Skip to main content
Top
Published in: Annals of Surgical Oncology 11/2015

01-10-2015 | Gastrointestinal Oncology

A Pathological Study of Residual Cancer in the Esophageal Wall Following Neoadjuvant Chemoradiotherapy: Focus on Esophageal Squamous Cell Carcinoma Patients with False Negative Preoperative Endoscopic Biopsies

Authors: Yin-Kai Chao, MD, PhD, Chang-Yo Tsai, MD, Hsien-Kun Chang, MD, Chen-Kan Tseng, MD, Yun-Hen Liu, MD, Chi-Ju Yeh, MD

Published in: Annals of Surgical Oncology | Issue 11/2015

Login to get access

Abstract

Background

Endoscopic biopsy examinations after neoadjuvant chemoradiotherapy (nCRT) are of limited value in patients with esophageal cancer due to the high rates of false negative (FN) findings. We sought to investigate the anatomical locations of residual tumors in esophageal squamous cell carcinoma (ESCC) patients with FN endoscopic biopsies with the ultimate goal of improving their clinical management.

Methods

ESCC patients with residual cancers after nCRT which were not identified by preoperative endoscopic biopsy were deemed eligible. All of the surgical specimens were re-reviewed with a special focus on (1) distribution of residual cancer in each esophageal layer; (2) tumor regression grade (TRG); and (3) shortest distance between the lumen and the residual tumor.

Results

Among the 49 ESCC patients with FN biopsy results, a strong ‘layer-dependent’ tumor regression was observed. There was a preferential clearing of esophageal cancer cells located in the adventitia, followed by muscle and the submucosal (SM) and mucosal (M) layers (p < 0.001). Residual malignancies located in the muscle layer or the adventitia without simultaneous involvement of the M/SM layers were rare (n = 3; 6.1 %). TRG following nCRT did not affect the rate of M/SM involvement (p = 0.55) but was inversely associated with the distance between the lumen and residual cancer (mean distance in patients with TRG of 2, 3, and 4 was 1.1, 0.82, and 0.37 mm, respectively; p = 0.041).

Conclusion

Most ESCC patients who show FN endoscopic biopsies following nCRT still have detectable lesions in the M/SM layers. Aggressive biopsy protocols may potentially improve detection rates.
Literature
1.
go back to reference Sjoquist KM, Burmeister BH, Smithers BM, et al. Survival after neoadjuvant chemotherapy or chemoradiotherapy for resectable oesophageal carcinoma: an updated meta-analysis. Lancet Oncol. 2011;12(7):681–92.CrossRefPubMed Sjoquist KM, Burmeister BH, Smithers BM, et al. Survival after neoadjuvant chemotherapy or chemoradiotherapy for resectable oesophageal carcinoma: an updated meta-analysis. Lancet Oncol. 2011;12(7):681–92.CrossRefPubMed
2.
go back to reference Donahue JM, Nichols FC, Li Z, et al. Complete pathologic response after neoadjuvant chemoradiotherapy for esophageal cancer is associated with enhanced survival. Ann Thorac Surg. 2009;87(2):392–9.PubMedCentralCrossRefPubMed Donahue JM, Nichols FC, Li Z, et al. Complete pathologic response after neoadjuvant chemoradiotherapy for esophageal cancer is associated with enhanced survival. Ann Thorac Surg. 2009;87(2):392–9.PubMedCentralCrossRefPubMed
3.
go back to reference Meredith KL, Weber JM, Turaga KK, et al. Pathologic response after neoadjuvant therapy is the major determinant of survival in patients with esophageal cancer. Ann Surg Oncol. 2010;17(4):1159–67.CrossRefPubMed Meredith KL, Weber JM, Turaga KK, et al. Pathologic response after neoadjuvant therapy is the major determinant of survival in patients with esophageal cancer. Ann Surg Oncol. 2010;17(4):1159–67.CrossRefPubMed
4.
go back to reference Van Hagen P, Hulshof M, Van Lanschot J, et al. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med. 2012;366(22):2074–84.CrossRefPubMed Van Hagen P, Hulshof M, Van Lanschot J, et al. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med. 2012;366(22):2074–84.CrossRefPubMed
5.
go back to reference Piessen G, Messager M, Mirabel X, et al. Is there a role for surgery for patients with a complete clinical response after chemoradiation for esophageal cancer? An intention-to-treat case-control study. Ann Surg. 2013;258(5):793–800.CrossRefPubMed Piessen G, Messager M, Mirabel X, et al. Is there a role for surgery for patients with a complete clinical response after chemoradiation for esophageal cancer? An intention-to-treat case-control study. Ann Surg. 2013;258(5):793–800.CrossRefPubMed
6.
go back to reference Castoro C, Scarpa M, Cagol M, et al. Complete clinical response after neoadjuvant chemoradiotherapy for squamous cell cancer of the thoracic oesophagus: is surgery always necessary? J Gastrointest Surg. 2013;17(8):1375–81.CrossRefPubMed Castoro C, Scarpa M, Cagol M, et al. Complete clinical response after neoadjuvant chemoradiotherapy for squamous cell cancer of the thoracic oesophagus: is surgery always necessary? J Gastrointest Surg. 2013;17(8):1375–81.CrossRefPubMed
7.
go back to reference Schneider PM, Metzger R, Schaefer H, et al. Response evaluation by endoscopy, rebiopsy, and endoscopic ultrasound does not accurately predict histopathologic regression after neoadjuvant chemoradiation for esophageal cancer. Ann Surg. 2008;248(6):902–8.CrossRefPubMed Schneider PM, Metzger R, Schaefer H, et al. Response evaluation by endoscopy, rebiopsy, and endoscopic ultrasound does not accurately predict histopathologic regression after neoadjuvant chemoradiation for esophageal cancer. Ann Surg. 2008;248(6):902–8.CrossRefPubMed
8.
go back to reference Molena D, Sun H, Badr A, et al. Clinical tools do not predict pathological complete response in patients with esophageal squamous cell cancer treated with definitive chemoradiotherapy. Dis Esophagus. 2014;27(4):355–9.CrossRefPubMed Molena D, Sun H, Badr A, et al. Clinical tools do not predict pathological complete response in patients with esophageal squamous cell cancer treated with definitive chemoradiotherapy. Dis Esophagus. 2014;27(4):355–9.CrossRefPubMed
9.
go back to reference Swisher SG, Maish M, Erasmus JJ, et al. Utility of PET, CT, and EUS to identify pathologic responders in esophageal cancer. Ann Thorac Surg. 2004;78(4):1152–60.CrossRefPubMed Swisher SG, Maish M, Erasmus JJ, et al. Utility of PET, CT, and EUS to identify pathologic responders in esophageal cancer. Ann Thorac Surg. 2004;78(4):1152–60.CrossRefPubMed
10.
go back to reference Miyata H, Yamasaki M, Takiguchi S, et al. Prognostic value of endoscopic biopsy findings after induction chemoradiotherapy with and without surgery for esophageal cancer. Ann Surg. 2011;253(2):279–84.CrossRefPubMed Miyata H, Yamasaki M, Takiguchi S, et al. Prognostic value of endoscopic biopsy findings after induction chemoradiotherapy with and without surgery for esophageal cancer. Ann Surg. 2011;253(2):279–84.CrossRefPubMed
11.
go back to reference Sarkaria IS, Rizk NP, Bains MS, et al. Post-treatment endoscopic biopsy is a poor-predictor of pathologic response in patients undergoing chemoradiation therapy for esophageal cancer. Ann Surg. 2009;249(5):764–7.CrossRefPubMed Sarkaria IS, Rizk NP, Bains MS, et al. Post-treatment endoscopic biopsy is a poor-predictor of pathologic response in patients undergoing chemoradiation therapy for esophageal cancer. Ann Surg. 2009;249(5):764–7.CrossRefPubMed
12.
go back to reference Yang Q, Cleary K, Yao J, et al. Significance of post‐chemoradiation biopsy in predicting residual esophageal carcinoma in the surgical specimen. Dis Esophagus. 2004;17(1):38–43.CrossRefPubMed Yang Q, Cleary K, Yao J, et al. Significance of post‐chemoradiation biopsy in predicting residual esophageal carcinoma in the surgical specimen. Dis Esophagus. 2004;17(1):38–43.CrossRefPubMed
13.
go back to reference Shaukat A, Mortazavi A, Demmy T, et al. Should preoperative, post‐chemoradiotherapy endoscopy be routine for esophageal cancer patients? Dis Esophagus. 2004;17(2):129–35.CrossRefPubMed Shaukat A, Mortazavi A, Demmy T, et al. Should preoperative, post‐chemoradiotherapy endoscopy be routine for esophageal cancer patients? Dis Esophagus. 2004;17(2):129–35.CrossRefPubMed
14.
go back to reference Bollschweiler E, Metzger R, Drebber U, et al. Histological type of esophageal cancer might affect response to neo-adjuvant radiochemotherapy and subsequent prognosis. Ann Oncol. 2009;20(2):231–8.CrossRefPubMed Bollschweiler E, Metzger R, Drebber U, et al. Histological type of esophageal cancer might affect response to neo-adjuvant radiochemotherapy and subsequent prognosis. Ann Oncol. 2009;20(2):231–8.CrossRefPubMed
15.
go back to reference Chirieac LR, Swisher SG, Ajani JA, et al. Posttherapy pathologic stage predicts survival in patients with esophageal carcinoma receiving preoperative chemoradiation. Cancer. 2005;103(7):1347–55.CrossRefPubMed Chirieac LR, Swisher SG, Ajani JA, et al. Posttherapy pathologic stage predicts survival in patients with esophageal carcinoma receiving preoperative chemoradiation. Cancer. 2005;103(7):1347–55.CrossRefPubMed
16.
go back to reference Shapiro J, ten Kate FJ, van Hagen P, Biermann K, Wijnhoven BP, van Lanschot JJB. Residual esophageal cancer after neoadjuvant chemoradiotherapy frequently involves the mucosa and submucosa. Ann Surg. 2013;258(5):678–89.CrossRefPubMed Shapiro J, ten Kate FJ, van Hagen P, Biermann K, Wijnhoven BP, van Lanschot JJB. Residual esophageal cancer after neoadjuvant chemoradiotherapy frequently involves the mucosa and submucosa. Ann Surg. 2013;258(5):678–89.CrossRefPubMed
17.
go back to reference 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(2):142–9.CrossRefPubMed 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(2):142–9.CrossRefPubMed
18.
go back to reference Gonzalez S, Yu WM, Smith MS, et al. Randomized comparison of 3 different-sized biopsy forceps for quality of sampling in Barrett’s esophagus. Gastrointest Endosc. 2010;72(5):935–40.PubMedCentralCrossRefPubMed Gonzalez S, Yu WM, Smith MS, et al. Randomized comparison of 3 different-sized biopsy forceps for quality of sampling in Barrett’s esophagus. Gastrointest Endosc. 2010;72(5):935–40.PubMedCentralCrossRefPubMed
19.
go back to reference Chao YK, Tseng CK, Wen YW, et al. Using pretreatment tumor depth and length to select esophageal squamous cell carcinoma patients for nonoperative treatment after neoadjuvant chemoradiotherapy. Ann Surg Oncol. 2013;20:3000–8.CrossRefPubMed Chao YK, Tseng CK, Wen YW, et al. Using pretreatment tumor depth and length to select esophageal squamous cell carcinoma patients for nonoperative treatment after neoadjuvant chemoradiotherapy. Ann Surg Oncol. 2013;20:3000–8.CrossRefPubMed
20.
go back to reference Cho HJ, Kim Y-H, Kim HR, et al. Oncologic outcomes according to remnant lymph node metastases in pathologic T0 (ypT0) esophageal squamous cell carcinoma following prospective neoadjuvant therapy and surgery. Ann Surg Oncol. 2014. doi:10.1245/s10434-014-4195-3. Cho HJ, Kim Y-H, Kim HR, et al. Oncologic outcomes according to remnant lymph node metastases in pathologic T0 (ypT0) esophageal squamous cell carcinoma following prospective neoadjuvant therapy and surgery. Ann Surg Oncol. 2014. doi:10.​1245/​s10434-014-4195-3.
21.
go back to reference Kim MP, Correa AM, Lee J, et al. Pathologic T0N1 esophageal cancer after neoadjuvant therapy and surgery: an orphan status. Ann Thorac Surg. 2010;90:884–91.CrossRefPubMed Kim MP, Correa AM, Lee J, et al. Pathologic T0N1 esophageal cancer after neoadjuvant therapy and surgery: an orphan status. Ann Thorac Surg. 2010;90:884–91.CrossRefPubMed
Metadata
Title
A Pathological Study of Residual Cancer in the Esophageal Wall Following Neoadjuvant Chemoradiotherapy: Focus on Esophageal Squamous Cell Carcinoma Patients with False Negative Preoperative Endoscopic Biopsies
Authors
Yin-Kai Chao, MD, PhD
Chang-Yo Tsai, MD
Hsien-Kun Chang, MD
Chen-Kan Tseng, MD
Yun-Hen Liu, MD
Chi-Ju Yeh, MD
Publication date
01-10-2015
Publisher
Springer US
Published in
Annals of Surgical Oncology / Issue 11/2015
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-015-4412-8

Other articles of this Issue 11/2015

Annals of Surgical Oncology 11/2015 Go to the issue