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HOME > Ann Coloproctol > Volume 42(1); 2026 > Article
Editorial
 Over and above what is visible and conventional: development of new territories in colorectal cancer management
In Ja Parkorcid
Annals of Coloproctology 2026;42(1):1-3.
DOI: https://doi.org/10.3393/ac.2026.00227.0032
Published online: February 27, 2026

Division of Colon and Rectal Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

Correspondence to: In Ja Park, MD, PhD Division of Colon and Rectal Surgery, Department of Surgery, Asan Medical Center, University of College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea Email: ipark@amc.seoul.kr
• Received: February 11, 2026   • Accepted: February 11, 2026

© 2026 The Korean Society of Coloproctology

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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The management of colorectal cancer (CRC) is currently undergoing a paradigm shift. While traditional approaches, such as surgical resection, chemotherapy, and radiotherapy, have been the mainstays of treatment, we are now entering an era of integrated treatment that combine precision molecular-targeted therapy, image-guided surgery, and insights into the host-microbe ecosystem. To realize a true paradigm shift, it is no longer sufficient to rely on generalized treatment protocols. Instead, we must embrace a multidisciplinary integration of these emerging frontiers. In the special section of this issue, we explore 3 pillars of modern CRC management: the strategic expansion of immunotherapy into the challenging domain of microsatellite stable (MSS) tumors, the transition of fluorescence-guided surgery (FGS) from a qualitative visual aid to a quantitative precision instrument, and the translation of gut microbiome research from the lab into clinical practice.
The treatment paradigm in oncology has shifted significantly with the introduction of immune checkpoint inhibitors (ICIs) [1]. In the CRC, the remarkable efficacy of programmed cell death protein 1 (PD-1) blockade in microsatellite instability-high (MSI-H) tumors, highlighted by the landmark findings in recent neoadjuvant trials for rectal cancer [2], has set a high bar for clinical expectations. However, the vast majority of CRC (85%–95%) are MSS. These tumors are characterized by a "cold" tumor microenvironment, defined by a low tumor mutational burden (TMB), poor T-cell infiltration, and the various immunosuppressive factors that limit the efficacy of ICI monotherapy.
Recent efforts to modify the cold tumor microenvironment through combination strategies have yielded inconsistent outcomes. Emerging combination strategies, such as the PD-1 and multikinase inhibitor regimens investigated aimed to address the immunosuppressive mechanisms of MSS tumors [3, 4]. Despite these efforts, clinical outcomes have been suboptimal, as response rates remain modest than the benchmarks set by MSI-H patients. These outcomes define a fundamental limitation in current management. The findings indicate that biomarker-driven stratification is essential to optimize the clinical impact of combination immunotherapy.
Future immunotherapy strategies must evolve beyond a primary focus on response rates. Beyond objective response rates, a more integrated assessment is required to optimize the trade-off between therapeutic efficacy, immune-related adverse events (irAEs), and practical clinical implementation. To achieve this, more precise targeting is essential. Beyond established markers like TMB, artificial intelligence–driven tools are now offering new insights by mapping the spatial distribution of tumor-infiltrating lymphocytes, which may help delineate responders within the MSS subgroup [1].
Alongside improved patient selection, the effective management of irAEs is now critical to therapeutic success. The clinical challenge with irAEs is their heterogeneous presentation, as they can manifest in any organ system with variable onset both during and after therapy. Moreover, the absence of validated, quantitative metrics to assess irAE severity remains a significant barrier to prompt clinical decision-making. This limitation is increasingly evident as clinical practice shifts toward intensified regimens, such as dual checkpoint blockade. While these combination therapies offer superior efficacy, they also escalate the risk of severe, multisystem toxicities. While these intensified regimens are intended to overcome the intrinsic resistance of MSS tumors, they concomitantly increase both the incidence and severity of toxicities. Future clinical efforts should focus on integrating treatment efficacy with standardized protocols for the early detection and objective quantification of irAEs, thereby improving patient outcomes in an era of intensified immunotherapy.
In the operating room, the implementation of FGS using indocyanine green (ICG) has significantly enhanced intraoperative visualization. Previously limited to anatomical mapping, this technology now incorporates multi-dimensional data to better inform surgical decision-making and ensure surgical reliability [5]. The utility of ICG-based fluorescence angiography for assessing tissue perfusion and confirming anastomotic viability is well established.
Despite its promise, the clinical impact of FGS remains inconclusive, as recent trials have yielded conflicting outcomes [6, 7]. These studies have shown inconsistent results regarding the ability to significantly reduce clinically relevant anastomotic leaks. Such inconsistencies arise because FGS, despite its goal of objectifying perfusion, is still interpreted through subjective observation, lacking the quantitative criteria needed for standardized decision-making. The brightness of fluorescence is perceived differently by different surgeons, and there is no universal consensus on what constitutes adequate perfusion. Furthermore, the limitations of current FGS are most evident in oncology, where functional precision is important. In lymphatic mapping, conventional ICG-based FGS cannot differentiate between metastatic and benign lymph nodes. It only visualizes lymphatic drainage patterns, often identifying sentinel nodes regardless of their oncological status. This lack of tumor-specificity prevents FGS from serving as a precise intraoperative tool for achieving complete oncological clearance while maximizing organ preservation.
Consequently, the growth of FGS requires 2 essential changes: broader clinical application and the use of standardized quantitative measures. We are already seeing the application of FGS in more complex procedures, such as lateral pelvic lymph node dissection for advanced rectal cancer, where FGS enhances anatomical plane identification and reduces blood loss. However, for FGS to become a standard of care, we must move beyond the direct vision. Objective parameters, such as time-to-peak, the slope of the fluorescence intensity curve, and the time ratio, must be integrated. These metrics provide a quantifiable measure of perfusion that is independent of the subjective perception, facilitating more accurate intraoperative decision-making.
Simultaneously, we must look beyond the limitations of ICG. New technologies are currently under development to solve the issues of tissue penetration and specificity. Near-infrared II (NIR-II) agents, which operate at longer wavelengths, allow for deeper tissue standoff and clearer imaging through blood and fat. Additionally, the development of hybrid positron emission tomography (PET)/NIR tracers and tumor-targeted fluorescent molecules promises a shift from anatomical imaging to biological imaging. This enhanced integration allows for the intraoperative visualization of tumor margins and metastatic deposits, offering superior accuracy over ICG-based systems.
A third key area of focus is the human gut microbiome, which is now recognized as a central mediator of colorectal carcinogenesis. Beyond its role in metabolic activity, the microbiome actively influences inflammation, metabolite production, and immune modulation. Its potential as a diagnostic tool and a therapeutic target has led to the development of microbiome-based interventions, such as fecal microbiota transplantation, next-generation probiotics, and dietary modifications, aimed at enhancing treatment efficacy and reducing the toxicities associated with chemotherapy and immunotherapy [8].
Despite this potential, translating these findings into clinical practice presents significant challenges. The primary obstacle in this transition is the inherent heterogeneity of microbiome data. Microbial composition varies widely across diverse populations, shaped by geographic, dietary, and lifestyle factors. This variability is further complicated by the lack of standardization in sampling protocols, sequencing platforms, and bioinformatic pipelines. Without a unified interpretative framework, it remains difficult to characterize a "healthy" microbiome in a manner that is clinically applicable [9].
Current understanding of host-microbe crosstalk remains limited. It is increasingly clear that functional output is a more critical determinant of health than microbial identity. Because an effect of strain depends on the internal environment, developing broad-spectrum microbiome interventions remains difficult.
In response to these barriers, the research regarding microbiome-based therapy needs to shift its focus. Future efforts should transition from small-scale, observational studies to formal, pragmatic clinical trials with well-designed and systematic safety assessments. Defining a standardized microbiome signature across diverse populations remains a priority. Furthermore, research must focus on the functional characterization of these microbial communities, specifically identifying the metabolites they produce and their interaction with the host immune system. These insights are essential to integrating microbiome-based interventions into standard clinical practice for CRC patients.
The management of CRC is currently undergoing a paradigm shift. Innovations in immunotherapy, FGS, and microbiome research provide a foundation for improving survival rates and moving toward preventative oncology. However, realizing this potential requires more than the adoption of new technologies; it necessitates a balanced strategy that integrates innovation with evidence-based clinical judgment and comprehensive scientific validation.
Through the more personalized and biomarker-driven application of immunotherapy, the systematic quantification of surgical technologies, and the standardization of microbiome research, we will move closer to achieving truly precision-based oncology in CRC. Our objective is to overcome current clinical limitations and meet the unmet needs for highly effective, individualized care in CRC. The special section in this issue presents a comprehensive framework for these advancements, identifying key challenges and the clinical impact these innovations will have on our field.

Conflict of interest

In Ja Park is the current editor-in-chief of this journal, but was not involved in the peer reviewer selection, evaluation, or decision process of this article. No other potential conflict of interest relevant to this article was reported.

Funding

None.

  • 1. Kim SY. Immunotherapy for microsatellite-stable colorectal cancer: overcoming resistance and exploring novel therapeutic strategies. Ann Coloproctol 2026;42:47–57. Article
  • 2. Cercek A, Dos Santos Fernandes G, Roxburgh CS, Ganesh K, Ng S, Sanchez-Vega F, et al. Mismatch repair-deficient rectal cancer and resistance to neoadjuvant chemotherapy. Clin Cancer Res 2020;26:3271–9. ArticlePubMedPMC
  • 3. Hecht JR, Park YS, Tabernero J, Lee MA, Lee S, Virgili AC, et al. Zanzalintinib plus atezolizumab versus regorafenib in refractory colorectal cancer (STELLAR-303): a randomised, open-label, phase 3 trial. Lancet 2025;406:2360–70. ArticlePubMed
  • 4. Liu R, Ji Z, Wang X, Zhu L, Xin J, Ma L, et al. Regorafenib plus sintilimab as a salvage treatment for microsatellite stable metastatic colorectal cancer: a single-arm, open-label, phase II clinical trial. Nat Commun 2025;16:1481.Article
  • 5. Lee KH. Fluorescence-guided surgery in colorectal cancer: current evidence, quantitative advances, and future perspectives. Ann Coloproctol 2026;42:58–71. Article
  • 6. Watanabe J, Takemasa I, Kotake M, Noura S, Kimura K, Suwa H, et al. Blood perfusion assessment by indocyanine green fluorescence imaging for minimally invasive rectal cancer surgery (EssentiAL trial): a randomized clinical trial. Ann Surg 2023;278:e688–94. ArticlePubMedPMC
  • 7. Jafari MD, Wexner SD, Martz JE, McLemore EC, Margolin DA, Sherwinter DA, et al. Perfusion assessment in laparoscopic left-sided/anterior resection (PILLAR II): a multi-institutional study. J Am Coll Surg 2015;220:82–92. ArticlePubMed
  • 8. Han JY, Kim MJ, Park JW, Jeong SY. Gut microbiome in colorectal cancer: recent advances and clinical implications. Ann Coloproctol 2026;42:72–85. Article
  • 9. Shanahan F, Ghosh TS, O'Toole PW. The healthy microbiome: what is the definition of a healthy gut microbiome? Gastroenterology 2021;160:483–94. ArticlePubMed

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        Over and above what is visible and conventional: development of new territories in colorectal cancer management
        Ann Coloproctol. 2026;42(1):1-3.   Published online February 27, 2026
        DOI: https://doi.org/10.3393/ac.2026.00227.0032
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