Supplementary Table 1. Diagnostic protocol for screening-detected lung nodules
1. Nodules detected at baseline
Solid or partially solid nodules
Nodules ≤5 mm: LD-CT one year later
Nodules 5.1-8 mm: LD-CT 3 months later
Nodules >8 mm: LD-CT 1 month later after antibiotic treatment; if nodule stable or progressing: PET-CT.
If PET-CT-negative: repeat 3 months later, if CT-PET-positive: biopsy.
Non-solid nodules
Nodules ≤5 mm: LD-CT one year later
Nodules 5.1-8 mm: LD-CT 6 months later
Nodules >8 mm: LD-CT 3 months later after antibiotics. If progressing in diameter or density: surgical
biopsy.
If stable LD-CT 1 year later
2. Nodules detected at subsequent screening rounds
New nodules are managed according to baseline algorithm
Nodules present at previous round are managed as follows:
Solid or partially solid
In progression
5.1-8 mm and VDT >600 days: LD-CT 1 year later
5.1-8 mm and VDT 400-600 days: LD-CT 6 months later
5.1-8 mm and VDT <400 days: LD-CT 3 months later or surgical biopsy
>8 mm and doubling time >600 days: LD-CT 6 months later
>8 mm and doubling time <600 days: surgical biopsy
Non-solid
Progressing in diameter or density, any doubling time
<8 mm: LD-CT 6 months later
>8 mm: surgical biopsy
1
Supplementary Table 2. Characteristics of delayed diagnosis nodules.
Characteristic
Value
Number of cases
14
Mean nodule size at cancer diagnosis (mm)
17.9
Mean nodule size one year before (mm)
8.4
Median VDT (days)
161
Small-cell lung cancers, N (%)
3 (21)
Three additional participants developed interval cancers (all small-cell).
2
Figure 1. Overall and lung cancer-specific survival of patients diagnosed with lung cancer in
screening cohort (42 deaths occurred, 35 attributed to lung cancer after a median follow-up of
5.2 years).
Overall survival
Lung cancer-specific survival
N patients at risk
175 162 151 143 127 97
64
33
N patients at risk
3
175 162 151 143 127 97 64 33 3
Overall survival (95% CI)
1-year
2-year
3-year
Lung cancer specific survival (95% CI)
5-year
93 (89-96) 86 (81-91) 83 (78-89) 78 (72-84)
1-year
2-year
3-year
5-year
93 (89-97) 87 (82-92) 85 (80-90) 82 (76-88)
3
Supplementary Figure 1. Overall survival in 16 screen-detected multifocal lung cancers (all
deaths due to lung cancer)
Overall survival
N patients at risk
16
15 14
13
12 11
7
3
0
Overall survival (95% CI)
1-year
2-year
3-year
5-year
94 (82-100) 88 (71-100) 88 (71-100) 81 (61-100)
4
Supplementary Figure 2. Overall and lung cancer-specific survival according to stage and
disease extent.
Overall survival
Lung cancer-specific survival
N patients at risk
N patients at risk
I
114 114 112 108 94 70
43
23 3
I
114 114 112 108 94 70 43 23 3
II-IV
61
21
10 0
II-IV
61 48 39 35 33 27 21 10 0
48 39
35
33 27
Overall survival (95% CI)
1-year
I
II-IV
100
2-year
3-year
Lung cancer-specific survival (95% CI)
5-year
98 (96-100) 96 (93-100) 91 (86-97)
79 (68-89) 64 (52-76) 59 (47-71) 54 (41-66)
1-year
I
II-IV
100
2-year
3-year
5-year
99 (97-100) 98 (96-100) 95 (91-99)
80 (70-90) 65 (53-77) 60 (48-72) 56 (44-69)
N patients at risk
N patients at risk
N0M0
136 133 130 125 110 85
54
31 3
N0M0
136 133 130 125 110 85 54 31 3
N+/M+
39
10
2
N+/M+
39 29 21 18 17 12 10 2
29 21
18
17 12
0
Overall survival (95% CI)
1-year
2-year
3-year
0
Lung cancer-specific survival (95% CI)
5-year
1-year
2-year
3-year
5-year
N0M0
98 (95-100) 96 (92-99) 94 (90-98) 89 (83-94)
N0M0
99 (96-100) 97 (94-100) 96 (93-99)
93 (88-97
N+/M+
74 (61-88) 54 (38-69) 46 (31-62) 40 (25-56)
N+/M+
74 (61-88) 54 (38-69) 46 (31-62) 43 (27-59)
5
Supplementary Figure 3. Overall survival for 11 patients with second primary
(metachronous) lung cancers (10 were stage 1, with local N0M0 disease at diagnosis).
Overall survival
N patients at risk
11
10 8
6
4
0
0
0
0
Overall survival (95% CI)
1-year
2-year
3-year
91 (74-100) 73 (46-99) 63 (34-92)
5-year
-
6