[PDF] - Adnexal Masses in Disclosure Menopausal Women Surgery or PDF Document

SLIDE 1

9/16/2017 1

Adnexal Masses in Menopausal Women

Surgery or Surveillance?

Fr Frederick R

R. Ueland, MD

Prof

fesso

essor and r and Dire Direct ctor Divisi Division of

f Gynec

Gynecolo logi gic Onco Oncolo logy Un Univ iver ersity of sity of Kentucky ucky

Disclosure I have no financial disclosures

Wind River Range, WY July, 2017

Past

1980’s “palpable ovary syndrome”
2000’s observation of unilocular cysts
2010’s observation of septate cysts

Present

10% require surgery for adnexal mass in their

lifetime1

13%-21% are malignant2

Ovarian Tumor Overview

1) Moore, McMeekin, Brown et al. Gynecol Oncol, 2009 2) Jordan. Current Biomarker Findings, 2013

SLIDE 2

9/16/2017 2

Ovarian Tumor Overview

 Many tumors, few cancers  15% are malignant

Germ cell tumors
LMP tumors
Epithelial cancers

 Benign tumors

70% functional cysts
20% neoplastic
10% endometriomas

 Other

Inflammatory

 Few tumors, many cancers  50% are malignant

Epithelial ovarian cancer
Metastatic cancer
Granulosa cell tumors

 Benign tumors

Cystadenoma
Fibroma
Thecoma

Premenopausal Menopausal

unilocular

Pavlik E, Ueland F, Miller R, et al. Obstet Gynecol, 2013

septate solid

39,337 ultrasounds performed 70% low risk (21%)

The Specifics

Normal Abnormal 70% 70% 30% 30%

30% high risk (9%)

cyst+solid

Menopausal Women

Incidence

Number of new ovarian cysts identified

8.2%1 3.3 million women2

Prevalence

Proportion who have cysts at any given time

17%1 6.8 million women2

1) Pavlik E, Ueland F, Miller, R. et al. Obstet Gynecol, 2013 2) United States Census Bureau, 2010

Most are low risk for malignancy

Ultrasound Ultrasound

Lessons Learned Reducing Subjectivity IOTA: Simple Rules, ADNEX Model Kentucky Morphology Index

SLIDE 3

9/16/2017 3

Lessons Learned

Tumor morphology helps stratify cancer risk Screening trial Surgeries per cancer

UKCTOCS

35.2

PLCO

19.5

Kentucky

 first decade (1990’S)

12.5

 second decade (2000’S)

5.2

 third decade (2010’S)

4.0

16-Sep-17 9

Limiting Subjectivity

■ First International Consensus Report1 ■ International Ovarian Tumor Analysis (IOTA)

Simple Rules2
ADNEX3

■ Kentucky Morphology index4 ■ Serial sonography5

1) J Ultrasound Med, 2017; 2) Ultrasound Obstet Gynecol, 2008; 3) Br Med J, 2014; 4) Gynecol Oncol, 2003; 5) Gynecol Oncol, 2014

IOTA Simple Rules

■

M1 Irregular solid

■

M2 Presence of ascites

■

M3 At least 4 papillary projections

■

M4 Irregular multilocular solid, largest diameter ≥ 10 cm

■

M5 Very strong blood flow

Timmerman et al. Simple ultrasound-based rules for the diagnosis of ovarian cancer. Ultrasound Obstet Gynecol 31; 681-690, 2008

■

B1 Unilocular

■

B2 Solid component < 7 mm

■

B3 Presence of acoustic shadows

■

B4 Smooth multilocular tumor, largest diameter < 10 cm

■

B5 No blood flow

SLIDE 4

9/16/2017 4

Simple Rules

Malign Malignan ant If one or more M-rules apply in the absence of a B-rule, the mass is classified as malignant Benig Benign If one or more B-rules apply in the absence of an M-rule, the mass is classified as benign. Inde Indeterminat ate If both M-rules and B-rules apply, the mass cannot be

classified. If no rule applies, the mass cannot be classified

Timmerman et al. Simple ultrasound-based rules for the diagnosis of ovarian cancer. Ultrasound Obstet Gynecol 31; 681-690, 2008

ADNEX Risk Model

Belgium, Italy, Czech Republic, Poland, UK, Sweden 14

IOTA - ADNEX model

1. Age of the patient at examination (years)
2. Oncology center (referral center for gyn-oncol)?
3. Maximal diameter of the lesion (mm)
4. Maximal diameter of the largest solid part (mm)
5. More than 10 locules?
6. Number of papillations (papillary projections)
7. Acoustic shadows present?
8. Ascites (fluid outside pelvis) present?
9. Serum CA-125 (U/ml)

C lear

___ __________ _____________ ____________________ ______ _______ ______ _____ _____

Van Calster et al. Evaluating risk of ovarian cancer before surgery using the ADNEX model. BMJ, 2014 Ueland F, DePriest P, Pavlik E, et al. Gynecol Oncol, 2003

Kentucky Morphology Index

Kentucky MI

MI MI Total Maligna nant nt ROM (%) (%) 1 2,349 1 0.04 2 2,365 0.00 3 2,635 3 0.11 4 1,579 7 0.44 5 1,061 29 2.73 6 241 9 3.73 7 87 11 12.64 8 30 8 26.67 9 18 5 27.78 10 3 1 33.33 Total 10,368 74 0.71

85%

Ueland F, DePriest P, Pavlik E, et al. Gynecol Oncol, 2003

Sensitivity 86% Specificity 98%

SLIDE 5

9/16/2017 5

Comparing Models

ADNEX Model

ROM correlates with

increased cancer risk

52% of cancers in

lowest ROM groups

Efficacy in surveillance

is unknown

Misses stage 1 cancers

Kentucky MI

ROM correlates with

increased cancer risk

15% of cancers in lowest

ROM groups

MI change over time is

useful for surveillance

Identifies stage 1 cancers

16-Sep-17 17

Lefringhouse J, Ueland F, Ore R, et al. SGO, 2016

Biomark Biomarkers

Diagnostic Triage Comparison

19

‘Diagnostic’ Biomarkers

CEA
CA19‐9
LDH
β‐hCG
AFP
HE‐4
CA125
OVA1*
ROMA
Overa+

*Multivariate Index Assay + MIA2G

Triage Biomarkers

20

CA125 Performance

Myers et al. Management of adnexal mass. Rockville (MD): U.S. Department of Health and Human Services, 2006

SLIDE 6

9/16/2017 6

21

OVA1

FDA-cleared September, 2009
Multivariate Index Assay

Triage Biomarker Tests

ROMA

FDA-cleared September, 2011
Dual marker test

CA125 + HE4

Range 0 nge 0-10 Prem emeno enopaus ausal Po Post st Low Risk < 5.0 < 4.4 High Risk ≥ 5.0 ≥ 4.4 Range 0 nge 0-10 Prem emeno enopaus ausal Po Post st Low Risk < 1.31 < 2.77 High Risk ≥ 1.31 ≥ 2.77

22

Triage Biomarker Tests

Overa

FDA-cleared September, 2016
Multivariate Index Assay-2G
CA125, HE-4, FSH, Apolipoprotein A1, Transferrin

Rang Range 0- e 0-10 Result sult Low Risk < 5.0 High Risk ≥ 5.0

Sensitivity Overa1 OVA12,3 ROMA4 CA125‐II2,5 All malignancies 91% 93% 89% 69% Epithelial ovarian cancers 95% 99% 94% 82% Early stage EOC 89% 98% 75% 66% Premenopausal women 90% 94% 76% 36% Postmenopausal women 92% 100% 92% 80% Specificity All malignancies 69% 54% 75% 87%

OVA1 detected 76% of malignancies missed by CA1251

Comparing Biomarkers

1) Coleman R, Herzog T, Chan D, et al. Am J Obstet Gynecol, 2016 2) Ueland F, DeSimone C, Seamon L, et al. Obstet Gynecol, 2011 3) Bristow R, Smith A, Zhang Z, et al. Gynecol Oncol, 2013 4) Moore R, McMeekin S, Brown A, et al. Gynecol Oncol, 2009 5) Myers et al. Management of adnexal mass. Rockville (MD): U.S. Department of HHS, 2006

Recommended Ev commended Evalu aluation tion

Determine Malignant Risk with Ultrasound

1. Low risk‐ surveillance
2. Indeterminate‐ secondary testing
3. High risk‐ refer to Gynecologic Oncologist

SLIDE 7

9/16/2017 7

Recommended Evaluation

Malignant Risk Low Indeterminate High Distribution 65% 25% 10% US morphology Unilocular

r septate

Partly solid, small wall abnormalities Mostly solid, papillary projections Secondary testing No YES No Surgery No Maybe YES

25

Low Risk

Unilocular cyst1,2 Septate cyst3

Smooth-walled
Unilocular or septate

1) Modesitt et al. Gynecol Oncol, 2003; 2) Bailey et al. Gynecol Oncol, 1998; 3) Saunders B. et al. Gynecol Oncol, 2010

Malignant Potential for Low Risk

16-Sep-17 27 Summary of Valentin et al, 2013 33% unilocular 1% malignant

0.54% Premenopausal
2.76% Postmenopausal

7/11 had solid or papillary component on visual surgical inspection

Valentin, Ameye, Franchi et al. Ultrasound Obstet Gynecol, 2013

Resolution for Low Risk

28

Re Resolution T Time

Ty Type o

f Abnormality

Cyst Cys Cyst & & Sep Septae Cys Cyst & & Soli Solid Soli

lid

Scans 6,239 1790 581 154 Abnormalities 1,288 366 122 24 Average Scans 4.8 4.9 4.8 6.4 Mean (mo) 31.0 26.5 23 26.4 Median (mo) 17 14.1 8.3 12.7 75th percentile (mo) 38.4 36.0 33.8 38.7 90th percentile (mo) 70.9 64.5 64.3 93.8

Ore R, Ueland F, Lefringhouse J, et al. SGO Annual Meeting abstract, 2016

SLIDE 8

9/16/2017 8

Recommended Evaluation

Malignant Risk Low Indeterminate High Distribution 65% 25% 10% US morphology Unilocular

r septate

Partly solid, small wall abnormalities Mostly solid, papillary projections Secondary testing No YES No Surgery No Maybe YES

29 16-Sep-17 30

Indeterminate Risk

Small, irregular wall abnormalities
Partly solid
Atypical, non-papillary projections

31

Tumor type MI score

Malignant

Increase

Non‐malignant

Stable or gradual rise

Resolving

Decrease

Elder J, Pavlik E, Long A et al. Gynecol Oncol 135; 8-12, 2014

Serial Morphology Index

*24 subjects had 1 scan only

N ∆MI MI

P-value

∆MI MI per month

P-value

Surgery for epithelial

varian malignancy

50* 1. 1.9

P<0.001

0.9 0.9

P<0.001

Surgery for non-malignancy 272 0.7 0.7

P<0.001

0.2 0.2

P<0.001

Resolved ovarian cysts 5811

2.7
2.7

P<0.001

1
1.1

P<0.001

SLIDE 9

9/16/2017 9

Recommended Evaluation

Malignant Risk Low Indeterminate High Distribution 65% 25% 10% US morphology Unilocular

r septate

Partly solid, small wall abnormalities Mostly solid, papillary projections Secondary testing No YES No Surgery No Maybe YES

33 16-Sep-17 34

High Risk

Irregular, solid
Papillations
Ascites
ROM >25%
Refer to Gyn