Computed tomography monitoring of small lung nodules: finding the right balance

Lung cancer has the highest mortality rate of all cancers worldwide and forecasts predict the same trend with an increase to approximately 3.5 million deaths per year by 2050 (1). The prognosis of lung cancer is significantly associated with the extent of the disease, portrayed by the TNM/UICC classification system. Early-stage lung cancer can be treated curatively with either surgery or stereotactic radiation. In this context, several studies have emerged that investigated screening in high-risk patients, with the goal of enabling curative treatment for patients. Among the biggest were the American National Lung Cancer Trial (2) and the European NELSON Trial (3). Both randomized studies revealed a significant reduction in lung cancer mortality in high-risk patients who underwent screening with low-dose computed tomography (CT) with an average effective dose of approximately 2 mSv, which is less than 70% of a standard CT (2,3). Finding a balance between the risk of radiation-induced cancer and the benefit in terms of cancer mortality reduction through CT monitoring in a real-world setting has already proven to be a difficult task (4,5). In light of this, the current commentary focuses on a subanalysis (6) of the Watch the Spot Trial (4,5).

This sub-analysis (6) investigated the radiation dose used within the above mentioned Trial (4,5) in CT follow-up scans in patients with already detected small pulmonary nodules (≤15 mm) either during screening or incidental chest CT. Altogether 28,639 patients from 22 centers were randomized to follow either more intensive or less intensive monitoring strategy (less and more intensive arm) and patients enrolled at one of these centers followed that center’s monitoring strategy. Of note, one of the twenty-two overall centers was excluded from the radiation dose analysis but was included in the cumulative dose analysis using its observed number of follow-up CTs and the average dose measured at the other sites. In both arms the guidelines that were recommended for CT monitoring depended upon whether the pulmonary nodules were detected on screening or incidental CT scan. In the less intensive study arm, CT monitoring of patients with pulmonary nodules found on screening was performed using the Lung Imaging Reporting and Data System (Lung-RADS) v1.0 guidelines (7), whereas for incidental pulmonal nodules the Fleischner Society 2017 guidelines (8) were applied. In the more intensive arm the CT monitoring of patients with pulmonary nodules found on screening was performed by using an upgraded version (one level higher category than original version) of the Lung-RADS v1.0 guidelines (7), while for patients with pulmonal nodules found on incidental CT scan the Fleischner Society 2005 (9) and 2013 guidelines (10) were used. The study showed that both arms (less intensive vs. more intensive) had almost the same 2-year average cumulative radiation dose from follow-up CT-imaging (18.6 vs. 19.0 mSv, P=0.90), which was much higher than anticipated. To illustrate, 61% of the follow-up CT scans (both arms combined) exceeded the size-adjusted threshold for computed tomography dose index-volume (CTDIvol) of ≤3.0 mGy for low-dose CT scans recommended by the American College of Radiology (ACR) and American Association of Physicists in Medicine (AAPM). In addition, 88% of the follow-up CT scans exceeded the size-adjusted dose-length-product (DLP) recommended threshold of <75 milligray centimeter (mGy·cm) (6). This analysis delivered very important data on radiation exposure in CT follow-up scans in patients with small pulmonary nodules in everyday clinical setting and clearly indicates that radiation doses were much higher than recommended. However, before final conclusions are drawn, there are several issues that have to be critically addressed.

Pragmatic studies are important for understanding how treatments and diagnostic procedures perform in real-world clinical settings and exactly for that reason they have a high degree of external validity. In contrast, their internal validity and ability to assess individual effects are comparatively low (11). In this analysis (6), based on a pragmatic study (4), randomization was not performed at the individual patient level, but cluster-site randomization was used instead, with monitoring recommendations for each centers. These recommendations however were not mandatory. This approach is very much a double-edged sword, on one side it reduces overlap between study arms and on the other it increases practice variation, thereby making an interpretation of the study results limited (11). This becomes evident when one considers the fact that the same number of CT scans were performed in both study arms. This is conflicting because more than 40% of all pulmonary nodules were ≤4 mm in size and another 30% were between 4–6 mm (6). If we assume that these were all high-risk patients with ≤4 mm that were in the less intensive arm (percentage distribution almost the same as above), CT monitoring would have been optional after 12 months in the incidental (8) and mandatory after 12 months (category 2) in the screening pulmonary nodules (7). In contrast, in the more intensive arm, CT monitoring would have been mandatory after 12 months (9) in the incidental and after 6 months in the screening pulmonary nodules (7). So in theory, the less intensive monitoring arm should have had fewer CTs per patient compared to the more intensive one, which potentially would have led to lower cumulative radiation dose, if the protocols would have been followed. Nevertheless, as the study shows, this doesn’t reflect clinical reality and both arms had an average cumulative radiation dose of almost 19.0 mSv.

Even more interesting is the fact that the cumulative size-adjusted DLP was almost the same in both less and more intensive arm (459 vs. 456 mGy·cm), although all of the monitoring guidelines strongly recommend using low-dose CT for surveillance of lung nodules (7-9). DLP is a measure for the total dose across the scanned area (CTDIvol × scan length) and a very useful parameter in assessing radiation dose from CT scans (12,13). The almost equal DLP in both arms can be attributed to multiple reasons, one of which is the potential use of higher settings in the CT protocols. Higher settings are normally selected in order to maximize image quality, frequently done in patients with high BMI especially in modern CTs with automatic exposure control systems (14). This could explain the over-the-threshold CTDIvol in the majority of the follow-up CTs regardless of the study arm. Consequently, this impacts DLP, since it is proportional to CTDIvol. However, when one looks at the range of both measurements (CTDIvol: 4.0–14 mGy; DLP: 157–443 mGy·cm), it is mathematically clear that they are not entirely proportional, which means that other factors also impacted DLP. This could mean that possibly longer ranges than required were scanned and multiphase protocols with contrast may have been applied. A potential reason for this is that specifically CT scans with contrast were indicated because of the individual clinical circumstances of each patient, may that be unrelated medical concerns or symptoms potentially suggestive of progression. The number of CTs with contrast as well as indications for them has not been evaluated in the trial and since they use more scan phases they could very well increase DLP.

Moreover, as we know from everyday clinical environment either the referring physician or the radiologist might be overly cautious and request a higher-quality CT (standard) scan to assess potential changes in the mediastinal lymph nodes, especially in light of suspicious findings from previous CT scan. In addition, some may opt to evaluate the liver and/or adrenal glands for possible metastatic lesions as well. Size is the decisive factor for malignancy stratification, and the malignancy risk is less than 1% for nodules measuring 4–6 mm (9), which makes the risk for metastasis even lower. Therefore, the key factor is assessing the size over time and its dynamics. The contrast between the lung tissue (air/black in CT) and the lung nodules (white in CT) is already by nature extremely high, which makes the edges of the nodules very sharp and clearly detectable in the low-dose CT scan. Consequently, there is no benefit to be expected from a standard CT and even less in one with contrast. In this context, the guidelines are quite clear and recommend that only the lung parenchyma (focus of interest) should be assessed using low-dose CT in the case of small lung nodules (7-10). From an oncological perspective, this also seems sufficient. Furthermore, this is in line with the widely adopted linear-no-threshold (LNT) model, which is the backbone of the as-low-as-reasonably-achievable (ALARA) radiation-protection principle. The LNT postulates that cancer risk increases with dose independent of a minimum dose threshold.

Needless to say, all of the aforementioned factors could have been responsible for the significant increase in DLP compared to the ACR/AAPM recommendations described in the analysis for both arms (6). In hindsight, the appropriateness of these clinical decisions cannot—for lack of information on the individual patient—be conclusively assessed. On top of that, the analysis (6) suggests that some patients may have received additional CT scans at private clinics, which makes it impossible to estimate the full radiation dose. This, however, reflects experiences in everyday clinical setting. Hence, the total radiation dose described in the analysis could have been underestimated (6). Consequently, the results of the analysis (6) may have potentially been subjected to information bias in addition to the potential for confounding by indication and site level practice variation, which could explain the wide range of both CTDIvol and DLP exhibited in the analysis.

In summary, this makes the interpretation of the study results somewhat difficult. Moreover, the question of what is optimal for every individual patient, and whether the benefit-risk ratio in terms of radiation dose exposure is favourable, remains unanswered. Therefore, the study results should be interpreted with a measure of caution. Regardless of that, we congratulate the authors on this splendid analysis (6), which indeed reflects our clinical experience and adds to the notion that recommended low-dose protocols are not consistently followed in everyday clinical environment and thereby underlines the necessity of randomized controlled trial with protocol optimization.

Acknowledgments

None.

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, Translational Cancer Research. The article has undergone external peer review.

Peer Review File: Available at https://tcr.amegroups.com/article/view/10.21037/tcr-2026-0475/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-2026-0475/coif). F.Z. serves as an unpaid editorial board member of Translational Cancer Research from April 2025 to March 2027. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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