Transcript Cervical cancer

GYNECOLOGICAL
ONCOLOGY
Prof. Roman Makarewicz
Department of Oncology and Brachytherapy
Collegium Medicum in Bydgoszcz
Cervical cancer
• Cancer of the cervix is the most common female genital
cancer in developing countries every year about 500,000
women, acquire the disease and 75% are from frame
developing countries.
• About 300,000 women also die from the disease annually
and of these 75% are from developing countries.
• Finland which has an advanced population based
screening program has one of the lowest rates in the
world.
Risk factors and an etilogy







Number of sexual partners: 6 sexual partners or more increase risk by
14.2 folds.
Smoking
Smoking for > 12 years increase the risk by 12.7 folds.
Male related risk factors:
number of the partners previous sexual relationships is relevant .
cervical cancer risk increased if partners has penile cancer
(circumcision)
Previous wife with cervical cancer.
Previous CIN
Poor uptake of screening program.
Long term use of the contraceptive pill increase the risk due to
increasing exposure to seminal fluids.
Immunosuppresion risk increased with immunosuppressed renal
transplant patients and in HIV positive women
Type of patient
• Multiparous
• Low socioeconomic class
• Poor hygiene
• Prostitutes
• Low incidence in Muslims and Jews
Symptoms
Early symptoms
- None
- Thin, watery, blood tinged
vaginal discharge frequently
goes unrecognized by the
patient
- Abnormal vaginal bleeding
Intermenstrual
Postcoital
Perimenopausal
Postmenopausal
- Blood stained foul vaginal
discharge
Late symptoms
- Pain, leg oedema
- Urinary and rectal symptoms
dysuria
haematuria
rectal bleeding
constipation
haemorrhoids
- Uraemia
Pathology type
•
•
Squamous cell carcinoma-90%
Adenocarcinoma-10%
Types of growth
•
•
•
Exophytic: is like cauliflower filling up the vaginal vualt
Endophytic: it appears as hard mass with a good deal
of induration
Ulcerative: an ulcer in the cervix
Examination
• Mainly vaginal examination using speculum nothing is
found in early stage
• Mass, ulcerating fungating in the cervix
• USG, NMR
Pretreatment evaluation
•
Review history
•
o
o
o
o
o
General examination:
Anaemia
Lymphadenopathy-Supraclavicular LN
Renal area
Liver or any palpable mass
Oedema
•
o
o
o
Laboratory tests:
Chest X- ray
MRI
Ultrasound
Staging
Best to follow FIGO system
• Examination under anaesthesia
• Bimanual palpation
• Cervical biopsy, uterine biopsy
• MRI
Stages of cancer cervix
• Once cancer cervix is found (diagnosed), more tests will
be done to find out if the cancer cells have spread to other
parts of the body. This testing is called staging
• TO PLAN TREATMENT, A DOCTOR NEEDS TO KNOW
THE STAGE OF THE DISEASE
Spread
Direct
Lymphatic
Dissemination
(late)
- Uteruq
- Vagina
- Parametrium
- Bladder and rectum
A- primary node:
Parametrial
Paracervical
Vesicovaginal
Rectovaginal
Hypogastric
Obturator and external iliac
- parametrial spread
causes obstruction of the
ureters, many deaths occur
due to uraemia
- Obstruction to the
cervical canal results in
pyometria
B-Secondary nodes:
Common iliac
Sacral
Vaginal
Paraaortic
Inguinal.
Differential diagnosis
•
•
•
Cervical ectropion
Cervical tuberculosis
Cervical syphilis, Schistosomiasis, and
Choriocarcinoma are rare causes
Treatment
• Surgical
• Radiotherapy
• Radiotherapy & Surgery
• Radiotherapy and Chemotherapy followed by Surgery
• Palliative treatment
The choice of treatment will depend on
• Fitness of the patients
• Age of the patients
• Stage of disease
• Type of lesion
• Experience and the resources available
Surgical procedure
• The classic surgical procedure is the Wertheim’s
hystrectomy for stage Ib, IIa, and some cases of IIb in
young and fat patient
Werthemeim’s hystrectomy
• Total abdominal hystrectomy including the parametrium
• Pelvic lymphadenectomy
• 3 cm vaginal cuff
• The original operation conserved the ovaries, since
squamous cell carcinoma does not spread directly to the
ovaries
• Oophorectomy should be performed in cases of
adenocarcinoma as there is 5-10% of ovarian metastases
Surgery offers several advantage
• It allows presentation of the ovaries (radiotherapy will
•
•
•
•
destroythem)
There is better chance of preserving sexual function
(vaginal stonosis occur in up 85% of irradiates
Psychological feeling of removing the disease from the
body
More accute staging and prognosis
Complications of surgery
•
•
•
•
•
•
Haemorrhage: primary or secondary
Injury to the bladder, ureters
Bladder dysfunction
Fistula
Lymphocele
Shortening of the vagina
INDICATIONS OF P/O XRT FOLLOWING WERTHEIM’S
HYSTERECTOMY (STAGE I, IIa):
• Positive pelvic lymph nodes
• Tumour close to resection margins and/or parametrial
extension
Radiotherapy
• Stage IIb and III
• Radical Radiotherapy
• External irradiation (Teletherapy)
• Intracavitary radiation (Brachytherapy)
• In some cases of stage IIa or b radio and chemotherapy
to be given then followed by simple hysterectomy
Prognosis
Depends on:
•
Age of the patient
•
Fitness of the patient
•
Stage of the disease
•
Type of the tumour
•
Adequacy of treatment
THE OVERALL 5-YEARS SURVIVAL FOLLOWING
THERAPY:
• Stage I
80%
• Stage II
50-60%
• Stage III
30-40%
• Stage IV
4%
Management of recurrent disease
•
•
1. Local recurrence:
Radiation - if not used
Pelvic exenturation
2. Distant disease
Chemotherapy
Conclusions
• Cancer of the cervix is still quite common, reduction in
incidence depends on the quality of the screening
program
• The etiology appears to be multifactorial the prime
oncogenic agent is probably [HPV-16,18]
• Clinical presentation is with intermenstrual, post coital,
postmenospausal bleeding or following abnormal cytology
• Tumour spreads locally to involve the uterus bladder,
vagina, parametrium, ureters, rectum and bone
• Spread also to the internal and external iliac, obdurator
and common iliac nodes then to para-aortic nodes
• Distant metastasis spread to liver, lung and bone
• Microinvasion squamous tumour carry a good prognosis
allowing conservative treatment initially if required
• Early invasive squamous cell disease (stage Ib, IIa and in
some cases of IIb) may be treated by either a Wertheime’s
hysterectomy or radiotherapy as first line treatment
• Advanced stage (IIb, III,IV) treated by radio or
chemotherapy
• Glandular tumours (adenocarcinomas) are not detectable
by screening are associated with skip lesions and require
radical surgery
Endometrial cancer
• The exact cause is unknown
• Estrogen
• Estrogen replacement therapy
• Tamoxifen
• Women who have been treated with tamoxifen,
a drug used to prevent and treat breast cancer
may have a slighty increased risk of developing endometrial cancer
Diagnosis
• Hysteroscope/endoscope tube with vision is inserted into
uterus through the cervix
• Allows the doctor to view the inside of the uterus and collect endometrial
tissue samples
Signs and symptoms
• Early symptoms
• Vaginal bleeding or spotting in postmenopausal women
• All bleeding without conection with periods between normal periods:
extremely long, heavy or frequent episods of bleeding after sexual
intercourses
• Vaginal discharge
• Late symptoms
• Weight loss
• Anemia
• Lower abdominal pain
Type of endometrial cancer
• Type 1
• Caused by excess estrogen
• Type 2
• Etiology unknown, but it doesn’t seem to be caused by too much
estrogen
Type 1
• Not very aggressive
• Slow to spread to other tissues
• Grades 1 or 2
• Occur most commonly in pre- and peri-
menopausal women
• History of estrogen exposure and endometrial
hyperplasia
• Carry a good prognosis
Type 2
• Occur in older, post-menopausal women
• More common in African-Americans
• More likely to grow and spread outside of the
uterus
• Carry a poorer prognosis
Endometrial adenocarcioma
• 80% of uterine neoplasms
• It arises from the glands of the endometrium
• Essential is grade which says how aggressive
cancer is
• 40% Grade 1, 20% Grade 2, 40% Grade 3
• Example of type II cancer
• The uterine papillary serous cancer (5% of cancers)
• The uterine clear cell cancer (2% of cancers)
• Both are aggressive and have high recurrence rate
Treatment for endometrial cancer
• Depends on:
• The stage of the disease
• Overall health of the patient
• Primary treatment is the surgery
• Radiation therapy, hormonotherapy and chemotherapy may be used
as an adjuvant treatment or in patients with metastatic or recurrent
disease
• Hysterectomy
• Simple
• Total including the cervix
• Total with salpingo-ophorectomy
• Total with salpingo-ophorectomy with nodal sampling
• With pelvic lymphadectomy
• The procedures are done using a low transverse incision or a vertical
incision
Chemotherapy
• Treatment that uses drugs to stop the growth of cancer
cells, either by killing the cells or by stopping the cells
from dividing
• Treatment usually involves a combination of two or three
drugs giving intravenously
• When chemotherapy is given
• Adjuvant tretment once every 21 days (6-8 cycles)
• Metastatic disease (to progression)
• When drugs are used to treat endometrial cancer
• Carboplatin
• Cisplatin
• Doxorubcin
• Paclitaxel
• Cyclophosphamide
Radiation therapy
• The purpose is:
• To get rid of any tumor cells that may be left in the body after surgery
• Candidates:
• Depends on:
• Grade 2 and 3
• How deeply is invasion
• Pathologic diagnosis
• Methods:
• Vaginal brachytherapy
• External beam RT
Hormonotherapy
• Progestins as the main hormone treatment for
endometrial cancer
• Medroxyprogesterone acelate (Provere)
• Megestrol acelate (Megace)
• There is no effective screening programme
• Occasionally cervical smears contain endometrial cancer
cells
• Ultrasound thickness more than 5 mm in postmenopausal
patients indicates a need for endometrial staging and one
attention
Ovarian cancer - symptoms
• Nonspecific
• Persistent
Symptoms
• Bloating
• Pelvic or abdominal pain
• Difficulty eating or feeling full quickly
• Urgency or urinary frequency
• Most common is abdominal enlargement
Symptoms
Other symptoms commonly reported
• Fatigue
• Indigestion
• Back pain
• Pain with intercourse
• Constipation
• Menstrual irregularities
Risk Factors
• Genetic predisposition
• Family history is strongest risk
• Breast-ovarian cancer syndrome
• Lynch II syndrome
• Cancer of colon, breast, endometrium and HNPCC
Age
Annual incidence in women age 50-75 is 50 per 100,000,
twice the rate in younger women
Risk Factors
• Decrease risk:
• Pregnancy
• Breast feeding
• Tubal ligation
• Hysterectomy
• Increase risk:
• Infertility
• Endometriosis
• Peri or postmenopausal
history of medications
Screening Tests
• There is no standardized test to detect ovarian cancer
at an early stage
• CA-125: most widely used screening method
 Specificity is limited
 False elevations in: endometriosis, fibroids, cirrhosis w/- ascites,
PID, cancers of breast, lung, pancreas, pleural
or peritoneal fluid due to any cancer
Staging The Federation Internationale de
Gynecologie et d'Obstetrique (FIGO) and the
American Joint Committee on Cancer (AJCC)
have designated staging.
Stage I ovarian cancer
• limited to the ovaries.
• Stage IA: tumour limited to 1 ovary, the capsule is
intact, no tumour on ovarian surface and no
malignant cells in ascites or peritoneal washings.
• Stage IB: tumour limited to both ovaries, capsules
intact, no tumour on ovarian surface and no
malignant cells in ascites or peritoneal washings.
• Stage IC: tumour is limited to 1 or both ovaries with
any of the following: capsule ruptured, tumour on
ovarian surface, malignant cells in ascites or
peritoneal washings.
Stage II ovarian cancer
• tumors involving 1 or both ovaries with pelvic
extension and/or implants.
• Stage IIA: extension and/or implants on the uterus
and/or fallopian tubes. No malignant cells in ascites
or peritoneal washings.
• Stage IIB: extension to and/or implants on other
pelvic tissues. No malignant cells in ascites or
peritoneal washings.
• Stage IIC: Pelvic extension and/or implants (stage
IIA or stage IIB) with malignant cells in ascites or
peritoneal washings.
Stage III ovarian cancer
• tumours involving 1 or both ovaries with microscopically
confirmed peritoneal implants outside the pelvis. Superficial
liver metastasis equals stage III.
•
• Stage IIIA: microscopic peritoneal metastasis beyond pelvis
(no macroscopic tumour).
• Stage IIIB: macroscopic peritoneal metastasis beyond pelvis
less than 2 cm in greatest dimension.
• Stage IIIC: peritoneal metastasis beyond pelvis greater than 2
cm in greatest dimension and/or regional lymph node
metastasis.
Stage IV ovarian cancer
 tumours involving 1 or both ovaries with distant
metastasis. Parenchymal liver metastasis equals
stage IV.
Treatment Options
• The treatment of ovarian cancers based on the
stage of the disease which is a reflection of the
extent or spread of the cancer to other parts of
the body.
• It also depends on histologic cell type, and
the patient's age and overall condition.
• There are basically three forms of treatment of
ovarian cancer:
• surgery
• Chemotherapy
• radiation treatment,
GENERAL GUIDELINES:
• Standard treatment is surgery (staging and optimal
debulking) followed by adjuvant chemotherapy in most
cases. Even if optimal surgery is not possible, removing
as much tumor as possible will provide significant
palliation of symptoms.
• Borderline lesions may be treated with conservative
surgery
GENERAL GUIDELINES:
• Germ cell tumors are treated with surgery and multi-agent
chemotherapy in most cases
• Advanced epithelial ovarian cancer is very sensitive to
chemotherapy with responses in the range of 70-80% to
first-line chemotherapy. The majority, however, relapse
and ultimately die of chemotherapy-resistant disease.
Second-line chemotherapy to date is disappointing in all
forms of epithelial ovarian cancer with virtually no chance
of successful second-line treatment following failure of
initial regime.
Stage I
• Generally a total abdominal hysterectomy, removal of both
ovaries and fallopian tubes, omentectomy, biopsy of
lymph nodes and other tissues in the pelvis and
abdomen,is done. Young women whose disease is
confined to one ovary are often treated by a unilateral
salpingo-oophorectomy without a hysterectomy and
removal of the opposite ovary being performed
• Depending on the pathologist's interpretation of the tissue
removed, there may be no further treatment if the cancer
is low grade, or if the tumor is high grade the patient may
receive combination chemotherapy.
Stage II
• Treatment is almost always hysterectomy and bilateral
salpingo-oophorectomy as well as debulking of as much
of the tumor as possible and sampling of lymph nodes
and other tissues in the pelvis and abdomen that are
suspected of harboring cancer. After the surgical
procedure, treatment may be one of the following: 1)
combination chemotherapy with or without radiation
therapy or 2) combination chemotherapy.
Stage III
• Treatment is the same as for Stage II ovarian cancer.
Following the surgical procedure, the patient may either
receive combination chemotherapy possibly followed by
additional surgery to find and remove any remaining
cancer.
Stage IV
• CYTOREDUCTIVE SURGERY/DEBULKING:
• surgery to remove as much of the tumor as possible.
• Most researchers consider residual disease of <1 cm to be optimal
debulking surgery. followed by combination chemotherapy
CHEMOTHERAPY
• Prolongs remission and survival
• Also used for palliative treatment in advanced n recurrent
disease
• Administered in all cases beyond stage Ia
• Earlier single agents were used, nowadays combination
therapy is favoured
CHEMOTHERAPY
• No chemotherapeutic agent kills all cancer cells in one
treatment ,Tf treatment needs to be repeated several
times
• All agents used should be active against that particular
tumor
• should have different modes of action to avoid drug
resistance n should have differenr mechanisms of toxicity.
CHEMOTHERAPY
• This allows each of them to be used as nearv to the full
dose as possible.
• Drugs are given at 3 weeks intervals
• Intraperitoneal chemotherapy is also done
• The initial treatment of ovarian cancer is called first-line
therapy.
• If the cancer continues to grow with first-line therapy or
returns after first-line therapy, additional treatment, called
second-line therapy, may be administered.
• If the tumor continues to grow after second-line therapy,
the next therapy is called third-line therapy, and so on.
First-Line Chemotherapy
• First-line chemotherapy for ovarian cancer typically
consists of two drugs given together. The combination
=paclitaxel + platinum drug—either carboplatin or
cisplatin.
• Select women may benefit from administration of
chemotherapy directly into the abdomen—called
intraperitoneal therapy—in addition to conventional
intravenous administration.
Second-Line Chemotherapy
• The choice of drugs for second-line therapy depends
largely on which drugs were administered for first-line
therapy and how long it has been since the first-line
therapy was stopped.
• chemotherapy drugs) for the treatment of ovarian cancer
that has returned:
GEMZAR (gemcitabine HCl for injection) plus
another chemotherapy, carboplatin, is indicated ,6 months
after their first-line therapy;
SIDE EFFECTS
While chemotherapy drugs kill cancer cells, they also damage
some normal cells, causing side effects. These side effects will
depend on the type of drugs given, the amount taken, and how
long treatment lasts. Temporary side effects might include the
following:
• nausea and vomiting
• loss of appetite
• hair loss
• hand and foot rashes
• kidney or nerve damage
• mouth sores
• an increased chance of infection (from a shortage of white
blood cells)
• bleeding or bruising after minor cuts (from a shortage of
platelets)
• tiredness (from low red blood cell counts)
Ovarian Cancer Follow up
• Monitor CA-125
• Physical Exam
• Including pelvic exam
• CT scan/PET scan as clinically indicated
• Consider family history evaluation if not done previously