TY - JOUR

T1 - The Advantage of Discordance

AU - Dalton, Leslie W.

AU - Gerds, Thomas A.

PY - 2017/1

Y1 - 2017/1

N2 - Discordance among multiple assessments has been a reason to criticize a biomarker. But, if different assessments are all relevant, the meaning of discordance requires explanation. As an example, for 1085 breast cancers, a low (score 1), intermediate (score 2) or high nuclear grade (NG) (score 3) was assigned in years 2013, 2015, 2016. Year apart readings allowed for memory lapse of prior readings. For each cancer, scores for NG2013, NG2015, NG2016 were added together to yield sum score nuclear grade (SSNG) with range 3 to 9. SSNG was used to find if discrepancy between NG readings carried information for patient outcome. Discrepancies were inherent with SSNG=4, 5, 7 or 8. Time-dependent receiver operator curves were central for evaluating discordance as related to patient outcome. Area under curves for SSNG, and the component NGs, in stage 1, stage 2, and stage 3 cancers were, respectively: SSNG: 70, 68, 75; NG2013: 70, 63, 71; NG2015: 67, 65, 74; and NG2016: 65, 66, 68. The area under curves of SSNG was not significantly lower than any of the components from which it was derived. This is despite discordant readings having been incorporated into SSNG. Among the 3 readings, 50.1% were discordant, yet only 2.1% were low/high discrepancy. Concordance in high-grade assignment (SSNG=9) corresponded to poor prognosis. If morphologic features are midway between 2 predefined levels it is sensible that separate readings will be distributed between adjacent levels. Shown has been how an "in-between" level helps predict survival then discordance discovery offers classification. Discordance discovery can conceivably be embraced for real-world applications.

AB - Discordance among multiple assessments has been a reason to criticize a biomarker. But, if different assessments are all relevant, the meaning of discordance requires explanation. As an example, for 1085 breast cancers, a low (score 1), intermediate (score 2) or high nuclear grade (NG) (score 3) was assigned in years 2013, 2015, 2016. Year apart readings allowed for memory lapse of prior readings. For each cancer, scores for NG2013, NG2015, NG2016 were added together to yield sum score nuclear grade (SSNG) with range 3 to 9. SSNG was used to find if discrepancy between NG readings carried information for patient outcome. Discrepancies were inherent with SSNG=4, 5, 7 or 8. Time-dependent receiver operator curves were central for evaluating discordance as related to patient outcome. Area under curves for SSNG, and the component NGs, in stage 1, stage 2, and stage 3 cancers were, respectively: SSNG: 70, 68, 75; NG2013: 70, 63, 71; NG2015: 67, 65, 74; and NG2016: 65, 66, 68. The area under curves of SSNG was not significantly lower than any of the components from which it was derived. This is despite discordant readings having been incorporated into SSNG. Among the 3 readings, 50.1% were discordant, yet only 2.1% were low/high discrepancy. Concordance in high-grade assignment (SSNG=9) corresponded to poor prognosis. If morphologic features are midway between 2 predefined levels it is sensible that separate readings will be distributed between adjacent levels. Shown has been how an "in-between" level helps predict survival then discordance discovery offers classification. Discordance discovery can conceivably be embraced for real-world applications.

KW - breast

KW - cancer

KW - concordance

KW - discordance

KW - discrepancy

KW - grade

KW - kappa

KW - Nottingham

KW - reproducibility

U2 - 10.1097/PAS.0000000000000886

DO - 10.1097/PAS.0000000000000886

M3 - Journal article

C2 - 28614207

AN - SCOPUS:85020704123

VL - 41

SP - 1105

EP - 1111

JO - Diagnostic Molecular Pathology

JF - Diagnostic Molecular Pathology

SN - 1052-9551

IS - 8

ER -