BOSS trial

The BOSS trial (Barrett’s Oesophagus Surveillance Study) was a landmark randomized controlled trial designed to evaluate whether scheduled endoscopic surveillance improves survival outcomes in patients with Barrett's esophagus compared to symptom-driven or "at-need" endoscopy. Below is a detailed summary of the trial:

### **Purpose and Background**

The primary aim of the BOSS trial was to determine if routine, scheduled surveillance endoscopy leads to better survival outcomes for patients with Barrett's esophagus, a condition that can increase the risk of developing esophageal adenocarcinoma (EAC). Historically, guidelines recommended regular surveillance for Barrett’s esophagus, based on an assumed annual progression rate to EAC of 1%. However, this trial sought to challenge that assumption and provide evidence-based guidance on the necessity of routine surveillance.

### **Study Design**

• **Participants:** 3453 patients diagnosed with Barrett’s esophagus.
• **Randomization:** Patients were randomized into two groups:

1. **Surveillance group:** Underwent scheduled endoscopy every 2 years.

2. **At-need group:** Underwent endoscopy only when clinically indicated by symptoms (e.g., dysphagia, bleeding, or other signs of disease progression).

• **Follow-up:** Median follow-up duration was 12.8 years, making it one of the longest trials for Barrett’s esophagus.
• **Centers:** Conducted across 109 centers in the UK.

### **Key Findings**

1. **Overall Survival:**

• No significant difference in overall survival between the two groups.
• Surveillance group: 19.2% deaths.
• At-need group: 20.7% deaths.
• Hazard ratio (HR): 0.95 (95% CI 0.82–1.10; P = .503).

2. **Cancer-Specific Survival:**

• No significant difference in cancer-related mortality.
• Surveillance group: 108 deaths.
• At-need group: 106 deaths.
• HR: 1.01 (95% CI 0.77–1.33).

3. **Esophageal Adenocarcinoma (EAC) Incidence:**

• EAC was diagnosed in 71 patients (2.1% of the cohort).
• Surveillance group: 40 cases.
• At-need group: 31 cases.
• Routine surveillance did not significantly reduce EAC incidence.

4. **Cancer Stage at Diagnosis:**

• The stage distribution of EAC was similar between groups.
• A slightly higher proportion of T1a cancers (early-stage) was detected in the surveillance arm, but this difference was not statistically significant.

5. **Adverse Events:**

• Serious endoscopy-related adverse events were rare and comparable between groups:
• Surveillance group: 0.46%.
• At-need group: 0.41%.

6. **Endoscopy Burden:**

• Surveillance patients underwent significantly more endoscopies:
• Surveillance group: 6124 procedures.
• At-need group: 2424 procedures.
• This translated to a 1.62-fold higher rate of procedures in the surveillance arm, with no corresponding survival benefit.

7. **Risk of EAC Progression:**

• The annual risk of developing EAC in the cohort was only 0.23% per year, far lower than the previously assumed rate of 1%.

8. **Impact by Age:**

• Subgroup analysis suggested a possible survival benefit for patients aged >65 years (HR 0.74, 95% CI 0.60–0.91), but no benefit was observed for younger patients. This finding requires cautious interpretation.

9. **Quality of Detection:**

• Surveillance increased detection of dysplasia (low-grade dysplasia [LGD] and high-grade dysplasia [HGD]), but this did not translate into reduced EAC incidence or mortality.

10. **Exit Endoscopy Findings:**

• At the end of the trial, additional endoscopies in the at-need group identified 8 cases of EAC and 9 cases of HGD, highlighting that delayed detection did not impact overall survival.

### **Conclusions**

• **Limited Benefit of Routine Surveillance:** Scheduled surveillance for nondysplastic Barrett’s esophagus did not improve overall survival or cancer-specific survival compared to symptom-triggered endoscopy.
• **Low Risk of Malignant Progression:** The annual progression rate to EAC was much lower than previously thought (0.23% vs the assumed 1%).
• **Guideline Implications:** The findings challenge current global guidelines recommending routine surveillance for nondysplastic Barrett’s esophagus, particularly for low-risk patients or those with short-segment Barrett’s esophagus.
• **Resource Utilization:** Routine surveillance programs may overuse healthcare resources without providing clear survival benefits.
• **Tailored Approach:** The study supports tailoring surveillance intervals or adopting “at-need” endoscopy for low-risk patients with Barrett’s esophagus.

### **Historical Context**

When the trial began in 2009, the prevailing belief was that Barrett’s esophagus carried a substantial risk of progression to EAC, warranting frequent surveillance. The BOSS trial has since reshaped this understanding, demonstrating that malignant progression is much rarer than previously estimated.

### **Real-World Representation**

The study's participants closely mirrored real-world Barrett’s populations:

• Mean age: 63 years.
• Gender: 71% male.
• Approximately 94% of participants were on proton pump inhibitors (PPIs), reflecting typical clinical management of Barrett’s esophagus.

### **Clinical Implications**

The BOSS trial provides robust evidence against routine surveillance for nondysplastic Barrett’s esophagus, particularly in low-risk patients. It reinforces the need for a more individualized approach to management, balancing the procedural burden against the actual risk of progression to EAC. For patients over 65 years, further research may be needed to explore potential age-related benefits.

### **Guideline Recommendations**

The trial’s findings suggest reconsideration of current guidelines advocating routine surveillance for nondysplastic Barrett’s esophagus, with a focus on risk stratification and resource optimization.

In summary, the BOSS trial represents a pivotal moment in the management of Barrett’s esophagus, offering long-term data to guide evidence-based clinical practice.