Surgical treatment of colorectal cancer: A multidimensional review

Abstract

Colorectal cancer (CRC) is the third most prevalent malignancy worldwide and the second leading cause of cancer-related mortality. Its global incidence increases annually, with most patients diagnosed at advanced stages. Despite substantial advancements in chemotherapy, radiotherapy, immune therapy, and targeted therapy, surgical treatment remains the mainstay for CRC management. Particularly, surgery is most effective for managing early-stage and locally advanced cancers. CRC surgery has evolved from conventional subtractive surgery to modern minimally invasive and precision-based techniques. Additionally, CRC treatment strategies have expanded from a single surgical therapy to a multi-modal integrated system encompassing endoscopic therapy, perioperative therapy, molecular targeted therapy, and immunotherapy. This review elucidates the evolution of CRC surgical treatment, describing its transition from early palliative surgery to radical surgery, and, finally, to functional surgery, minimally invasive surgical techniques, and personalized treatment. It reflects the transformation in CRC treatment from simplistic to complex, from generalized to precise, and from singular to comprehensive techniques, providing a holistic perspective on advancements in CRC surgical treatment.

Key Words: Colorectal cancer; Surgical treatment; Precision therapy; Comprehensive treatment; Multidisciplinary team; Targeted therapy

Core Tip: This review systematically examines how colorectal cancer treatments vary across patient subgroups, exploring the historical progression of surgical interventions, evaluating technical and clinical innovations at each stage, and highlighting future directions to address unmet needs in personalized care.

INTRODUCTION

Understanding the role of treatments in colorectal cancer (CRC) management is critical for improving patient outcomes. CRC is a malignant neoplasm characterized by high incidence and mortality, with its prevalence steadily increasing because of evolving lifestyle patterns and an aging population[1]. Moreover, the prognosis for CRC remains largely unfavorable because a substantial proportion of cases are diagnosed at advanced stages. Surgical intervention remains the cornerstone of CRC management and helps in achieving curative outcomes, particularly in early-stage and locally advanced CRC[2,3]. Nevertheless, the landscape of CRC treatment has undergone a transformation, propelled by remarkable advancements in surgical techniques and the widespread adoption of multidisciplinary team (MDT) approaches. This evolution has transitioned from palliative surgeries to a comprehensive therapeutic model comprising radical resection, function-preserving procedures, minimally invasive techniques, and precision medicine (Table 1). How do treatments used for CRC differ across various patient populations? This review systematically examines how CRC treatments vary across patient subgroups, exploring the historical progression of surgical interventions, evaluating technical and clinical innovations at each stage, and highlighting future directions to address unmet needs in personalized care.

Table 1 Surgical approaches for colorectal cancer: Stages and techniques.

Stage	Main surgical procedures	Characteristics and indications
Early palliative surgery	PTR[5], SEMS[6-8], S/B[9], Hartmann's procedure[10]	Used to relieve symptoms like obstruction/bleeding, suitable for early-stage patients or those unable to undergo radical surgery. SEMS is preferred for advanced bowel obstruction relief
Radical surgery	Right/left hemicolectomy[18], hemicolectomy[18], transverse colectomy[18], radical sigmoidectomy[18], D3 lymph node dissection[19,20]	Complete tumor and regional lymph node removal, primarily for locally advanced CRC, to improve DFS and OS
Function-preserving surgery	LAR[24,25], TaTME[24,30-32], TME[30-32], APR[24]	Tumor location-based selection, prioritizing sphincter preservation, especially in low rectal cancers, to maintain quality of life. APR is considered when sphincter preservation is not feasible
Minimally invasive surgery	Laparoscopic surgery[35,38,39], SILS[40,41], TAMIS[42,43], RAS[44,45]	Less trauma, faster recovery, and shorter hospital stays. Robotic and laparoscopic techniques improve surgical precision and reduce complications, particularly in low CRC and obese patients
Precision medicine surgery	Genomic-guided personalized surgery[53,54], AI-assisted surgical decision-making[55-58], liquid biopsy for post-operative monitoring[59,60]	Combines molecular diagnostics, AI, and post-operative monitoring for precise, tailored treatment plans, improving surgical outcomes and recurrence prediction

CRC: Colorectal cancer; SEMS: Self-expanding metal stents; PTR: Primary tumor resection; S/B: Stoma/bypass; DFS: Disease-free survival; OS: Overall survival; LAR: Low anterior resection; TaTME: Transanal total mesorectal excision; TME: Total mesorectal excision; APR: Abdominoperineal resection; MIS: Minimally invasive surgery; SILS: Single incision laparoscopic surgery; TAMIS: Transanal minimally invasive surgery; RAS: Robotic-assisted surgery; AI: Artificial intelligence.

EARLY PALLIATIVE SURGERY

In the early stages of CRC treatment, surgical intervention was primarily aimed at alleviating clinical symptoms, such as intestinal obstruction and hemorrhage. This limitation originated from an insufficient understanding of tumor biology and anatomy. During this period, cytoreductive surgery, which focuses on partially removing tumor tissues to relieve suffering, was the mainstay treatment. However, it did not attain complete tumor eradication because of inadequate conceptual and technical support for curative treatment, resulting in suboptimal long-term survival rates. Early palliative surgical strategies included primary tumor resection (PTR), stoma creation/bypass (S/B), Hartmann's procedure, and self-expanding metal stents (SEMS)[4,5]. PTR is the standard treatment for early-stage CRC (e.g., cT1N0M0) or patients with symptoms suggesting malignancy but no pathological diagnosis. Additionally, PTR has demonstrated satisfactory clinical efficacy[5]. This aligns with clinical guidelines that recommend PTR as the first-line treatment for early-stage CRC due to its curative potential and favorable long-term outcomes. However, the latest meta-analysis suggests that SEMS has emerged as the preferred treatment for patients with advanced obstructive CRC, particularly patients with limited life expectancy or surgical contraindications. This can be attributed to its minimally invasive nature and rapid symptom relief[6]. Analogous studies further demonstrated that SEMS yields superior clinical success rates, reduces complications, and improves survival outcomes in the management of malignant colorectal obstruction, compared with traditional palliative surgical interventions[7,8]. These findings align with guidelines favoring SEMS for palliation, given its immediate relief, reduced invasiveness, and lower surgical risks. S/B is primarily utilized to alleviate CRC symptoms in patients with unresectable or advanced diseases, thereby improving their quality of life. A retrospective study suggested that whereas bypass surgery alleviates bowel obstruction in patients with advanced CRC, it fails to eradicate tumors[9]. Similar to S/B, Hartmann's procedure is indicated for clinical situations, such as acute bowel obstruction, perforation, or infection caused by CRC[10]. Hartmann’s procedure is recommended in emergencies for sepsis control, though more invasive than SEMS.

These indications for palliative surgical interventions vary considerably, with diverse effects on patient outcomes, prognosis, and survival. PTR demonstrates superior efficacy in symptom relief and in reducing long-term complications. In patients with early-stage CRC, PTR achieved a significant long-term survival benefit, with survival rates of up to 94.0%, 84.7%, and 78.4% at 1, 3, and 5 years after surgery, respectively[11]. Furthermore, in asymptomatic patients with stage IV CRC with unresectable metastases, PTR alone significantly improved the 3-year overall survival [hazards ratio (HR) = 0.69, 95% confidence interval (95%CI) = 0.57-0.83, P = 0.0001] and 5-year overall survival (HR = 0.77, 95%CI = 0.62-0.95, P = 0.01)[12,13]. These findings support PTR for early-stage CRC (improving survival and long-term control) and select advanced cases if survival benefit is demonstrated. Moreover, the clinical success rate of SEMS can reach 82% to 94.8%. Nevertheless, the long-term patency rate is limited, with a median patency time of 55 to 343 days[14,15]. The mean interval for stoma closure after Hartmann's procedure is 7.8 months, with an average hospitalization period of 16.5 days after stoma reversal. Additionally, the procedure is associated with a low success rate of stoma reversal and a high incidence of postoperative complications[10,16]. A retrospective study reported a high incidence of early postoperative complications after colostomy, with surgical site infection, anastomotic leakage, and bowel obstruction being the most common complications[17] Clinical guidelines stress SEMS's limited durability and Hartmann's procedure challenges, underscoring the importance of patient selection, perioperative optimization, and surveillance to improve CRC surgery outcomes.

Overall, although these surgical approaches can serve as palliative treatment modalities for CRC, their indications and prognostic outcomes differ substantially. Therefore, in clinical practice, the individualized characteristics of patients should be considered while selecting the optimal treatment strategy.

RADICAL OPERATION AND FUNCTION-PRESERVING PROCEDURES

With an in-depth understanding of CRC pathophysiology and anatomy, radical surgery has become the mainstay of treatment. Its core concept is the precise removal of the tumor along with the complete excision of regional lymph nodes, thus reducing the risk of local recurrence and distant metastasis. For CRC, the primary radical surgical modalities include right hemicolectomy, transverse colectomy, left hemicolectomy, and radical sigmoidectomy[18]. D3 lymph node dissection has been gradually established as the standard procedure for radical surgery[19,20]. It can significantly improve both disease-free survival (DFS) and overall survival (OS) in patients with stage T3 and T4 CRC[21]. Furthermore, compared with D2 dissection, D3 lymph node dissection not only improves the 5-year OS in patients with CRC but also reduces both local recurrence and distant metastasis[22,23]. Studies confirm D3 lymphadenectomy as the preferred CRC approach, providing complete tumor removal and superior survival outcomes.

The choice of radical surgery for CRC depends on the location of the tumor from the anal verge and includes the following procedures: Transanal total mesorectal excision (TME) and TME (≥ 5 cm); low anterior resection (LAR) (≥ 5 cm); and abdominoperineal resection (APR) (< 5 cm)[24]. Among these approaches, APR is associated with a higher incidence of postoperative complications because of the inevitable loss of anal function[25]. In contrast, other sphincter-preserving surgeries significantly improve the postoperative quality of life while ensuring oncological radicality[26]. Furthermore, these approaches fall within the domain of function-preserving surgery. Both function-preserving and radical surgeries aim to ensure complete tumor resection[27]. However, their surgical philosophies vary substantially. Function-preserving surgery, while aiming for radical tumor resection, emphasizes the maximal preservation of physiological functions, reducing postoperative complications and improving the quality of life[28,29]. Clinical guidelines recommend tumor location-based surgical selection to optimize oncologic and functional outcomes, favoring sphincter-preserving approaches over APR to maintain quality of life while ensuring oncologic efficacy. A systematic review and meta-analysis demonstrated that transanal TME (TaTME) significantly outperformed laparoscopic TME in treating mid-to-low CRC, with a lower rate of positive circumferential resection margin [odds ratio (OR) = 0.68], a higher R0 resection rate (OR = 1.74), and a reduced conversion to open surgery (OR = 0.16), while maintaining comparable postoperative complications and 30-day mortality[30]. Moreover, both TaTME and TME yield excellent oncological outcomes in patients with mid-to-high CRC, significantly improving DFS and OS[31,32]. These findings support guidelines favoring TaTME for mid-low rectal cancer (superior oncology, comparable safety) over laparoscopic TME, while endorsing both TaTME and TME for mid-high tumors to improve survival.

Radical surgery serves as the mainstay of CRC treatment and primarily aims at the complete resection of the tumor and its regional lymph nodes to achieve tumor-free survival. Its continuous refinement and advancement have laid a solid foundation for the subsequent emergence of function-preserving surgery.

MINIMALLY INVASIVE SURGERIES

Minimally invasive surgery (MIS) represents a noteworthy advancement in CRC treatment. Techniques, such as laparoscopic and robotic-assisted surgery, have gained clinical attention because of their advantages in reduced trauma, faster recovery, and shorter hospital stays[33,34]. In CRC treatment, MIS encompasses several advanced techniques, including laparoscopic surgery, single incision laparoscopic surgery (SILS), transanal MIS (TAMIS), TaTME, and robot-assisted surgery (RAS)[35]. MIS yields outcomes comparable to those of open surgery concerning tumor eradication and long-term survival, while significantly reducing postoperative complications[36,37]. Guidelines increasingly recommend MIS over open surgery due to comparable oncologic outcomes, fewer complications, faster recovery, and better patient-tailored treatment. Data from the CLASICC and COLOR trial demonstrated no significant differences in DFS (45.2% vs 43.2%) and OS (48.4% vs 46.7%) between laparoscopic and open surgery groups, confirming laparoscopic surgery as an oncologically equivalent alternative to open surgery[38,39]. These findings support laparoscopic surgery as a standard CRC treatment, offering comparable oncologic outcomes with lower morbidity than open surgery. SILS—an innovative approach in laparoscopic techniques—further reduces surgical trauma and minimizes abdominal scar formation, while yielding superior minimally invasive outcomes and cosmetic advantages[40,41]. TAMIS leverages its direct and magnified surgical field, thus enabling precise tissue resection and suturing, which eventually improves the preservation of urinary and sexual functions while reducing hospital stays and postoperative pain[42]. TAMIS achieves superior circumferential resection margin and distal resection margin negativity rates, compared with conventional approaches, with oncological outcomes at least equivalent to standard laparoscopic surgery[43]. Guidelines endorse SILS/TAMIS as advanced minimally invasive options for select CRC patients, offering less trauma, better cosmesis, function preservation, and reduced pain. With the continuous advancement of surgical technology, RAS is being increasingly applied to CRC treatment[44,45]. RAS offers unique advantages in managing low CRC and in patients with obesity. Its precise manipulation and optimized surgical field facilitate better preservation of pelvic autonomic nerves, thus reducing postoperative sexual and urinary dysfunction[46,47]. In locally advanced T4 tumors, RAS lowers the conversion rate to open surgery (8.9% vs 17.9%), besides improving the 5-year OS by 12.8% (56.2% vs 43.4%), compared with conventional laparoscopic surgery[48-50]. These findings support guidelines recommending RAS for select CRC cases (e.g., low-lying tumors, obesity) given its precision and superior oncologic outcomes.

MIS has revolutionized CRC treatment, with laparoscopic and robotic techniques significantly improving outcomes through enhanced precision and reduced trauma. The integration of artificial intelligence (AI) and 5G technologies promises to further advance MIS, enabling remote operations and intelligent assistance for more precise, personalized surgical approaches.

PRECISION MEDICINE

Rapid advancements in molecular biology and genomic technologies have driven a paradigm shift in CRC treatment. Clinical therapeutic strategies have progressively evolved from traditional treatment approaches toward precision and personalized medicine[51,52]. In CRC, genomics-guided precision oncology highlights the critical role of detecting molecular biomarkers in preoperative evaluation. Through mutational analysis of key driver genes, such as Kirsten rat sarcoma viral oncogene homolog, B-Raf proto-oncogene, serine/threonine kinase, and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha, clinicians can accurately assess tumor molecular characteristics, predict biological behavior and therapeutic response, and formulate tailored treatment plans[53,54]. Guidelines strongly recommend integrating molecular biomarkers and precision medicine into CRC management for accurate tumor profiling and personalized therapy. AI-based surgical systems integrate real-time data analysis, automated operation platforms, and multi-omics technologies; they can optimize surgical decision-making, reduce operational errors, and facilitate the precise implementation of tailored treatment strategies[55,56]. By integrating genomic profiles, clinicopathological data, and multimodal imaging information, AI-based surgical systems enable precise tumor resection, ensuring curative outcomes while maximizing the preservation of healthy tissue function[57,58]. These findings support guideline-recommended AI integration in surgery to enhance precision, decision-making, and oncologic/functional outcomes. These technologies enhance precision in CRC postoperative care. Liquid biopsy technologies (circulating tumor cells and circulating tumor DNA) enable dynamic monitoring of residual disease, accurate recurrence risk assessment, and optimized adjuvant therapy based on pathological findings. Therefore, they facilitate comprehensive management[59,60]. Guidelines endorse liquid biopsy for postoperative care, enabling dynamic monitoring, recurrence risk assessment, and optimized adjuvant therapy.

Precision medicine spans the entire treatment, utilizing MDT approaches for personalized care. It focuses on precise preoperative assessments for treatment planning, advanced techniques for tumor resection, and dynamic postoperative monitoring with timely adjustment. MDT teams integrate multidisciplinary expertise to develop optimally tailored treatment plans, ensuring radical tumor removal while emphasizing rehabilitation to enhance the quality of life and long-term outcomes[61].

CONCLUSION

The surgical landscape for CRC has undergone a transformation from traditional open surgery to laparoscopic and minimally invasive procedures, further advancing to robot-assisted surgical systems. This technological progression has not only enhanced surgical precision but also reduced perioperative complications, substantially improving long-term survival outcomes. Nevertheless, numerous challenges persist in CRC surgical treatment: (1) The need for optimized strategies to prevent and control postoperative recurrence and metastasis; (2) The refinement of standardized and personalized multidisciplinary treatment models; (3) Addressing technical bottlenecks in the clinical translation of precision medicine; and (4) Improving the cost-effectiveness of robotic surgical systems. Additionally, the integration of emerging therapeutic technologies with traditional surgical approaches, developing systematic assessments for long-term quality of life, and ensuring equitable regional allocation of medical resources require further exploration. Overcoming these challenges will advance CRC treatment toward greater precision, efficacy, and patient-centered care. Our analysis contributes to the field by providing a comprehensive overview of the current state and future directions of CRC surgical treatment, highlighting key challenges and potential solutions. Iterative advancements in robotic surgical systems, deeper integration of AI-assisted decision-making, refined applications of liquid biopsy technologies, and innovations in multidisciplinary treatment models will drive future improvements in CRC management. Additionally, the rationalized control of treatment costs and surgical management of CRC are poised to achieve dual improvements in precision and accessibility. This evolutionary trajectory will enhance not only long-term survival outcomes but also functional recovery and quality of life, finally facilitating a transformation from disease treatment to health management. Future research should focus on several promising areas. For instance, exploring the efficacy of new therapies, such as immunotherapies and targeted treatments, could offer more effective options for patients with advanced or recurrent CRC. Additionally, addressing the needs of underserved populations, including those in low-income regions or with limited access to advanced medical care, is crucial to ensure equitable treatment outcomes. Systematic studies on the long-term quality of life for CRC survivors and the development of cost-effective precision medicine strategies are also recommended.