The Impact of Biopsy Tool Choice and Rapid On-Site Evaluation on Diagnostic Accuracy for Malignant Lesions in the Prospective: Multicenter NAVIGATE Study

Abstract

Background: The diagnostic yield of electromagnetic navigation bronchoscopy (ENB) is impacted by biopsy tool strategy and rapid on-site evaluation (ROSE) use. This analysis evaluates usage patterns, accuracy, and safety of tool strategy and ROSE in a multicenter study.

Methods: NAVIGATE (NCT02410837) evaluates ENB using the superDimension navigation system (versions 6.3 to 7.1). The 1-year analysis included 1215 prospectively enrolled subjects at 29 United States sites. Included herein are 416 subjects who underwent ENB-aided biopsy of a single lung lesion positive for malignancy at 1 year. Use of a restricted number of tools (only biopsy forceps, standard cytology brush, and/or bronchoalveolar lavage) was compared with an extensive multimodal strategy (biopsy forceps, cytology brush, aspirating needle, triple needle cytology brush, needle-tipped cytology brush, core biopsy system, and bronchoalveolar lavage).

Results: Of malignant cases, 86.8% (361/416) of true positive diagnoses were obtained using extensive multimodal strategies. ROSE was used in 300/416 cases. The finding of malignancy by ROSE reduced the total number of tools used. A malignant ROSE call was obtained in 71% (212/300), most (88.7%; 188/212) by the first tool used (49.5% with aspirating needle, 20.2% with cytology brush, 17.0% with forceps). True positive rates were highest for the biopsy forceps (86.9%) and aspirating needle (86.6%). Use of extensive tool strategies did not increase the rates of pneumothorax (5.5% restricted, 2.8% extensive) or bronchopulmonary hemorrhage (3.6% restricted, 1.1% extensive).

Conclusion: These results suggest that extensive biopsy tool strategies, including the aspirating needle, may provide higher true positive rates for detecting lung cancer without increasing complications.

FIGURE 1

Analysis Set. The NAVIGATE US cohort enrolled 1215 consecutive subjects at 29 sites. The current subgroup analysis includes 416 subjects who underwent ENB-aided biopsy of a single lung lesion that was diagnosed as true positive for malignancy as of 12-month follow-up. ENB indicates electromagnetic navigation bronchoscopy.

FIGURE 2

Procedure Time and ROSE Usage. ROSE was available in 72.1% (300/416) of cases overall. A, The use of an extensive biopsy tool strategy did not increase the overall procedure time, regardless of whether ROSE was used. The overall median procedure time (bronchoscope in to bronchoscope out) was 50 minutes. B, Finding of malignancy by ROSE reduced the mean total number of tools used compared with cases without a malignant ROSE call. Among all 416 subjects included in the analysis, a mean of 2.9±1.1 biopsy tools were used (range: 1 to 6 tools). ROSE indicates rapid on-site evaluation.

FIGURE 3

Biopsy tool order. Tool order in subjects with rapid on-site evaluation available (A, n=300) and subjects without rapid on-site evaluation available (B, n=116). BAL indicates bronchoalveolar lavage.

FIGURE 4

Site-specific tool usage. Trending plots in sites enrolling 25 or more subjects, showing the first, second, third, etc., tools used in each case across the x-axis and subject count on the y-axis. Consistently peaked patterns indicate that the same tools were used in the same order for every subject. For example, site 1 used the aspirating needle first, the cytology brush second, and the biopsy forceps third in all 11 subjects that site contributed to the analysis set. In contrast, a more varied pattern was used in site 16, with the first tool being the triple needle cytology brush in 53% of cases, the aspirating needle in 35%, the cytology brush in 6%, and the needle-tipped brush in 6%.

FIGURE 5

Individual tool results. ROSE concordance (A) and true positive rates (B) for individual tools. By design, all lesions included in this analysis were ultimately proven to be positive for malignancy based on final pathology results of the ENB-aided sample. Any individual tool yielding only benign or inconclusive results was considered a false negative while any tool yielding at least one malignant result was considered a true positive. C, Individual impact of each individual tool on multimodality success. Among all 416 subjects with single lesions ultimately proven to be true positive for malignancy, this analysis examines the impact of “ignoring” each tool in turn within the analysis. For example, if only the biopsy forceps yielded a malignant result and all other tools yielded negative results, the overall result for that case would be considered negative when the biopsy tool was ignored in the analysis. The impact of ignoring each tool in turn is shown. For example, within the context of the multimodality sampling strategy, if the biopsy forceps had not been used, 9.3% of true positive malignant cases would have been missed (or in other words, adding biopsy forceps to the tool strategy increased the true positive rate by 9.3%). ROSE indicates rapid on-site evaluation.