OVARIAN CANCER

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OVARIAN CANCER

• February 26, 2007
• Paula Kwong, RPh
• Pharm D Candidate

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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

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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

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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

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PRESENTATION-symptoms (2)

• May also complain of
• Dyspareunia
• Low back pain
• Lack of energy
• Menstrual irregularities

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PRESENTATION-physical signs

• 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

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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

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DIFFERENTIAL (1)

• Ovarian Cysts
• Ectopic Pregnancy
• Pelvic Inflammatory Disease
• Uterine Fibroids
• Other gynecologic cancers
• Other cancers GI, pancreatic, colon/rectal

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DIFFERENTIAL (2)

• Pelvic kidney
• Diverticulitis
• Hepatic failure
• Colitis
• Irritable Bowel Syndrome
• Inflammatory Bowel Disease

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METASTATIC SPREAD

• Intraperitoneal pelvic abdominal viscera,
  omentum
• Bladder bowel
• Transdiaphragmatic spread to pleura, liver
• Lymphatics
• Hematogenous spread (advanced stage)

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RISK FACTORS (1)

• Inherited gene mutations
• Age
• Family history
• Menstrual periods
• Nulliparity/Infertility/1st child after 30yo
• Obesity
• HRT (hormone replacement therapy)

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RISK FACTORS (2)

• Breast Cancer
• Ovarian Cysts
• Sedentary lifestyle
• Smoking alcohol
• Talc
• Clomid

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PREVENTION

• BCP (birth control pills)
• Tubal ligation/hysterectomy/oophorectomy
• Pregnancy and breast feeding
• Diet/Exercise
• Aspirin
• Acetaminophen

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DIAGNOSIS

• Thorough Physical Exam
• Comprehensive Family History
• Chest X-ray
• Imaging studies MRI/CT/Ultrasound/Mammogram
• Colonoscopy, UGI
• Lab tests
• SURGERY

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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

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TUMOR MARKERS

• CA-125 Normal lt35 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

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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

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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

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EPITHELIAL CLASSIFICATION

• Developed by WHO/FIGO
• Serous gt50 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

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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

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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

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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

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INITIAL TREATMENT

• 1st step-Surgical debulking at staging laparotomy
• 2nd-Adjuvant chemotherapy
• 3rd-Radiation
• Participation in clinical trials encouraged

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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 lt0.5cm median survival of 40
  months 0.5-218 months gt2cm 6-12 months

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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)

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SCREENING GUIDELINES cont.

• Hereditary Cancer Syndromes yearly CA-125 TVS
  until age 35 or childbearing complete.
  Prophylactic bilateral oophorectomy should then
  be considered to reduce overall risk.
• Screening trials

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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 gt12x/mo, lt12mo
• Correlated to presence of ovarian cancer
• Symptoms similar in both early/late stage

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CANCER Jan 15, 2007 continued

• Screening test sensitivity 56.7 early stage
  79.5 for late stage
• Specificity was 90 for women gt 50 years old and
  86.7 for women lt 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

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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

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REFERENCES (1)

• National Comprehensive Cancer Network-Practice
  guidelines in Oncology-Ovarian Cancer. V.1. 2007
  www.nccn.org/professionals/physician_gls/PDF/ovari
  an.pdf
• DiPiro, JT et al. PHARMACOTHERAPY, A Pathologic
  Approach. 6th edition, 2005. Ovarian Cancer.
  Section 17, pp 2467-84.

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REFERENCES (2)

• American Family Physician Sep 15, 2003. Serum
  Tumor Markers. www.aafp.org/afp/20030915/1075.htm
  l
• American Family Physician December 15, 2004. US
  Preventative Services Task Force-Screening
  Recommendations for Ovarian Cancer.
  www.aafp.org/afp/20050215/us.html

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REFERENCES (3)

• Naational Cancer Institute Announces Preferred
  Method of Treatment for Advanced Ovarian Cancer.
  Jan 4, 2006. www.cancer.govnewscenter/pressrelease
  s/IPchemotherapyrelease