The OVA1 Test Improves the Preoperative Assessment of

Ovarian Tumors

Frederick Ueland, Chris Desimone, Leigh Seamon, Rachel Ware, Scott Goodrich, Iwona Podzielinski, Lori Sokoll, Alan Smith, Joseph Santoso, John R. van Nagell Jr., Zhen Zhang.

NIH Consensus Statement1994

“Women with ovarian masses who have been identified preoperatively as having a significant risk of ovarian cancer should be

given the option of having their surgery performed by a gynecologic oncologist”

The OVA1 Test• Biomarker panel

– CA125, transthyretin (prealbumin), apolipoprotein A1beta 2 microglobulin, transferrin

• OvaCalc software algorithm• OVA1 risk index, range 0-10

Premenopausal Postmenopausal

Low Risk < 5.0 < 4.4

High Risk ≥ 5.0 ≥ 4.4

Objectives

Evaluate the performance of the OVA1 test alone, and in conjunction with current clinical parameters, in estimating the risk of malignancy in women scheduled for surgery with an ovarian mass.

Eligibility

• Female subjects age 18 years or older• Agreeable to phlebotomy• Documented ovarian tumor on imaging• Planned surgical intervention within 3 months of

imaging• Signed informed consent

Methods• 27 primary care and specialty sites throughout U.S.• Preoperative evaluation

– imaging to confirm ovarian tumor– serum collection for CA125– physician assessment (cancer? “yes or no”)

• Centralized assay at Quest Diagnostics• Validation assays

– Johns Hopkins– Specialty Laboratories

• Independent data analysis– Applied Clinical Intelligence

Study Population All Subjects

Non-GO Physicians

GO Physicians

Patients 516 269 247Mean age, yr (SD) 52 (14) 50 (14) 55 (14)Median age, yr 52 48 54Range (min, max) 18 to 92 19 to 90 18 to 92

Menopausal Status, n (%)Pre 235 (46%) 144 (54%) 91 (37%)Post 281 (54%) 125 (46%) 156 (63%)

Pathology Diagnosis, n (%)Benign ovarian condition 355 (69%) 197 (73%) 158 (64%)Epithelial ovarian cancer (EOC) 96 (19%) 45 (17%) 51 (21%)Other primary ovarian malignancy 9 (2%) 5 (2%) 4 (2%)Low malignant potential (borderline) 28 (5%) 12 (4%) 16 (6%)

Non-primary ovarian malignancy with involvement of the ovaries

18 (4%) 5 (2%) 13 (5%)

Non-primary ovarian malignancies with no involvement of ovaries

10 (2%) 5 (2%) 5 (2%)

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

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0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1

Tru

e p

osi

tive

rate

(S

en

siti

vit

y)

False positive rate (1-Specificity)

Premenopausal, AUC= 0.80 (95% CI: 0.73-0.88)Postmenopausal, AUC=0.82 (95% CI: 0.77-0.87)

OVA1 Test Alone

Receiving-operator-characteristic Curve

Sensitivity 92%

Specificity 43%

PPV 42%

NPV 93%

Premenopausal Postmenopausal

PerformancePreoperativ

e assessment

Preoperative assessment plus OVA1

Preoperative

assessment

Preoperative assessment plus OVA1

Sensitivity, % 60 89 81 98

95% CI 46 to 73 76 to 95 73 to 87 94 to 100

Specificity, % 83 40 74 28

95% CI 77 to 88 34 to 48 67 to 81 22 to 35

PPV, % 46 26 69 49

95% CI 34 to 58 20 to 34 61 to 76 43 to 55

NPV, % 90 94 85 96

95% CI 84 to 93 86 to 97 78 to 90 86 to 99

Negative Likelihood Ratio

0.48 0.27 0.25 0.06

95% CI 0.33 to 0.69 0.12 to 0.64 0.17 to 0.37 0.02 to 0.25

Prevalence 19% (45/235) 41% (116/281)

non-GO physicians GO physicians

PerformancePreoperativ

e assessment

Preoperative

assessment plus OVA1

Preoperative

assessment

Preoperative assessment plus OVA1

Sensitivity, % 72 92 78 99

95% CI 61 to 81 83 to 96 68 to 85 94 to 100

Specificity, % 83 42 75 26

95% CI 77 to 87 35 to 49 67 to 81 20 to 33

PPV, % 60 36 63 43

95% CI 50 to 70 30 to 44 54 to 72 36 to 50

NPV, % 89 93 86 9895% CI 84 to 93 86 to 97 79 to 90 88 to 100

Negative Likelihood Ratio

0.34 0.20 0.30 0.04

95% CI 0.23 to 0.49 0.09 to 0.44 0.20 to 0.45 0.01 to 0.31

Prevalence 27% (72/269) 36% (89/247)

OVA1 Sensitivity

Tumor subtype Cancer stage

Stage Sensitivity

I 90%

II 100%

III 100%

IV 100%

Epithelial OC 99%

Non EOC 78%

LMP 75%

Metastases 94%

Conclusions

1. The OVA1 test successfully classifies patients into high or low probability of malignancy.

2. OVA1 has high sensitivity in premenopausal women and all stages of epithelial ovarian cancers. These results are independent of physician specialty.

3. When combined with other clinical information, the OVA1 test can help determine the risk of malignancy for an ovarian tumor before surgery, and facilitate decisions about referral to a gynecologic oncologist.