Transcript OVARIAN CANCER - Dr Ted Williams

OVARIAN CANCER
February 26, 2007
Paula Kwong, RPh
Pharm D Candidate
INTRODUCTION
• 6th most common malignancy in women
(excluding skin cancers)
• 4th leading cause of cancer related death in
women
• Incidence highest in US, Europe, Israel
• Lowest incidence developing countries & Japan
• 1 in 56 to 1 in 70 women will develop ovarian
cancer; lifetime risk of about 1-2%
• 2006 estimates: 20,180 cases and 15,310
deaths
INTRODUCTION…
• 5 yr survival for all stages nearly 50%
• Survival for patients with localized disease
nearly 90%, but only 10-30% with
disseminated disease
• 70% of patients diagnosed with
disseminated disease
• Early detection is critical
PRESENTATION- symptoms
• Vague and non-specific; can be confused
with GI, urinary tract, stress, and
menstrual problems
• Early symptoms: nausea, dyspepsia,
flatulence, bloating, fullness, early satiety,
abdominal pain, urinary urgency &
frequency
PRESENTATION-symptoms (2)
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May also complain of:
Dyspareunia
Low back pain
Lack of energy
Menstrual irregularities
PRESENTATION-physical signs
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May have palpable abdominal mass
May have lymphadenopathy
May have signs of ascites
May have abnormal hair growth
Red flag: palpable ovary in
postmenopausal woman or before puberty
PRESENTATION- other facts
• Two-thirds of women with ovarian cancer
are 55yo or older
• More common in caucasians
• Can occur in females before puberty
• Majority of cases occur sporadically with
only 5 to 10% being familial
DIFFERENTIAL (1)
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Ovarian Cysts
Ectopic Pregnancy
Pelvic Inflammatory Disease
Uterine Fibroids
Other gynecologic cancers
Other cancers: GI, pancreatic,
colon/rectal
DIFFERENTIAL (2)
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Pelvic kidney
Diverticulitis
Hepatic failure
Colitis
Irritable Bowel Syndrome
Inflammatory Bowel Disease
METASTATIC SPREAD
• Intraperitoneal: pelvic & abdominal
viscera, omentum
• Bladder & bowel
• Transdiaphragmatic spread to pleura, liver
• Lymphatics
• Hematogenous spread (advanced stage)
RISK FACTORS (1)
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Inherited gene mutations
Age
Family history
Menstrual periods
Nulliparity/Infertility/1st child after 30yo
Obesity
HRT (hormone replacement therapy)
RISK FACTORS (2)
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Breast Cancer
Ovarian Cysts
Sedentary lifestyle
Smoking & alcohol
Talc
Clomid
PREVENTION
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BCP (birth control pills)
Tubal ligation/hysterectomy/oophorectomy
Pregnancy and breast feeding
Diet/Exercise
Aspirin
Acetaminophen
DIAGNOSIS
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Thorough Physical Exam
Comprehensive Family History
Chest X-ray
Imaging studies:
MRI/CT/Ultrasound/Mammogram
• Colonoscopy, UGI
• Lab tests
• SURGERY
LAB TESTS for DIAGNOSIS
• Chem profile including tests for hepatic
and renal function
• CBC: assess internal bleeding
• Pregnancy test if premenopausal
• Pap smear
• Tumor markers: CA-125, hCG, AFP, CEA
TUMOR MARKERS
• CA-125: Normal= <35 u/ml
• Elevated in 85% of ovarian cancers but
only 50% of the time in early stage
• Elevated in other cancers/benign
conditions
• Lacks sensitivity and specificity therefore
is not diagnostic for ovarian cancer
• Most useful for monitoring response to
therapy and in detecting recurrence
PROBLEMS WITH CURRENT
SCREENING TOOLS
• Rectovaginal Pelvic Exam: lacks
sensitivity and specificity
• Cancer Antigen-125: CA-125 elevated
only 50% of the time in early stage
• Transvaginal Sonography: TVS lacks
specificity
HISTOLOGY
• Three major histologic (cell) types of
ovarian cancer:
• Epithelial Cell: 85-95% of cases, cells
covering ovaries; 45-75yo
• Stromal Cell: connective tissue cells that
hold the ovary together and that make
hormones
• Germ Cell: egg producing cells; most
common before age 20
EPITHELIAL CLASSIFICATION
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Developed by WHO/FIGO
Serous: >50% of cases
Mucinous: approx 12%
Endometrioid: approx 10%
Clear cell: approx 3%
Transitional (Brenner), Undifferentiated, Mixed
Low-malignant Potential “Borderline”
Metastatic from other primary
Benign
EPITHELIAL HISTOLOGY
Grading Important
• Gx: grade cannot be assesed
• G1: well differentiated
• G2: moderately differentiated
• G3: poorly differentiated
• Grade 1 more closely resembles normal
tissue and G3 the least
FIGO STAGING OF EPITHELIAL
OVARIAN CANCER
• Stage I – tumor confined to one or both ovaries
• Stage II – tumor involves one or both ovaries
with pelvic extension (metastasis with in pelvis)
• Stage III – tumor involves one or both ovaries
with metastasis outside pelvis +/- lymph node
involvement
• Stage IV – distant metastasis beyond the
peritoneal cavity
TREATMENT OF EPITHELIAL
OVARIAN CANCER
• Guidelines developed by the American
Cancer Society and the National
Comprehensive Cancer Network
• NCCN guidelines available at
www.nccn.org
INITIAL TREATMENT
• 1st step-Surgical debulking at staging
laparotomy
• 2nd-Adjuvant chemotherapy
• 3rd-Radiation
• Participation in clinical trials encouraged
PROGNOSIS
• Related to stage, subtype & grade, volume
of residual disease
• Well differentiated IA/IB have 5 yr survival
rates of 90% vs 5-10% Stage IV
• Survival strongly correlated to size of
residual tumors after debulking surgery
• Residual tumors <0.5cm: median survival
of 40 months; 0.5-2=18 months; >2cm= 612 months
NIH SCREENING GUIDELINES
• No reliable, sensitive, specific screening
tool exists for women of average risk
• ALL WOMEN: assess family history and
yearly rectovaginal pelvic exam with Pap
smear
• No family Hx or 1 relative: participation in
ovarian cancer screening trials
• Pos family Hx in 2+ relatives: counseling
by gynecologic oncologist (specialist)
SCREENING GUIDELINES cont.
• Hereditary Cancer Syndromes: yearly CA125 + TVS until age 35 or childbearing
complete. Prophylactic bilateral
oophorectomy should then be considered
to reduce overall risk.
• Screening trials
CANCER Jan 15, 2007
Goff, Barbara et al
• Case-control: 149 cancer/458 controls
• Symptom index developed
• Pelvic/abdominal pain, urinary
urgency/frequency, abdominal bloating,
early satiety
• Frequency/Duration: >12x/mo, <12mo
• Correlated to presence of ovarian cancer
• Symptoms similar in both early/late stage
CANCER Jan 15, 2007
continued
• Screening test sensitivity = 56.7% early
stage & 79.5% for late stage
• Specificity was 90% for women > 50 years
old and 86.7% for women < 50 years old
• National Institute of Health website
(medlineplus) says doctors and patients
can use the screening test now but more
research needed to see if results hold up
in larger study
ROLE OF PHARMACIST
• Inpatient/IV infusion pharmacist: dose as
per protocol, medication related side
effects, nutrition, monitoring for the “fifth”
vital sign (JCAHO requirement)
• Retail: symptom recognition & referral,
medication related side effects, “fifth” vital
sign
REFERENCES (1)
• National Comprehensive Cancer NetworkPractice guidelines in Oncology-Ovarian
Cancer. V.1. 2007
www.nccn.org/professionals/physician_gls/
PDF/ovarian.pdf
• DiPiro, JT et al. PHARMACOTHERAPY, A
Pathologic Approach. 6th edition, 2005.
Ovarian Cancer. Section 17, pp 2467-84.
REFERENCES (2)
• American Family Physician Sep 15, 2003.
Serum Tumor Markers.
www.aafp.org/afp/20030915/1075.html
• American Family Physician December 15,
2004. US Preventative Services Task
Force-Screening Recommendations for
Ovarian Cancer.
www.aafp.org/afp/20050215/us.html
REFERENCES (3)
• Naational Cancer Institute Announces
Preferred Method of Treatment for
Advanced Ovarian Cancer. Jan 4, 2006.
www.cancer.govnewscenter/pressreleases
/IPchemotherapyrelease