Noordman BJ, et al. - Researchers assessed the accuracy of different diagnostic approaches for detecting residual disease after neoadjuvant chemoradiotherapy for esophageal cancer. They also tried to determine the optimal combination of diagnostic techniques for clinical response evaluations. They found that, for the detection of locoregional residual disease following neoadjuvant chemoradiotherapy for esophageal cancer, the endoscopic ultrasonography, bite-on-bite biopsies, and fine-needle aspiration of suspicious lymph nodes was adequate for clinical response assessment, with PET–CT for detection of interval metastases.

Methods

• A prospective, multicenter, diagnostic cohort study, the preSANO trial, was conducted at six centers in the Netherlands.
• The following patients were eligible for inclusion in the study: patients aged 18 years or older, had histologically proven, resectable, squamous cell carcinoma or adenocarcinoma of the esophagus or esophagogastric junction, and were eligible for potential curative therapy with neoadjuvant chemoradiotherapy (five weekly cycles of carboplatin [area under the curve 2 mg/mL per min] plus paclitaxel [50 mg/m² of body-surface area] combined with 41.4 Gy radiotherapy in 23 fractions) followed by esophagectomy.
• Neoadjuvant chemoradiotherapy was administered for 4–6 weeks, followed by esophagogastroduodenoscopy with biopsies and endoscopic ultrasonography with measurement of maximum tumor thickness.
• Immediate surgical resection was performed in patients with histologically proven locoregional residual disease or no-pass during endoscopy and without distant metastases.
• A second clinical response evaluation was carried out in the remaining patients (PET–CT, esophagogastroduodenoscopy with biopsies, endoscopic ultrasonography with measurement of maximum tumor thickness, and fine-needle aspiration of suspicious lymph nodes), with surgery 12–14 weeks after completion of neoadjuvant chemoradiotherapy.
• The primary endpoint was the correlation between clinical response during clinical response evaluations and the final pathological response in resection specimens, as shown by the proportion of tumor regression grade (TRG) 3 or 4 (>10% residual carcinoma in the resection specimen) residual tumors that was missed during clinical response evaluations.

Results

• A total of 219 patients were included between July 22, 2013 and Dec 28, 2016, and researchers analyzed 207 of these patients.
• Endoscopy with regular biopsies and fine-needle aspiration missed eight of 26 TRG3 or TRG4 tumors (31% [95% CI 17–50]).
• Bite-on-bite biopsies and fine-needle aspiration missed four of 41 TRG3 or TRG4 tumors (10% [95% CI 4–23]).
• TRG3 or TRG4 residual tumors in 11 of 39 patients (28% [95% CI 17–44]) were missed by endoscopic ultrasonography with maximum tumor thickness measurement.
• Findings demonstrated PET–CT missed six of 41 TRG3 or TRG4 tumors (15% [95% CI 7–28]).
• In 18 (9%) of 190 patients (one squamous cell carcinoma, 17 adenocarcinomas), interval distant histologically proven metastases were detected on PET–CT.