Predictive value of endoscopic esophageal findings for residual esophageal cancer after neoadjuvant chemoradiotherapy

Abstract

Background Endoscopic evaluation of the esophageal mucosa may play a role in an active surveillance strategy after neoadjuvant chemoradiotherapy (nCRT) for esophageal cancer. This study investigated the yield of endoscopic findings for detection of residual disease.

Methods Patients from the multicenter preSANO cohort, who underwent nCRT followed by surgery for esophageal or junctional cancer, were included. Upper endoscopy was performed 6 and 12 weeks after nCRT. Patients with residual disease at 6 weeks underwent immediate surgery. Endoscopic records were reviewed for presence of stenosis, suspicion of residual tumor, scar tissue, and ulceration. Presence and type of endoscopic findings were compared with outcome of the resection specimen.

Results 118 of 156 patients (76 %) had residual disease in the resection specimen. Endoscopic suspicion of residual tumor was significantly associated with presence of residual disease. At 6 weeks, 40/112 patients with residual disease and 4/33 patients with complete response had endoscopic suspicion of residual tumor (36 % vs. 12 %; P = 0.01), while this was reported in 16/73 and 0/28 patients, respectively, at 12 weeks (22 % vs. 0 %; P < 0.01). Positive predictive value of endoscopic suspicion of residual tumor was 91 % at 6 weeks and 100 % at 12 weeks. Endoscopic findings of non-passable stenosis, passable stenosis, scar tissue, or ulceration were not associated with residual disease.

Conclusions Endoscopic suspicion of residual tumor was the only endoscopic finding associated with residual disease. Based on its positive predictive value, this endoscopic finding may contribute to the diagnostic strategy used in active surveillance.

Publication History

Received: 28 September 2020

Accepted: 15 December 2020

Article published online:
02 March 2021

• References

• 1 van Hagen P, Hulshof MC, van Lanschot JJ. et al. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med 2012; 366: 2074-2084
• 2 Yang H, Liu H, Chen Y. et al. Neoadjuvant chemoradiotherapy followed by surgery versus surgery alone for locally advanced squamous cell carcinoma of the esophagus (NEOCRTEC5010): a phase III multicenter, randomized, open-label clinical trial. J Clin Oncol 2018; 36: 2796-2803
• 3 Shapiro J, van Lanschot JJB, Hulshof M. et al. Neoadjuvant chemoradiotherapy plus surgery versus surgery alone for oesophageal or junctional cancer (CROSS): long-term results of a randomised controlled trial. Lancet Oncol 2015; 16: 1090-1098
• 4 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
• 5 van der Wilk BJ, Eyck BM, Spaander MCW. et al. Towards an organ-sparing approach for locally advanced esophageal cancer. Dig Surg 2019; 36: 462-469
• 6 ClinicalTrials.gov. Comparison of systematic surgery versus surveillance and rescue surgery in operable oesophageal cancer with a complete clinical response to radiochemotherapy. https://ClinicalTrials.gov/show/NCT02551458
• 7 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
• 8 van der Wilk BJ, Noordman BJ, Neijenhuis LKA. et al. Active surveillance versus immediate surgery in clinically complete responders after neoadjuvant chemoradiotherapy for esophageal cancer: a multicenter propensity matched study. Ann Surg 2019;
• 9 Habr-Gama A, Perez RO, Wynn G. et al. Complete clinical response after neoadjuvant chemoradiation therapy for distal rectal cancer: characterization of clinical and endoscopic findings for standardization. Dis Colon Rectum 2010; 53: 1692-1698
• 10 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
• 11 Nagai Y, Yoshida N, Baba Y. et al. Clinical significance of evaluating endoscopic response to neoadjuvant chemotherapy in esophageal squamous cell carcinoma. Dig Endosc 2020; 32: 39-48
• 12 Chao YK, Yeh CJ, Lee MH. et al. Factors associated with false-negative endoscopic biopsy results after neoadjuvant chemoradiotherapy in patients with esophageal squamous cell carcinoma. Medicine (Baltimore) 2015; 94: e588
• 13 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
• 14 Brown WA, Thomas J, Gotley D. et al. Use of oesophagogastroscopy to assess the response of oesophageal carcinoma to neoadjuvant therapy. Br J Surg 2004; 91: 199-204
• 15 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: 678-689
• 16 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
• 17 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
• 18 Shapiro J, van Hagen P, Lingsma HF. et al. Prolonged time to surgery after neoadjuvant chemoradiotherapy increases histopathological response without affecting survival in patients with esophageal or junctional cancer. Ann Surg 2014; 260: 807-814
• 19 van der Werf LR, Dikken JL, van der Willik EM. et al. Time interval between neoadjuvant chemoradiotherapy and surgery for oesophageal or junctional cancer: a nationwide study. Eur J Cancer 2018; 91: 76-85