| Study | Nodule measurement | Positive non-calcified nodule# | Evaluation of non-calcified lesion according to nodule size | Growth criteria for malignancy | New nodule or change or repeat CT | Decision of work-up |
| Single-arm trials | ||||||
| Swensen [21], [22], 2003, 2005 | Average of the largest and perpendicular transverse diameters | Any | Recommended: >4 mm: repeat CT in 6 months 4–7 mm: repeat CT in 3 months 8–20 mm: CT nodule enhancement protocol or PET >20 mm: CT, PET biopsy or removal indicated | NR | NR | Letter with recommendations from investigators to patient and physician |
| Pastorino [27], 2003; Veronesi [28], 2010 | Maximum diameter | >5 mm | >5 mm: thin-section CT of 1 mm with 3D analysis and contrast enhancement if density of >0 HU If ≥7 mm: also PET If ≥7 mm with positive contrast enhancement or positive PET: biopsy | NR | NR | Recommendations were made according to protocol by the radiologists |
| Henschke [19], 2006 (IELCAP) | Average of length and width | Solid >5 mm; non-solid >8 mm | Recommended: 5–14 mm: repeat CT in 3 months or PET; if growth or PET positive: biopsy or FNA >14 mm: biopsy or PET or repeat CT in 3 months | NR | <3 mm: repeat CT in 6 months 3–5 mm: repeat CT 3 months >5 mm: antibiotics for 2 weeks; repeat CT 1 month No resolution or growth: biopsy or PET; if negative, repeat CT 3 months | By patient and physician |
| Veronesi [23], [24], 2008 | Maximum axial diameter | >5 mm | 5.1–8 mm: repeat CT in 3 months >8 mm (unless clearly benign appearance): PET or enhancement CT | VDT 30–400 days | If <8 mm: PET or enhancement CT Benign characteristics: repeat CT in 3 months | MDT |
| Suspected malignancy: diagnostic procedure Suspected infection: antibiotics for 10 days, repeat CT in 1–3 months | ||||||
| Wilson [25], 2008 (PLuSS) | Average of the largest and perpendicular transverse diameters | >5 mm | Recommended: ≤4 mm: during first year repeat CT in 6 months, no further evaluation 5–9 mm without spiculations: CT or PET or repeat CT in up to 3 months 5–9 mm with spiculations or >9 mm: diagnostic procedure | Increase in size or density or any other suspicious change | NR | MDT written report with recommendations sent to patient and personal physician |
| Menezes [26], 2010 | According to IELCAP protocol | 5–14 mm: repeat CT in 3 months ≥15 mm: biopsy or antibiotics and repeat CT in 1 month | Any | <3 mm: repeat CT in 6 months 3–5 mm: repeat CT in 3 months >5 mm: repeat CT in 1 month | NR | |
| Randomised controlled trials | ||||||
| DANTE [29], [30], 2008, 2009 | Diameter | ≥10 mm; <10 mm with spiculated margins | Recommended: 6–9 mm with smooth surface: repeat CT in 3, 6, 12 months 6–9 mm: antibiotics; HRCT after 6–8 weeks; if no regression, a case-by-case evaluation and consideration of invasive procedure 10–20 mm: HRCT after 6–8 weeks; if no regression, PET or case-by-case evaluation and consideration of invasive procedure >20 mm: oral antibiotics and HRCT or standard contrast-enhanced CT and PET scan; if positive: diagnostic procedure | NR | Case-by-case evaluation | By clinician |
| DLCST [31], [32], 2009, 2012 | Maximal diameter | >4 mm except if benign characteristics | 5–15 mm: repeat CT in 3 months >15 mm: diagnostic procedure | Increase in volume by 25%: diagnostic procedure | NR | Conferences between a pulmonologist and the radiologists |
| NELSON [34], [47], [48], 2006, 2009, 2013 | Volume (automated software) | NODCAT 3–4: solid or solid component: >50 mm3; solid, pleural based: 5 mm; non-solid, pure or component: ≥8 mm | NODCAT 3: repeat CT at 3 months; if no growth, annual repeat CT in 8–9 months NODCAT 4: volume >500 mm3 or pleural based >10 mm: diagnostic procedure | VDT <400 days or new solid component in a non-solid lesion: diagnostic procedure | NODCAT 3: repeat CT in 6–8 weeks; if growth, refer to chest physician NODCAT 4: refer to chest physician | MDT |
| ITALUNG [36], [37], 2009, 2013 | Mean diameter | Solid: 5 mm; non-solid: 10 mm; any part-solid nodule | 5–7 mm: repeat CT in 3 months; if growth, PET or tissue diagnosis ≥8 mm: PET; if positive, FNA; if negative, CT in 3 months Inflammatory appearance: repeat CT in 1 month; if no complete resolution, repeat CT in 2 months or PET and consider diagnostic procedure | ≥1 mm | ≤3 mm: repeat CT in 6 months >3 to <5 mm: repeat CT in 3 months ≥5 mm or inflammatory appearance: antibiotics, repeat CT in 1 month; if no complete resolution, repeat CT in 2 months Pure non-solid ≥10 mm or new non-solid or part solid ≥8 mm: if persisted after antibiotics, CT-guided FNAB | Not specified |
| LSS [38], [39], 2004, 2005 | Diameter (NR) | ≥4 mm or any spiculated nodule | No protocol | No protocol | No protocol | Evaluation by healthcare provider, referral to specialist was optional |
| NLST [41]–[43], 2011, 2013 | Maximum diameter | ≥4 mm | No uniform protocol¶ | No uniform protocol¶ | No uniform protocol¶ | Recommendations were sent to patients by NLST radiologists; evaluation by healthcare provider |
| MILD [45], 2012 | Volume or diameter | ≥60 mm3 or ≥4.8 mm | 60–250 mm3 or 5–8 mm: repeat CT in 3 months 250 mm3: PET and/or biopsy | Volume >25% in 3 months: further evaluation | NR | Not specified |
| LUSI [46], 2012 | Average of length and width (according to IELCAP protocol) | ≥5 mm | 5–7 mm: repeat CT in 6 months for VDT measurement 8–10 mm: repeat CT in 3 months for VDT measurement >10 mm: highly suspicious for malignancy, immediate recall; if not, repeat CT in 3 months | VDT 400–600 days or VDT ≤400 days and nodule diameter >10 mm: immediate recall | No specific protocol; evaluated by office-based pulmonologist | Reports were sent to participants to contact a physician of choice for further advice |
PET: positron emission tomography; NR: not reported; FNA: fine-needle aspiration; VDT: volume doubling time; MTD: multidisciplinary team; HRCT: high-resolution CT; NODCAT: nodule category (based on size). #: or suspicious calcification such as speckled or peripheral; ¶: some centres developed practice guidelines.