Pathologic complete response in rectal cancer: advocating for local excision

Daniel Gonzalez-Nunez; Luis Torres; Mauricio Gonzalez-Dorado; Juan C. Reyes

doi:10.3393/ac.2025.00829.0118

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Brief Communication Colorectal cancer Pathologic complete response in rectal cancer: advocating for local excision: Daniel Gonzalez-Nunez, Luis Torres, Mauricio Gonzalez-Dorado, Juan C. Reyes; Annals of Coloproctology 2025;41(6):592-595.
DOI: https://doi.org/10.3393/ac.2025.00829.0118
Published online: December 24, 2025

Department of Colorectal Surgery, San Jose Hospital, Bogota, Colombia

Correspondence to: Daniel Gonzalez-Nunez, MD Department of Colorectal Surgery, San Jose Hospital, Calle 10 No. 18-75, Bogota 111001, Colombia Email: dgonzalez8805@gmail.com

• Received: July 10, 2025 • Revised: September 5, 2025 • Accepted: September 21, 2025

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Rectal cancer continues to pose significant challenges in related specialties, with a rising incidence, particularly in younger individuals, requiring for evolving treatment alternatives. The advent of neoadjuvant chemoradiotherapy in the 1990s unveiled a new frontier—the potential for pathological complete response (pCR). Habr-Gama et al. [1] demonstrated that 27% of patients achieved a clinical complete response (cCR) after neoadjuvant chemoradiotherapy, while 14% of those who underwent surgical resection achieved a pCR, with near-equivalent survival to surgically resected stage I disease. This discovery catalyzed the "watch and wait" movement, offering selected patients with cCR an alternative to radical surgery. Achievement of cCR and pCR following neoadjuvant therapy, with improved survival rates and potential for organ preservation has acquired maximal importance. However, the current tools for assessing response remain far from ideal. New imaging modalities and local excision may improve decision-making and improve functional outcomes. We explore the current landscape of cCR identification, the role of imaging and circulating tumor DNA (ctDNA), ultimately advocating for the integration of local excision in select patient populations to avoid high rates of unnecessary radical treatment.

Chemoradiotherapy has changed oncological perspectives, especially in locally advanced rectal cancer, after the groundbreaking surgical standardization towards reducing local recurrence rates in total mesorectal excision (TME). Traditional treatment strategies with conventional chemoradiotherapy and definitive surgery are declining, while organ preservation approaches become a functional target. Two major challenges remain: distant metastasis and the long-term quality of life. As survival and recurrence rates improve, there is an increasing need to limit the morbidity associated with radical surgery, especially in patients who achieve cCR.

The pCR is considered a highly favorable outcome, where no viable tumor cells in the specimen remain after neoadjuvant therapy. This outcome correlates with excellent long-term results, with 5-year disease-free survival approaching 83% and local recurrence rates below 3% [2]. The diagnostic uncertainty in pCR warrants a paradigm shift in treatment. These patients may present with an undetected pCR, potentially exposing them to morbid radical resections associated with compromised function and quality of life, without a corresponding oncological benefit [3]. The concept of achieving pCR also gains importance, as it is determined through digital rectal examination, magnetic resonance imaging (MRI), and endoscopy, which allow for noninvasive evaluation of tumor response. However, while cCR offers optimism, the reality is that these modalities are not always reliable in predicting a pCR.

High resolution MRI has become crucial in post–neoadjuvant therapy assessment, particularly with diffusion-weighted imaging. However, the technique is not without its limitations. A significant issue is overstaging, where approximately 25% of patients with a pCR are misclassified as having residual disease. Similarly, colonoscopy findings are often unreliable, as mucosal abnormalities may not correspond to deep involvement, and rectal ulcers can be present in 33% of true cCR cases [4]. Furthermore, biopsies, traditionally used to confirm the presence of residual disease, are now considered to have a high false-negative rate (>30%) due to heterogeneous tumor distribution and are not recommended for response confirmation [5].

Despite these limitations, a combination of clinical examination and advanced imaging, such as MRI and endoscopy, can still provide a negative predictive value for residual disease up to 98% when all suggest complete regression [6]. However, if all assessments indicate persistent disease, there remains a 15% chance of misdiagnosis, where pCR has still been achieved [7].

In recent years, positron emission tomography (PET)-computed tomography and PET-MRI have shown promise in providing more accurate assessments compared to conventional imaging. PET-MRI has been shown to outperform MRI alone in evaluating both primary tumors and nodal status, making it a valuable tool for post-treatment staging [8]. However, further validation is required before it becomes a standard part of clinical practice. In addition to imaging, ctDNA has emerged as a promising biomarker for detecting minimal residual disease. Studies suggest that ctDNA possesses a high negative predictive value, up to 94%, for ruling in pCR, although further research is needed to assess its cost-effectiveness and broader applicability in clinical practice [9].

An approach that has gained attention in response to these diagnostic challenges is local excision. For near-complete responders, those who exhibit only small residual lesions or mucosal irregularities on imaging, local excision can be used as a diagnostic and therapeutic tool. This method allows for histological confirmation of pCR in cases where noninvasive techniques lack accuracy (post-radiation changes such as fibrosis, edema, and inflammation). Moreover, in selected noncomplete responders with superficial residual disease, local excision provides a way to avoid unnecessary radical surgery while still ensuring oncologic safety.

Studies have demonstrated that local excision can offer oncologic outcomes comparable to more invasive procedures. Trials such as the STAR-TREC and GRECCAR 2 have supported the use of local excision in patients with minimal residual disease, particularly when part of a precise treatment protocol [10, 11]. Furthermore, local excision has the potential to identify pCR in patients who would otherwise undergo unnecessary radical surgery. Studies including ACOSOG Z6041 have demonstrated that in selected patients with cT2N0 distal disease, chemoradiotherapy followed by local excision can achieve acceptable rates of local control and disease-free survival. This approach has sparked significant interest in integrating local excision into the treatment algorithm for rectal cancer [12].

When incorporated into the decision-making process, local excision can offer several benefits: it allows for the confirmation of pCR in near-complete responder cases, reduces the risk of overtreatment by avoiding unnecessary TME, and improves patient quality of life by offering organ-preserving alternatives. For patients with minimal residual disease, the TAU-TEM trial, a multicenter, randomized phase III trial, directly compared chemoradiotherapy followed by local excision with TME in patients with cT2–T3abN0M0 rectal cancer. The trial demonstrated that, in carefully selected patients, the organ preservation strategy allowed 78% of patients to avoid radical surgery (based on the modified intention-to-treat analysis) compared to the standard TME approach. While the TME group achieved slightly better oncologic outcomes in terms of local recurrence control, the functional outcomes in the organ-preservation group were very superior, with significantly fewer reports of bowel/sexual dysfunction, and urinary incontinence. The TAU-TEM trial highlights the evolving role of local excision after neoadjuvant therapy as a valid alternative to radical surgery in rectal cancer management, particularly when preserving rectal function is a priority [13]. Local excision can also serve as a staging tool to inform further treatment decisions. If residual disease is confirmed, radical surgery is warranted; however, if no viable tumor is found, patients can avoid the morbidity of more radical surgery.

Local excision as a salvage strategy in cases of tumor regrowth has shown superior oncologic outcomes in some series when compared to salvage TME [14]. However, these outcomes must be interpreted with caution, as the majority of patients undergoing salvage local excision presented with early-stage tumors (T1–T2) at baseline, making the procedure technically feasible and contributing to the favorable outcomes. Metastatic lymph nodes not identified on pretreatment MRI could very well be the Achilles heel of a local excision approach, being unable to correctly identify “occult” nodal metastases, with up to 20% found in the control group of TME in the TAU-TEM trial. This, however, did not alter recurrence rates and therefore could be statistically insignificant [13]. These results support the consideration of salvage local excision as a valid option in patients with early-stage tumors at baseline prioritizing organ preservation .

Despite its functional advantages, full-thickness local excision in previously irradiated tissue with minimal margins of 10 mm carries inherent risks that must be carefully considered. This approach has been associated with complication rates of up to 30%, including persistent proctalgia during the first year, as well as reinterventions due to abscess formation and rectal bleeding [13].

As research continues, the combination of clinical assessments, advanced imaging, and biomarkers like ctDNA is expected to refine patient stratification and help guide treatment decisions. Nomograms including clinical, radiological, and molecular data are already in development, offering individualized risk assessments for rectal cancer patients. These models, once validated, could become the foundation for personalized treatment algorithms [15].

The future of rectal cancer treatment lies in integrating these evolving strategies, with local excision playing a pivotal role in increasing organ preservation rates and improving quality of life without compromising oncological outcomes. By leveraging advanced diagnostic tools, clinicians can better select patients for appropriate therapies, avoiding overtreatment while ensuring effective treatments.

Modern neoadjuvant therapy regimens offer rectal cancer patients a growing chance of achieving a complete response. Nonetheless, the current tools for assessing this lack the strength to orient decisions in many cases. When incorporated into decision-making, local excision can offer several benefits: it enables confirmation of pCR in near-complete responders, reduces the risk of overtreatment by avoiding unnecessary TME, and improves patient quality of life by providing organ-preserving alternatives. For near-complete responders and carefully selected noncomplete responders, local excision offers a balance between oncologic safety and quality of life. In an era increasingly focused on personalized medicine, local excision may well be the pillar that enables safer organ preservation while ensuring similar oncological outcomes. However, its role is limited by baseline T category and the risk of procedure-related morbidity, all of which highlight the critical importance of rigorous patient selection and informed decision-making within an experienced multidisciplinary team.

ARTICLE INFORMATION

Conflict of interest

No potential conflict of interest relevant to this article was reported.

Funding

None.

Author contributions

Conceptualization: all authors; Investigation: DGN; Resources: MGD; Writing–original draft: DGN, LT; Writing–review & editing: LT, MGD, JCR. All authors read and approved the final manuscript.

REFERENCES

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Pathologic complete response in rectal cancer: advocating for local excision

Ann Coloproctol. 2025;41(6):592-595. Published online December 24, 2025

DOI: https://doi.org/10.3393/ac.2025.00829.0118

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Pathologic complete response in rectal cancer: advocating for local excision