Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 May;32(5):3089-3097.
doi: 10.1245/s10434-025-16962-1. Epub 2025 Feb 7.

Predictors of Pathologic Non-response to Neoadjuvant Approaches in Locally Advanced Rectal Cancer

Jyi Cheng Ng  1 , Annaclara Sileo  1   2 , Richard Sassun  1   2 , Sara Aboelmaaty  1 , Tommaso Violante  1   3 , Ibrahim A Gomaa  1 , Anne-Lise D'Angelo  1 , Kristen K Rumer  1 , Kellie L Mathis  1 , David W Larson  4
Affiliations

Predictors of Pathologic Non-response to Neoadjuvant Approaches in Locally Advanced Rectal Cancer

Jyi Cheng Ng et al. Ann Surg Oncol. 2025 May.

Abstract

Background: Approximately 10-20% of rectal cancer patients do not respond to neoadjuvant treatment. While the current literature has focused on pathological complete response, pinpointing those who will fail to benefit entirely from neoadjuvant approaches is crucial.

Objective: This study aimed to determine the risk factors associated with pathological non-response (pNR) to neoadjuvant treatment.

Methods: Patients with stage II-III rectal adenocarcinoma who underwent neoadjuvant treatment followed by curative surgical resection between 2018 and 2023 at a high-volume center were retrospectively reviewed. Patients were divided into two cohorts (pNR and pathologic responder [pR]) based on their response to neoadjuvant therapy. The pNR group included patients with a Tumor Regression Score of grade 3 or those upstaged on the final pathological report.

Results: Of the 405 patients included in this study, 53 (13%) were pNR and 352 (87%) were pR. Among patients treated with standard neoadjuvant chemoradiation, 12% were pNR compared with 14% among those treated with total neoadjuvant therapy. Significantly more patients in the pNR cohort had perineural (31% vs. 8%; p < 0.001) and lymphovascular (22% vs. 6%, p = 0.001) invasions when compared with the pR cohort. After adjusting for age, sex, clinical T stages, and clinical nodal status on multivariable analysis, the presence of extramural vascular invasion (EMVI) on pretreatment magnetic resonance imaging (odds ratio 2.08, 95% confidence interval 1.03-4.20, p = 0.04) was identified as a significant predictor of pNR.

Conclusion: EMVI was an independent risk factor of pNR in patients with rectal cancer. Identifying pretreatment factors that predict pNR to neoadjuvant therapy is crucial as it allows for better risk stratification and personalized treatment strategies.

Keywords: EMVI; Neoadjuvant treatment; Rectal cancer; Treatment response.

PubMed Disclaimer

Conflict of interest statement

Disclosures: The authors have no relevant disclosure.

References

    1. Benson AB, Venook AP, Al-Hawary MM, et al. rectal cancer, version 2.2022, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2022;20(10):1139–67. https://doi.org/10.6004/jnccn.2022.0051 . - DOI - PubMed
    1. Wolthuis AM, Penninckx F, Haustermans K, Ectors N, Van Cutsem E, D’Hoore A. Outcome standards for an organ preservation strategy in stage II and III rectal adenocarcinoma after neoadjuvant chemoradiation. Ann Surg Oncol. 2011;18(3):684–90. https://doi.org/10.1245/s10434-010-1324-5 . - DOI - PubMed
    1. Chen HY, Feng LL, Li M, et al. College of American pathologists tumor regression grading system for long-term outcome in patients with locally advanced rectal cancer. Oncologist. 2021;26(5):e780–93. https://doi.org/10.1002/onco.13707 . - DOI - PubMed - PMC
    1. Fokas E, Strobel P, Fietkau R, et al. Tumor regression grading after preoperative chemoradiotherapy as a prognostic factor and individual-level surrogate for disease-free survival in rectal cancer. J Natl Cancer Inst. 2017. https://doi.org/10.1093/jnci/djx095 . - DOI - PubMed
    1. Flom E, Schultz KS, Pantel HJ, Leeds IL. The predictors of complete pathologic response in rectal cancer during the total neoadjuvant therapy era: a systematic review. Cancers (Basel). 2023. https://doi.org/10.3390/cancers15245853 . - DOI - PubMed

LinkOut - more resources