Growing small solid nodules in lung cancer screening: safety and efficacy of a 200 mm3 minimum size threshold for multidisciplinary team referral

Abstract

The optimal management of small but growing nodules remains unclear. The SUMMIT study nodule management algorithm uses a specific threshold volume of 200 mm³ before referral of growing solid nodules to the multidisciplinary team for further investigation is advised, with growing nodules below this threshold kept under observation within the screening programme. Malignancy risk of growing solid nodules of size >200 mm³ at initial 3-month interval scan was 58.3% at a per-nodule level, compared with 13.3% in growing nodules of size ≤200 mm³ (relative risk 4.4, 95% CI 2.17 to 8.83). The positive predictive value of a combination of nodule growth (defined as percentage volume change of ≥25%), and size >200 mm³ was 65.9% (29/44) at a cancer-per-nodule basis, or 60.5% (23/38) on a cancer-per-participant basis. False negative rate of the protocol was 1.9% (95% CI 0.33% to 9.94%). These findings support the use of a 200 mm³ minimum volume threshold for referral as effective at reducing unnecessary multidisciplinary team referrals for small growing nodules, while maintaining early-stage lung cancer diagnosis.

Trial registration: ClinicalTrials.gov NCT03934866.

Keywords: imaging/CT MRI etc; lung cancer.

Figure 1

CONSORT diagram for participants in this analysis. Numbers in italics are nodule volume range (median) in mm³. Participant numbers add up to greater than total due to participants having multiple nodules in different categories +96 growing nodules includes 79 nodules noted at baseline and 17 nodules present but not marked on initial scan and subsequently seen to be growing (‘retronodules’) Ppt, participant.

Figure 2

Outcomes of growing solid nodules >200 mm³ at first interval scan. Numbers given at per-nodule and per-participant level. Numbers in italics are nodule volume range and (median), mm³. ^AProtocol deviation due to radiologist assessment: interpreted as intrapulmonary lymph nodes (n=2) or likely inflammatory (n=5). ^BDefined as VDT >600 days. ^CRadiologists’ decision based on morphology. MDT, multidisciplinary team; ppt, participant; VDT, volume doubling time.

Figure 3

Outcomes of growing solid nodules ≤200 mm³ at first interval scan. Numbers given at per-nodule and per-participant level. ^An=2 growing solid nodule >200 mm³ covered in figure 2, n=1 lymph node mass, n=3 growing part-solid nodules. ^BProtocol deviation due to radiologist interpretation: (likely inflammatory n=2, IPLNs n=7). ^CNo thoracic cancer diagnosis. ^DNon-lung cancer cause of mortality. ^EVDT >600 days. ^FProtocol deviation due to radiologist interpretation (benign morphological appearances n=2, No growth since 3-month scan n=4). ^GSmall cell lung cancer separate to nodule under surveillance. IPLN, intrapulmonary lymph node; MPT, multidisciplinary team; ppt, participant; VDT, volume doubling time.

Figure 4

Panel A: Growing nodule subsequently diagnosed as lung cancer. (A) Baseline scan, volume 42 mm³ (B) 3 months, volume 92 mm³, PVC +117%, VDT 98 days. (C) 6-month scan (performed at 8 months), volume 246 mm³, PVC +168%, VDT 109 days (referred at this time). Panel B: Growth seen at first interval scan, subsequently stable over 2 years. (A) Baseline, volume 82 mm³ (B) 3 months, volume 126 mm³, PVC+53%, VDT 153 days. (C) 6-month scan (performed at 8 months), volume 74 mm³, PVC −41%. (D) 12 months, volume 53 mm³, PVC -28% (E) 24 months, volume 58 mm³. PVC, percentage volume change; VDT, volume doubling time.