What is the critical appraisal of the Step-Up trial for Bronchial Thermal Vapor Ablation (BTVA)?

Critical Appraisal of the STEP-UP Trial for Bronchial Thermal Vapor Ablation (BTVA)

The STEP-UP randomized controlled trial demonstrates that Bronchial Thermal Vapor Ablation (BTVA) is an effective treatment option for emphysema patients with collateral ventilation who would not benefit from valve therapy, showing significant improvement in lung function with acceptable safety profile. 1

Study Design and Population

The STEP-UP trial was a randomized controlled study specifically evaluating BTVA in emphysema patients, with particular attention to those with collateral ventilation (CV+). Key design elements include:

• Post-hoc fissure analysis of baseline CT scans using VIDA Diagnostics Apollo software
• Patients classified as CV+ if either treated upper lobe was adjacent to a fissure <90% complete
• 78% (35/45) of treatment arm patients and 79% (19/24) of control arm patients were CV+
• Primary endpoints: FEV1 and St. George's Respiratory Questionnaire (SGRQ-C)

Efficacy Outcomes

The trial demonstrated clinically meaningful improvements in the CV+ population:

• At 12 months, FEV1 improved by 9.2% in the treatment arm compared to a 5.4% decrease in the control group
• This resulted in a significant between-group difference of 14.6% (p=0.0137)
• SGRQ-C showed an improvement of 8.4 points compared to control (p=0.0712), approaching but not reaching statistical significance
• These results are particularly important as they represent improvements in both objective lung function and patient-reported quality of life

Safety Profile

The safety analysis revealed:

• Increased respiratory-related serious adverse events immediately following treatment
• Most adverse events resolved with routine care
• The risk-benefit profile appears favorable given the improvements in lung function and quality of life

Strengths of the Study

1. Addressed a critical unmet need for emphysema patients with collateral ventilation who cannot benefit from valve therapy
2. Used validated objective measures (FEV1) and patient-reported outcomes (SGRQ-C)
3. Demonstrated sustained benefits at 12 months, suggesting durability of treatment effect
4. Included rigorous CT analysis for fissure completeness assessment

Limitations of the Study

1. Post-hoc analysis rather than pre-specified subgroup analysis
2. Relatively small sample size in the CV+ subgroup analysis
3. SGRQ-C improvement approached but did not reach statistical significance (p=0.0712)
4. Open-label design potentially introducing bias in subjective outcomes

Clinical Implications

BTVA represents an important therapeutic option for emphysema patients with collateral ventilation, who previously had limited treatment options. The STEP-UP trial provides evidence that:

• BTVA can achieve meaningful improvement in lung function in CV+ patients
• The procedure has an acceptable safety profile with manageable adverse events
• This approach fills a significant gap in the treatment algorithm for advanced emphysema

Algorithmic Approach to Patient Selection for BTVA

1. Confirm emphysema diagnosis with pulmonary function tests and CT imaging
2. Assess fissure completeness using quantitative CT analysis
3. Identify patients with collateral ventilation (fissures <90% complete)
4. Evaluate upper lobe predominant disease pattern
5. Assess patient's ability to tolerate potential post-procedure adverse events
6. Proceed with BTVA in appropriate candidates

The STEP-UP trial provides compelling evidence that BTVA is a viable solution for emphysema patients with collateral ventilation, offering clinically meaningful improvements in both lung function and quality of life with an acceptable safety profile.