OVARIAN CANCER 101 JESSICA MCALPINE, MD

Ovarian Cancer 101
Jessica McAlpine, MD

Outline: Ovarian Cancer
•Different types of ovarian cancer:
   •Presentation, behavior, site of origin
   •Primary treatment: surgery, chemo, +/-radiation
   •Role of geneticsempowering decision making
•Screening (lack of) and PREVENTION!
•Surveillance: screening for other cancers, treatment
effects, interplay of other health issues

Old School….
         Germ Cell                                         Sex Cord-Stromal
          (3%-5%)                                              (2%-3%)

              Secondary
             (Metastatic)
                                                             Epithelial (EOC)
                 (5%)
                                                                  (90%)

Figure modified from Gartner, L.P. & Hiatt, J.L. eds. In Color Atlas of Histology.
        3rd ed. (2000) Lippincott Williams & Wilkins: Philadelphia, PA.

New Era: “epithelial ovarian cancer”
 encompasses ~5 distinct diseases
          Serous   Endometrioid   Mucinous   Clear cell   Transitional   Undifferentiated

Grade 1   3.5%     10%

                                  4%
Grade 2

                                             10%
Grade 3   70%

2% NOS

Grouping reflects epidemiology, germline genetics,
somatic genetics, clinical presentation and response to
therapy

New Era!
The only true “ovarian” cancers=germ cell and sex
  cord stromal

EOC=primarily non-ovarian
 HGS: from the FT
 Clear cell and EM: from endometrioisis
 Mucinous: ? Paratubal cysts

                              Kurman and Shih, 2011

Anatomy 101

HGS: site of origin is the fallopian
               tube

Does the fallopian tube make sense?

• Histology of the
  fallopian tube
  epithelium is serous
• The surface area of
  the fimbriated end of
  the tube is massive
  compared the ovary

Evidence: ascending inflammation

Increases risk:         Decreases risk:
                          -Tubal ligation
   -PID                   -OCP
   -Tubal infertility     -Pregnancy

Anatomy: why are symptoms vague?

Symptoms
frustrating as
non-specific :
Gastrointestinal
Bladder
Pelvic

Stage and Grade: what do the mean?

Stage basics:
I-confined to one or both ovary(ies)
II-confined to pelvis
III-spread to abdomen (microscopicbig or nodes)
IV-distant
Grade: how abnormal the cells look….aggressive
features like high ratio nuclei : cytoplasm, mitoses

Treatment for ovarian cancer

• Surgery: remove ovaries, tubes, uterus,
  omentum…”debulk”

             +                   =>

Treatment for ovarian cancer

• Most patients will undergo 6 cycles of outpatient
  intravenous and/or intraperitoneal chemotherapy
• Chemotherapy may start before surgery (i.e., for
  3-4or even 6 cycles) or after….
• Most common agents used:
   – carboplatin and paclitaxel every 3-4 weeks
• IV~3-5 hours to administer=outpatient

Chemotherapy Treatment for ovarian cancer

• Intraperitoneal chemotherapy (IP) may be combined
  with IV. Drugs are injected into the abdominal cavity
  by a catheter attached to a port. Longer infusion.
• Theory of “bathing the cells in drug”, higher dose
  absorbed…better survival in some series but weekly
  taxol and other regimens ~ comparable (?!)
• It is inserted at staging or interval debulking surgery
• Side effects (especially nausea) can be more severe
  than traditional chemotherapy

Intraperitoneal chemotherapy

Side effects of treatment

• First few days post Rx: fatigue, nausea, bony
  aches
• Nausea  adjustment medications/options
• 7-12 days post treatment: more
  vulnerable to infection, low blood
  counts/anemia
• Loss of hair after 1st or 2nd cycle
• Tingling/paresthesias in stocking-glove
  distribution

Treatment for ovarian cancer

• Radiation sometimes used …primarily for
  endometrioid and clear cell histologies

Communicate your symptoms! MD needs to listen!

What about family?

Lifetime risk

Family history
• General pop lifetime risk: 1.6%
• If only one first-degree relative is affected by
   ovarian cancer: 5%
• BRCA 1: 40-63% by age 70
  • Lifetime risk breast cancer 60-80%
• BRCA 2: 20-27% risk by age 75
  • Lifetime risk breast cancer 60-80%
• HNPCC: 10-12% lifetime risk
  • Lifetime risk colorectal cancer 60-80%

Considerations for family members

• Both HNPCC and BRCA mutations are
  inherited in an autosomal dominant fashion

• This means a child who has a parent with a
  mutation has a 50% chance of inheriting that
  mutation. A brother, sister, or parent of a
  person who has a mutation also has a 50%
  chance of having the same mutation.

Referral to Hereditary Cancer Program
• Local Hereditary Cancer program-when to refer, who,
  how…..
   – Family history good but will miss MANY
   – Histology based referral very effective
   – >20% HGS cancers will have BRCA1/2 mutation
• ANY high grade serous ovarian cancer should be referred
  for BRCA testing OR ANY clear cell or endometrioid
  ovarian or endometrial cancer patient where pathology
  comments on absent MMR proteins should be tested for
  HNPCC
   **Now recommends referral on pathology form
   in a growing number of centers**

What about screening?

Screening
• 3 large randomized controlled trials have thus far
  shown no appreciable difference in outcomes with
  an unacceptable amount of unnecessary surgery
  (even in high risk women)
• We recommend to NOT order CA125 levels and/or
  ultrasounds in the absence of specific symptoms
  suggesting presence of disease

What can we do?

• Annual abdominal and pelvic examination
  (including pelvirectal)

• Risk reduction with oral contraceptive pill

• Risk reducing surgery: tubal ligation,
  salpingectomy, and for BRCA mutation
  carriers/HNPCC consider BSO at completion
  of childbearing

Prevention
Fallopian tube in situ lesions are precursor to
“ovarian cancer”….

             Remove the precursor!

Change Surgical Convention

• ~18% of BC’s population of
  women with ovarian cancer
  had undergone
  hysterectomy
• Hysterectomy and tubal
  ligation are common
• WHY NOTE REMOVE THE
  FALLOPIAN TUBE?
• Perform salpingectomy with
  hysterectomy and consider
  in place of tubal ligation
 September 2010 Campaign

Projected Outcome
• Conservatively, up to 40% reduction in ovarian
  cancer deaths after 20 years
  – Through salpingectomy at time of hysterectomy
  – Through salpingectomy instead of tubal ligation
  – Through risk-reducing BSO in patients with BRCA
    mutations

Living with ovarian cancer

• Goal (and truly can be) =curable disease!

Survivorship encompasses the physical, psychological, social,
and spiritual domains of individuals with cancer from the time
of diagnosis, through treatment, and on…

Even for 1 disease the survivorship needs can vary with different QOL considerations
            over the course of care e.g., along the survivorship continuum
 Diagnosis and Primary
 Treatment
 A. Physical                                                         Treatment for
       nausea  emesis                                              recurrent or
       neuropathy                                                                                           End-of-Life
                                  Maintenance/                       refractory disease
       nephropathy                                                                                          Support/Palliation
       fatigue                   Consolidation Therapy              A – E. as in primary
                                                                     therapy                                 A. Physical
       hair loss                 A. Physical                                                                       Pain
                                                                          cumulative
       bone health                  • cumulative toxicities                                                        Bowel obstruction
                                                                           treatment toxicities
       hormonal changes          F. Socioeconomic                                                                  Pleural effusions
                                                                          Increase
       sexual health                • additional costs and visits                                                  Ascites
                                                                           hypersensitivity
       infertility                                                                                          C – D. Psychosocial &
                                                                           reactions
       pain                                                                                                 socioeconomic
                                                                           (platinum)
       change in bladder or
                                                                                                                  Advance directives
        bowel function
                                                                                                                  Power of attorney
 B. Cognitive                     Cancer Surveillance/                                                       E. Spiritual
     memory loss                 Observation                                                                     Peace/resolution;
     concentration               A. Physical                                                                      friends/family/self/
 C. Psychosocial                      fatigue                                                                     God(s)
     anxiety                         sequelae of chemotherapy
     depression                       or surgery (i.e.,
     fear of recurrence               neurotoxicity)
     partners/family             B – E. as in primary therapy
      relationships
                                  F. Preventive health               Long-term (>5 years) Survival
     body image                                                     A. Physical
                                      (re-)initiation of general
 D. Socioeconomic                      healthcare                        sequelae of treatment
     cost of treatment                guidelines/screening                  - i.e., neurotoxicity
     demand of hospital visits       referral to hereditary                 -i.e., end organ disease
     consideration of end-of-         cancer program                        - i.e., secondary cancers
      life financial planning         fracture risk/bone health     B – E. as in primary therapy
 E. Spiritual                                                        F. Preventive health
     personal strength &                                                 as in surveillance period + screening for secondary cancers
      growth

Surveillance:
• Regular intervals w/ physical examinations
• Some reliance on symptoms/changes
• We DON’T tend to do:
   – Routine imagingradiation dose accumulation
   – Routine CA125 no improvement in survival and
     risk of decreasing the amount of good QOL time

What can we do/what should we ask?
• What type was my cancer, what was done, what is
  known about this specific disease now?
• Family testing and follow-up with action if +
• Side effects; perhaps we can help?
• Catch up on general health recommendations!
• Support and empowerment: Inspire Health, OCC,
  OCNA, patient and family counseling….
• New changes/symptoms; maybe we should examine?

Recurrence: not doom and gloom!
Chemical vs. Imaging vs. Symptomatic recurrence

• OR/Surgery
   – for isolated recurrence or very long time since primary
   – disease that is resistant to chemotherapy
   – for bowel obstruction/acute event
• Chemotherapy for ~ all others-consider clinical trials
  or molecular targeted therapy? Rarely radiation.
• Observation or supportive care?

• Questions?

BCCA 604 877 6000 x 2367
jessica.mcalpine@vch.ca