Early detection of ovarian cancer using the risk of ovarian cancer algorithm with frequent CA125 testing in women at increased familial risk – Combined results from two screening trials

Steven J. Skates, Mark H. Greene, Saundra S. Buys, Phuong L. Mai, Powel Brown, Marion Piedmonte, Gustavo Rodriguez, John O. Schorge, Mark Sherman, Mary B. Daly, Thomas Rutherford, Wendy R. Brewster, David M. O'Malley, Edward Partridge, John Boggess, Charles W. Drescher, Claudine Isaacs, Andrew Berchuck, Susan Domchek, Susan A. Davidson & 17 others Robert Edwards, Steven A. Elg, Katie Wakeley, Kelly Anne Phillips, Deborah Armstrong, Ira Horowitz, Carol J. Fabian, Joan Walker, Patrick M. Sluss, William Welch, Lori Minasian, Nora K. Horick, Carol H. Kasten, Susan Nayfield, David S Alberts, Dianne M. Finkelstein, Karen H. Lu

Research output: Contribution to journalArticle

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Abstract

Purpose: Women at familial/genetic ovarian cancer risk often undergo screening despite unproven efficacy. Research suggests each woman has her own CA125 baseline; significant increases above this level may identify cancers earlier than standard 6- to 12-monthly CA125 > 35 U/mL. Experimental Design: Data from prospective Cancer Genetics Network and Gynecologic Oncology Group trials, which screened 3,692 women (13,080 woman-screening years) with a strong breast/ovarian cancer family history or BRCA1/2 mutations, were combined to assess a novel screening strategy. Specifically, serum CA125 q3 months, evaluated using a risk of ovarian cancer algorithm (ROCA), detected significant increases above each subject's baseline, which triggered transvaginal ultrasound. Specificity and positive predictive value (PPV) were compared with levels derived from general population screening (specificity 90%, PPV 10%), and stage-at-detection was compared with historical high-risk controls. Results: Specificity for ultrasound referral was 92% versus 90% (P = 0.0001), and PPV was 4.6% versus 10% (P > 0.10). Eighteen of 19 malignant ovarian neoplasms [prevalent ¼ 4, incident = 6, risk-reducing salpingo-oophorectomy (RRSO) = 9] were detected via screening or RRSO. Among incident cases (which best reflect long-term screening performance), three of six invasive cancers were early-stage (I/II; 50% vs. 10% historical BRCA1 controls; P = 0.016). Six of nine RRSO-related cases were stage I. ROCA flagged three of six (50%) incident cases before CA125 exceeded 35 U/mL. Eight of nine patients with stages 0/I/II ovarian cancer were alive at last follow-up (median 6 years). Conclusions: For screened women at familial/genetic ovarian cancer risk, ROCA q3 months had better early-stage sensitivity at high specificity, and low yet possibly acceptable PPV compared with CA125 > 35 U/mL q6/q12 months, warranting further larger cohort evaluation.

Original languageEnglish (US)
Pages (from-to)3628-3637
Number of pages10
JournalClinical Cancer Research
Volume23
Issue number14
DOIs
StatePublished - Jul 15 2017

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Early Detection of Cancer
Ovarian Neoplasms
Ovariectomy
Neoplasms
Research Design
Referral and Consultation
Breast Neoplasms
Mutation
Serum
Research
Population

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Early detection of ovarian cancer using the risk of ovarian cancer algorithm with frequent CA125 testing in women at increased familial risk – Combined results from two screening trials. / Skates, Steven J.; Greene, Mark H.; Buys, Saundra S.; Mai, Phuong L.; Brown, Powel; Piedmonte, Marion; Rodriguez, Gustavo; Schorge, John O.; Sherman, Mark; Daly, Mary B.; Rutherford, Thomas; Brewster, Wendy R.; O'Malley, David M.; Partridge, Edward; Boggess, John; Drescher, Charles W.; Isaacs, Claudine; Berchuck, Andrew; Domchek, Susan; Davidson, Susan A.; Edwards, Robert; Elg, Steven A.; Wakeley, Katie; Phillips, Kelly Anne; Armstrong, Deborah; Horowitz, Ira; Fabian, Carol J.; Walker, Joan; Sluss, Patrick M.; Welch, William; Minasian, Lori; Horick, Nora K.; Kasten, Carol H.; Nayfield, Susan; Alberts, David S; Finkelstein, Dianne M.; Lu, Karen H.

In: Clinical Cancer Research, Vol. 23, No. 14, 15.07.2017, p. 3628-3637.

Research output: Contribution to journalArticle

Skates, SJ, Greene, MH, Buys, SS, Mai, PL, Brown, P, Piedmonte, M, Rodriguez, G, Schorge, JO, Sherman, M, Daly, MB, Rutherford, T, Brewster, WR, O'Malley, DM, Partridge, E, Boggess, J, Drescher, CW, Isaacs, C, Berchuck, A, Domchek, S, Davidson, SA, Edwards, R, Elg, SA, Wakeley, K, Phillips, KA, Armstrong, D, Horowitz, I, Fabian, CJ, Walker, J, Sluss, PM, Welch, W, Minasian, L, Horick, NK, Kasten, CH, Nayfield, S, Alberts, DS, Finkelstein, DM & Lu, KH 2017, 'Early detection of ovarian cancer using the risk of ovarian cancer algorithm with frequent CA125 testing in women at increased familial risk – Combined results from two screening trials', Clinical Cancer Research, vol. 23, no. 14, pp. 3628-3637. https://doi.org/10.1158/1078-0432.CCR-15-2750
Skates, Steven J. ; Greene, Mark H. ; Buys, Saundra S. ; Mai, Phuong L. ; Brown, Powel ; Piedmonte, Marion ; Rodriguez, Gustavo ; Schorge, John O. ; Sherman, Mark ; Daly, Mary B. ; Rutherford, Thomas ; Brewster, Wendy R. ; O'Malley, David M. ; Partridge, Edward ; Boggess, John ; Drescher, Charles W. ; Isaacs, Claudine ; Berchuck, Andrew ; Domchek, Susan ; Davidson, Susan A. ; Edwards, Robert ; Elg, Steven A. ; Wakeley, Katie ; Phillips, Kelly Anne ; Armstrong, Deborah ; Horowitz, Ira ; Fabian, Carol J. ; Walker, Joan ; Sluss, Patrick M. ; Welch, William ; Minasian, Lori ; Horick, Nora K. ; Kasten, Carol H. ; Nayfield, Susan ; Alberts, David S ; Finkelstein, Dianne M. ; Lu, Karen H. / Early detection of ovarian cancer using the risk of ovarian cancer algorithm with frequent CA125 testing in women at increased familial risk – Combined results from two screening trials. In: Clinical Cancer Research. 2017 ; Vol. 23, No. 14. pp. 3628-3637.
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title = "Early detection of ovarian cancer using the risk of ovarian cancer algorithm with frequent CA125 testing in women at increased familial risk – Combined results from two screening trials",
abstract = "Purpose: Women at familial/genetic ovarian cancer risk often undergo screening despite unproven efficacy. Research suggests each woman has her own CA125 baseline; significant increases above this level may identify cancers earlier than standard 6- to 12-monthly CA125 > 35 U/mL. Experimental Design: Data from prospective Cancer Genetics Network and Gynecologic Oncology Group trials, which screened 3,692 women (13,080 woman-screening years) with a strong breast/ovarian cancer family history or BRCA1/2 mutations, were combined to assess a novel screening strategy. Specifically, serum CA125 q3 months, evaluated using a risk of ovarian cancer algorithm (ROCA), detected significant increases above each subject's baseline, which triggered transvaginal ultrasound. Specificity and positive predictive value (PPV) were compared with levels derived from general population screening (specificity 90{\%}, PPV 10{\%}), and stage-at-detection was compared with historical high-risk controls. Results: Specificity for ultrasound referral was 92{\%} versus 90{\%} (P = 0.0001), and PPV was 4.6{\%} versus 10{\%} (P > 0.10). Eighteen of 19 malignant ovarian neoplasms [prevalent ¼ 4, incident = 6, risk-reducing salpingo-oophorectomy (RRSO) = 9] were detected via screening or RRSO. Among incident cases (which best reflect long-term screening performance), three of six invasive cancers were early-stage (I/II; 50{\%} vs. 10{\%} historical BRCA1 controls; P = 0.016). Six of nine RRSO-related cases were stage I. ROCA flagged three of six (50{\%}) incident cases before CA125 exceeded 35 U/mL. Eight of nine patients with stages 0/I/II ovarian cancer were alive at last follow-up (median 6 years). Conclusions: For screened women at familial/genetic ovarian cancer risk, ROCA q3 months had better early-stage sensitivity at high specificity, and low yet possibly acceptable PPV compared with CA125 > 35 U/mL q6/q12 months, warranting further larger cohort evaluation.",
author = "Skates, {Steven J.} and Greene, {Mark H.} and Buys, {Saundra S.} and Mai, {Phuong L.} and Powel Brown and Marion Piedmonte and Gustavo Rodriguez and Schorge, {John O.} and Mark Sherman and Daly, {Mary B.} and Thomas Rutherford and Brewster, {Wendy R.} and O'Malley, {David M.} and Edward Partridge and John Boggess and Drescher, {Charles W.} and Claudine Isaacs and Andrew Berchuck and Susan Domchek and Davidson, {Susan A.} and Robert Edwards and Elg, {Steven A.} and Katie Wakeley and Phillips, {Kelly Anne} and Deborah Armstrong and Ira Horowitz and Fabian, {Carol J.} and Joan Walker and Sluss, {Patrick M.} and William Welch and Lori Minasian and Horick, {Nora K.} and Kasten, {Carol H.} and Susan Nayfield and Alberts, {David S} and Finkelstein, {Dianne M.} and Lu, {Karen H.}",
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TY - JOUR

T1 - Early detection of ovarian cancer using the risk of ovarian cancer algorithm with frequent CA125 testing in women at increased familial risk – Combined results from two screening trials

AU - Skates, Steven J.

AU - Greene, Mark H.

AU - Buys, Saundra S.

AU - Mai, Phuong L.

AU - Brown, Powel

AU - Piedmonte, Marion

AU - Rodriguez, Gustavo

AU - Schorge, John O.

AU - Sherman, Mark

AU - Daly, Mary B.

AU - Rutherford, Thomas

AU - Brewster, Wendy R.

AU - O'Malley, David M.

AU - Partridge, Edward

AU - Boggess, John

AU - Drescher, Charles W.

AU - Isaacs, Claudine

AU - Berchuck, Andrew

AU - Domchek, Susan

AU - Davidson, Susan A.

AU - Edwards, Robert

AU - Elg, Steven A.

AU - Wakeley, Katie

AU - Phillips, Kelly Anne

AU - Armstrong, Deborah

AU - Horowitz, Ira

AU - Fabian, Carol J.

AU - Walker, Joan

AU - Sluss, Patrick M.

AU - Welch, William

AU - Minasian, Lori

AU - Horick, Nora K.

AU - Kasten, Carol H.

AU - Nayfield, Susan

AU - Alberts, David S

AU - Finkelstein, Dianne M.

AU - Lu, Karen H.

PY - 2017/7/15

Y1 - 2017/7/15

N2 - Purpose: Women at familial/genetic ovarian cancer risk often undergo screening despite unproven efficacy. Research suggests each woman has her own CA125 baseline; significant increases above this level may identify cancers earlier than standard 6- to 12-monthly CA125 > 35 U/mL. Experimental Design: Data from prospective Cancer Genetics Network and Gynecologic Oncology Group trials, which screened 3,692 women (13,080 woman-screening years) with a strong breast/ovarian cancer family history or BRCA1/2 mutations, were combined to assess a novel screening strategy. Specifically, serum CA125 q3 months, evaluated using a risk of ovarian cancer algorithm (ROCA), detected significant increases above each subject's baseline, which triggered transvaginal ultrasound. Specificity and positive predictive value (PPV) were compared with levels derived from general population screening (specificity 90%, PPV 10%), and stage-at-detection was compared with historical high-risk controls. Results: Specificity for ultrasound referral was 92% versus 90% (P = 0.0001), and PPV was 4.6% versus 10% (P > 0.10). Eighteen of 19 malignant ovarian neoplasms [prevalent ¼ 4, incident = 6, risk-reducing salpingo-oophorectomy (RRSO) = 9] were detected via screening or RRSO. Among incident cases (which best reflect long-term screening performance), three of six invasive cancers were early-stage (I/II; 50% vs. 10% historical BRCA1 controls; P = 0.016). Six of nine RRSO-related cases were stage I. ROCA flagged three of six (50%) incident cases before CA125 exceeded 35 U/mL. Eight of nine patients with stages 0/I/II ovarian cancer were alive at last follow-up (median 6 years). Conclusions: For screened women at familial/genetic ovarian cancer risk, ROCA q3 months had better early-stage sensitivity at high specificity, and low yet possibly acceptable PPV compared with CA125 > 35 U/mL q6/q12 months, warranting further larger cohort evaluation.

AB - Purpose: Women at familial/genetic ovarian cancer risk often undergo screening despite unproven efficacy. Research suggests each woman has her own CA125 baseline; significant increases above this level may identify cancers earlier than standard 6- to 12-monthly CA125 > 35 U/mL. Experimental Design: Data from prospective Cancer Genetics Network and Gynecologic Oncology Group trials, which screened 3,692 women (13,080 woman-screening years) with a strong breast/ovarian cancer family history or BRCA1/2 mutations, were combined to assess a novel screening strategy. Specifically, serum CA125 q3 months, evaluated using a risk of ovarian cancer algorithm (ROCA), detected significant increases above each subject's baseline, which triggered transvaginal ultrasound. Specificity and positive predictive value (PPV) were compared with levels derived from general population screening (specificity 90%, PPV 10%), and stage-at-detection was compared with historical high-risk controls. Results: Specificity for ultrasound referral was 92% versus 90% (P = 0.0001), and PPV was 4.6% versus 10% (P > 0.10). Eighteen of 19 malignant ovarian neoplasms [prevalent ¼ 4, incident = 6, risk-reducing salpingo-oophorectomy (RRSO) = 9] were detected via screening or RRSO. Among incident cases (which best reflect long-term screening performance), three of six invasive cancers were early-stage (I/II; 50% vs. 10% historical BRCA1 controls; P = 0.016). Six of nine RRSO-related cases were stage I. ROCA flagged three of six (50%) incident cases before CA125 exceeded 35 U/mL. Eight of nine patients with stages 0/I/II ovarian cancer were alive at last follow-up (median 6 years). Conclusions: For screened women at familial/genetic ovarian cancer risk, ROCA q3 months had better early-stage sensitivity at high specificity, and low yet possibly acceptable PPV compared with CA125 > 35 U/mL q6/q12 months, warranting further larger cohort evaluation.

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