Upload
others
View
2
Download
0
Embed Size (px)
Citation preview
Uterine Cancer Review for
Health Care Professionals
Created by the GOC Nursing Committee:
Joanne Power, Janet Giroux, Nancy Drummond, Heidi
Thomas, Carrie Thornton, Joanne Brodeur and Elisha
Andrews, Joanne Power, Rebecca Sirois
Medical Advisor: Dr. X. Zeng
Updated: November 2019
The slides presented are meant to be used as an
orientation package for health care providers new to
gynecologic oncology; to review the management and
treatment of uterine cancers.
Variation across the country can occur in accordance with
provincial guidelines.
Remember that not all patients are the same and that some
deviation CAN and often does occur.
Uterus Review • Pear-shaped, hollow, and fibro
muscular organ located in a woman’s pelvis between the bladder and rectum
• Varies greatly in size • Made up of 3 sections
– Cervix (lower)
– Corpus (middle)
– Fundus (top) • The inside of the uterus
has two tissue layers
– Endometrium (inner)
– Myometrium (outer)
Cartwright-Alcarese & O’Sullivan, 2010
The walls of the uterus are
composed of muscular
tissue called myometrium
(middle layer).
The superficial (outside
layer) of the uterus is called
the serosa and is
continuous with the pelvic
peritoneum.
• The epithelial membrane
(lining of uterus) is called
the endometrium.
dfddfdfddfdfdfdfdf
dfdfdfdfdfdfdfdfdf
dfdfdfdfdfddfdfdfd
fdfdfdfdfdfdfdfdfdf
dfdfdfdfddfdfdfdfd
fdfdfdfdfdfdfdfdfd
dfdfdfddfdfddfdfdf
dfdfdfdfdfdfdfdfdf
dfdfdfdfdfdfdfdfdf
dfdfdfdfdfdfdfdfdf
Serosa
Cartwright-Alcarese & O’Sullivan, 2010
The Role of Estrogen and Progesterone • Estrogen stimulates the uterine lining to proliferate
and grow
• Progesterone inhibits the proliferative growth effects of estrogen, and provides structural support to the endometrium
• With the withdrawal of progesterone at the end of the menstrual cycle, the structural support to this thickened endometrium is weakened, and shedding of the uterine lining occurs (menses)
Landrum, Zuna & Walker, 2012; Redlin Frazier, 2010
Incidence of Endometrial Cancer
• Most common gynecologic cancer
• Estimated that 7300 Canadian women were
diagnosed in 2018, 1150 died from it
• 4th most common cancer in Canadian women, 8th
most common cause of cancer death
• Lifetime risk in Canada is 1 in 38 women
Canadian Cancer Society, 2018
Endometrial Cancer Risk Factors Lifestyle Factors Hormonal and Reproductive
Factors
Age > 50 Early menarche
Obesity (more than 50 pounds over
normal BMI)
Postmenopausal
Never given Birth**
Diet/lack of exercise Late menopause (>55)
Personal Breast/Colon Cancer
History
Endometrial Hyperplasia
Diabetes **
Genetic Factors
Prolonged use of estrogen without
opposing progesterone
Tamoxifen use
Polycystic Ovarian syndrome
Amant Moerman, Neven, Timmerman, Van Limbergen & Vergote, 2005; Burke, 2005;
Creasman & Scott Miller, 2012; Farley-Omerod & Fusco, 2010; Lockwood, 2008; Redlin Frazier, 2010;
Tiffen & Mahon, 2006, Canadian Cancer Soceity; Endometrial Cancer 2019
Lynch II Syndrome (HNPCC)
• An inherited disorder that increases the risk of many
types of cancer, particularly cancers of the colon
(large intestine) and rectum, which are collectively
referred to as colorectal cancer.
• People with Lynch syndrome also have an increased
risk of cancers of the stomach, small intestine, liver,
gallbladder ducts, upper urinary tract, brain, and skin.
Additionally, women with this disorder have a high
risk of cancer of the ovaries and lining of the uterus
(the endometrium).
Ahnen & Axell, 2015
Lynch II Syndrome (HNPCC) “Red Flags”
• Onset of colorectal cancer before age 50
• Onset of endometrial cancer before age 50
• Two or more HNPCC cancers in an
individual or family
Endometrial Cancer Risk Factor: Obesity
• Widely recognized risk factor for endometrial
cancer
• Affects both premenopausal and postmenopausal
risk for endometrial cancer
• Those with high amount of body fat can be up to
10x more likely to develop Uterine Cancer
Farley-Omerod & Fusco, 2010; Redlin Frazier, 2010;, Renehen et al., 2008; Tiffen & Mahon, 2006, CCS, 2019
Bariatric Surgery Decreases Risk of
Endometrial Cancer
• Bariatric surgery, which results in dramatic weight loss in formerly severely obese women, reduces the risk of endometrial (uterine) cancer by 71% immediately after weight loss and 81% if healthy weight is maintained after surgery
Ward et al., 2014
Unopposed Estrogen Exposure • In an environment of chronically unopposed estrogen
exposure (such as seen in obesity), the endometrial
layer undergoes a progression of abnormal cellular
changes from benign endometrial hyperplasia to
endometrial intraepithelial neoplasia (EIN) and
endometrial adenocarcinoma
• Use of estrogen replacement therapy for menopause
does not increase the risk of endometrial cancer as
long as concurrent progesterone is given.
Redlin Frazier, 2010
Endometrial Cancer Risk Factor
Selective Estrogen Receptor Modulators • Used as both treatment and chemoprevention of breast
cancer
• SERMS: Tamoxifen, Raloxifene
• Although Tamoxifen is an anti-estrogen in breast tissue, it
paradoxically has estrogen-like properties in the
endometrium and increases the risk of endometrial cancer
• It is also associated with thromboembolism and stroke
• It provides protection against bone loss, osteoporosis and
fractures, but does not appear to carry an increased risk of
myocardial infarction
Landrum, Zuna & Walker, 2012
Endometrial Cancer: Risk Reducing Factors
Use of combination oral
contraceptives
Diet modifications (low fat, increase
fruit and vegetable intake)
Multiparity Decrease phyto-estrogen (soy)
intake
Exercise and physical activity Weight control/loss to reflect ideal
BMI of < 25
Tubal Ligation
Genetic counselling and risk
assessment of women at risk
Mirena IUD
Amant et.al, 2005; Farley-Omerod & Fusco, 2010; Redlin Frazier, 2010
Endometrial Cancer: Screening
• No good screening test for endometrial cancer
• The pelvic exam enables the clinician to detect
only an abnormally sized uterus
• Sampling of the endometrium is neither cost-
effective nor indicated in the general population
and is not required before or during HRT (hormone
replacement therapy) in asymptomatic women
Amant et.al, 2005; Burke, 2005; Farley-Omerod & Fusco, 2010; Redlin Frazier, 2010; Tiffen & Mahon,
2006;
Endometrial Cancer: Signs & Symptoms
Post menopausal
women • Post menopausal bleeding (PMB) after menopause is the most common symptom
– About 90% of women diagnosed with endometrial cancer have abnormal uterine bleeding as presenting symptom
Premenopausal
women • Increased menstrual flow and bleeding between periods may be the only symptoms
• Other signs may include: • A yellow, watery vaginal discharge
• Pyometria (accumulation of pus in the uterus)
• Pain in the hypogastric or lumbosacral areas or the pelvis
• Pain during intercourse
• Ascites
• Weight loss
Amant et.al, 2005; Burke, 2005;;Farley-Omerod & Fusco, 2010; Lockwood, 2008; Otto, 2001;
Tiffen & Mahon, 2006; Canadian Cancer Society, 2019
Postmenopausal Bleeding
• Most PMB is caused by benign conditions
– Most common benign causes are endometrial polyps, sub-
mucosal fibroids and atrophy of the endometrium, HRT and
Tamoxifen use
• Cancer and hyperplasia are present in 20%
of women with PMB
• A biopsy should be performed to evaluate the
endometrium in women with abnormal uterine
bleeding after age 40
Amant et.al, 2005; Farley-Omerod & Fusco, 2010; Lockwood, 2008; Singh et al., 2013
Endometrial Cancer Diagnosis
• Ultrasound
(TransVaginal-TVUS) to
look at thickness of
endometrial lining and
localize lesions – An endometrium thicker
than 16 mm in
premenopausal women and
in postmenopausal women
thicker than 5 mm is a
predictor of abnormal
endometrial pathology
• Endometrial biopsy to
sample lining of the
uterus – Most cost effective when the
prevalence of endometrial
cancer is over 15%
– +/- Hysteroscopy/D&C
(Dilatation & Curettage)
• Pathology
• Other Imaging Studies
– MRI, CT scan, Chest x-
ray
Amant et.al, 2005; Farley-Omerod & Fusco, 2010; Lockwood, 2008; Redlin Frazier, 2010;; Tiffen & Mahon, 2006
Endometrial Biopsy/Pipelle
Image retrieved June 4, 2015 from http://www.nlm.nih.gov/medlineplus/ency/imagepages/17059.htm
Diagnostic Tests for Uterine Abnormalities
Endometrial Hyperplasia
• An overgrowth of the endometrial lining of the uterus as a result of stimulation of the endometrium
• Typically presents clinically as abnormal bleeding
• Hyperplasia with atypia is a complex pattern with overcrowding of the glands; the presence of atypical cells indicates high risk for the progression to endometrial cancer
– Endometrial hyperplasia with atypia is considered a precursor state to endometrial cancer
Farley-Omerod & Fusco, 2010; Lockwood, 2008
• The scientific explanation for the low incidence rates for endometrial hyperplasia is that it is a lesion that is usually unrecognized and asymptomatic until cancer develops
• Women with cellular atypia is considered to be premalignant; whereas those without atypia are benign. Hysterectomy is the standard of treatment when atypia is present
• Patients with hyperplasia should be treated with progestins or hysterectomy if atypical cells are associated with the hyperplasic cells – Patient’s age, fertility plans & need for contraception, comorbidities and
personal preferences play an important role in the management of these lesions
Endometrial Hyperplasia
Farley-Omerod & Fusco, 2010; Landrum, Zuna & Walker, 2012; Lockwood, 2008
Uterine Cancers: Classification
● The primary types of uterine cancers are endometrioid
carcinoma, adenocarcinoma, sarcomas, mucinous
carcinoma, serous carcinoma, and clear cell carcinoma
● More than 95% are endometrial adenocarcinomas and
less than 5% are sarcomas ● Endometriod makes up 75-80%
● Serous makes up roughly 10%
● Clear cell roughly 5%
● Sarcoma roughly 2-5%
Otto, 2001, WHO 2014
Endometrial Cancer
• Neoplasm that occurs within the lining
of the uterus
• Arises from the glandular component of
the endometrial mucosa
• Divided into 2 subtypes (Type I and
Type II)
Amant et.al, 2005 ; Brown, 2008 ;Farley-Omerod & Fusco, 2010;
Lockwood, 2008; Redlin Frazier, 2010; Tiffen & Mahon, 2006;
Endometrial Cancer Subtypes
Type I
• Well or moderately
differentiated estrogen
dependent subtypes that tend
to have a better prognosis
(tends to be diagnosed early
stage and has a better
prognosis). Prolonged
exposure to estrogen
Type II • Aggressive, non-estrogen
dependent subtypes such as
clear cell and serous which
has a poorer prognosis related
histologically to a higher grade
or poorer differentiation and is
more often diagnosed at a late
stage, it has a propensity for
metastases or because it is a
non-endometrioid subtype
Amant et.al, 2005 ; Brown, 2008 ;Farley-Omerod & Fusco, 2010;
Lockwood, 2008; Redlin Frazier, 2010; Tiffen & Mahon, 2006;
Endometrial Cancer
• Morbidity and mortality increases with age and
stage, making early diagnosis a priority in order
to achieve better outcomes
Redlin Frazier, 2010
Endometrial Cancer: Grading
• The grade of the tumour signifies how closely
the tumour resembles the tissue of origin
• In endometrial cancer, the tumor grows in a
solid fashion, whereas the normal tissue grows
in a glandular fashion
Lockwood, 2008
Endometrial Cancer Grading Grade Differentiation % of Tumour Showing
a Solid Growth Pattern
I Well differentiated 5% or less
II Moderately differentiated 6% - 50%
III Poorly differentiated > 50%
Lockwood, 2008
Endometrial Cancer Staging
Stage Extent of Uterine Involvement
I Tumor confined to the corpus uteri
IA No or less than half myometrial invasion
IB Invasion equal to or more than half of the myometrium
II Tumor invades cervical stroma, but does not extend beyond the uterus
III Local and/or regional spread of the tumor
IIIA Tumor invades the serosa of the corpus uteri and/or
adnexae
IIIB Vaginal involvement and/or parametrial involvement
IIIC Metastases to pelvic and/or para‐aortic lymph nodes
IIIC1 Positive pelvic nodes
IIIC2 Positive para‐aortic nodes +/- positive pelvic nodes
IV Tumor invades bladder and/or bowel mucosa, and/or distant metastases
IVA Tumor invasion of bladder and/or bowel mucosa
IVB Distant metastasis, including intra‐abdominal metastases
and/or inguinal nodes) Amant et al., 2018
Endometrial Cancer • Endometrial cancer is surgically staged
– Histological assessment of the hysterectomy specimen remains the
gold standard
• Workup for biopsy proven Endometrial Cancer
includes a clinical examination. Other diagnostic
tests may include Transvaginal Ultrasound, Chest
X-ray, CT, MRI.
• CA-125 is a potential tumour marker
Amant et.al, 2005; Brown, 2008; Farley-Omerod & Fusco, 2010; Lockwood, 2008;
Treatment for Endometrial Cancer
• Surgery
– Hysterectomy
– Lymphadenectomy
• Radiation Therapy
• Chemotherapy
Redlin Frazier, 2010
Hormone Therapy
• Hormone therapy with Progestin may be considered in certain cases of grade 1 when there is no invasive disease and patient wants fertility preservation
• The use of progestin-secreting IUD has been utilized in cases where surgical morbidity prevents traditional treatment
Montz, Bristow, Bovicelli, Tomacruz & Kurman, 2002; Redlin Frazier, 2010
Endometrial Cancer
Surgical Management • Depends on the stage and grade of the cancer; considers
the usual spread pattern of endometrial cancer to the lymph nodes nearest to the uterus
• Surgery includes Total Hysterectomy and Bilateral Salpingo-Oophorectomy (TH BSO) +\- surgical staging – Approach may be abdominal or minimally invasive
– Removal of the adnexa at time of surgery is thought to be important given that approximately 5% of endometrial cancers have metastatic disease to the ovaries and/or fallopian tubes
– Removal of the upper vagina does not appear to decrease vault recurrences
• Pelvic +/- para aortic lymph node dissection may be done depending on grade and/or histology of endometrial biopsy
Creasman & Scott Miller, 2012; Redlin Frazier, 2010
Role of Lymphadenectomy • Sentinel lymph node mapping in patients with apparent early
stage disease may be considered
• Pelvic lymphadenectomy, with or without paraaortic
lymphadenectomy, plays an important role in the surgical
staging of endometrial cancer, and thus provides more accurate
prognostic information
• The therapeutic role of lymphadenectomy and its ability to
modify adjuvant therapy continues to evolve
– Impacts the addition or deletion of radiation/chemotherapy
postoperatively
– Need to discuss the pros/cons of lymph node dissection and
potential for complications in the future
Creasman & Scott Miller, 2012; Hacker, 2000, NCCN, 2019
Pathologist Review • Measures the depth of myometrial invasion in
relationship to myometrial thickness and the size
and location of the tumour and then makes a
determination as to the extent of disease
• Examines the specimen(s) microscopically and
the histologic subtype, grade and presence of
lymphovascular space invasion
Redlin Frazier, 2010
Poor Prognostic Features
• Papillary Serous, Clear Cell Histology
• Grade 3 (poorly differentiated)
• More advanced stage
• Myometrial invasion > 50%
• Positive pelvic lymph node(s)
• Positive para-aortic lymph node(s)
(highest risk feature)
Carcinosarcoma • Uterine carcinosarcomas, or formerly referred to as
Malignant Mixed Müllerian tumours (MMMTs), are highly
aggressive cancers with a 5-yr survival rate reported as 18-
39%
• Usually arise in women older than 65 and commonly
present at an advanced stage
• Considered a high-risk variant of endometrial
adenocarcinoma because carcinosarcomas share
similarities in epidemiology, risk factors, and clinical
behavior more closely with endometrial carcinoma as
opposed to uterine sarcomas. Dulko, 2010; Lockwood, 2008; McMeekin, 2012; Penson & Powell, 2014
Carcinosarcoma
• Uterine carcinosarcoma displays both epithelial and
stromal differentiation and is further subdivided into
homologous and heterologous subtypes based on the
sarcomatous component
• Recently, carcinosarcomas have been treated more as a
carcinoma rather than sarcoma
• Uterine carcinosarcoma tends to spread by local extension
to pelvic structures, but may metastasize with the manner
of spread being mainly through the lymphatic system rather
than through the blood
Dulko, 2010; Lockwood, 2008; McMeekin, 2012
Adjuvant Treatment
• The need for adjuvant treatment is determined
by the final pathology report
• Adjuvant treatment may include:
– External beam radiotherapy
– Brachytherapy
– Chemotherapy
– Hormonal therapy
Redlin Frazier, 2010
GOG Criteria for Determining Adjuvant
Radiotherapy Treatment in Stage I or II
1. Patients who are age 70 or older and any 1 of the
following risk factors:
– Tumour grade 2 or 3
– Outer third myometrial invasion
– Presence of lymphovascular space involvement.
2. Patients 50 years of age or older and any 2 of the risk
factors described above.
3. Patients of any age and all 3 factors described
above.
Keys et al., 2004; Kupets & Le, 2013
Radiation Therapy
• Radiation therapy has been the
mainstay of adjuvant therapy for
endometrial cancer – Adjuvant radiotherapy following primary surgery
significantly improves pelvic tumour control, but has no
measurable impact on overall survival
– Vault Brachytherapy is being recommended more often
for lower stage disease and for all high stage disease.
Creasman & Scott Miller, 2012; Lockwood, 2008, NCCN 2019
Radiation Therapy
• Treatment may include external beam radiation therapy and/or brachytherapy (intravaginal)
• For patients who are at high risk for
recurrence, radiation therapy is used to improve loco-regional control
• Radiation therapy utilization has
been widely variable
Lockwood, 2008; Redlin Frazier, 2010
Radiation Side Effects • Depending on area
that is irradiated, may
include:
– Skin Changes
– Bowel Changes
– Urinary Changes
– Vaginal Changes
– Fatigue
– Psychological
Lockwood, 2008; Smith & McLaughlin, 2012; Redlin Frazier, 2010
Brachytherapy • Health Care professionals should not underestimate the
physiologic and psychological effects of intravaginal radiation therapy
• Women who receive this treatment should be counselled carefully prior to treatment with a mindfulness that it may be humiliating, disturbing and in some cases of previous sexual abuse, an exceptionally difficult treatment to undergo
• Any woman receiving pelvic radiation (external or internal) needs to be advised/taught to use vaginal dilators to maintain vaginal patency and to prevent agglutination
Miles et al., 2012; Redlin Frazier, 2010
PORTEC 3 Treatment
• Consists of 5 weeks of external beam radiation of
48Gy in 25 fractions with Concurrent Cisplatin at
50mg/m2 on week 1 and 4. Followed by a 2 week
break from treatment and then 4 cycles of Carboplatin
and Paclitaxel.
• This protocol shows better distant recurrence control
vs local control
• Better overall survival vs RT alone (79% vs 70%)
• Better failure free survival vs RT alone (69% vs 58%)
de Boer, et al. 2018
Chemotherapy
• The role of chemotherapy in the treatment of
endometrial cancer is complex and evolving
– Was traditionally reserved for patients with recurrent or
disseminated cancer
• Systemic therapy may be used
– In cases of initial advanced disease
• Advanced and high-risk early-stage
– At the time of relapse
Amant, et.al, 2005; Creasman & Scott Miller, 2012; Lockwood, 2008; Redlin Frazier, 2010
Chemotherapy
• These therapies are often provided in the outpatient setting
• See next slides for common agents and side effects
• Incidence and severity of any of these side effects is largely dependent of the patient’s characteristics such as diagnosis, stage, performance status, comorbidities and individual treatment regimen – agent, dosage and schedule
• Nurses have an essential role in teaching, monitoring and managing side effects related to gynecologic cancer treatments
Hydzik & O’Connor, 2010
Clinical Trials
• Provide novel treatments that show promise in treatment of endometrial cancer
• Available clinical trials should always be presented as an option to eligible patients
Combination of Chemotherapy Agents
• Studies have found the combination of Cisplatin or
Carboplatin with other agents (Doxorubicin,
Taxanes—Paclitaxel) to have significant activity in
endometrial cancer treatments
• Combining two or more active agents has been an
important strategy (Phase III studies) – Better response rates when agents are combined compared to used
alone
Creasman & Scott Miller, 2012
Paclitaxel • Often given in combination with Carboplatin
• Has potential for hypersensitivity reactions, patients need to be premedicated
with steroids
• Indicated for patients with ovarian cancers, cervical cancers and endometrial
cancers.
• Potential side effects:
– Alopecia -Neutrophil nadir—Day 10-12
– Mucositis -Platelet nadir—Day 8-9
– Myelosuppresion -Cardiovascular—hypotension, bradycardia,
– Myalgia, arthralgia hypertension
– Peripheral neuropathy -Injection site reactions—erythema, tenderness,
– Visual disturbances skin discoloration, swelling—extravasation
– Ototoxicity hazard irritant
– Diarrhea -Elderly patients have more myelosuppression,
– Nausea, vomiting neuropathy and cardiovascular toxicities
Carboplatin • Usually infused over 60 minutes.
• Often given in combination with Taxol.
– Taxol should be given before Carboplatin to increase efficiency and
limit myelosuppression.
• Indicated for patients with ovarian cancers, cervical cancers and
endometrial cancers.
Side effects: -↓Na, ↓Mg, ↓Ca, ↓K
-Vomiting
-↑ Creatinine
-↑liver function
–Myleosupression (Neutropenia/thrombrocytopenia)
–Neuropathies
–Ototoxicity
–Potential allergic reaction (typically in 2nd line)
Cisplatin • Pre-treatment hydration VERY important
before Cisplatin.
• Compatible with NS (normal saline)
Side effects:
- Significant nausea and vomiting
– Myelosuppression
– Nephrotoxicity
– ↓Mg
– Neurotoxicity and autotoxicity
Hypersensitivity Reactions • An exaggerated or inappropriate immune response that may
be localized or systemic, occurring during or within hours of a
drug administration – Medical emergency as can result in respiratory failure, cardiovascular collapse
and possibly death
– Certain classes of chemotherapy agents are more commonly associated with
hypersensitivity reactions including the taxanes and platinum compounds
• Can be prevented with (prophylaxis of anaphylaxis) – Corticosteroids (Dexamethasone)
– H₁ Blockers (antihistamines such as Diphenhydramine [Benadryl])
– H₂ Blockers (Ranitidine)
– Longer infusion time
Holmes Gobel, 2005; Hydzik & O’Connor, 2010; Myers, 2001; Polovich, White & Kelleher, 2005;
Winkeljohn, 2006
Hypersensitivity Reaction Clinical Manifestations of HSR &
Anaphylaxis • Uneasiness or agitation • Tightness in chest • Shortness of breath (dyspnea), with or
without wheezing (stridor/bronchospasms), 🡫 O₂ sat
• Hypotension • Tachycardia • Urticaria (hives) or rash and/or itching • Flushing • Periorbital or facial edema
(angioedema) • Lightheadedness or dizziness • Abdominal cramping, diarrhea,
nausea, vomiting • *Back pain—Paclitaxel HSR is
believed to be d/t cremophor vehicle
Hydzik & O’Connor, 2010; Otto, 2001; Polovich, Whitford & Olsen, 2009; Young & Markman, 2000
Image retrieved on April 13, 2015 from:
http://synergyhw.blogspot.ca/2013/01/magnesium-part-3-wrath-of-histamine.html
Doxorubicin
• Anthracycline and Anti-tumour Antibiotic
• Myelosuppression
• Increase in Liver Function Tests
• Nausea & Vomiting
• Skin Changes/Radiation Recall
• Skin Hyperpigmentation
• Mucositis or Esophagitis
• Diarrhea
• Alopecia
• Vein Discolouration
• Red urine
• Cardiac Toxicity – Maximum lifetime dose 550 mg/m²
• Potent vesicant – Extravasation may lead to tissue necrosis
Hydzik & O’Connor, 2010; Smith & McLaughlin, 2012;
Gemcitabine
• Antimetobolite • Myelosuppression
• Increase Liver Function Tests
• Diarrhea
• Flu-like Symptoms
– Muscle pain, fever, headache, chills,
fatigue, nausea and poor appetite
• Rash
• May experience alopecia
• Mucositis
• Edema
Hydzik & O’Connor, 2010; Smith & McLaughlin, 2012
Hormonal Therapy • Progestins have been the cornerstone of hormonal treatment
of metastatic endometrial cancer, and response is related to
the presence of steroid-hormone receptors
• Used with the aim of prolonging progression-free interval
• Used in patients with hormone-dependent Type I tumours
• Types of hormone therapy include progestins and aromatase
inhibitors
– i.e. Provera and Megestrol Acetate (Megace)
Amant, et.al, 2005; Creasman & Scott Miller, 2012; Lockwood, 2008; Tsoref & Oza, 2011
Oral Hormonal Therapies • Progestin
– Medroxyprogesterone acetate (Provera®)
– Megestrol Acetate (Megace®)
• The precise mechanism by which Megace® produces its antineoplastic effects against endometrial carcinoma is unknown at the present time
• Generally, these drugs work by slowing the growth of endometrial cancer cells
• Side effects can include – Hot flashes – Night sweats – Weight gain (from fluid retention
and ↑appetite) – Worsening of depression – For women with diabetes,
progestins can cause increased blood sugar levels
– Rarely, serious blood clots can happen
Creasman & Scott Miller, 2012; Polovich, Whitford & Olsen, 2009; Redlin Frazier, 2010
Immunotherapy • In September 2019 the US Food and Drug
Administration (FDA), the Australian Therapeutic
Goods Administration (TGA), and Health Canada
(HC) simultaneously approved a new two-drug
combination for the treatment of advanced
endometrial carcinoma.
• The approvals were granted to lenvatinib in
combination with pembrolizumab for the treatment of
patients with advanced endometrial carcinoma. All
three approvals were conditional and will require
further evidence of efficacy.
Follow-up • Weight loss, pain and vaginal bleeding can suggest recurrent
disease, which mostly occurs during the first 2-3 years after
primary treatment
• Retrospective data suggest that there is no difference in
survival between symptomatic and asymptomatic
recurrences or between women with recurrences detected
during routine follow-up visits
– Psychological benefit for most patients (reassured)
Amant, et.al, 2005; Creasman & Scott Miller, 2012; Redlin Frazier, 2010
Follow-Up
• Follow up includes a speculum exam with a bimanual
pelvic-rectal exam
• Women need to be counselled to contact their
healthcare team in case of vaginal bleeding
– Surveillance assessments and questions includes:
pelvic, leg or back pain, vaginal bleeding, urinary
changes, changes in bowel habits
• Surveillance should focus on detection of potentially
curable vaginal recurrences
Creasman & Scott Miller, 2012
UTERINE SARCOMAS
Uterine Sarcoma • Rare type of uterine cancer that forms in the connective or
stromal tissues of the uterus
– Group of aggressive and rare cancers that originate from
mesenchymal tissue
• Embryonic mesoderm from which blood vessels, lymphatic
vessels and connective tissue arise
• Two main types of sarcoma
– Leiomyosarcoma
– Endometrial stromal sarcoma (low or high grade)
Dulko, 2010; Lockwood, 2008; McMeekin, 2012; Smith & McLaughlin, 2012
Diagnosis of Sarcomas and
Clinical Presentation • Diagnosis is made following histologic evaluation of the
tumour
• Often found incidentally at the time of a hysterectomy or
myomectomy
• Symptoms include postmenopausal or abnormal vaginal
bleeding, uterine cramping, uterine enlargement and
possible malodorous vaginal discharge
– An enlarged uterus is palpated in about 50% of patients with uterine
sarcomas, and tumour may be seen protruding from the cervix
particularly in women with carcinosarcoma
Amant et al., 2009; Dulko, 2010; Lockwood, 2008; McMeekin, 2012; Tropé et al, 2012
Uterine Leiomyosarcoma (LMS)
• Most common uterine sarcoma
• Uterine LMS arises within the uterine smooth muscle;
therefore, biopsy of the malignant tissue is difficult and many
lesions are found only at final pathology
• Rapidly enlarging mass (sometimes thought to be fibroids)
should be a red flag
• Median age at diagnosis is in the early 50s, with most cases
occurring in women aged 30-50 years
• Risk factors for the development of uterine LMS are not well known
Dulko, 2010; Lockwood, 2008; McMeekin, 2012; Smith & McLaughlin, 2012;
Uterine Leiomyosarcoma (LMS) • LMS is usually
described as a large,
inhomogeneous, oval-
shaped mass with an
area of central
necrosis
• Symptoms
– Pain
– Heavy Vaginal Bleeding
– Presence of a Pelvic
Mass
• 50% of women present with
Stage 1 disease, which means
that the tumour is confined to the
uterus
• No adjuvant therapy has been
shown to be effective in
prolonging survival
– As with other high-risk uterine
cancers, it has been managed
postoperatively by radiation therapy
or chemotherapy
McMeekin, 2012; Smith & McLaughlin, 2012
Endometrial Stromal Sarcoma (ESS)
• Endometrial stromal sarcoma is a heterogeneous
histopathologic entity that is considered less aggressive
and has a better outcome than other uterine sarcomas
• ESS account for 7-15% of all uterine sarcomas
• ESS is malignant with as many as 30% of women with low-
grade ESS having extra uterine disease at presentation
• Most common symptom is irregular vaginal bleeding
• Standard management is surgery
Dulko, 2010; Lockwood, 2008; McMeekin, 2012
Endometrial Stromal Sarcoma (ESS) • Begins in connective tissue cells
• ESS is divided into 2 subtypes:
– Low-grade
– High-grade
• ESS tumours have usually an slow growing clinical course with
an 80-100% 5-yr survival, but approximately 37-60% of
patients eventually recur and 15-25% of women die of the
disease
• The most powerful predictor of clinical outcome whether
measured in terms of survival, number of relapses, or time to
first relapse is surgical stage
Dulko, 2010; Lockwood, 2008; McMeekin, 2012
Staging of Uterine Sarcomas
I A Tumor limited to uterus < 5 cm
I B Tumor limited to uterus > 5 cm
II A Tumor extends to the pelvis, adnexal
involvement
II B Tumor extends to extra-uterine pelvic tissue
III A Tumor invades abdominal tissues, one site
III B Tumor invades abdominal tissues, more than
one site
III C Metastasis to pelvic and/or para-aortic lymph
nodes
IV A Tumor invades bladder and/or rectum
IV B Distant metastasis
Treatment of Sarcomas
• Standard treatment for sarcomas involves surgical resection
of the tumour (exploratory laparotomy)
• Usually involves hysterectomy and bilateral salpingo-
oophorectomy +/- lymph node dissection
• CT scan is done to determine local resectability and to rule
out extra uterine spread in suspected sarcomas
• If extra uterine disease is known or suspected, a CXR or CT
scan is warranted to rule out pulmonary metastasis
Amant et al., 2009; Dulko, 2010; Lockwood, 2008; McMeekin, 2012; Smith & McLaughlin, 2012; Tropé et al.,
2012
Adjuvant Treatment
• Role of radiation therapy is controversial, no studies
have shown a survival benefit associated with post-
operative radiation therapy
• Therapy may reduce the rate of local recurrences, it
has no significant impact on overall survival as most
patients with recurrent disease have distant failures
• Useful in palliative setting to distant sites, bone/brain
Amant, 2009; Dulko, 2010; Lockwood, 2008; Smith & McLaughlin, 2012; Tropé et al., 2012;
Adjuvant Treatment • Most common chemotherapy regimens used include:
– Docetaxol and gemcitabine
– Doxorubicin, cisplatin, and ifosfamide
– Paclitaxel and carboplatin
• No prospective study has shown an improvement in
survival outcomes for treatment with chemotherapy
• Available clinical trials should always be presented as
an option to eligible patients
Gockley et al., 2014; McMeekin, 2012
Ifosfamide
• Alkylating agent
• Key points to remember
– Maintain high fluid intake
– Administered with Mesna
• For the prevention of urinary tract toxicity (hemorrhagic cystitis)
• Side Effects
– Myelosuppression
– N&V
– Alopecia
– Hemorrhagic cystitis
– Neurotoxicity
Hydzik & O’Connor, 2010; Polovich, Whitford & Olsen, 2009
Recurrent Disease • The treatment of recurrent sarcoma often requires the use of
multiple therapeutic modalities
– Rare cases of resectable, isolated pulmonary metastases may occur
• Enrolment into clinical trials is strongly recommended to
facilitate the identification of new active agents for these
malignancies
• In women with poorer performance status or multiple co-
morbidities, palliative measures and supportive care should
be the mainstay of treatment
Dulko, 2010; Smith & McLaughlin, 2012
References
• Ahnen, D. & Axell, L. Lynch syndrome (hereditary nonpolyposis colorectal cancer):
Clinical manifestations and diagnosis. In: UpToDate, Lamont, T. (Ed), UpToDate,
Waltham, MA. (Accessed on June 29, 2015.)
• Amant, F., Coosemans, A., Debiec-Rychter, M., Timmerman, D. & Vergote, I.
(2009). Clinical Management of Uterine Sarcomas, Lancet Oncology, 10, 1188-98.
• Amant, F., Mirza, M.R., Koskas, M. & Creutzberg, C.L. (2018). Cancer of the
Corpus Uteri. International Journal of Gynecology & Obstetrics, 143 (Suppl), 37-50.
• Amant, F., Moerman, P., Neven, P., Timmerman, D., Van Limbergen, E., &
Vergote, I. (2005). Endometrial cancer. Lancet, 366, 491–505.
• Brown, L. (2008). Pathology of Uterine Malignancies, Clinical Oncology, 20, 433-
447.
• Burke, C. (2005). Endometrial cancer and tamoxifen. Clinical Journal of Oncology
Nursing, 9, 247–249.
• Canadian Cancer Society (2018) Canadian Cancer Statistics 2018 Toronto:
Canadian Cancer Society.
• Cartwright-Alcarese, F. (2010). Anatomy, Physiology and Pathophysiology. In L.
Almadrones-Cassidy (Ed.), Gynecologic cancers: Site-Specific cancer series.
Pittsburgh, Pennsylvania: Oncology Nursing Society.
• Creasman, WT & Scott Miller, D. (2012). Adenocarcinoma of the uterine corpus.
In PJ Di Sala & WT Creasman (Eds.), Clinical Gynecologic Oncology, 8th Ed. (pp.
141-174). Philadelphia, PA: Elsevier Saunders.
• Dulko, D. (2010). Gynecologic sarcomas. In L. Almadrones-Cassidy (Ed.),
Gynecologic cancers: Site-Specific cancer series (pp. 103-111). Pittsburgh,
Pennsylvania: Oncology Nursing Society.
• Farley-Omerod, K. & Fusco, E. (2010). Prevention and early detection of cancers
of the cervix, ovaries, and endometrium. In L. Almadrones-Cassidy (Ed.),
Gynecologic cancers: Site-Specific cancer series (pp. 28-31). Pittsburgh,
Pennsylvania: Oncology Nursing Society.
• Gockley, Rauh-Hain, & del Carmen. (2014). Uterine Leiomyosarcoma: A Review
Article. International Journal of Gynecological Cancer, 24, 1538-1542.
References
References • Hacker, NF. (2000). Uterine cancer. In JS Berek & NF Hacker (Eds.), Practical
gynecologic oncology, 3rd Ed. (pp. 407-455). Philadelphia, PA: Lippincott Williams
& Wilkins.
• Holmes Gobel, B. (2005). Metabolic emergencies. In JK Itano & KN Taoka
(Eds.), Core Curriculum for oncology nursing, 4th Ed. (pp. 412-417). St. Louis,
Missouri: Oncology Nursing Society.
• Hydzik, C. & O’Conner, KA. (2010). Acute symptom management. In L.
Almadrones-Cassidy (Ed.), Gynecologic cancers: Site-Specific cancer series (pp.
149-162). Pittsburgh, Pennsylvania: Oncology Nursing Society.
• Keys, H.M., Roberts, J.A., Brunetto, V.L., Zaino, R.J., Spirtos, N.M., et al. (2004). A
phase III trial of surgery with or without adjunctive external pelvic radiation therapy
in intermediate risk endometrial adenocarcinoma: a Gynecologic Oncology Group
study. Gynecologic Oncology, 92, 744-751.
References • Kupets, R. & Le, T. (2013). The role of adjuvant therapy in endometrial cancer.
Journal of Obstetrics and Gynaecology of Canada, 35(4 eSuppl B):S1–S9
• Landrum, LM, Zuna, RE & Walker, JL. Endometrial hyperplasia, estrogen therapy,
and the prevention of endometrial cancer. In PJ Di Sala & WT Creasman (Eds.),
Clinical Gynecologic Oncology, 8th Ed. (pp. 121-139). Philadelphia, PA: Elsevier
Saunders.
• Lockwood, S. (2008). Contemporary Issues in Women’s Cancers. Sudbury, MA:
Jones and Bartlett Publishers.
• McMeekin, SD. (2012). Sarcoma of the uterus. In PJ Di Sala & WT Creasman (Eds.), Clinical Gynecologic Oncology, 8th Ed. (pp. 175-187). Philadelphia, PA: Elsevier Saunders.
• Miles, T. et al. (2012). International Guidelines on Vaginal Dilation after Pelvic Radiotherapy.
• Montz, FJ., Bristow, RE., Bovicelli, A., Tomacruz, R., & Kurman, RJ. (2002). Intrauterine progesterone treatment of early endometrial cancer. American Journal of Obstetrics and Gynecology, 186, 4, 651-657.
References • Myers, JS. (2001). Oncologic complications. In SE Otto (Ed.), Oncology
Nursing, 4th Ed. (pp. 544-548). St. Louis, Missouri: Mosby. • National Comprehensive Cancer Network.(2019). NCCN Clinical Practice
Guidelines in Oncology. Uterine Neoplasms. Version 4.2019. Retrieved October 31, 2019 from https://www.nccn.org/professionals/physician_gls/pdf/uterine.pdf.
• Otto, SE. (2001). Gynecologic cancers. In SE Otto ((Ed.). Oncology Nursing, 4th Ed. (pp. 257-260). St. Louis, Missouri: Mosby.
• Penson, R., & Powell, M. (2014). Clinical features, diagnosis, staging, and treatment of uterine carcinosarcoma. Retrieved November 2, 2015 from: http://www.uptodate.com/contents/clinical-features-diagnosis-staging-and-treatment-of-uterine-carcinosarcoma?source=search_result&search=uterine+carcinosarcoma&selectedTitle=1~13
• Polovich, M., White, J.M., & Kelleher, L. (2005). Chemotherapy and biotherapy guidelines and recommendations for practice (2nd ed). Pittsburgh, PA: Oncology Nursing Society.
• Polovich, M, Whitford, JM & Olsen, M. (Eds.). (2009). Chemotherapy and biotherapy guidelines and recommendations for practice, 3rd Ed. Pittsburgh, PA: Oncology Nursing Society.
References • Redlin Frazier, S. (2010). Endometrial cancer. In L. Almadrones-Cassidy (Ed.),
Gynecologic cancers: Site-Specific cancer series (pp. 63-73). Pittsburgh, Pennsylvania: Oncology Nursing Society.
• Renehen, A., Tyson, M., Egger, M., Heller, R., & Zwahlen, M. (2008). Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. The Lancet, 371, 569-578.
• Singh, S., Best, C., Dunn, S., Leyland, N., Wolfman, W. et al., (2013). Abnormal uterine bleeding in pre-menopausal women. SOGC Clinical Practice Guideline. Journal of Obstetrics and Gynecology Canada, 35, S1.
• Smith, T. & McLaughlin, P. (2012). Uterine leiomyosarcoma: Diagnosis, treatment, and nursing management. Clinical Journal of Oncology Nursing, 16, 3, 267-272.
• Tiffen, J.M., & Mahon, S.M. (2006). Educating women regarding the early detection of endometrial cancer—What is the evidence? Clinical Journal of Oncology Nursing, 10, 102-104.
References • Tropé, C., Abeler, V. & Kristensen, G. (2012). Diagnosis and treatment
of sarcoma of the uterus. A review. Acta Oncologica, 51, 694-705.
• Tsoref, D. & Oza, A. (2011). Recent advances in systemic therapy for advanced endometrial cancer. Current Opinion in Oncology, 23, 494-500
• Young, RC & Markman, M. (2000). Chemotherapy. In JS Berek & NF Hacker (Eds.), Practical gynecologic oncology, 3rd Ed. (pp. 407-455). Philadelphia, PA: Lippincott Wiliams & Wilkins.
• Ward, KK, Roncancio, AM, Shah, NR, Davis, MA, Saenz, CC, McHale, MT, & Plaxe, SC. (2014). Bariatric surgery decreases the risk of uterine malignancy. Gynecologic Oncology, 133, 1, 63-66
• Winkeljohn, D. (2006). Carboplatin hypersensitivity reactions. Clinical Journal of Oncology Nursing, 10, 5, 595-598.