Retrospective Cohort Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Dec 15, 2017; 9(12): 466-474
Published online Dec 15, 2017. doi: 10.4251/wjgo.v9.i12.466
Tumor-stroma ratio as prognostic factor for survival in rectal adenocarcinoma: A retrospective cohort study
René Scheer, Alexi Baidoshvili, Shorena Zoidze, Marloes A G Elferink, Annefleur E M Berkel, Joost M Klaase, Paul J van Diest
René Scheer, Annefleur E M Berkel, Joost M Klaase, Department of Surgery, Medisch Spectrum Twente, Enschede 7500 KA, The Netherlands
Alexi Baidoshvili, Shorena Zoidze, Laboratory for Pathology East-Netherlands, Hengelo 7550 AM, The Netherlands
Marloes A G Elferink, Netherlands Comprehensive Cancer Organization, Location Enschede, Enschede 7511 JP, The Netherlands
Paul J van Diest, Department of Pathology, University Medical Center Utrecht, Utrecht 3508 GA, The Netherlands
Author contributions: Scheer R and Klaase JM designed the research; Scheer R and Zoidze S performed the research; Baidoshvili A supervised the histological scoring and took final decisions in case of discrepancy in scores between Scheer R and Zoidze S; Elferink MAG collected data from the population-based The Netherlands Cancer Registy and analyzed the data; Berkel AEM, Klaase JM and van Diest PJ supervised and interpreted the results; Scheer R and Zoidze S wrote the paper; all authors critically reviewed and accepted the final version of the manuscript.
Institutional review board statement: The requirement for informed consent and ethical approval was waived because of the retrospective study design. The study is conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines.
Conflict-of-interest statement: The authors declare no conflict of interests.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at Participants’ informed consent was not obtained, but the presented data are anonymized and risk of identification is low.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Joost M Klaase, MD, PhD, Surgical-Oncologist, Department of Surgery, Medisch Spectrum Twente, PO Box 50.000, Enschede 7500 KA, The Netherlands.
Telephone: +31-53-4873441 Fax: +31-53-4872526
Received: June 22, 2017
Peer-review started: July 14, 2017
First decision: August 7, 2017
Revised: September 17, 2017
Accepted: October 15, 2017
Article in press: October 15, 2017
Published online: December 15, 2017

To evaluate the prognostic value of the tumor-stroma ratio (TSR) in rectal cancer.


TSR was determined on hematoxylin and eosin stained histological sections of 154 patients treated for rectal adenocarcinoma without prior neoadjuvant treatment in the period 1996-2006 by two observers to assess reproducibility. Patients were categorized into three categories: TSR-high [carcinoma percentage (CP) ≥ 70%], TSR-intermediate (CP 40%, 50% and 60%) and TSR-low (CP ≤ 30%). The relation between categorized TSR and survival was analyzed using Cox proportional hazards model.


Thirty-six (23.4%) patients were scored as TSR-low, 70 (45.4%) as TSR-intermediate and 48 (31.2%) as TSR-high. TSR had a good interobserver agreement (κ = 0.724, concordance 82.5%). Overall survival (OS) and disease free survival (DFS) were significantly better for patients with a high TSR (P = 0.01 and P = 0.02, respectively). A similar association existed for disease specific survival (P = 0.06). In multivariate analysis, patients without lymph node metastasis and an intermediate TSR had a higher risk of dying from rectal cancer (HR = 5.27, 95%CI: 1.54-18.10), compared to lymph node metastasis negative patients with a high TSR. This group also had a worse DFS (HR = 6.41, 95%CI: 1.84-22.28). An identical association was seen for OS. These relations were not seen in lymph node metastasis positive patients.


The TSR has potential as a prognostic factor for survival in surgically treated rectal cancer patients, especially in lymph node negative cases.

Keywords: Rectal cancer, Adenocarcinoma, Prognosis, Recurrence, Pathology, Tumor-stroma ratio

Core tip: The tumor-stroma ratio (TSR) can be determined accurately on routine histopathological sections by different observers. The TSR has potential as a prognostic factor for survival in surgically treated rectal cancer patients, especially in lymph node negative cases. It could therefore be useful in decision making regarding adjuvant treatment in individual patients.