Table 3.
Screening Performance Characteristics
| Screen Type | Total Screened Population (N = 3,563) |
BRCA1 and BRCA2 Mutation Carriers (n = 538) |
Unknown Mutation Status at Enrollment (n = 3,065) |
LS Mutation or Family History (n = 99) |
||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Prevalent |
Incident* |
Incident† |
Prevalent |
Incident‡ |
Prevalent |
Incident* |
Incident† |
Prevalent |
Incident |
|||||||||||
| % | 95% CI | % | 95% CI | % | 95% CI | % | 95% CI | % | 95% CI | % | 95% CI | % | 95% CI | % | 95% CI | % | 95% CI | % | 95% CI | |
| Sensitivity | ||||||||||||||||||||
| Occult FN | 90.0 | 55.5 to 99.8 | 81.3 | 54.3 to 96.0 | 76.5 | 50.1 to 93.2 | 85.7 | 42.1 to 99.6 | 76.9 | 46.2 to 95.0 | NA§ | 91.7 | 61.5 to 99.8 | 75.0 | 19.4 to 99.4 | 100 | 29.2 to 100 | 100 | 2.5 to 100 | |
| Occult TP | 100 | 69.2 to 100 | 87.5 | 61.7 to 98.5 | 82.4 | 56.6 to 96.2 | 100 | 59.0 to 100 | 91.7 | 61.5 to 99.8 | NA§ | 100 | 73.5 to 100 | 75.0 | 19.4 to 99.4 | 100 | 29.2 to 100 | 100 | 2.5 to 100 | |
| Specificity∥ | 99.7 | 99.5 to 99.9 | 98.9 | 98.5 to 99.2 | 98.9 | 98.5 to 99.2 | 99.2 | 98.0 to 99.8 | 99.2 | 97.9 to 99.8 | 99.7 | 99.4 to 99.8 | 99.8 | 98.3 to 99.2 | 99.8 | 98.3 to 99.2 | 100 | 96.1 to 100 | 100 | 96.1 to 100 |
| PPV | ||||||||||||||||||||
| Occult FN | 42.9 | 21.8 to 66.0 | 25.5 | 14.3 to 40.0 | 25.5 | 14.3 to 40.0 | 60.0 | 26.2 to 87.8 | 71.4 | 41.9 to 91.6 | NA§ | 23.9 | 12.6 to 38.8 | 23.9 | 12.6 to 38.8 | 100 | 29.2 to 100 | 100 | 2.5 to 100 | |
| Occult TP | 45.4 | 24.4 to 67.8 | 27.0 | 15.6 to 41.0 | 27.0 | 15.6 to 41.0 | 63.6 | 30.1 to 89.1 | 73.3 | 44.9 to 92.2 | NA§ | 25.5 | 14.0 to 40.3 | 25.5 | 14.0 to 40.3 | 100 | 29.2 to 100 | 100 | 2.5 to 100 | |
| NPV | ||||||||||||||||||||
| Occult FN | 100 | 99.8 to 100 | 99.9 | 99.8 to 100 | 99.9 | 99.7 to 100 | 99.8 | 98.9 to 100 | 99.4 | 98.2 to 99.9 | 99.9 | 99.8 to 100 | 99.9 | 99.7 to 100 | 100 | 99.8 to 100 | 100 | 96.1 to 100 | 100 | 96.1 to 100 |
| Occult TP | 100 | 99.9 to 100 | 99.9 | 99.8 to 100 | 99.9 | 99.8 to 100 | 100 | 99.3 to 100 | 99.6 | 98.5 to 100 | 99.9 | 99.8 to 100 | 100.00 | 99.9 to 100 | 100 | 99.8 to 100 | 100 | 96.1 to 100 | 100 | 96.1 to 100 |
| Screen Type | Prior Study for Comparison24¶
|
||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Occult Status | No. of Cancers |
Sensitivity |
Specificity |
PPV |
NPV |
||||||
| Total | Prevalent | % | 95% CI | % | 95% CI | % | 95% CI | % | 95% CI | ||
| Incident plus prevalent | Occult excluded | 7 | 2 | 42 | 14 to 70 | 99 | 98 to 99 | 23 | 5 to 40 | 99 | 99 to 100 |
| Incident plus prevalent | Occult FN | 12 | 2 | 71 | 38 to 11 | 99 | 98 to 99 | 23 | 5 to 40 | 100 | 100 to 100 |
Abbreviations: FN, false negative; LS, Lynch syndrome; NA, not applicable; NPV, negative predictive value; PPC, primary peritoneal cancer; PPV, positive predictive value; TP, true positive.
*
Excluding PPC.
†
Including PPC.
‡
No PPCs in BRCA carriers occurred within 1 year of prior screen.
§
Not applicable because no prevalent cancers occurred in unknown mutation status group.
∥
Occult cancers not applicable (specificity does not depend on false-negative or true-positive rate).
¶
Only large prior study to our knowledge with data reported in a fashion that allows some comparison of performance characteristics with our study.