Endometrial & Ovarian Cancer Endometrial & Ovarian Cancer

Karen A. Zempolich, M.D. Karen A. Zempolich, M.D. Division of Gynecologic Oncology, Division of Gynecologic Oncology, Dept. of Obstetrics & Gynecology Dept. of Obstetrics & Gynecology
University of Utah University of Utah Huntsman Cancer Institute Huntsman Cancer Institute

Endometrial & Ovarian Cancer Endometrial & Ovarian Cancer Overview Overview
Epidemiology Epidemiology Signs & symptoms Signs & symptoms Management / outcome Management / outcome When to refer to a sub When to refer to a subspecialist specialist

 Follow Follow-up surveillance up surveillance

Endometrial Cancer Endometrial Cancer Epidemiology Epidemiology

36,000 cases/yr; 6,500 deaths 36,000 cases/yr; 6,500 deaths 4th most common cancer in women 4th most common cancer in women

 (breast, lung, colon) (breast, lung, colon)

75% postmenopausal (avg. age 58 y.o.) 75% postmenopausal (avg. age 58 y.o.) 5% cases: < 40 years old 5% cases: < 40 years old

Endometrial Cancer Endometrial Cancer

Risk Factors Risk Factors - Deleterious Deleterious

Relative Risk Relative Risk Obesity Obesity 2-11 11 Family history Family history 1.5 1.5-2.8 2.8 Nulliparity Nulliparity 3 Infertility ( Infertility (>3yrs) 3yrs) 3 Endogenous estrogens Endogenous estrogens 1.5 1.5 - 4
Estrogen Estrogen-secreting tumors secreting tumors

Unopposed exogenous estrogens Unopposed exogenous estrogens 2 12 12 Diabetes Diabetes 2 - 10 10 Tamoxifen Tamoxifen 2 - 7

Endometrial Cancer Endometrial Cancer

Risk Factors Risk Factors - Protective Protective

 Oral contraceptives (1 Oral contraceptives (1-5 years) 5 years) 0.3 0.3-0.5 0.5 Cigarette smoking Cigarette smoking 0.4 0.4-.08 .08 Parity Parity 0.3 0.3-0.5 0.5

Endometrial Cancer Endometrial Cancer-- --Risk

Factors Risk Factors

Hereditary Hereditary Nonpolyposis Nonpolyposis Colorectal Cancer Colorectal Cancer 5% of colorectal cancers 5% of colorectal cancers Mutations in DNA mismatch repair genes Mutations in DNA mismatch repair genes Lifetime Lifetime risk of developing: risk of developing:
Colorectal cancer 80% Colorectal cancer 80% Endometrial cancer 40% Endometrial cancer 40%

 Ovarian cancer 10% Ovarian cancer 10% Other GI cancer 20% Other GI cancer 20%

Endometrial Cancer Endometrial Cancer

Carcinogenesis Carcinogenesis Precancerous Lesions Precancerous Lesions

Hyperplasia Hyperplasia Progression to Cancer Progression to Cancer

Simple Simple 1% 1% Complex Complex 3% 3% Simple, atypical Simple, atypical 8% 8% Complex, atypical Complex, atypical 29% 29%
Kurman, 1985

Endometrial Cancer Endometrial Cancer

Symptoms Symptoms

 Postmenopausal bleeding Postmenopausal bleeding

Present in > 90% menopausal cases of Present in > 90% menopausal cases of endometrial cancer endometrial cancer 20% patients with PMB 20% patients with PMB malignancy malignancy 5% patients with PMB 5% patients with PMB endo endo hyperplasia hyperplasia

Premenopausal Premenopausal patients

patients abnormal uterine abnormal uterine bleeding bleeding

Endometrial Cancer Endometrial Cancer

Signs Signs
Most exams are normal Most exams are normal May have: May have:
enlarged uterus enlarged uterus Peripheral Peripheral adenopathy adenopathy Ascites Ascites

 vaginal vaginal mets mets adnexal adnexal mass mass cul cul-de de-sac sac nodularity nodularity

Endometrial Cancer Endometrial Cancer

Diagnosis Diagnosis Pap Smear Pap Smear
In patients with endometrial cancer: In patients with endometrial cancer:

 40 40-50% suspicious 50% suspicious endo endo cells on Pap cells on Pap 2-5% normal endometrial cells 5% normal endometrial cells
Montz 2001, Win 2001, Ashfag 2001, Sarode 2001

Endometrial Cancer Endometrial Cancer

Diagnosis Diagnosis Pap Smear Pap Smear

Postmenopausal women with normal Postmenopausal women with normal endo endo cells on cells on pap: pap: 20 20-40% pathology 40% pathology
Polyps Polyps Hyperplasia 10 Hyperplasia 1015% 15% Cancer 1 Cancer 1-5% 5%

2-5% asymptomatic 5% asymptomatic pts with normal endometrial pts with normal endometrial cells: cells: cancer cancer
Montz 2001, Win 2001, Ashfag 2001, Sarode 2001

Endometrial Cancer

Endometrial Cancer
Diagnosis Diagnosis Biopsy Biopsy
Inpatient (operative) dilation and curettage Inpatient (operative) dilation and curettage (fractional) (fractional) Outpatient endometrial biopsy Outpatient endometrial biopsy

Pipelle Pipelle Vabra Vabra, Novak , Novak

Endometrial Cancer Endometrial Cancer

Diagnosis Diagnosis Endometrial Biopsy Endometrial Biopsy
Metaanalysis Metaanalysis 39 studies (5 prospect) 39 studies (5 prospect)

Office Office bx bx compared to D&C, compared to D&C, hyst hyst, or both , or both

 Cancer: Cancer:
Sensitivity Sensitivity 68 to 81% 68 to 81% Specificity Specificity 99.6 to 99.9% 99.6 to 99.9% Hyperplasia Hyperplasia Sensitivity Sensitivity 75% 75% Specificity Specificity 99% 99%
Dijkhuizen et al. Cancer 2000 Garnti JAAGL 2001

Endometrial Cancer

Endometrial Cancer
Hysteroscopy Hysteroscopy CAVEAT CAVEAT
Transtubal Transtubal spread of spread of endo endo cells cells Obermaier Obermaier et al et al (Cancer 2000) (Cancer 2000) 113 pts 113 pts
HSC/D&C HSC/D&C vs vs D&C alone D&C alone

12% 12% vs vs 2.5% pos. peritoneal cytology (p<0.05)

2.5% pos. peritoneal cytology (p<0.05)

Zerbe Zerbe et al et al (Gyn Gyn Onc Onc 2000) 2000) 222 pts 222 pts
HSC 2.5x more likely HSC 2.5x more likely positive cytology positive cytology

Impact on survival Impact on survival not known not known AVOID AVOID hysteroscopy if cancer suspicion high hysteroscopy if cancer suspicion high

Endometrial Cancer Endometrial Cancer

Diagnosis Diagnosis Transvaginal Transvaginal Ultrasound Ultrasound
Metaanalysis Metaanalysis TVUS & office biopsy TVUS & office biopsy

 Endometrial thickness Endometrial thickness <5mm <5mm threshold threshold

96% sensitivity (cancer) 96% sensitivity (cancer) 92% sensitivity (cancer, polyp, hyperplasia) 92% sensitivity (cancer, polyp, hyperplasia) (regardless of HRT) (regardless of HRT) False positives: False positives: HRT users 23% HRT users 23% Non HRT users 8% Non HRT users 8%

Poor positive predictor value (~10%) Poor positive predictor value (~10%)

 High High negative predictive value (99%) negative predictive value (99%)
Smith-Bindman JAMA 1998 Langer, NEJM 1997

Endometrial Cancer Endometrial Cancer

Diagnosis Diagnosis Summary Summary
Office endometrial biopsy Office endometrial biopsy preferred preferred

method method
Accurate, convenient Accurate, convenient

TV U/S TV U/S can effectively r/o disease if can effectively r/o disease if <5mm stripe <5mm stripe If continued symptoms If continued symptoms repeat sampling repeat sampling (Hysteroscopy, D&C, (Hysteroscopy, D&C, hysterosonography hysterosonography)

Endometrial Cancer Endometrial Cancer Surgical Surgical

Staging Staging
Stage I Stage I Uterus Uterus (75 to 80%) (75 to 80%) A. A. endometrium endometrium B. B. < myometrium myometrium C. C. > myometrium myometrium

Stage II Stage II Cervix Cervix (6 to 10%) (6 to 10%) A. A. glands glands B. B. stroma stroma

Endometrial Cancer Endometrial Cancer Surgical Surgical

Staging Staging
Stage III Stage III Extrauterine Extrauterine (8%) (8%)

A. A. serosa serosa, , adnexa adnexa, peritoneal cytology , peritoneal cytology B. B. vagina, pelvic peritoneum vagina, pelvic peritoneum C. C. lymph nodes (pelvic/abdominal) lymph nodes (pelvic/abdominal) Stage IV Stage IV Distant Distant (5%) (5%) A. A. bowel/bladder mucosa bowel/bladder mucosa B. B. intraabdominal intraabdominal, inguinal

nodes, extra , inguinal nodes, extra abdominal abdominal

Endometrial Cancer Endometrial Cancer

Treatment Treatment---Surgery Surgery
Hysterectomy / Hysterectomy / salpingoophorectomy salpingoophorectomy (BSO) (BSO)

 If clinical cervical involvement: If clinical cervical involvement: Radical Radical hyst hyst vs vs preop preop radiation radiation Staging Staging selected patients selected patients
Peritoneal cytology Peritoneal cytology Lymph node dissection Lymph node dissection Omentectomy Omentectomy (papillary serous/clear cell histology) (papillary serous/clear cell histology)

Endometrial Cancer

Endometrial Cancer
Treatment TreatmentSurgery 2005 Surgery 2005
Increased role for Increased role for laparoscopic laparoscopic staging staging
LAVH/ BSO, staging if indicated LAVH/ BSO, staging if indicated Regardless of age, body mass index Regardless of age, body mass index

 75 to 95% have full staging by LSC 75 to 95% have full staging by LSC Conversion to open lap for obesity, Conversion to open lap for obesity, intraperitoneal intraperitoneal cancer, bleeding cancer, bleeding

Endometrial Cancer Endometrial Cancer

Treatment TreatmentSurgery 2005 Surgery 2005

 Laparoscopic Laparoscopic hyst hyst/ BSO/ staging / BSO/ staging

Equal node count Equal node count Equal survival Equal survival Decreased length of stay Decreased length of stay Longer OR time (230 min Longer OR time (230 min vs vs 150 min) 150 min) Shorter delay for radiation (if indicated) Shorter delay for radiation (if indicated)

Endometrial Cancer

Endometrial Cancer
Staging Staging Patient Selection Patient Selection
Risk of pelvic lymph node Risk of pelvic lymph node grade, depth of grade, depth of invasion invasion Depth Depth G1 G1 G2 G2 G3 G3 Endometrium Endometrium 0 3

0 Inner 1/3 Inner 1/3 3 5 9 Middle 1/3 Middle 1/3 0 9 4 Outer 1/3 Outer 1/3 11 11 19 19 34% 34%
Creasman 1987

Endometrial Cancer Endometrial Cancer Staging Staging Patient Selection Patient Selection

Risk of lymph node Risk of lymph node tumor location Pelvic LN Aortic LN Fundus 8% 4% Isthmus cervix 16% 14%
Creasman 1987

Endometrial Cancer Endometrial Cancer - Staging Staging

Patient Selection Patient Selection

Pre Pre-op Prediction ? op Prediction ?

Grade 1 lesion Grade 1 lesion 1 in 3 1 in 3 will require staging will require staging

10 to 15% : outer 10 to 15% : outer invasion invasion 10% : isthmus / cervix involvement 10% : isthmus / cervix involvement 20% upgraded 20% upgraded intraop intraop

Endocervical Endocervical curettage curettage

 10% false negative rate 10% false negative rate High false positive (80 High false positive (80-90%), unless 90%), unless stromal stromal invasion seen invasion seen

Endometrial Cancer Endometrial Cancer - Staging Staging

Patient Selection Patient Selection Pre Pre-op

Prediction? op Prediction?
Transvaginal Transvaginal ultrasound/MRI ultrasound/MRI

80% accurate: 80% accurate: myometrial myometrial invasion invasion 33% accurate: cervix / isthmus involvement 33% accurate: cervix / isthmus involvement

Therefore: no good Therefore: no good preop preop predictor of need predictor of need

for staging for staging

Postoperative Treatment Postoperative Treatment Stage I Controversy Stage I Controversy

Intermediate risk (5 Intermediate risk (5-10% recur) 10% recur)

Grade 1 or 2 with: Grade 1 or 2 with: Middle 1/3 Middle 1/3 myoinvasion myoinvasion or cervix / isthmus or cervix / isthmus

 High risk (>10% recur) High risk (>10% recur)

Grade 3 or outer 1/3 invasion Grade 3 or outer 1/3 invasion

?? ?? whole pelvis radiation vs. whole pelvis radiation vs. vaginal vaginal brachytherapy brachytherapy vs. vs. surgery alone surgery alone ?? ??

Endometrial Cancer

Endometrial Cancer
Stage I Controversy Stage I Controversy---Radiation

Radiation

GOG 99 GOG 99
Stage IB Stage IB-II, 390 pts II, 390 pts TAH/BSO/LND TAH/BSO/LND pelvic pelvic rad rad or no or no rad rad Decreased Decreased pelvic recurrence (12% pelvic recurrence (12% vs vs 1.7 % 1.7 % )

 Improved Improved disease free survival (94% disease free survival (94% vs vs 85% ) 85% ) No difference No difference in overall survival in overall survival

Endometrial Cancer Endometrial Cancer

Stage I Controversy Stage I Controversy---Radiation

Radiation

 GOG 99 GOG 99more controversy! more controversy!

Final analysis only reported 2 yr survival data Final analysis only reported 2 yr survival data Only 20% pts high risk (outer 1/3, Only 20% pts high risk (outer 1/3, Gr Gr 3) 3)

Endometrial Cancer Endometrial Cancer

Stage I Controversy Stage I Controversy--

--Radiation

Radiation
pts 715 pts

PORTEC: PORTEC: 715

Stage IB Stage IB Gr Gr 2,3 , IC 2,3 , IC Gr Gr 2 TAH / BSO TAH / BSO pelvic pelvic rad rad or no or no rad rad Decreased Decreased pelvic recurrence (14% pelvic recurrence (14% 4%) 4%) No difference No difference in survival in survival BUT BUT: Excluded IC, : Excluded IC, Gr Gr 3

Endometrial Cancer Endometrial Cancer

Stage I Controversy Stage I Controversy Radiation Radiation

Vaginal Vaginal Brachytherapy Brachytherapy (post op) (post op) 18 to 22 18 to 22 Gy Gy Decreases vaginal recurrence 12% to 2% Decreases vaginal recurrence 12% to 2%

 RT for local recurrence RT for local recurrence Vaginal recur: Vaginal recur: 68% 5 yr survival 68% 5 yr survival Pelvic recur: Pelvic recur: 20 to 50% 5 yr survival 20 to 50% 5 yr survival Pelvic control of tumor: 50 to 65% Pelvic control of tumor: 50 to 65%
Ackerman 1996, Sears 1994, Morgan 1993, Wylie 2000 Ackerman 1996, Sears 1994, Morgan 1993, Wylie 2000

Endometrial Cancer Endometrial Cancer

Stage I Treatment Stage I Treatment U of U / LDSH U of U / LDSH

Patients: TAH/BSO and extended pelvic/aortic LND Patients: TAH/BSO and extended pelvic/aortic LND Myometrial Myometrial Invasion Invasion None None <50% <50% >50% >50% G1 G1 0 0 V G2 G2 0 V V G3 G3 V V V+P
(V = vaginal RT; P = pelvic RT)

Endometrial Cancer Endometrial Cancer Stage I Treatment Stage I Treatment U of U / LDSH U of U / LDSH
Patients: Patients: no no lymph node dissection lymph node dissection Myometrial Myometrial Invasion Invasion None None <50% <50% >50% >50%

G1 G1 0 0 V+P G2 G2 0 V P+V G3 G3 V V+P P+V

(V = vaginal RT; P = pelvic RT)

Endometrial Cancer Endometrial Cancer

Subspecialty Impact Subspecialty Impact
Primary management: Primary management: Gyn Gyn onc onc vs vs OB/GYN OB/GYN

 207 cases, 49% 207 cases, 49% Gyn Gyn onc onc / 51% GYN / 51% GYN Gyn Gyn onc onc pts: pts:
Complete staging 2x more often (94 Complete staging 2x more often (94 vs vs 45%) 45%) In hi risk Stage I, even more often (96 In hi risk Stage I, even more often (96 vs vs 19%) 19%) Higher Higher avg avg # nodes (20 # nodes (20 vs vs 8) 8)
Roland 2004 Roland 2004

Endometrial Cancer Endometrial Cancer

Subspecialty Impact Subspecialty Impact

Fewer Fewer Gyn Gyn onc onc pts received adjuvant radiation pts received adjuvant radiation
8.6 8.6 vs vs 21.7% 21.7%

No No Gyn Gyn onc onc pts with T1, N0 disease

rec pts with T1, N0 disease recd radiation radiation 18 GYN pts with T1, N0 or NX rec 18 GYN pts with T1, N0 or NX recd radiation d radiation
Roland 2004 Roland 2004

Endometrial Cancer Endometrial Cancer

Treatment Treatment Stage III Stage III

 Survival, 5 yr Survival, 5 yr

10 to 30% gross extra uterine disease 10 to 30% gross extra uterine disease 40 to 80% microscopic 40 to 80% microscopic

Treatment: Treatment:

Nodes/ Nodes/ serosa serosa/ / adnexa adnexa/ vagina / vagina RT RT Positive Cytology Positive Cytology
High dose High dose progestins progestins if PR positive if PR positive Chemo vs. whole abdominal RT Chemo vs. whole abdominal RT

Endometrial Cancer Endometrial Cancer

Treatment Treatment Stage IV Stage IV
Survival, 5 year Survival, 5 year
5 - 10% 10%

Treatment: Treatment:

Hormonal therapy Hormonal therapy Chemotherapy Chemotherapy

 Local radiation Local radiation

Endometrial Cancer Endometrial Cancer

Controversy: Estrogen Replacement Controversy: Estrogen Replacement Therapy Therapy Arguments against: Arguments against: Increase recurrence Increase recurrence ?
Epidemiologic studies: Epidemiologic studies:

Unopposed estrogen Unopposed estrogen risk developing risk developing endo endo ca ca In vitro studies: In vitro studies: growth of cultured cells with estrogen therapy growth of cultured cells with estrogen therapy

Endometrial Cancer Endometrial Cancer

Controversy: Estrogen Replacement Controversy: Estrogen Replacement

Therapy Therapy Arguments in support: Arguments in support:

Benefits: Benefits: bone / bone / neuro neuro / symptoms / symptoms Likelihood of ( Likelihood of (oncologic oncologic) harm: ) harm:
Early stage, low grade: ER positive Early stage, low grade: ER positive Least Least recurrent recurrent High stage, high grade: higher recurrence High stage, high grade: higher recurrence most most ER negative ER negative

Endometrial Cancer

Endometrial Cancer

Estrogen Replacement Therapy Estrogen Replacement Therapy

249 pts, stages I, II, III (cohort study) 249 pts, stages I, II, III (cohort study)

130 pt 130 pt ERT (50% with progesterone) ERT (50% with progesterone) Age/stage matched controls (75 pairs) Age/stage matched controls (75 pairs) Similar in Similar in surgicopathology

surgicopathology, treatment , treatment ERT users ERT users 1% recurrence 1% recurrence Non ERT Non ERT 14% recurrences 14% recurrences Suriano Suriano et al 2001 et al 2001

Endometrial Cancer Endometrial Cancer

Treatment TreatmentERT protocol ERT protocol
GOG 137 GOG 137

 Stage I / occult stage II endometrial cancer Stage I / occult stage II endometrial cancer Premarin 0.625/ day vs. placebo Premarin 0.625/ day vs. placebo Plan: 3 years treatment, 2yr fl/u Plan: 3 years treatment, 2yr fl/u Closed prematurely due to accrual Closed prematurely due to accrual

Endometrial Cancer Endometrial Cancer

ERT protocol ERT protocolGOG 137 GOG 137

Median f/u 30 mo, 1234 pts Median f/u 30 mo, 1234 pts ERT: ERT:
Recurrence 12 pts (1.9%) Recurrence 12 pts (1.9%) Death due to Death due to endom endom Ca 3 pts (0.5%) Ca 3 pts (0.5%)

Placebo: Placebo:

Recurrence 10 pts (1.6%) Recurrence 10 pts (1.6%)

 Death due to Death due to endom endom Ca 4 pts (0.6%) Ca 4 pts (0.6%)

(NOT statistically valid) NOT statistically valid)

Endometrial Cancer Endometrial Cancer

Summary Summary
4th th most common cancer in women most common cancer in women
Caught early, excellent survival Caught early, excellent survival

 Abnormal bleeding merits evaluation Abnormal bleeding merits evaluation

Office biopsy, pursue diagnosis if persists! Office biopsy, pursue diagnosis if persists!

Family predisposition Family predisposition endometrial, HNPCC endometrial, HNPCC

Family Cancer Assessment Clinic Family Cancer Assessment Clinic

Endometrial Cancer

Endometrial Cancer
Summary Summary
Full staging may forego radiation Full staging may forego radiation Grade 1 Grade 1 preop preop biopsies biopsies 33% need staging 33% need staging Laparoscopy is the new paradigm in Laparoscopy is the new paradigm in endometrial cancer endometrial cancer

Ovarian Cancer Ovarian Cancer

Second most common gynecologic cancer Second most common gynecologic cancer in the US in the US Responsible for 25,000 cases annually Responsible for 25,000 cases annually 14,500 deaths annually 14,500 deaths annually Most lethal gynecologic cancer Most lethal gynecologic cancer

 70% of women are diagnosed present with 70% of women are diagnosed present with advanced disease advanced disease
American Cancer Society 2000

Ovarian Cancer: Ovarian Cancer: Stage Distribution and Survival Stage Distribution and Survival

Stage Stage Percent Percent Survival Survival

I-- --ovary ovary 24 24 95% 95% II II-- --pelvis pelvis 6 65% 65% III III-- -abdomen abdomen 55 55 15 15-30% 30% IV IV-- --distant distant 15 15 0-20% 20% Overall Overall 50% 50%
American Cancer Society 2000 American Cancer Society 2000

Ovarian Cancer: Risk Factors

Ovarian Cancer: Risk Factors

Increase Increase Decrease Decrease
Age Age Oral Contraceptives Oral Contraceptives (50% decrease) (50% decrease) Family history Family history Pregnancy Pregnancy and and Breastfeeding Breastfeeding Infertility/low parity Infertility/low parity

Personal cancer Personal cancer history history Hysterectomy/Removal Hysterectomy/Removal of Both Ovaries of Both Ovaries

Ovarian Cancer: Hereditary Risks Ovarian Cancer: Hereditary Risks

Family History of Ovarian Family History of Ovarian Cancer Cancer Lifetime Risk Lifetime Risk

None None 1.8% 1.8% 1 first 1 first-degree relative degree relative 5% 5% 2 first 2 first-degree relatives degree relatives 7% 7% Hereditary ovarian cancer Hereditary ovarian cancer syndrome syndrome 40% 40% Known BRCA1 or BRCA2 Known BRCA1 or BRCA2

inherited mutation inherited mutation 35 35-65% 65%

Ovarian Cancer: Ovarian Cancer: Hereditary Syndromes Hereditary Syndromes

Account for only 10% of ovarian cancer Account for only 10% of ovarian cancer Inherited from either parent Inherited from either parent

 Incomplete Incomplete penetrance penetrance Associated with breast, colon, prostate Associated with breast, colon, prostate and endometrial cancers and endometrial cancers

Ovarian Cancer: Ovarian Cancer: How is Ovarian Cancer Diagnosed? How is Ovarian Cancer Diagnosed?

 Vaginal Vaginal rectal exam rectal exam Transvaginal Transvaginal ultrasound ultrasound CA 125 blood test CA 125 blood test Surgical biopsy / resection Surgical biopsy / resection

Ovarian Carcinoma Ovarian Carcinoma---Symptoms Symptoms

95% of women DO report symptoms 95% of women DO report symptoms 80 to 90% of pts with Stage I/ II disease 80 to 90% of pts with Stage I/ II disease More often, more acute onset of More often, more acute onset of sx sx, more , more severe severe Vague and often non Vague and often non-gynecologic gynecologic
abdominal bloating, abdominal bloating, incr incr girth, pressure girth, pressure Fatigue Fatigue

GI (nausea, gas, constipation, diarrhea) GI (nausea, gas, constipation, diarrhea) Urinary frequency/ incontinence Urinary frequency/ incontinence Abdominal/ pelvic pain Abdominal/ pelvic pain Weight loss/ gain Weight loss/ gain Shortness of breath Shortness of breath

Ovarian Carcinoma Ovarian Carcinoma Primary Management Primary Management

Initial surgery Initial surgery

Thorough surgical staging Thorough surgical staging Aggressive tumor resection ( Aggressive tumor resection (debulking debulking, , cytoreduction cytoreduction) Combination chemotherapy Combination chemotherapy
6 cycles: 6 cycles: carboplatin carboplatin & paclitaxel paclitaxel

Ovarian Carcinoma Ovarian Carcinoma Primary Management Primary Management Initial Surgery Initial Surgery
Surgical Staging Surgical Staging
Hyst Hyst / BSO / / BSO / Omentectomy Omentectomy Washings, peritoneal biopsies Washings, peritoneal biopsies Pelvic/ Pelvic/ Paraaortic Paraaortic Lymphadenectomy Lymphadenectomy

80% of ovarian cancer pts receive inadequate 80% of

ovarian cancer pts receive inadequate staging from non staging from non gyn gyn-onc onc surgeon surgeon May translate into choice between 2 May translate into choice between 2nd nd surgery or surgery or chemotherapy chemotherapy

Ovarian Carcinoma Ovarian Carcinoma Primary Management Primary Management Initial Surgery Initial Surgery

Reoperation Reoperation within 3 months for within 3 months for debulking debulking/ staging / staging
Population based study, 3355 pts Population based study, 3355 pts Pts Pts less likely to have less likely to have reoperation reoperation if if done: done: In high In high- or or intermed intermed- volume hospital (RR 0.24) volume hospital (RR 0.24) By By Gyn Gyn Onc Onc (RR 0.04) (RR 0.04) By general Ob/ By general Ob/ Gyn Gyn (RR 0.37) (RR 0.37) By high volume surgeon (RR 0.09) By high volume surgeon (RR 0.09) (> 10 ovarian cancer cases/ yr) (> 10 ovarian cancer cases/ yr)

Elit et al, Gyn Oncol 200

Ovarian Carcinoma Ovarian Carcinoma Primary Management Primary Management Debulking Debulking
Residual Disease Residual Disease 5 yr survival 5 yr survival < 1 cm < 1 cm 50% 50% 1 to 2 cm 1 to 2 cm 20% 20% > 2 cm > 2 cm 13% 13%
Baker et al, Cancer 1994

Ovarian Carcinoma Ovarian Carcinoma

Primary Management Primary Management Debulking Debulking

Residual Disease Residual Disease Median survival Median survival < 0.5cm < 0.5cm 40 months 40 months 0.5 to 1.5 cm 0.5 to 1.5 cm 18 months 18 months > 1.5 cm > 1.5 cm 6 months 6 months
Hacker N, Ob & Gyn 1983

Ovarian Carcinoma Ovarian Carcinoma

Primary Management Primary Management Initial Surgery Initial Surgery

Survival advantage for advanced stage pts treated Survival advantage for advanced stage pts treated by by gyn gyn onc onc
25% reduction in death at 3yrs, ( 25% reduction in death at 3yrs, (vs vs general Ob/ general Ob/Gyn Gyn)
Junor Junor et al, Br J et al, Br J Ob&Gyn Ob&Gyn 1999 1999

Survival advantage for pts treated in high Survival advantage for pts treated in high-volume volume

hospital hospital
55% 55% vs vs 34% 5 yr survival for high 34% 5 yr survival for high vs vs low volume low volume
Ioka Ioka et al, Cancer et al, Cancer Sci Sci 2004 2004

Pelvic Mass: Preoperative Pelvic Mass: Preoperative Prediction of Malignancy Prediction of Malignancy
5 to 25% 5 to 25% premenopausal premenopausal are malignant are malignant

1/3 1/3rd rd in pts < 21 y.o. (solid/ cystic) in pts < 21 y.o. (solid/ cystic) > 50% in > 50% in premenarchal premenarchal pts (solid/ cystic) pts (solid/ cystic)

35 to 63% postmenopausal are malignant 35 to 63% postmenopausal are malignant Preop Preop assessment of likelihood of assessment of likelihood of

malignancy can allow appropriate malignancy can allow appropriate surgical planning surgical planning

Preoperative Prediction of Malignancy Preoperative Prediction of Malignancy

Indicators (suspicious) Indicators (suspicious)
Pelvic examination Pelvic examinationfixed, nodular, fixed, nodular, ascites ascites

Tumor markers Tumor markers

CA125 > 35U/ CA125 > 35U/ mL mL AFP >10 AFP >10 ng ng/ / mL mL or or hCG hCG >15 >15 mIU mIU/ / mL mL (non (non pregnant) pregnant) LDH > 350 U/ L LDH > 350 U/ L

Ultrasonographic Ultrasonographic findings findings solid, cystic with solid, cystic with mural nodules mural nodules
Roman et al, Ob & Gyn 1997

Preoperative Prediction of Malignancy

Preoperative Prediction of Malignancy

If all 3 indicators If all 3 indicators nonsuspicious nonsuspicious::
99% of pre 99% of pre- & postmenopausal masses & postmenopausal masses benign benign

If all 3 indicators If all 3 indicators suspicious suspicious, ,

77% of 77% of premenopausal premenopausal masses masses malignant malignant

1/3 1/3rd rd borderline, 2/3 borderline, 2/3rd rd invasive invasive Nodules >2cm, size>10cm most predictive Nodules >2cm, size>10cm most predictive

83% of postmenopausal masses 83% of postmenopausal masses malignant malignant

borderline, borderline, invasive invasive CA125 > 100, suspicious U/S most predictive CA125 > 100, suspicious U/S most predictive Roman 1997

ACOG / SGO Referral Guidelines

ACOG / SGO Referral Guidelines Newly Diagnosed Pelvic Mass Newly Diagnosed Pelvic Mass
Premenopausal Premenopausal (<50) (<50)
CA125 > 200 U/ ml CA125 > 200 U/ ml ascites ascites abd abd/ distant / distant mets mets Family Family Hx Hx Breast/ Breast/

Ovarian cancer (1st Ovarian cancer (1st degree) degree)

Postmenopausal (>50) Postmenopausal (>50)

CA125 > 35 U/ ml CA125 > 35 U/ ml ascites ascites abd abd/ distant / distant mets mets Family Family Hx Hx Breast/ Breast/ Ovarian cancer (1st Ovarian cancer (1st degree) degree) nodular/ fixed mass nodular/ fixed mass ACOG Committee Opinion 2002 Im et al, Ob & Gyn 2005

ACOG / SGO Referral Guidelines ACOG / SGO Referral Guidelines Predictive Value Predictive Value
1,035 pts, 7 hospitals 1,035 pts, 7 hospitals 30% ovarian cancer 30% ovarian cancer 25% of cancer cases 25% of cancer cases-- -premenopausal premenopausal

chart / path review chart / path review

CA125 CA125 preop preop pelvic exam pelvic exam imaging studies imaging studies path report path report
Im et al, Ob &Gyn 2005

Referral Guidelines Referral Guidelines Predictive Value Predictive Value---Pre Premenopausal menopausal
Criteria PPV (%) NPV (%)

CA125 70 85 Ascites 58 89 Mets 64 89 Family Hx 19 82 Overall 34 92

Im et al, Ob &Gyn 2005

Referral Guidelines Referral Guidelines Predictive Value Predictive Value---Post Postmenopausal menopausal
Criteria PPV (%) NPV (%) CA125 74 85

Ascites 79 72 Pelvic exam 66 61 Mets 84 77 Family Hx 42 56 Overall 60 91

Im et al, Ob &Gyn 2005

Referral Guidelines Referral Guidelines Patient Distribution Patient Distribution

Specialty Ovarian Cancer Benign Mass Premenopausal Gyn Onc 70% 31% OB/ Gyn 30% 69% Postmenopausal Gyn Onc 94% 42%

OB/ Gyn 6% 58%

Modified Referral Guidelines Modified Referral Guidelines

Premenopausal Premenopausal (<50) (<50)

CA125 > 50 U/ ml CA125 > 50 U/ ml ascites ascites abd abd/ distant / distant mets mets

Postmenopausal (>50) Postmenopausal (>50)

CA125 > 35 U/ ml CA125 > 35 U/ ml ascites ascites abd abd/ distant / distant mets mets
Im et al, Ob & Gyn 2005 Im et al, Ob &Gyn 2005

Referral Guidelines Referral Guidelines Patient Distribution Patient Distribution

Specialty Ovarian Cancer Benign Mass Premenopausal Gyn Onc 85% 27% OB/ Gyn 15% 73% Postmenopausal

Gyn Onc 90% 24% OB/ Gyn 10% 76%

Ovarian & Endometrial Cancer Ovarian & Endometrial Cancer Surveillance Surveillance

Frequency: Frequency: Q 3 months x 2 yrs Q 3 months x 2 yrs Q 4 months x 1 yr Q 4 months x 1 yr Q 6 months until year 5, Q 6 months until year 5,

then, annually then, annually (roughly 75 to 90% recur (roughly 75 to 90% recur in 1st 3 years) in 1st 3 years) Each visit: Each visit: Physical / Physical / Pelvic exam Pelvic exam Pap smear Pap smear Tumor markers (CA125, Tumor markers (CA125, CEA) CEA) Annual: Annual: Chest Xray Chest Xray CBC, metabolic panel CBC, metabolic panel

Endometrial & Ovarian Cancer

Endometrial & Ovarian Cancer

Early detection Early detection-- --improve improves survival s survival

Heighten awareness of sympto Heighten awareness of symptoms! ms!

Staging & complete Staging & complete debulking debulking decreases decreases morbidity and increases survival morbidity and increases survival

 Consider consultation with gynecologic Consider consultation with gynecologic oncologist (801 oncologist (801-585 585-2477) 2477)