic
chronic hepatitis
hepatitis BB infection
infection.
@
◈ Vaccine demonstrates
Vaccine demonstrates high
high efficacy
efficacy in
in preventing
preventing persistent
persistent
strain-specific HPV
strain-specific HPV infections.
infections.

28

 SURGICAL PREVENTION
SURGICAL PREVENTION OF
OF CANCER
CANCER
@
◈ Women with
Women with severe
severe cervical
cervical dysplasia
dysplasia are
are treated
treated with
with laser
laser or
or
loop electrosurgical
loop electrosurgical excision
excision or
or conization
conization and
and occasionally
occasionally even
even
hysterectomy.
hysterectomy.
@
◈ Colectomy is
Colectomy is used
used to
to prevent
prevent colon
colon cancer
cancer in
in patients
patients with
with familial
familial
polyposis or
polyposis or ulcerative
ulcerative colitis.
colitis.
@
◈ Prophylactic bilateral
Prophylactic bilateral mastectomy
mastectomy may
may bebe chosen
chosen for
for breast
breast
cancer prevention
cancer prevention among
among women
women with
with genetic
genetic predisposition
predisposition to
to
breast cancer.
breast cancer.
@
◈ Prophylactic salpingo-oophorectomy
Prophylactic salpingo-oophorectomy may
may also
also be
be employed
employed for
for the
the
prevention of
prevention of ovarian
ovarian and
and breast
breast cancers
cancers among
among high-risk
high-risk women.
women.
29

CANCER SCREENING
CANCER SCREENING
◈ Screening
Screening is is a
a means
means of of early
early detection
detection
in asymptomatic
in asymptomatic individuals,
individuals, with
with the
the
goal of
goal of decreasing
decreasing morbidity
morbidity and
and
mortality.
mortality.

30
 © A
◈ Ascreening test’s accuracy
screening test’s accuracy or or ability
ability to to
discriminate
discriminate
i :
diseases Sensitivity
disease is described by four
STATIN
indices:
ind ices: Specificity
also
1 minus
the
the
called the
also called true-positive rate
the true-positive
the false-positive
proportion
proportion of persons
of persons with
rate
rate the
with the
◆¢ sensitivity
sensitivity porta disease
do
screen
screen
tem who
el Rsyereproportion
the
not have
(i.e., the
(i.e.,
LOSI E in
CSMof persons
ATOM test positive
disease
the ability
ability of
who
of that
UAT=
MAM the
the test
the test to
to
◆o Specificit
Specificity Ee test
detect diseaseinwhen
§6detectnegative
disease
test (i.e., the ability of
when itit is
the screening
Positive
a
present).
is present).
test
predictive
to
value
5◆ positive
-—-
3S yer -— ——--

positive predictive
predicti valu
correctly
correctly Meee)
indicate thatNegative
Negative
the
proportion predictive
predictive
of
disease
disease is is not
not present).
pre. value
value is
is the
the
◆¢ negative
negative predictive
predictive value value— proportion Be eiirecn
persons who test
positive thattesting
actually
negative
negative
have that
the that do not
do
disease. not31
have the
have the disease.
disease.

 nt of the Value
of a D: :
CONDITION PRESENT CONDITION ABSENT
Positive test e b
Negative test | c | d
a = true positive
56 = false positrve
c = faise negative
d = true negatrve
Sensitnny | The proportion of persons with the condition who
_ test positive: ae /la +c)
Specificity The proportion of persons without the condition
_who test negative: d /(6 + a)
Positive predictive value The proportion of persons with a positive test who
(PPy) _have the condmion: a /(@ + 6)
Negative predictive value The proportion of persons with a negatme test who
_do not have the condition: d /[(c + d)
Prevalence, sensitivty, and specificrty Getermine PPV
prevalence x sensitivity
PPV =
(prevalence = sensitivity) + (1 —prevalence)(1 — specificity)

*For Gisesses of low prewalence, such ss cancer, poor specificity nas 3 dramatic
adwerse effect on PPV such that only 32 small fraction of posmive tests are true
positives.
32
Common Biases
Common Biases in
in screening
screening:

Lead-time bias
Lead-time bias !> occurs whether
occurs whether or
or not
not aa test
test influences
influences the
the natural
natural history
history of
of the
the
disease; the
disease; the patient
patient is is merely
merely diagnosed
diagnosed atat an
an earlier
earlier date.
date. Survival
Survival appears
appears
increased even
increased even ifif life
life is
is not
not prolonged.
prolonged.

Length-biased sampling
Length-biased sampling !> occurs because
occurs because screening
screening tests
tests generally
generally can
can more
more
easily detect
easily detect slow-growing,
slow-growing, less
less aggressive
aggressive cancers
cancers than
than fast-growing
fast-growing cancers.
cancers.
Cancers diagnosed
Cancers diagnosed due
due to
to the
the onset
onset of
of symptoms
symptoms between
between scheduled
scheduled screenings
screenings
are on
are on average
average more
more aggressive,
aggressive, andand treatment
treatment outcomes
outcomes areare not
not as
as favorable.
favorable.

Selection bias
Selection bias !
> occurs because
occurs because the
the population
population most
most likely
likely to
to seek
seek screening
screening often
often
differs from
differs from the
the general
general population
population to
to which
which the
the screening
screening test
test might
might be
be applied.
applied.

33
:

Risks associated
Risks associated with with screening
screening include
include harm
harm caused
caused by by the
the
screening intervention
screening intervention itself,
itself, harm
harm due
due to to the
the further
further
investigation of
investigation of persons
persons with with positive
positive tests
tests (both
(both true
true and
and
false positives),
false positives), and and harm
harm fromfrom the
the treatment
treatment of of persons
persons
with a
with a true-positive
true-positive result,
result, whether
whether or or not
not life
life is
is extended
extended
by treatment
by treatment (e.g.,
(e.g., even
even ifif a a screening
screening testtest reduces
reduces relative
relative
cause-specific mortality
cause-specific mortality by by 20–30%,
20-30%, 70–80%
70-80% of of those
those
diagnosed still
diagnosed still go
go on
on toto die
die of
of the
the target
target cancer).
cancer).

34
◈
@ Good
Good clinical
clinical trial
trial design
design can can offset
offset some
some biases
biases of
of
screening and
screening and demonstrate
demonstrate the the relative
relative risks
risks and
and benefits
benefits
of a
of a screening
screening test.
test. AA randomized
randomized controlled
controlled screening
screening trial
trial
with cause-specific
with cause-specific mortality
mortality as
as the
the endpoint
endpoint provides
provides the
the
strongest support
strongest support forfor aa screening
screening intervention.
intervention.

35
 ©) Y)
» ©=
S (D
OQ (D
©
=

Cancers
) =_
(©
_
O
=
GY)
(D
©)
=h
©)
Screening for Specific

36
BREAST CANCER
BREAST CANCER
◈
© Breast self-examination,
Breast self-examination, clinical
clinical breast
breast examination
examination by
by aa
Caregiver, mammography,
caregiver, mammography, andand magnetic
magnetic resonance
resonance imaging
imaging (MRI)
(MRI)
have all
have all been
been variably
variably advocated
advocated as as useful
useful screening
screening tools.
tools.
©
◈ Digital breast
Digital breast tomosynthesis
tomosynthesis isis an
an emerging
emerging method
method of of breast
breast
cancer screening
cancer screening that
that reconstructs
reconstructs multiple
multiple x-ray
x-ray images
images ofof the
the
breast into
breast into superimposed
superimposed “three-dimensional”
“three-dimensional” slices.
slices.
◈
@ Genetic screening
Genetic screening forfor BRCA1
BRCA1 andand BRCA2
BRCA2 mutations
mutations and
and other
other
mark- ers
mark- ers ofof breast
breast cancer
cancer risk
risk has
has identified
identified a
a group
group of
of women
women atat
high risk
high risk for
for breast
breast cancer.
cancer.

37

CANCER TYPE TEST OR PROCEDURE

Breast Self-examination | *D" {Not in current recommendations; from 2009) | Women, all ages: No specific recommendation
Clinical examination Women 240 years: “I” (as a standalone without Women, all ages: Do not recommend
mammography) (Not in current recommendations; from
009)
Mammography ‘Women 40-49 years: The decision to start screening ‘Women 40-44 years: Provide the opportunity to
mammography in women prior to age 50 years should begin annual screening
be an individual one. Women who place a higher value | Women 45-54 years: Screen annually
on the potential benefit than the potential harms may
hs . Women 255 years: Transition to biennial screening or
choose to begin biennial screening between the ages of :
40 and 49 years. {*C") have the opportunity to continue annual screening
Women 240 should continue screening
mammography as long as their overall health is good
and they have a life expectancy of 10 years or longer
Women 50-74 years: Every 2 years (*B")
| Women 275 years: “I” |
Magnetic resonance “I” (Not in currant recommendations; from 2009) Women with >20% lifetime risk of breast cancer:
imaging (MRI) Screen with MRI plus mammography annually
Women with 15-20% lifetime risk of breast cancer:
Discuss option of MR plus mammography annually
Women with <15% lifetime risk of breast cancer: Do
not screen annually with MRI
Tomosynthesis Women, all ages: “I” No specific recommendation
38
 CERVICAL CANCER
CERVICAL CANCER
◈
@ Screening with
Screening with Papanicolaou
Papanicolaou (Pap)
(Pap) smears
smears decreases
decreases cervical
cervical
cancer mortality.
cancer mortality.
◈
@ Screening guidelines
Screening guidelines recommend
recommend regular
regular Pap
Pap testing
testing for
for all
all
women who
women who have
have reached
reached the
the age
age of
of 21
21 (before
(before this
this age,
age, even
even inin
individuals that
individuals that have
have begun
begun sexual
sexual activity,
activity, screening
screening may
may cause
cause
more harm
more harm than
than benefit).
benefit).

39

 tis
CANCER TYPE TEST OR PROCED URE USPSTF ACS
Cervical Pap test (cytology) Women 21-65 years: Screen every 3 years (“A”) Women 21-29 years: Screen every 3 years
Women <21 years: “D" Women 30-65 years: Acceptable approach to screen
Women >65 years, with adequate, normal prior Pap with cytology every 3 years (see HPV test below)
screenings: “D” Women <21 years: No screening
Women >65 years: No screening following adequate
negative prior screening
Women after total hysterectomy for noncancerous Women after total hysterectorny for noncancerous
causes: “D" causes: Do not screen
HPY test Women 30-65 years: Screen in combination with Women 30-65 years: Preferred approach to screen
cytology every 5 years if woman desires to lengthen the with HPV and cytology cotesting every 5 years (see
screening interval (see Pap test above) ("A") Pap test above)
Women <30 years: “D" Women <30 years: Do not use HPV testing
Women >65 years, with adequate, normal prior Pap Women >65 years: No screening following adequate
screenings: “D" negative prior screening
Women after total hysterectomy for noncancerous Women after total hysterectomy for noncancerous
causes: “D" causes: Do not screen

40
◈
COLORECTAL CANCER
COLORECTAL
Fecal occult blood testingCANCER... examination (DRE),
(FOBT), digital rectal examination (DRE), rigid
rigid and
and
flexible sigmoidoscopy,
flexible sigmoidoscopy, colonoscopy,
colonoscopy, and
and computed
computed tomography
tomography (CT)
(CT)
colonography have
colonography have been
been considered
considered for
for colorectal
colorectal cancer
cancer screening.
screening.
◈
@ Fecal immunochemical
Fecal immunochemical tests
tests (FIT)
(FIT) have
have higher
higher sensitivity
sensitivity for
for colorectal
colorectal cancer
cancer
than nonrehydrated
than nonrehydrated FOBT
FOBT tests.
tests.
◈
@ Methylated SEPT9
Methylated SEPT9 gene
gene associated
associated with
with colorectal
colorectal cancer
cancer isis available
available but
but its
its
sensitivity is
sensitivity is low
low and
and itit is
is not
not recommended
recommended as as a a
first-line screening test.
first-line screening test.
◈
@ One-time colonoscopy
One-time colonoscopy detects
detects ∼25%
~25% more
more advanced
advanced lesions
lesions (polyps
(polyps >10
>10 mm,
mm,
villous adenomas,
villous adenomas, adenomatous
adenomatous polyps
polyps with
with high-grade
high-grade dysplasia,
dysplasia, invasive
invasive
cancer) than
cancer) than one-time
one-time FOBT
FOBT with
with sigmoidoscopy
sigmoidoscopy.
◈
@ CT colonography,
CT colonography, ifif done
done at
at expert
expert centers,
centers, appears
appears to
to have
have a
a sensitivity
sensitivity for
for
polyps ≥6
polyps =6 mm
mm comparable
comparable to to colonoscopy
colonoscopy

41

 mec

CANCER TYPE TEST OR PROCEDURE

Colorectal Sigmoidoscopy Adults, 50-75 years: “A” Screen for colorectal cancer; | Adults 250 years : Screen every 5 years
the risks and benefits of the different screening methods

Adults, 76 to 85 years: °C” The decision to screen

should be an individual one, taking into account the
patient's overall health and prior screening history
Every 5 years; modeling suggests improved benefit if
performed every 10 years in combination with annual FIT |
Fecal occult blood testing Adults 250 years : Screen every year
(FOBT)
Colonoscopy | Adults 250 years : Screen every 10 years
Fecal DNA testing Every 1 or 3 years Adults 250 years : Screen, but interval uncertain
Fecal immuno-chemical Adults 250 years : Screen every year
testing (FIT)
| CT colonography | Adults 250 years: Screen every 5 years

42
LUNG CANCER
LUNG CANCER
®
◈ Chest x-ray
Chest x-ray and
and sputum
sputum cytology
cytology have
have been
been evaluated
evaluated in
in several
several randomized
randomized
lung cancer
lung cancer screening
screening trials.
trials.
©
◈ Prostate, Lung,
Prostate, Lung, Colorectal,
Colorectal, and and Ovarian
Ovarian (PLCO)
(PLCO) cancer
cancer screening trial !
screening trial >
compared with
compared with usual
usual care,
care, annual
annual chest
chest x-ray
x-ray did
did not
not reduce
reduce the
the risk
risk of
of dying
dying
from lung
from lung cancer
cancer (relative
(relative risk
risk 0.99;
0.99; 95%
95% confidence
confidence interval
interval 0.87–1.22)
0.87—1.22) after
after
13 years.
13 years. Low-dose
Low-dose CT CT has
has also
also been
been evaluated
evaluated inin several
several randomized
randomized trials.
trials.
The most
The most recent
recent and
and largest
largest (n(n =
= 154,901)
154,901).
◈ National Lung
National Lung Screening
Screening Trial
Trial (NLST)
(NLST) !was
>was a a randomized
randomized controlled
controlled trial
trial of
of
screening for
screening for lung
lung cancer
cancer inin ∼53,000
~53,000 persons
persons ageage 55–74
55—74 years
years with
with a
a 30+
30+
pack-year smoking
pack-year smoking history.
history. ItIt demonstrated
demonstrated a a statistically
statistically significant
significant relative
relative
reduction of
reduction of about
about 15–20%
15—20% in in lung
lung cancer
cancer mortality
mortality in in the
the CT
CT arm
arm compared
compared to to
the chest
the chest x-ray
x-ray arm
arm (or
(or about
about 3 3 fewer
fewer deaths
deaths per
per 1000
1000 people
people screened
screened with
with
CT). The
CT). The largest
largest and
and longest
longest of of screening
screening trials
trials
43

 Corn elt Pe eh El rt i }
CANCER TYPE TEST OR PROCEDURE USPSTF ACS

Lung ‘Londose computed Adults 55-80 years, with a 230 pack-year smoking history, “Men and women, 55-74 years, with 230 pack-year
tomography (CT) scan still smoking or have quit within past 15 years: “B” smoking history, stil smoking or have quit within
Discontinue once a person has not smoked for 15 years Past £5 years: Discuss benefits limitations, and
or develops a health problem that substantially limits life | Potential harms of screening; only perform screening
expectancy or the ability to have curative lung surgery | facilities with the nght type of CT scanner and with
high expertise/ specialists

44
OVARIAN CANCER
OVARIAN CANCER
®
◈ Adnexal palpation,
Adnexal palpation, transvaginal
transvaginal ultrasound
ultrasound (TVUS),
(TVUS), and
and serum
serum CA-125
CA-125
assay have
assay have been
been considered
considered for
for ovarian
ovarian cancer
cancer screening.
screening.
©
◈ A large
A large randomized
randomized controlled
controlled trial
trial has
has shown
shown that
that an
an annual
annual screening
screening
program of
program of TVUS
TVUS and
and CA-125
CA-125 in in average-risk
average-risk women
women does
does not
not reduce
reduce
deaths from
deaths from ovarian
ovarian cancer
cancer (relative
(relative risk
risk 1.21;
1.21; 95%
95% confidence
confidence interval
interval
0.99-1.48).
0.99–1.48).

45

 } COrmMenc

CANCER TYPE TEST OR PROCEDURE USPSTF

Ovarian | CA125 ‘Women, all ages: “D" There is no sufficiently accurate test proven effective
Transvaginal ultresound Women, all ages: “D" m the early detection of ovarian cancer. For women
at high risk of ovarian cancer and/or who have
unexplained, persistent symptoms, the combination
of CA-125 and transvaginal ultrasound with pelvic
| exam may be offered.

46
PROSTATE CANCER
PROSTATE CANCER
◈
@ The most
The most common
common prostate
prostate cancer
cancer screening
screening modalities
modalities are
are
digital rectal
digital rectal exam
exam (DRE)
(DRE) and
and serum
serum PSA
PSA assay
assay.
◈
@ Two major
Two major randomized
randomized controlled
controlled trials
trials ofof the
the impact
impact of
of PSA
PSA
screening on
screening on prostate
prostate cancer
cancer mortality
mortality:
◆
¢ The PLCO
The PLCO Cancer
Cancer Screening
Screening Tria
Trial
◆
¢ The European
The European Randomized
Randomized Study
Study of of Screening
Screening for
for Prostate
Prostate
Cancer (ERSPC)
Cancer (ERSPC)

47
l

CONLED TYPE TEST OP PROCEDURE USPSTF

Prostate Prostate-specific antigen Men, all ages: °D" Starting at age 50, men should talk to a doctor
(PSA) about the pros and cons of testing so they can
decide if testing is the right chotca for them. If
African American or have a father or brother who had
prostate cancer before age 65, men should have this
talk starting at age 45. How often they are tested w
| depend on their PSA level
Digital rectal examination No individual recommendation As for PSA; if men decide to be tested, they should
(DRE) have the PSA blood test with or without a rectal
eam

48
SKIN CANCER
SKIN CANCER
@ Visual
◈ Visual examination
examination of of all
all skin
skin surfaces
surfaces by
by the
the patient
patient or
or by
by
a health
a health care
care provider
provider is
is used
used in
in screening
screening for
for basal
basal and
and
squamous cell
squamous cell cancers
cancers andand melanoma.
melanoma.

49
 etpeebinice '

CANCER TYPE TEST OR PROCEDURE USPSTF

Skin Complete skin | Adults, all ages: “I” | Self-examination monthly; clinical exam as part of
examination by clinician routine cancer-related checkup
or patiant

50
 istening
Thank You for listening

Se
51