Uterine Cervix

Carcinoma

Epidemiology
Highly prevalent in developing nations
A large proportion of cervix cancer can be
characterized as a sexually transmitted disease,
with early age of first intercourse, history of
multiple sexual partners, and large number of
pregnancies as risk factors
The role of human papilloma virus (HPV) as a
causative agent of cervical cancer is well
established, and the detection of HPV types 16 and
18, predominantly, carries prognostic importance in
some studies
An association between cigarette smoking and
development of cervical cancer has been reported

Natural History and Patterns

of Spread
Squamous-cell carcinoma of the uterine cervix
usually originates at the squamous columnar junction
(transformation zone) of the endocervical canal and
the portio of the cervix.
The lesion is frequently associated with severe
cervical dysplasia and carcinoma in situ, usually
progressing to invasive carcinoma over 10 to 20 years
in the majority of patients .
The tumor, if untreated, may spread to the adjacent
vaginal fornices or to the paracervical and parametrial
tissues.

Clinical Presentation
Postcoital spotting
Metrorrhagia
Serosanguineous or yellowish,
foul-smelling vaginal discharge
If chronic bleeding: fatigue and anemia
Pain in the pelvis or hypogastrium
Urinary and rectal symptoms
(hematuria rectal bleeding)
Pain in the lumbosacral area for
para-aortic lymph node Involvement with
extension into the lumbosacral roots or
hydronephrosis

Diagnostic Work-Up
General
History
Physical examination, including bimanual pelvic and rectal
examinations
Diagnostic procedures
Cytologic smears (Papanicolaou) if not bleeding
Colposcopy
Conization (subclinical tumor)
Punch biopsies (edge of gross tumor, four quadrants)
Dilatation and curettage
Cytoscopy, rectosigmoidoscopy (stages IIB, III, and IVA)
Radiographic studies
Chest radiography
CT or MRI
Laboratory studies
Complete blood count
Blood chemistry
Urinalysis

Staging: FIGO Classification

Stage
IB

Clinical lesions confined to

the cervix or preclinical
lesions greater than IA

Stage
IIA

Tumor without parametrial

invasion

Stage
IIB

Tumor with parametrial

invasion

Staging: FIGO Classification

Stage
IIIA

Stage
IIIB

Stage
IVA

Tumor involves lower

third of the vagina, with
no extension to pelvic
wall

Tumor extends to pelvic

wall and/or causes
hydronephrosis or
nonfunctioning kidney

Tumor invades mucosa of

the bladder or rectum
and/or extends beyond the
true pelvis

Pathologic Classification
Squamous-cell carcinoma: >
90%
Adenocarcinoma: 7-10%
Clear-cell: 1-2%

General Management: Stage

IA

Lesions <1 mm in depth can be treated with

conization, provided all margins are tumor free.
Early invasive carcinoma of the cervix (stage
IA2) is usually treated with a total abdominal or
modified radical hysterectomy, but it can be treated
with intracavitary RT.
When the depth of
penetration of the stroma by
tumor is <3 mm, the
incidence of lymph node
metastasis is 1% or less,
and a lymph node
dissection or pelvic
external irradiation is not

General Management: Stage

IB, IIA

STAGE
IB AND
IIA

PREOPERATIV
E RT +
RADICAL
SURGERY

General Management: Stage

IIB, III

STAGE
IIB
AND III

RADIOTHERA
PY +
CHEMOTHER
APY

General Management: Stage

IVA

STAGE
IVA

EBRT WHOLE PELVIS

or
INTRACAVITARY
INSERTIONS +
PARAMETRIAL RT
or
PELVIC
EXENTERATION

General Management:
Stage IVB

STAGE
IVB

CHEMOTHERAPY

General Management:
Postoperative Radiation
Therapy

2 positive pelvic lymph nodes

microscopic positive or close (<3

mm)
margins of resection
deep stromal invasion
vascular/lymphatic permeation

Radiation Therapy
Techniques
The two main modalities of irradiation
are external photon beam and
brachytherapy.
External irradiation is used to treat the
whole pelvis and the parametria
including the common iliac and
para-aortic lymph nodes, whereas
central disease (cervix, vagina, and
medial parametria) is primarily

External-Beam Irradiation:
Volume

In treatment of invasive carcinoma of the

uterine cervix,
it is important to deliver adequate doses of
irradiation
not only to the primary tumor but also to the
pelvic lymphnodes to maximize tumor control.

Intracavitary Brachytherapy
FLETCHER APPLICATOR

Intracavitary Brachytherapy
ADVANTAGES

DISAVANTAGES

the conformation of the

vagina and the uterine cavity
lends itself to placement of
radioactive preparations;

the rapid fall of the dose not

allow to administer cancericide
doses at areas more distal

local anatomy is often

distorted by the tumor does
not always allow optimal
placement of radioactive

structures directly in contact

with radioactive preparations
(cervix, vagina) have
tolerance to high doses of RT;
the rapid fall of the dose
allows for protection of
organs at risk (rectum,
bladder).

preparations.

Intracavitary Brachytherapy:
Disadvantages
the rapid fall of the dose not allow to
administer cancericide doses at areas more
distal
local anatomy is often distorted by the tumor
does not always allow optimal placement of
radioactive preparations.

Chemotherapy
Chemotherapy is being more extensively used in
bulky and advanced cervical cancer; some
cytotoxic agents have shown encouraging efficacy
in patients with advanced and recurrent cervical
carcinoma.

Carboplatin
+
Carboplatin + Paclitaxel
Paclitaxel

Endometrial
Carcinoma
(EC)

Epidemiology
The most common gynecologic
malignancy
It is primarily a disease of
postmenopausal women
The median age at diagnosis is 61
years
Approximately 25% of cases occur in
premenopausal patients, including
5% that are diagnosed in patients
younger than 40 years of age

Risk Factors

Obesity
Diabetes
Early menarche
Late menopause
Unopposed estrogen therapy or
tamoxifen
Anovulatory cycles
Traditionally,
Nulliparity
EC has been divided into type I and
type II categories characterized by distinct biologic
and clinical behavior, with different causes.

Type I EC
85% of all EC
associated with a hyperestrogenic state
generally are low-grade, indolent tumors of
endometrioid histology

Type II EC
15% of all EC
estrogen-independent
arise in the setting of uterine atrophy and
generally consist of poorly differentiated, tumor
(MMMT)
patients are more often multiparous, older, and

Clinical Presentation
postmenopausal vaginal bleeding
discharge
in more advanced disease:
-urinary or rectal bleeding,
-constipation, pain;
- lower extremity lymphedema;
-abdominal distension due to ascites;
-cough and/or or hemoptysis.

Diagnostic Work-Up
Pathologic examination
Transvaginal ultrasonography
Hysteroscopy
CT or MRI
Ca-125

Pathologic Classification
Endometrioid adenocarcinoma:
75-80%
Uterine papillary serous: 10%
Clear-cell: 4%
Mucinous carcinoma: 1%

Degree of differentiation:
FIGO definition
G1 (well differentiated)
5% of a nonsquamous or nonmorular solid growth
pattern

G2 (moderately differentatiated)
6%50% of a nonsquamous or nonmorular solid
growth pattern

G3 (poorly differentiated)
>50% of a nonsquamous or nonmorular solid growth
pattern

Staging: FIGO Classification

Staging: FIGO Classification

2009
FIGO

Stage 0 Atypical endometrial hyperplasia, carcinoma in situ.

Histologic findings are suspicious of malignancy. Cases of stage 0
should not be included in any therapeutic statistics
Stage I
IA
IB

Tumor limited to the uterus

Tumor limited to the endometrium or invasion to <50% of the
myometrium
Invasion to 50% of the myometrium

Stage II Extension to the cervix but not beyond the uterus

Stage
III
IIIA
IIIB
IIIC1
IIIC2

Extension outside of the uterus/cervix +/- regional metastasis

Tumor invades serosa or adnexum
Vaginal metastasis or extension to parametrium
Metastasis to pelvic lymph nodes
Metastasis to paraaortic lymph nodes

Stage
IV
IVA
IVB

Tumor invades bladder and/or bowel mucosa

Distant metastasis including intra-abdominal and/or inguinal
lymph nodes

RISK GROUPS:

LOW RISK (55%):

Stage IA (< 50% invasion) grade 1, 2
Endometrioid carcinoma
INTERMEDIATE RISK (30%):
Stage IB (> 50% invasion) grade 1,2
Stage IA (< 50% invasion) grade 3
Endometrioid carcinoma
HIGH RISK (15%):
Stage IB (> 50% invasion) grade 3
Stage II III IV
Any stage and serous or clear cell carcinoma
Figo 2009 Staging Pecorelli 2009

Risk Groups in Early-Stage

(FIGO I-II):
Treatment Recommendations
STAGE
IA G1-G2

SURGERY
ALONE

Risk Groups in Early-Stage

(FIGO I-II):
Treatment Recommendations
STAGE IA G3
STAGE IB G1-2

SURGERY +
INTRAVAGINAL
BRACHYTHERAPY ALONE

Risk Groups in Early-Stage

(FIGO I-II):
Treatment Recommendations
HIGH RISK

STAGE IB
G3:
SURGERY+
EBRT

STAGE II:
SURGERY+
EBRT+
VAGINAL
BRACHYTHERAPY

Risk Groups in Advanced-Stage

(FIGO III-IV) :Treatment
Recommendations
ADVANCED
STAGE:
STAGE III

STAGE III A-B-C:

SURGERY+ EBRT TO THE WHOLE
PELVIS +/- BRT
CHT ?

Risk Groups in Advanced-Stage

(FIGO III-IV) :Treatment
Recommendations
ADVANCED
STAGE:
STAGE IV
SURGERY+ DIFFERENT
APPROACHES IN THE ADJUVANT
SETTING :PELVIC RT, EXTENDED
FIELDS RT (PELVIC PLUS
PERIAORTIC RT), WHOLE
ABDOMINAL IRRADIATION (WAI)

Preoperative Irradiation
It may have a role for those patients with gross
involvement of the cervix or vagina (FIGO clinical
stages IIB and III, respectively).
Intracavitary brachytherapy alone or in combination
with pelvic EBRT may be used.
Patients with gross pelvic or retroperitoneal nodal
disease, without distant metastasis, could be
considered for preoperative extended-field RT
(EFRT) and brachytherapy to be followed by
surgical staging.

Postoperative Irradiation
It has been shown to improve
pelvic tumor control and
disease-free survival, when
compared with observation,
without impact in overall survival.

External-Beam Irradiation:
Volume

External-Beam Irradiation:
Dose

45 60 Gy(1,8-2
Gyx1x5)
depending on
radiotherapy
intent

Vaginal
Carcinoma

Epidemiology
1% to 2% of all female genital neoplasia
most of vaginal neoplasms, 80% to 90%, are
metastatic from other primary gynecologic
(cervix or vulva) and non-gynecologic sites,
involving the vagina by direct extension or
lymphatic or hematogenous routes
incidence peaks in the sixth and seventh
decades of life
It is increasingly in younger women, due to
HPV infection or other sexually transmitted
disease

Pathologic Classification
squamous cell carcinomas or
adenocarcinomas: 92%
melanoma: 4%
sarcoma: 3%
other: 1%

Diagnostic Work-Up
Pathologic examination
Digital palpation
Colposcopic and cytologic evaluation
CT or MRI
Cystoscopy, proctoscopyon

(patients with
symptoms suggestive of bladder or rectal infiltration)

Staging: FIGO Classification

FIGO
Stage 0 Carcinoma in situ, intraepithelial neoplasia grade III
Stage I

Limited to the vaginal wall

Stage
II

Involvement of the subvaginal tissue but without extension to the

pelvic side wall
Extension to the pelvic side wall

Stage
III

Extension beyond the true pelvis or involvement of the bladder

or rectal mucosa. Bullous edema as such does not permit a case
to be allotted to Stage IV.

Stage
IV
IVA
IVB

Spread to adjacent organs and/or direct extension beyond the

true pelvis
Spread to distant organs

Carcinoma in Situ (VAIN)FIGO 0

VAIN: both surgically and medically approach.
Treatment options range from partial or
complete
vaginectomy to more conservative approaches:
- local excision;
- electrocoagulation, laser vaporization;
- topical 5% fluorouracil administration;
- intacavitary brachytherapy alone.
The reported control rates are very similar
among the
different approaches

Invasive Squamous Cell

Carcinoma (SCC)
SCC : RT is the main treatment .

Surgery can be used in in well-selected patients

(survival from 75% to 90% ).
Lesions in the mid-lower vagina may require
vulvovaginectomy, in addition to dissection of
inguinofemoral nodes or even exenteration to achieve
negative margins.
If the margins are found to be close or positive after
resection, adjuvant RT is recommended.
However, for lesions requiring extensive resection,
definitive RT
is the treatment of choice since it offers excellent results,
with isolated central failures offered exenteration.

Radiation Approach: Stage I

BRACHYTHERAPY (ICB)
ALONE

LOCAL CONTROL: 95-100%

Radiation Approach: Stage II

IIA: EBRT 20
Gy + ICB/ITB
45-50 Gy

LOCAL CONTROL: 70

IIB: EBRT 5060 Gy +

ICB/ITB 30-35
Gy

LOCAL CONTROL: 6

Radiation Approach: Stage

III-IVA

EBRT 60 Gy + ICB/ITB
15-20 Gy

LOCAL CONTROL STAGE III: 30-50%

Carcinoma
of the Vulva

Epidemiology
3% to 4% of all female genital
neoplasias
Patients with vulvar cancer,
intraepithelial and invasive, have a
higher incidence of nongenital
second primary tumors than the
general population
It is increasingly seen in younger
women, possibly due to HPV infection
or other sexually transmitted disease

Clinical Presentation

Pruritus
Spotting or bleeding
Pain
Discharge

Depending on the extent and the location of

the tumor,
patients may also complain of dysuria,
difficulty with
defecation, and may also report difficulty or
discomfort

Pathologic Classification
squamous cell carcinomas : 85%
melanoma
sarcoma
basaloid (cloacogenic)
adenocarcinoma (Bartholin's glands)
neuroendocrine carcinomas (Merkel cell)

15%

Staging: FIGO Classification

FIGO
Stage
0

Carcinoma in situ

Stage
IA

Confined to vulva/perineum, size 2 cm, stromal invasion 1

mm.

Stage
IB

Confined to vulva/perineum, size 2 cm, stromal invasion >1

mm.

Stage
II

Confined to vulva/perineum, size >2 cm.

Stage
III

Adjacent spread to lower urethra and/or vagina or anus.

Unilateral regional nodes metastases

Stage
IVA

Bilateral regional lymph node metastasis.

Stage
IVB

Distant metastasis (Including pelvic lymph node metastasis).

Diagnostic Work-Up
Pathologic examination
Digital palpation
CT or MRI
Cystoscopy, proctoscopy
(patients with symptoms suggestive of bladder or rectal infiltration)

Early Invasive Disease:

Surgery
Small, favorable lesions (2 cm diameter, 5 mm
depth) can be treated with radical, local excision
rather than a radical vulvectomy in order to minimize
surgical morbidity.
Anterior lesions close to the clitoris may not be
amenable to radical, local excision or may require a
radical vulvectomy to obtain satisfactory margins.
Patients with lesions with >5 mm invasion or with
lesions with
vascular space involvement, or poorly differentiated
lesions, are at higher risk for inguinal node metastasis

Early Invasive Disease:

Radiotherapy
PREOPERATI
VE
45-50 Gy
+/CHEMOTHER
APY
(MitomycinC,
5Fluorouracil,
Cisplatin)

TUMOR CLOSE TO:

URETHRA
CLITORIS
RECTUM

Early Invasive Disease:

Radiotherapy
POSTOPERA
TIVE

POSITIVE MARGINS

50 Gy to the
tumor bed area

MARGINS < 8 mm

50-60 Gy to the
lymphnodes

DEEP INVASION

65-70 Gy if there
is gross residual
postsurgery

LYMPHATIC-VASCULAR
INVASION

Advanced Disease
Surgery alone for patients with advanced disease has
yielded
disappointing results and this has led to the use of
multimodality
treatment for this type of patients .

MULTIMODALITY
TREATMENT:
CHEMOTHERAPY +
RADIOTHERAPY

Preoperative Radiation
Therapy

Patients with locally advanced lesions and/or

clinically fixed/ulcerated lymph nodes may be best
managed with preoperative chemoradiation or with
preoperative radiation alone, if chemotherapy is
contraindicated with same doses and drugs used for
preoperative treatment in early stage.

Definitive Chemoradiation
Therapy
Definitive chemoradiation is used for patients with
advanced tumors considered unresectable at
presentation, or for patients who are medically
inoperable. In these patients the chemotherapy
should be continued throughout the course of
radiation for the purpose of radiosensitization of the
tumor in the treatment volume and possible
eradication of subclinical disease outside the
radiation field. With appropriate field reductions,
the radiation dose should be brought up to 60
to 70 Gy.