Ovarian Cancer “The Silent Killer” Strategies in the Caribbean
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Transcript Ovarian Cancer “The Silent Killer” Strategies in the Caribbean
Eloise Chapman-Davis, M.D.
Assistant Professor
Weill Cornell School of Medicine
Division of Gynecologic Oncology
New York Presbyterian Hospital
Gynecologic Cancer Burden in the
Caribbean
Cervical Cancer- most common, most preventable
Uterine Cancer- most curable; modifiable risk factors
Ovarian Cancer- most deadly**
Review epidemiology
Review screening options
Review treatment options
Discuss future directions
Cervical Cancer
Worldwide 2nd most common cause of cancer-related deaths
among women
Most common gyn cancer in Caribbean
Guyana, Surinam, Haiti, DR, TNT, Jamaica have highest rates in WI
The central cause for almost all cervical cancer is HPV
HPV infections are common & asymptomatic
Screening available:
Pap Smears
HPV DNA test ( Hybrid C2/ Cobas)
VIA (visual inspection with acetic acid)
Preventable
HPV vaccination
Uterine Cancer
Second most common Gyn Cancer in the Caribbean
Risk Factors
Related to exposure to estrogen
Obesity
Hormone replacement therapy
Irregular periods, polycystic ovarian syndrome
Diabetes/Hypertension
Women who take Tamoxifen (Breast CA tx)
Women with family history of colon cancer, GI,prostate,
breast/ovary may have genetic syndrome
BleedingEndometrial biopsyDiagnosis & Tx = CURE !!!
Ovarian Cancer
Most lethal gynecological cancer in the western world
Approximately 200,000 women living with ovarian cancer
worldwide
There will be 22,000 new cases and 14,000 patients will die
this year
5th leading cause of cancer death in women, after lung,
breast, colon and pancreatic cancer (more than leukemia,
melanoma and brain cancers)
A woman’s risk of getting ovarian cancer is 1 in 72
Ovary - WHO Classification
Epithelial
Sex cord-stromal
Germ cell
Soft tissue tumors not
specific to the ovary
Unclassified
Secondary (metastatic)
GI tumors
Breast
Lymphoma
Epithelial ovarian cancer
Risk factors
Increased risk
Decreased risk
advancing age
prolonged breast
family history
feeding
oral contraceptives
multiparous
reproductive
surgery/tubal ligation
BSO (cannot
eliminate primary
peritoneal cancer)
nulliparity
BRCA/Lynch
syndrome
talc powder (?)
high fat diet(?)
fertility drugs
Epithelial ovarian cancer
“The Silent Killer”
Signs
Symptoms
Abdominal mass
Abdominal pain
Pelvic mass
Urinary frequency
Pleural effusion
Constipation or diarrhea
Ascites
Abnormal vaginal
Ventral hernia
bleeding
Abdominal distension
Dyspnea
Inguinal nodes
95% of women do report symptoms
Epithelial Ovarian cancer
Stage I: growth limited to
one or both of the ovaries
Stage II: growth to
ovaries+ pelvic extension
Stage III: same as Stage II
with peritoneal implants
outside the true pelvis
and/or (+) retroperitoneal
nodes
Stage IV: growth involving
one or both the ovaries
with distant metastasis
Outcome
Stage
IA
IB
IC
II
III A
III B
IIIC
IV
Survival
90%
86%
83.4%
65-70%
46%
42%
35%
18%
Early Stage
Only 20% of patients
diagnosed Stage I
75% patient diagnosed
with advance stage*
Screening & Prevention Strategies
Ovarian cancer Screening???
Who should we offer to? How often do you test? Which
tests do you use? How to interpret results?
Should offer screening ONLY to patients with Inherited Risks
No clear evidence that screening detects ovarian cancer at an
early stage in any risk group
No evidence that screening results in a survival benefit
Screening tests of premenopausal women have high false
positive rates
Screening- PLCO trial
Randomized control trial 78,216 women aged 55 to 74
Annual screening (n=39105) CA 125 x 6 yr TVUS x4 yrs
Usual Care (n= 39,111)
13 year follow up
Invasive cancer diagnosed in 212 screen vs 176 usual care
126 dx during screening phase
78% with advanced (Stage III/IV) cancer in both groups
Low PPV: CA125 3.7%; TVUS 1%
Both abnormal PPV 23.5%
Would miss 60% of invasive cancers if referral for consultation was based
on both abnormal
No difference in overall survival between groups
Buys et al JCO 2011.Buys SS et al. Am J Obstet Gynecol 2005;193: 1630-9.
Early detection strategies
for Ovarian Cancer
Risk of Ovarian Cancer Algorithm (ROCA)
Incorporates change in CA 125 over time and age to estimate risk
Next annual CA-125 (low risk)
3 month repeat CA-125 (intermediate risk)
or TVS & referral to gyn onc (high risk)
Two large prospective Studies
US prospective n=3258 ;50-74 postmenopausal avg risk
No screening vs ROCA
PPV 37.5%
UKCTOS n= 200,000 50-74 postmenopausal avg risk
no screening vs yearly TVUS vs ROCA (MMS)
PPV 35%
Both Studies showed Specificity 99.8%**
UK Collaborative Trial of Ovarian Cancer
Screening- Mortality Results
Diagnosed 1282 invasive ovarian cancer (2001-2005);
11 yr f/u
338 MMS; 314 US; 630 No screening
NO difference in mortality reduction 15% MMS vs 11% US
Difference found when prevalent cases excluded
20% overall reduction, (8% yr 1-7; 28% yr 7-14)
Future directions…... ROCA 2.0
Already approved test but should it be??
Jacobs et al Lancet 2015
Hereditary Risk of Epithelial
Ovarian Cancer
Family History of Ovarian Cancer Lifetime Risk
None
1.5%
1 first-degree relative
5%
2 first-degree relatives
7%
Hereditary ovarian cancer syndrome 40%
Known BRCA1 or BRCA2
15-65%
germline mutation
Hereditary Breast & Ovarian Cancer (HBOC)
BRCA Mutation Carriers
Up to 87% lifetime risk of
breast cancer
Up to 60% lifetime risk of
2nd breast CA
Lifetime risk of
ovarian CA
BRCA 1+ 40-60%
BRCA 2 + 10- 25%
**↑ risk for prostate,
pancreatic, gastric,
melanoma,
male breast cancer
• BRCA tumor suppressor gene
• Mutation results in defect in
DNA repair mechanism
multiple cancers
• Autosomal Dominant, effects
multiple generations
Malignancies associated with Lynch Syndrome
<1% Brain 3.7%
<1% Stomach 13%
<1% Biliary Tract 2%
<1% Small Intestine 5%
<1% Urinary Tract 4%
1.3% Ovary 12%
1.5% Endometrium 60%
2% Colon/Rectum 82%
Woman with Lynch Syndrome
Average risk woman
(Age 70)
(Age 70)
Results from defects in DNA mismatch repair genes
Most common form of hereditary colorectal cancer
Prognosis is better than sporadic CRC
Who should have genetic testing?
Any women with ovarian cancer
Women with family history of early onset breast or ovarian
cancer, or multiple cases of these cancers
Early onset of cancers (< 50 years of age)
Dx of Triple negative Breast CA
Ashkenazi jewish descent
Anyone with family history of male breast cancer
Endometrial cancer dx under 50
Especially if BMI<30 or family history of a Lynch malignancy
Which patients should consider risk
reduction strategies?
Women with BRCA 1 or BRCA 2 mutations
Women with known Lynch Syndrome
High-risk personal or family history who had
inconclusive genetic testing
High-risk personal or family history who have not
had genetic testing
* genetic counseling/testing still preferred approach
for this group
Ovarian Cancer Risk Reduction
Strategies
Screening
CA-125* , Transvaginal ultrasound, Pelvic exam
Every 6-12 months
The problem???
Only elevated in 20% pts with Stage I ovarian cancer
Chemoprevention
Birth Control pills-OCP
50% reduction ovarian cancer
Unclear impact on breast CA
Ovarian Cancer Surgical
Risk Reduction
BSO age 35-40 or after completion of childbearing ***
96% reduction in risk for Ovary/fallopian tube CA.
53% reduction breast cancer.
Can be done with or without hysterectomy
Short term HRT can be used in select pts
Risk Reducing Salpingectomy
Lower incidence of ovarian cancer in women with BTL or
salpingectomy then gen pop
Unilateral salpingectomy HR .71 (CI .56 to .91)
Bilateral salpingectomy HR 0.35 (CI .17 to .73)
Should we be doing salpingectomy at time of hysterectomy
for benign indications???
Falconer etal J Natl Cancer Inst 2015
Ovarian Cancer Treatment
Overview of the management of
epithelial ovarian cancer
Surgery - comprehensive staging
— Diagnosis
— Staging – Hysterctomy/BSO/lymph nodes/omentectomy
— Tumor Debulking
Chemotherapy -Who to treat?
Stage IA and IB, grade 3 and other adverse histology (clear cell), or
ruptured (IC)
Any patient with Stage IC or higher
6 cycles of paclitaxel/carboplatin IV or IP
80% patient with CR (platinum sensitive)
20% patient platinum resistant/refractory
Reasons for Surgery:
optimal tumor debulking
Physiologic
Remove ascites
Improve GI function
Improve pressure
symptoms and pain
Tumor perfusion
Remove bulky tumor with
poor vascular supply
Cell kinetics
Improved growth fraction
Lower tumor burden
Immunologic factors
Amount of residual disease and survival
Problem??
Where are the specialty trained surgeons in the
Caribbean?? Which island? Costs of postoperative
care?? Inoperable disease????
Neoadjuvant treatment
RCTs Stage III-IV ovarian cA pts
EORTC study (n=670 women
Primary surgery chemo vs NACT (3 cycles) surg chemo
Lower rate complications
Higher rate optimal cytoreduction <10mm res (81% vs 42%)
No difference in PFS (12 mth each arm) or OS (29mth vs 30)
CHORUS study (n=550
Primary surgery vs NACT- non inferiority trial
18% pts optimally debulked primary surge
No difference in PFS or OS
Vergote et al N Engl J med 2010; Kehoe S et al Lancet 2015
By Treatm ent Group
1. 0
0. 9
IV: 18 mos
IP: 24 mos
HR: 0.79, P= 0.027
P r opor t i on S ur vi vi ng
0. 8
0. 7
0. 6
0. 5
IV: 50 mos
67 mos
0.71, P= 0.008
0.HR:
3
0.IP:
4
0. 2
Rx G r oup
IV
IP
0. 1
0. 0
0
12
Alive Dead Tot al
93 117 210
117 88 205
24
36
M onths on Study
Increase toxicity vs IV approach
48
60
Future DirectionsTargeted Therapies
Angiogenesis Inhibitors
Overexpression of VEGF in serous ca drives abnl angiogenesis
Bevacizumab- Recombinant humanized monoclonal antibody that binds to and
inhibits the activity of VEGF
sorafenib/afibercept/ sunitinib
Parp-Inhibitors
Parp-I is nuclear enzyme involved in DNA repair
Increase activity in cells with BRCA mutation
olaparib/niraparib Phase II/III trials
35% ORR, PFS 8 mths
Study as maintenance drug/ recurrent setting
Immunotherapy
Immune checkpoint blockade
CTL4/PD-1 inhibitors 10-15% RR
Bevacizumab works best in recurrent
setting
Bev single agent: 21% response rate, 4.7 month PFS
Bev + cyclophosphamide: 24% response rate, 7.2 month
time to progression
Burger R, et al: JCO 25:5165,2007.
Garcia AA, et al: JCO 26;76-82,2008.
Gemcitabine + carboplatin + bev: 78% response rate, 12
month PFS
Richardson DL, et al: Gynecol Oncol 111;461-6,2008.
Taxol +Bev : 53% RR vs 30%, PFS 10 mths vs 4mth
best regimen in platinum resistant pts
Bev+doxil; Bev+ topotecan improved PFS (Aurelia study)
Pujade-Lauraine E, etal : J Clin Oncol 2014
Progression
Evaluation
Diagnosis
Symptoms
Chemo #1
Surgery
Maintenance
Survivorship
Death
Secondary
Surgery
Chemo
#2
Chemo
#3
Supportive
Care
Conclusions
Ovarian cancer is most lethal of all gyn malignancies
75% present with advance stage disease (Stage III-IV)
Screening of general population not currently
recommended as will not improve detection or
survival
Screening is recommended in patients with hereditary
risks for ovarian cancer
BRCA mutation carriers/ Lynch Syndrome
Risk reducing surgery is the best method for
prevention of ovarian cancer
Conclusions
Goals of treatment include optimal tumor debulking
surgery and adjuvant chemotherapy treatment for
almost ALL STAGES
Stage IA grade 1-2 no adjuvant chemo
Neoadjuvant chemotherapy can be used in patients
with advanced (Stage IV) or inoperable patients with
good response
Targeted therapies can be used with chemo or alone
for treatment with best response seen in the recurrent
setting