Transcript 58a0c2462f24fefd5a441fbdaed7ec45

Faustino R. Pérez-López
University of Zaragoza Faculty of Medicine and Lozano-Blesa University Hostpital, Zaragoza 50009, Spain
ENDOMETRIAL AND OTHER
CANCERS IN THE MENOPAUSE
Learning Objectives
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Recognize
the
current
evidence-based
recommendations for women in their second
half of life regarding genital cancer risk and
diagnosis
Describe current general approaches for the
management of genital cancer
Cancer and menopause
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Menopause is not associated with increased
cancer risk
However, cancer rates increase with age and
cancer is the second leading cause of death in
women
Special attention should be provided about
oncologic issues during the second half of life
Genetic factors and cancer
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Genetics may contribute to the risk of various
cancers
Mass screening for specific mutations cannot be
used in the general population
There are no clear screening tests for some
cancers (endometrial, ovarian, vulvar, lung)
Preventive measures are based upon early organ
extirpation in genetic mutation carriers
Lifestyle and cancer:
modifiable risk factors
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Smoking
Alcohol
High body mass index
Dietary factors
Physical activity
Use of hormones
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Infertility treatments
Hormone contraception
Menopause hormone therapy
Outline
1. Endometrial cancer
2. Uterine sarcoma
3. Ovarian cancer
4. Cervix cancer
5. Vulvar cancer
6. Other cancers
Endometrial cancer
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It is the most common gynecological cancer
It occurs most often in postmenopausal
women, with less than 5% diagnosed under
40 years of age
There is no effective screening program, but
occasionally
cervical
smears
contain
endometrial cells or double ultrasound
endometrial thickness of 4 mm or more
indicating the need for endometrial sampling
Risk factors for
endometrial cancer
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Age
Family history of endocrinerelated cancers (breast, ovary)
Previous breast or ovarian
cancer
Endometrial hyperplasia in the
past
Radiation therapy to the pelvis
High number of menstrual
cycles (early menarche, late
menopause)
Polycystic ovarian syndrome
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Nulliparity
Infertility or failure of
ovulation
Unopposed estrogen therapy
Tamoxifen treatment
Diabetes
Obesity
Sedentarism
Metabolic syndrome
Diet high in animal fat
Protective factors for
endometrial cancer
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Pregnancies
Physical activity
Use of oral
contraceptives
Use of IUD
Smoking
Symptoms of
endometrial cancer
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Non-menstrual bleeding or discharge
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Dysuria
Pain:
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Especially post-menopausal bleeding
Heavy bleeding
During intercourse (dyspareunia)
Pain and/or mass in pelvic area
Back pain
Weight loss
Endometrial cancer
diagnosis
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Pelvic examination
Pap smear (may detect cancer spread to cervix)
Transvaginal ultrasound
Endometrial sampling (hysteroscopy) or curettage
is mandatory
Who needs a biopsy?
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Postmenopausal bleeding
Perimenopausal intermenstrual bleeding
Abnormal bleeding with history of anovulation
Postmenopausal women with endometrial cells
on PAP
Thickened endometrial stripe via sonography
Histopathology
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Endometrioid adenocarcinoma (70-80%)
Clear cell and serous tumor are more
aggressive and probably present at a more
advances age (8-12%)
Adenosquamous (4%)
Mucinous (2%) and others
Endometrial cancer:
Type I and II
Type I
 Estrogen-related
 Younger and heavier patients
 Low grade
 Background of hyperplasia
 Perimenopausal
 Exogenous estrogen
Type II (~10% of total cases)
 Aggressive
 High grade
 Unfavourable histology
 Unrelated to estrogen
stimulation
 Occurs in older and thinner
women
Familial/genetic (~15% of total cases)
Lynch II syndrome/HNPCC
Familial trend
HNPCC = Hereditary Non-Polyposis Colon Cancer
Genetic syndromes: HNPCC
(Lynch síndrome)
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Autosomal dominant inheritance
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Early age of colon cancer: mean 45 years
Endometrial cancer: second most common malignancy
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MMR (mismatch repair) mutations
hMSH2 (chromosome 2)
hMLH1 (chromosome 3)
20% cumulative incidence by age 70
Earlier age of onset than sporadic cancer
Other: ovary (3.5-8 fold), stomach, pancreas, etc
Endometrial cancer
treatment
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Surgery
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Hysterectomy
Salpingo-oophorectomy
Pelvic lymph node dissection
Radiation therapy
Hormone
therapy:
antiestrogens
Chemotherapy
progestogens,
Overall results
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The overall results are better than for cervix
carcinoma, not because it is less malignant, yet
because treatment is received earlier
Postmenopausal bleeding is much more difficult
to ignore than the irregular bleeding of younger
woman
Cancer dissemination seems to be more rapid
for cervix carcinoma than for endometrial
spread
Recurrence of endometrial
cancer
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The incidence of recurrence within 5 years is in
the range of 20 to 30%, depending on the stage
at diagnosis, treatment and individual
characteristics
The majority recurrences appear within 3 years
of treatment. Early recurrence has a poor
prognosis
Progestogens
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Many endometrial cancers are hormone
dependent and progestogens have been used as
part of a combined primary treatment as well as
for recurrent or metastatic growths
Between 15% and 50% recurrences respond to
medroxyprogesterone,
with
or
without
tamoxifen
Outline
1. Endometrial cancer
2. Uterine sarcoma
3. Ovarian cancer
4. Cervix cancer
5. Vulvar cancer
6. Other cancers
Uterine sarcoma
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Accounts for fewer than 10% of all corpus
cancers
Abnormal vaginal bleeding the most frequent
presenting symptoms for all histologic types
Types: carcinosarcoma (60%), leiomyosarcoma
(30%), endometrial sarcoma (10%), and
adenosarcoma (<1%)
Uterine sarcomas:
general characteristics
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Exposure to radiation may enhance the
development of uterine sarcomas (seen mainly in
mixed sarcomas)
Mean age 65-75 for carcinosarcoma but earlier for
leiomyosarcoma and endometrial stroma sarcoma
Early hematogenous spread to liver and lung is
common
In patients without extrauterine disease, 40%
chance of distant recurrence
Uterine sarcomas:
management
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Surgery is the hallmark of treatment with
hysterectomy and bilateral salpingo-oophorectomy
being the standard
For patients with advanced or recurrent disease,
aggressive surgical intervention is unlikely to
influence outcome
Adjuvant radiotherapy has been shown to improve
local control, effect on overall survival unknown
Outline
1. Endometrial cancer
2. Uterine sarcoma
3. Ovarian cancer
4. Cervix cancer
5. Vulvar cancer
6. Other cancers
Ovarian tumors
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Nearly 25% of all ovarian neoplasms are
malignant
Approximately 80% are primary malignancies
of the ovary
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80% of all cases of primary carcinomas of the
ovary arise in serous or mucinous cysts
The remainder are secondary tumors, usually
carcinomas
Epidemiology of
ovarian cancer
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9th most common cancer among women
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5th most common cause of cancer death
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1st most common genital cancer death
Epithelial ovarian cancer
(EOC)
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Most common type of ovarian cancer
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Epithelial (75%)
Germ cell (15-20%)
Sex-cord stromal (5%)
Median age of presentation 65
Overall lifetime risk 1 in 70
75-80% of patients are diagnosed with
stage III or IV disease
Ovarian cancer risk factors
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Age is the most important risk factor
Family history (2 or more first degree
relatives)
Nulliparity
Early menarche, late menopause
Late childbirth
Environmental factors
Ovarian cancer
protective factors
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Multiparity
First pregnancy before age 30
Oral contraceptives
Breast feeding
Tubal ligation
Salpingectomy
Hysterectomy
Risk reduction oophorectomy
Hereditary ovarian cancer
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BRCA1 and BRCA2 mutations
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Account for 10% of EOC
Hereditary non polyposis colorrectal cancer
(HNPCC), Lynch II
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Colorectal cancer before age 50
Endometrial cancer before age 50
Other cancer localizations: ovarian, pancreas,
gastric, small bowel, etc
Epithelial carcinogenesis:
ovarian vs the fallopian tubes
Ref. Levanon K, Crum C, Drapkin R. New insights into the pathogenesis of serous
ovarian cancer and its clinical impact. J Clin Oncol. 2008 Nov 10;26:5284-93.
Malignant tumor symptoms
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Lack of any specific symptom, tumors are often large
by the time the professional is consulted
Menstrual function is seldom upset, and any
irregularity is attributed to the patient’s “time of life”
Weight gain, abdominal swelling or pressure
symptoms
Very large tumors may cause respiratory
embarrassment and edema or leg varicosities
Cachexia due to interference with alimentary function
General clinical rule
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An experienced examiner will recognize an ovarian
tumor mainly because ovarian tumor is the most
likely diagnosis
A fluid thrill may be elicited from an ovarian cyst,
and ascites and tumor may coexist, but as a rule
the distinction should be easily made
All abdominal swelling should be subjected to
ultrasound and X-ray examination
Other clinical complications
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Rupture of a cyst
Pseudomyxoma peritonei is a rare condition that
follows the rupture of a mucionous tumor. The
epithelial cells implant on the peritoneum which
is not absorbed, producing abdominal visceral
spreading
Hydrothorax may accompany ascites due to any
cause or as an accompaniment of a lung tumor.
Sometimes this conditions is associated with
ascites (the so-called Meigs’ syndrome)
Features suggestive of
malignancy
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Age: if the patient is > 50 the
chance of malignancy is over
50% as opposed to less than
15% in premenopausal.
Tumors in childhood are
usually malignant
Rapid growth
Ascites
Solid tumors, especially
when bilateral
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Multilocular cysts with solid
areas
Pain, especially when referred
pain suggests malignant
involvement of nerve roots
Tumor markers, such as
CA125, may be measured in
the blood, but a normal level
does not exclude malignancy
Principles and purpose of
ovarian cancer surgery
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Staging of disease
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Prognosis and treatment depend upon surgical findings
and subsequent stage
Debulking (cytoreduction)
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Overall reduction of tumor burden to less than 1 cm
(preferably no gross residual disease) improves survival
Palliation of symptoms
Goldie-Coldman
Hypothesis:
resistance
to
chemotherapy will develop in fraction of remaining
viable cells
Ovarian cancer surgical
management
Biopsies
(Staging)
Exploration
TAH/BSO
Washings/Ascites
(Staging)
TAH = total abdominal hysterectomy
BSO = bilateral salphingo-oophorectomy
Goals (Debulking)
•Assessment of extent of disease
•Optimal tumor reduction
First-line therapy: Standard
treatment options
Surgery with maximum cytoreduction effort
<1 cm residual disease
Platinum + Taxane Chemotherapy
(Carboplatin + Paclitaxel)
Goals of treatment:
relapsed ovarian cancer
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Prolong survival
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Delay time to progression
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Control disease-related symptoms
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Maintain or improve quality of life
Outline
1. Endometrial cancer
2. Uterine sarcoma
3. Ovarian cancer
4. Cervix cancer
5. Vulvar cancer
6. Other cancers
Cervix cancer and
menopause
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PAP test every 3 years (or every 5 years if
combined with HPV test) after a normal report 3
years in a row for women
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Screening not necessary ≥ age 65 with 3 or more
normal PAP tests in a row, no abnormal PAP in
past 10 years, or 2 or more negative HPV tests in
past 10 years
Cervical cancer
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Incidence in Europe 8-12%
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Associated with
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Young age at first intercourse
Number of sexual partners
HPV 16,18, 33 and others
Smoking
Immunosupression
Pathology of cervix cancer
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Peaks 35-44 and 75-85 years
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Squamous (70%)
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Adenocarcinoma (12%)
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Adenosquamous (12%)
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Direct spread - anatomical
Clinical features at
presentation
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Abnormal bleeding
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Postcoital, intermenstrual, postmenopausal
bleeding
Abnormal smears
Advanced disease related with
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Offensive vaginal discharge
Neuropathic pain
Renal failure
Deep venous thrombosis
Cervical cancer
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Microinvasive
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Cone biopsy, trachelectomy, hysterectomy
Invasive
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Radical hysterectomy, node dissection
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Radical vaginal hysterectomy, laparoscopic
node dissection
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Chemoradiotherapy
Outline
1. Endometrial cancer
2. Uterine sarcoma
3. Ovarian cancer
4. Cervix cancer
5. Vulvar cancer
6. Other cancers
Vulvar cancer
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3-4% of all gynecologic malignancies
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The incidence increases with age
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Longevity
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Increased prevalence of HPV infections
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Increased smoking habit
Vulvar cancer: risk factors
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Human papillomavirus infection
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Genital condilomas are detected in 5% of vulvar
cancer
Vulvar intraepitelial neoplasia (VIN)
Medical history
Previous squamous cell carcinoma of the
cervix or vagina
Chronic immunosuppression
Smoking
Vulvar cancer diagnosis
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Patients do not ask for early consultation
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Patients consider symptoms as trivial skin conditions
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Physicians may neglect small skin lesions
Clinical symptoms
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Chronic pruritus vulvae
Palpable vulvar lesion
Asymptomatic: in 20% of patients the lesion is
detected during examination for unrelated condition
Later the lesion becomes necrotic cauliflower or hard
ulcerated
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Bleeding, watery discharge, superinfection and pain
Melanomas frequently appear as bluish black,
pigmented, or papillary lesions
Prevention of vulvar cancer
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Detection and management of Lichen and VIN
Proper management of all cases with pruritus
vulvae
All vulval lesions should be diagnosed
accurately especially those arising during the
second half of life
All pigmented vulvar lesions should be
assessed for biopsy
Vulvar surgery options
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Skinning vulvectomy: this is an option for
treating extensive VIN
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Simple vulvectomy
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Radical vulvectomy
Vulvar radiotherapy
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Malignant disease of the vulva is not commonly
managed by radiotherapy
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Postoperative radiotherapy can reduce regional
recurrences and inguinal lymph node metastases
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Chemotherapy as radiation sensitizer
improve response of the malignant tissue
can
Vulvar melanoma
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Rare: incidence 0.1/100,000 women
Second most common vulvar malignancy
No symptoms (most)
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Itching, bleeding, groin mass
Labia minora, clitoris
Vulvar nevi are junctional, precursor lesion to
melanomas
Outline
1. Endometrial cancer
2. Uterine sarcoma
3. Ovarian cancer
4. Cervix cancer
5. Vulvar cancer
6. Other cancers
Vaginal cancer
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< 1% of gynecological malignancies
Average age at diagnosis is 65
High risk factors
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HPV infection of the cervix or the vulva
Exposure to diethylstilbestrol in utero
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It might progress to clear cell adenocarcinoma of the
vagina and cervix
The mean age at diagnosis is 19 years
Colorectal cancer risk factors
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Age
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More than 90% of colorrectal cancer is found in people
ages 50 and over
Familial history (in a mother, father, brother, sister,
or child):
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Colorectal cancer, adenomatous polyps or “adenomas”
Ovarian or endometrial cancer before age 50
Inflammatory colitis and Crohn´s scolitis
Smoking, high fat diet, obesity in premenopausal women
Lung cancer risk and
protective factors
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Incidence and mortality rates begin to increase
between the ages 45 and 54 and rise progressively
until 75
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In the US African-Americans have the highest
incidence and mortality
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Median age at diagnosis 70
In developing countries female cigarette use is low
Beneficial micronutrients in fruits and vegetables
Prevention of lung cancer
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Cigarette smoking causes 90% of lung cancer deaths
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Avoid second hand smoking
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Get you home tested for radon
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Avoid carcinogens at work