Randomized Study on Early Detection of Lung Cancer with MSCT in Germany: Results of the First 3 Years of Follow-up After Randomization

Abstract

Introduction:The German Lung Cancer Screening Intervention Trial (LUSI) is one of the European randomized trials investigating the efficacy of low-dose multislice computed tomography (MSCT) as a screening tool for lung cancer. In the evaluation of the first (prevalence) screening round, we observed exceptionally high early recall rates, which made the routine application of MSCT screening questionable. Because screening may behave differently in subsequent (incidence) screening rounds, we analyzed (a) basic characteristics for the annual rounds 2 to 4, which have now also been completed, and (b) the first 3 years with complete follow-up since time of randomization. Methods: Data material was the data record of LUSI after the fourth screening round and the 3-year follow-up had been completed. Basic characteristics of screening, e.g., early recall rate, detection rate, and interval cancers as well of proportion of advanced cancers, were descriptively evaluated and, if informative, group differences were tested for statistical significance. Results: Early recall rates were significantly lower in the subsequent screening rounds than in the first one if the MSCT information from the previous screening rounds was available. Detection and biopsy rates were approximately 1% or lower, ratio of benign:malignant biopsies: 1:1.6 to 1:3. Conclusion: Our recent data may not only settle one concern regarding high recall rates in routine MSCT screening but also indicate that screening must be strictly organized to be effective. Performance indicators are similar to those in mammography screening. Nevertheless, possible consequences for the participants (diagnostic workup of suspicious findings, biopsies) are more invasive than in mammography screening.

Low-dose computed tomography for lung cancer screening: comparison of performance between annual and biennial screen

“…The higher recall rate at T0 in both LDCT arms was also observed by other European studies and NLST [15,17,18]. However, the recall rates across the screening rounds of MILD (1-15 % in LDCT1 and 3.1-14 % in LDCT2) were lower than those reported by the other studies (3.8-27.9 %) [15,17,18].…”

“…However, the initial detection rate in LDCT2 (0.52) was lower than those reported by other trials (0.8-2.2 %), and increased among participants shifted into the LDCT2 arm with annual follow-up, as compared to those who remained in the arm with biennial follow-up. [17,18]. This finding suggests that a tighter follow-up would be more appropriate for participants with indeterminate or positive findings, despite negative initial diagnostic workup.…”

“…Importantly, we found that the detection rate of early stage lung cancers was similar between the LDCT arms. This is important, as the proportion of early stage cancers is considered a surrogate measure for the effectiveness of screening, since effective screening should detect and eradicate cancers in an early state before they can grow into advanced stage [18].…”

Screen-detected multiple primary lung cancers in the ITALUNG trial

“…At least one subject with MPLC was reported in 11/33 studies (5,13-18,24-35), with a mean cumulative frequency of 0.18% (136 subjects) in 71,901 screenees and of 11.6% in 1,170 subjects with at least one screen-detected lung cancer (19)(20)(21)(22)(23)(36)(37)(38)(39)(40)(41)(42)(43)(44). The MPLC were considered synchronous in 123/136 (90%) subjects and metachronous in 13 (10%).…”

Recommendations on screening for lung cancer

“…Three low-quality trials compared annual screening with low-dose CT to no screening or usual care and found no difference in lung cancer-specific mortality (RR 1.30, 95% CI 0.81-2.11) or all-cause mortality (RR 1.38, 95% CI 0.86-2.22) after five years or less of followup. 12 A recent update of the literature search found one randomized study 15 presenting interim results on early detection of lung cancer with low-dose multislice CT (compared with no screening) in Germany after five years of follow-up. The addition of these new results to the all-cause mortality analysis did not significantly alter the results (RR 1.20, 95% CI 0.83-1.73).…”