Bite-on-bite biopsies for the detection of residual esophageal cancer after neoadjuvant chemoradiotherapy

Abstract

Background Active surveillance after neoadjuvant treatment is increasingly implemented. The success of this strategy relies on the accurate detection of residual cancer. This study aimed to assess the diagnostic value of a second (bite-on-bite) biopsy for the detection of residual esophageal cancer and to correlate outcomes to the distribution of residual cancer found in the resection specimen.

Methods A multicenter prospective study of esophageal cancer patients undergoing active surveillance after neoadjuvant chemoradiotherapy was performed. At clinical response evaluations, an upper gastrointestinal (GI) endoscopy was performed with at least four bite-on-bite biopsies of the primary tumor site. First and second biopsies were analyzed separately. Patients with histopathological evidence of residual cancer were included in the primary analysis. Two pathologists blinded for biopsy outcome examined all resection specimens.

Results Between October 2017 and July 2020, 626 upper GI endoscopies were performed in 367 patients. Of 138 patients with residual cancer, 112 patients (81 %) had at least one positive biopsy. In 14 patients (10 %) only the first biopsy was positive and in 25 patients (18 %) only the second biopsy (P = 0.11). Remarkably, the rates of patients with tumor-free mucosa and deeper located tumors were higher in patients detected by the first biopsy. The second biopsy increased the false-positive rate by 3 percentage points. No adverse events occurred.

Conclusions A second (bite-on-bite) biopsy improves the detection of residual esophageal cancer by almost 20 percentage points, at the expense of increasing the false-positive rate by 3 percentage points. The higher detection rate is explained by the higher number of biopsies obtained rather than by the penetration depth.

Publication History

Received: 05 December 2021

Accepted after revision: 06 April 2022

Article published online:
03 June 2022

• References

• 1 Noordman BJ, Wijnhoven BPL, Lagarde SM. et al. Neoadjuvant chemoradiotherapy plus surgery versus active surveillance for oesophageal cancer: a stepped-wedge cluster randomised trial. BMC Cancer 2018; 18: 142
• 2 van der Valk MJM, Hilling DE, Bastiaannet E. et al. Long-term outcomes of clinical complete responders after neoadjuvant treatment for rectal cancer in the International Watch & Wait Database (IWWD): an international multicentre registry study. Lancet 2018; 391: 2537-2545
• 3 Renehan AG, Malcomson L, Emsley R. et al. Watch-and-wait approach versus surgical resection after chemoradiotherapy for patients with rectal cancer (the OnCoRe project): a propensity-score matched cohort analysis. Lancet Oncol 2016; 17: 174-183
• 4 Klotz L, Zhang L, Lam A. et al. Clinical results of long-term follow-up of a large, active surveillance cohort with localized prostate cancer. J Clin Oncol 2010; 28: 126-131
• 5 Vokes EE, Kies MS, Haraf DJ. et al. Concomitant chemoradiotherapy as primary therapy for locoregionally advanced head and neck cancer. J Clin Oncol 2000; 18: 1652-1661
• 6 Rodel C, Weiss C, Sauer R. Trimodality treatment and selective organ preservation for bladder cancer. J Clin Oncol 2006; 24: 5536-5544
• 7 Noordman BJ, Spaander MCW, Valkema R. et al. Detection of residual disease after neoadjuvant chemoradiotherapy for oesophageal cancer (preSANO): a prospective multicentre, diagnostic cohort study. Lancet Oncol 2018; 19: 965-974
• 8 Dumonceau JM, Deprez PH, Jenssen C. et al. Indications, results, and clinical impact of endoscopic ultrasound (EUS)-guided sampling in gastroenterology: European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline – Updated January 2017. Endoscopy 2017; 49: 695-714
• 9 Faulx AL, Kothari S. Standards of Practice Committee. et al. The role of endoscopy in subepithelial lesions of the GI tract. Gastrointest Endosc 2017; 85: 1117-1132
• 10 Shapiro J, ten Kate FJ, van Hagen P. et al. Residual esophageal cancer after neoadjuvant chemoradiotherapy frequently involves the mucosa and submucosa. Ann Surg 2013; 258: 678-688 ; discussion 688-679
• 11 Chao YK, Chuang WY, Yeh CJ. et al. Anatomical distribution of residual cancer in patients with oesophageal squamous cell carcinoma who achieved clinically complete response after neoadjuvant chemoradiotherapy. Eur J Cardiothorac Surg 2018; 53: 201-208
• 12 van der Wilk BJ, Eyck BM, Doukas M. et al. Residual disease after neoadjuvant chemoradiotherapy for oesophageal cancer: locations undetected by endoscopic biopsies in the preSANO trial. Br J Surg 2020; 107: 1791-1800
• 13 Rice TW, Patil DT, Blackstone EH. 8th edition AJCC/UICC staging of cancers of the esophagus and esophagogastric junction: application to clinical practice. Ann Cardiothorac Surg 2017; 6: 119-130
• 14 Chirieac LR, Swisher SG, Ajani JA. et al. Posttherapy pathologic stage predicts survival in patients with esophageal carcinoma receiving preoperative chemoradiation. Cancer 2005; 103: 1347-1355
• 15 van der Bogt RD, van der Wilk BJ, Nikkessen S. et al. Predictive value of endoscopic esophageal findings for residual esophageal cancer after neoadjuvant chemoradiotherapy. Endoscopy 2021; 53: 1098-1104
• 16 Valkema MJ, van der Wilk BJ, Eyck BM. et al. Surveillance of clinically complete responders using serial (18)F-FDG PET/CT scans in patients with esophageal cancer after neoadjuvant chemoradiotherapy. J Nucl Med 2021; 62: 486-492
• 17 Komanduri S, Keefer L, Jakate S. Diagnostic yield of a novel jumbo biopsy "unroofing" technique for tissue acquisition of gastric submucosal masses. Endoscopy 2011; 43: 849-855
• 18 Duldulao MP, Lee W, Streja L. et al. Distribution of residual cancer cells in the bowel wall after neoadjuvant chemoradiation in patients with rectal cancer. Dis Colon Rectum 2013; 56: 142-149