INTRODUCTION
Colon cancer is a common malignancy of the digestive tract. Its 5-year survival rate progressively declines with increasing T stage[1]. T4 disease accounts for 10%-15% of all colon cancer cases[2-4] and is associated with a poor prognosis. Statistics indicate a 5-year survival rate of only 20% for patients with T4, node-positive colon cancer[5,6]. Even for patients with T4N0 disease, the 5-year disease-free survival (DFS) is only 74%[7]. Within the broader category of stage II colorectal cancer, T4 status serves as an independent risk factor, significantly influencing subsequent treatment planning and oncological outcomes.
There is significant controversy about the diagnosis and management of T4 colon cancer, primarily involving two key issues: (1) The low concordance between pathological and clinical staging (cT) for T4 disease; and (2) The indications for neoadjuvant therapy or hyperthermic intraperitoneal chemotherapy (HIPEC). This review analyzes the current literature to address these issues and discuss emerging trends.
LITERATURE SEARCH STRATEGY
Given the narrative nature of this review, a systematic literature search was not performed; however, a structured and transparent approach was adopted to identify relevant studies. We conducted a comprehensive search of the PubMed, Web of Science, and Cochrane Library databases for articles published up to October 2025. The search strategy combined Medical Subject Headings and free-text terms, including but not limited to “T4 colon cancer”, “colorectal cancer staging”, “pathological staging”, “clinical staging”, “intraoperative staging”, “neoadjuvant therapy”, “immunotherapy”, “dMMR/MSI-H”, “hyperthermic intraperitoneal chemotherapy”, and “peritoneal metastasis”. Reference lists of relevant original articles and previous reviews were also manually screened to identify additional eligible studies. We included peer-reviewed original research, meta-analyses, systematic reviews, and major guideline recommendations (e.g., NCCN, ESMO, ASCO, and CSCO) that addressed the management of T4 colon cancer. Non-English publications, conference abstracts without full text, and case reports were excluded. The selection of cited literature was guided by relevance to the key controversies discussed in this review-namely, staging discrepancies, neoadjuvant and immunotherapeutic strategies, and the role of prophylactic HIPEC. This approach, while not systematic, ensures a balanced and comprehensive coverage of the available evidence and enhances the transparency of our review process.
DIAGNOSIS OF T4 STAGE
Pathological T4
According to the AJCC 8th edition TNM staging system for colorectal cancer, pathological T4 (pT4) is defined as tumor perforating the visceral peritoneum or directly invading or adhering to adjacent organs or structures. This is subdivided into pT4a: Tumor perforating the visceral peritoneum (including gross perforation of the bowel at the tumor site and continuous tumor infiltration through areas of inflammation to the visceral peritoneal surface); and pT4b: Tumor directly invading or adhering to adjacent organs or structures. Direct invasion in pT4b includes penetration of the serosa to involve another bowel segment, confirmed histologically (e.g., cecal cancer invading the sigmoid colon). For tumors in retroperitoneal or subperitoneal segments, direct invasion involves penetration beyond the muscularis propria into other organs or structures, such as a tumor on the posterior wall of the descending colon invading the left kidney or lateral abdominal wall, or mid-to-lower rectal cancer invading the prostate, seminal vesicles, cervix, or vagina. Gross adherence of the tumor to adjacent organs or structures is staged as cT4b; if microscopic examination of the adherence reveals no tumor cells, the stage is pT3.
During pathological examination of surgical specimens to determine pT stage, pathologists typically section the tumor tissue along the long axis of the bowel wall, parallel to the bowel wall. Samples are taken based on tumor size, depth of invasion, and areas with varying texture or color. At least one full-thickness section of the tumor and bowel wall is taken from the deepest area of invasion to determine the maximal depth of infiltration, with careful attention to serosal involvement. The serosa is the membrane covering the colon and the rectum above the peritoneal reflection, a continuation of the visceral peritoneum and mesentery. A layer of fibrovascular adipose tissue, the subserosa, lies between the serosa and the muscularis propria; tumor invasion into this layer constitutes pT3. Diagnosis of pT4a requires the tumor to have reached or penetrated the serosal layer.
The presence of tumor cells within 1 mm of the serosal surface, accompanied by fibroinflammatory changes and mesothelial hyperplasia, may constitute histological evidence of serosal penetration and should be classified as pT4a[8]. Tumors approaching the serosa with associated fibroinflammatory reactions behave similarly to tumors directly contacting the serosa, suggesting this scenario should also be considered evidence of serosal penetration[9]. The AJCC 8th edition acknowledges this controversy but still mandates definitive tumor penetration through the serosa for pT4a classification due to conflicting data. Diagnostic challenges arise from fibroinflammatory reactions at the tumor edge and reactive mesothelial hyperplasia, which can obscure individual tumor cells or small clusters on the serosal surface[9,10]. pT3 colorectal cancers with elastic lamina invasion (ELI) have a worse prognosis than those without ELI[11]. Some data suggest that the prognosis of pT3/ELI+ is comparable to pT4a, but it may be intermediate between pT3/ELI- and pT4a[11,12]. Even the pathological distinction between pT3 and pT4a remains debated.
Pathologists frequently underdiagnose serosal involvement. Confirming peritoneal involvement necessitates meticulous pathological analysis. This often requires extensive sampling and serial sectioning, a standard rarely achieved in routine practice. pT4 disease is prone to underdiagnosis in conventional histopathological examinations; up to 26% of tumor specimens classified as pT3 by histological examination alone test positive for malignant cells on serosal scraping cytology[9,13].
Clinical T4
Beyond pathological staging, cT is commonly employed, primarily using imaging modalities such as contrast-enhanced abdominal computed tomography (CT). No definitive diagnostic criteria exist for CT-based cT of colon cancer. Radiologists generally consider CT findings indicative of clinical T4 (cT4) disease to include tumor perforation, peritumoral abscess formation, and direct invasion of adjacent organs[14,15].
Due to the inherent limitations of imaging, cT staging accuracy is generally lower than that of pT staging. Discrepancies between preoperative cT and postoperative pT are common, with the latter taking precedence. A large Dutch retrospective study on colon cancer reported an overall concordance of 59% for T stage and 57% for N stage between clinical and pathological assessments. Using pathology as the reference, CT demonstrated a sensitivity of 80% [95% confidence interval (CI): 0.79-0.80] and a specificity of 76% (95%CI: 0.75-0.77) for detecting cT3-cT4 tumors, with a positive predictive value of 92% (95%CI: 0.92-0.92)[16]. Another meta-analysis indicated that CT has an overall sensitivity of 90% (95%CI: 83-95) and specificity of 69% (95%CI: 62-75) for detecting the depth of colon cancer invasion, with nearly one-third of patients experiencing overstaging[17]. This overstaging may result from radiologists interpreting pericolonic fat stranding due to benign desmoplastic reactions as tumor infiltration to minimize the risk of understaging. The analysis further noted that while CT demonstrates good accuracy in distinguishing cT1-2 from cT3-4, challenges remain in further differentiating cT1-3ab from cT3cd-4.
These studies indicates that CT examinations have limited accuracy in the cT of colon cancer, particularly in distinguishing cT3 from cT4, where over-staging may occur. It is also important to recognize, as aforementioned in the pathological staging, that the boundary between pT3 and pT4 remains contentious. This ambiguity may likewise carry a risk of underdiagnosis for pT3. A Korean retrospective study grouped patients diagnosed postoperatively with pT3 based on their preoperative stage (cT3 vs cT4). No significant differences were found in postoperative pathology or chemotherapy administration between the groups. The results showed no significant differences in 5-year overall survival (OS) and DFS between the cT3 and cT4 groups (87.7% vs 79.6%, P = 0.470; and 82.7% vs 71.5%, P = 0.286, respectively). The cT4 group had a significantly higher local recurrence rate (9.1%) compared to the cT3 group (1.4%), and its 5-year local DFS was significantly lower (84.0% vs 98.6%, P < 0.001)[14]. The authors suggested that pathological staging, limited by sampling constraints, often fails to identify microscopic perforations, leading to underdiagnosis in some patients. They argued that incorporating cT staging might provide a more reliable basis for postoperative treatment planning in such cases[14,18].
Another Korean study reached a different conclusion. This study categorized patients preoperatively staged as cT4 colon cancer into postoperative pT3 and pT4 groups, comparing them with a matched cohort of patients staged as both cT3 and pT3. The results showed significant differences in DFS and OS between the cT4/pT3 and cT4/pT4 groups (88.6% vs 68.6%, P < 0.001; and 91.2% vs 76.5%, P = 0.002, respectively). However, no significant differences in DFS or OS were observed between the cT3/pT3 and cT4/pT3 groups (88.6% vs 89.6%, P = 0.151; and 91.2% vs 94.3%, P = 0.503, respectively)[17]. The authors concluded that when planning preoperative neoadjuvant therapy for locally advanced colon cancer, there is a genuine risk of overstaging, potentially leading to overtreatment.
These two studies differ slightly in their grouping methodology, but their conflicting results highlight the ongoing debate about clinical and pathological staging for T4 colon cancer. Given that both are single-center retrospective studies with relatively small sample sizes, further research is needed to clarify the accuracy of cT and its role in guiding treatment decisions.
Surgical T4
Surgical staging (sT), a surgeon-driven assessment, is less commonly employed than pathological and cT. sT relies on the surgeon’s description of the tumor during surgical exploration and after specimen retrieval. This staging has significant limitations and is inherently subjective. Nevertheless, it offers a unique perspective in differentiating T3 from T4 disease, particularly in assessing T4a and T4b status. A retrospective study found that among the patients with sT3 disease, 87.8% ultimately had a pathological diagnosis of pT3 and 12.2% had pT4. Conversely, among patients with surgical T4 (sT4) disease, only 29.6% were confirmed as pT4, while 70.4% were pT3[19]. The study also reported significant differences in 5-year OS and DFS between the sT4 and sT3 groups (92.6% vs 97.7%, P = 0 .024; and 88.6% vs 97.7%, P = 0.017, respectively). Multivariate Cox regression analysis identified sT4 as an independent predictor of tumor recurrence (P = 0.023). Another study corroborated these findings, showing that intraoperative serosal invasion (i.e., sT4) was an independent risk factor for recurrence [hazard ratio (HR): 4.750, 95%CI: 1.381-16.334, P = 0.013] in a multivariate analysis of 375 patients with stage IIA colon cancer[20]. The above study highlights the importance of sT for prognosis. In particular, tumor serosal invasion (sT4a) or adhesion/invasion of surrounding tissues (sT4b) observed during surgery may be a continuation of malignant components. Even if histologically staged as pT3, the prognosis is markedly poorer than that of typical pT3 cases, and these findings should be considered risk factors for colon cancer.
To facilitate grouping and analysis, Chinese researchers have proposed a modified staging system. Their study found no significant prognostic differences between pT3/sT4b and pT4a/sT1-4a (P = 0.599), nor between pT4a/sT4b and pT4b (P = 0.351)[21]. They reclassified patients with pT3/sT4b into a modified category, r-pT4a, with a prognosis comparable to pT4a, and patients with pT4a/sT4b into r-pT4b, with a prognosis similar to pT4b. Survival analysis demonstrated that this modified r-pT staging system had superior predictive power compared to standard pT staging (Harrell’s C: 0.668 vs 0.636, P = 0.002) and was an independent prognostic factor in multivariate regression analysis (HR: 1.846, 95%CI: 1.566-2.176, P < 0.001) (Figure 1).
Figure 1 Survival curves of patients with colorectal cancers according to r-pathological staging category.
A: Survival curves of patients in pathological staging (pT) 3 and pT4a. There were no significant differences between pT3/sT4b and pT4a/sT1-4a (P = 0.599), or between pT4a/sT4b and pT4b (P = 0.351); B: Survival curves of patients stratified by r-pT category. There were significant differences among the patients. pT: Pathological staging. Citation: Liang JW, Gao P, Wang ZN, Song YX, Xu YY, Wang MX, Dong YL, Xu HM. The integration of macroscopic tumor invasion of adjacent organs into TNM staging system for colorectal cancer. PLoS One 2012; 7: E52269. Copyright ©The Author(s) 2012. Published by Public Library of Science (PLoS)[21]. The article is open access (Supplementary material).
Nevertheless, sT staging has significant limitations. It is highly subjective, depending on the surgeon's experience and visual inspection, especially for diagnosing sT4a, where standardized criteria are lacking. It is also difficult to reliably distinguish sTis, sT1, and sT2 using only visual inspection; its utility is mainly confined to differentiating T3 from T4.
Having reviewed pathological, imaging, and intraoperative staging for T4 disease, we note that pathological differentiation between pT3 and pT4 is subject to underdiagnosis, while their prognostic difference is more of a leap than a gradient. This is further underscored by the increased staging weight assigned to pT4 in the AJCC 9th edition. This evidence may point to an intermediate stage between pT3 and pT4. Despite their modest overall accuracy, imaging and intraoperative staging offer complementary perspectives in discriminating T3 from T4. We hypothesize that a macroscopic T-staging system integrating preoperative imaging with intraoperative findings could compensate for pathological limitations and approximate this intermediate category. Nevertheless, this hypothesis requires validation through ample data and prospective studies.
NEOADJUVANT THERAPY FOR T4 COLON CANCER
For pT4 colon cancer, regardless of whether it is stage II or III, the risk of recurrence remains high even after adjuvant chemotherapy with fluorouracil and oxaliplatin, suggesting potential benefit from neoadjuvant therapy[22,23]. The advantages of neoadjuvant therapy include: (1) Improved R0 resection rates and DFS, along with early systemic treatment to address micrometastases; and (2) Assessment of the antitumor efficacy of adjuvant therapy based on post-treatment tumor regression. Recent randomized controlled trials comparing perioperative chemotherapy with standard upfront surgery for locally advanced colon cancer have yielded encouraging results, yet debates persist.
Neoadjuvant therapy for proficient mismatch repair locally advanced colon cancer
The largest study investigating neoadjuvant therapy for locally advanced colon cancer is the FOxTROT trial[23]. This trial randomized 1053 patients with cT3-4 disease (2:1 ratio) to receive either 3 preoperative cycles of OxFu (oxaliplatin, levofolinate, and 5-fluorouracil) every 2 weeks or 2 cycles of OxCap (oxaliplatin and capecitabine) every 3 weeks, followed by surgery and postoperative chemotherapy, or upfront surgery followed by postoperative chemotherapy (standard arm). A secondary randomization within the neoadjuvant arm assessed the addition of panitumumab for patients with RAS wild-type tumors. The neoadjuvant group achieved an absolute 4.6% reduction in the primary endpoint (residual or recurrent tumor at 2 years) [16.9% vs 21.5%; risk ratio (RR) = 0.72, 95%CI: 0.54-0.98, P = 0.037, Figure 2]. Similar proportional reductions were observed for disease-specific mortality (RR = 0.74, 95%CI: 0.52-1.05, P = 0.095) and all-cause mortality (RR = 0.76, 95%CI: 0.55-1.06, P = 0.104), though these did not reach statistical significance. Neoadjuvant chemotherapy significantly reduced pathological tumor stage, with lower postoperative pT and pN stages compared to the upfront surgery group. Notably, the proportion of pT4 disease decreased from 30.5% to 20.7%, and R0 resection rates were higher (94% vs 89%, P < 0.001). The FOxTROT study demonstrated high treatment compliance and safety: 90% of patients in the neoadjuvant group completed all three cycles, and over 99% underwent successful surgery. Another significant study, the OPTICAL trial from China[24], randomized 744 patients with CT-assessed cT3 or cT4 (any N) colon cancer (1:1 ratio). The neoadjuvant group received 3 months of mFOLFOX6 or CAPOX chemotherapy followed by surgery, and then an additional 3 months of adjuvant chemotherapy. The upfront surgery group underwent immediate resection, with adjuvant chemotherapy administered based on postoperative pathology. Compared to the upfront surgery group, the neoadjuvant group had a lower proportion of patients with pathologically advanced tumors (pT3-4: 77% vs 94%, P < 0.001), lower lymph node metastasis rates (pN1-2: 31% vs 46%, P < 0.001), and less perineural invasion (9% vs 17%, P < 0.001). In the neoadjuvant group, 27 patients (7%) achieved pathological complete response (pCR), more patients had pT0-2 disease (23% vs 6%) or pN0 disease (69% vs 54%), and there was a 10% reduction in pT4 and a 5% reduction in pN2 disease. Long-term follow-up showed that the 3-year DFS rate was 82.1% in the neoadjuvant group compared to 77.5% in the upfront surgery group, a trend favoring neoadjuvant therapy that did not reach statistical significance (stratified HR: 0.74, 95%CI: 0.54-1.03). The 3-year OS rate was significantly higher in the neoadjuvant group (95.1%, 95%CI: 92.8-97.4) compared to the upfront surgery group (89.6%, 95%CI: 86.4-92.9).
Figure 2 Risk of recurrence or persistent disease.
RR: Risk ratio; CI: Confidence interval; NAC: Neoadjuvant chemotherapy. Citation: Morton D, Seymour M, Magill L, Handley K, Glasbey J, Glimelius B, Palmer A, Seligmann J, Laurberg S, Murakami K, West N, Quirke P, Gray R; FOxTROT Collaborative Group. Preoperative Chemotherapy for Operable Colon Cancer: Mature Results of an International Randomized Controlled Trial. J Clin Oncol 2023; 41: 1541-1552. Copyright ©The Author(s) 2023. Published by American Society of Clinical Oncology[23]. The article is open access (Supplementary material).
Despite the positive results from FOxTROT and OPTICAL, concerns remain, most notably regarding overtreatment. In both trials, approximately 25% of patients in the upfront surgery group were ultimately diagnosed with stage I or low-risk stage II disease (pT1-3N0), for whom adjuvant chemotherapy is not indicated. Accurately identifying high-risk patients among those with locally advanced colon cancer remains a critical challenge for implementing neoadjuvant strategies.
Neoadjuvant therapy for locally advanced colon cancer with deficient mismatch repair
A notable finding from both FOxTROT and OPTICAL was the poor response of deficient mismatch repair (dMMR) colon cancer to neoadjuvant chemotherapy. In FOxTROT, patients with proficient mismatch repair (pMMR) tumors were significantly more likely to achieve moderate or greater tumor regression compared to those with dMMR tumors (23% vs 7%, P < 0.001). Furthermore, 70.4% of dMMR cancers showed no tumor regression following preoperative treatment[25]. Consistent with this, the OPTICAL trial also reported poor response to chemotherapy in dMMR colon cancer, with 51.2% of patients showing no or poor response[26].
dMMR colon cancer represents a distinct subtype, comprising approximately 11% of locally advanced cases[25], and generally carries a better prognosis than pMMR disease. These tumors express a high number of neoantigens, contributing to their relative resistance to conventional chemotherapy but making them highly sensitive to immune checkpoint inhibitors[26,27]. The NICHE-1 study was the first prospective trial to investigate neoadjuvant immunotherapy in dMMR colon cancer[28]. Among 21 patients with dMMR disease (47% with cT4, 78% node-positive), 20 were treated with ipilimumab and two cycles of nivolumab. All 20 treated patients showed a pathological response, with 95% (19 patients) achieving major pathological response (MPR) and 60% (12 patients) achieving pCR; only one patient (5%) had a partial response. At a median follow-up of 32 months, the recurrence-free survival (RFS) rate was 100%. The NICHE-2 trial expanded on these findings, evaluating the same nivolumab and ipilimumab regimen in 112 patients with resectable, non-metastatic dMMR colon cancer (63% cT4, 62% N2+)[29]. MPR was achieved in 95% of patients, and pCR in 67%. With a median follow-up of 13.1 months, RFS was 100%. The NICHE-3 trial assessed two cycles of nivolumab combined with four weekly doses of an anti-LAG-3 antibody (relatlimab) in 19 patients with locally advanced dMMR colon cancer, reporting a pCR rate of 79% and an MPR rate of 89%[30].
Neoadjuvant immunotherapy has proven highly effective in dMMR locally advanced colon cancer, yielding significant tumor downstaging, improved pCR rates and RFS, and a widely recognized safety profile. Based on these encouraging findings, the 2026 CSCO guidelines have recommended this approach for dMMR/MSI-H locally advanced colon cancer.
PROPHYLACTIC HIPEC FOR T4 COLON CANCER
Peritoneal metastasis is a form of distant metastasis associated with the worst prognosis in colon cancer. T4 stage or tumor perforation are independent risk factors for the development of metachronous peritoneal metastases[31]. The 3-year rate of metachronous peritoneal metastases following surgery for pT4 colon cancer is approximately 20%-30%[32,33]. HIPEC is widely used in the treatment of synchronous or metachronous peritoneal metastases from gastrointestinal cancers, with demonstrated efficacy[34,35]. Recently, interest has grown in the role of prophylactic HIPEC to prevent peritoneal metastases in locally advanced colon cancer, but trial results have been conflicting.
The Dutch COLOPEC trial enrolled 204 patients with resectable primary cT4N0-2M0, pT4N0-2M0, or colon cancer with perforation[36]. Patients were randomized to receive either adjuvant systemic chemotherapy plus prophylactic HIPEC (n = 102, performed either synchronously with surgery or 5-8 weeks postoperatively using oxaliplatin 460 mg/m² at 42 °C-43 °C for 30 minutes) or adjuvant systemic chemotherapy alone (n = 102). There was no significant difference in 18-month peritoneal metastasis-free survival between the HIPEC and control groups (80.9% vs 76.2%, P = 0.28) and no significant differences in 5-year OS (69.6% vs 70.9%, P = 0.692) or DFS (55.7% vs 52.3%, P = 0.875).
The Spanish HIPECT4 trial randomized 184 patients with cT4N0–2M0 colorectal cancer to undergo curative-intent surgery with cytoreduction (laparoscopic or open) plus intraoperative HIPEC (mitomycin C 30 mg/m2 for 60 minutes; n = 89) or surgery alone (n = 95)[37]. Both groups received standard adjuvant systemic chemotherapy. Among the 128 patients analyzed (63 in the HIPEC group and 65 in the control group), the HIPEC group showed a significantly improved 3-year local control rate (97.6% vs 87.6%, P = 0.03; HR: 0.21, 95%CI: 0.05-0.95). This benefit was more pronounced in the pT4 subgroup (98.3% vs 82.1%, P = 0.003; HR: 0.09, 95%CI: 0.01-0.70). No significant differences were observed in 3-year DFS (81.2% vs 78.0%, P = 0.22; HR: 0.71, 95%CI: 0.41-1.22) or OS (91.7% vs 92.9%, P = 0.68; HR: 0.79, 95%CI: 0.26-2.37).
A Chinese retrospective propensity score-matched (PSM) cohort study analyzed 220 patients[38]. After 1:3 PSM (HIPEC group, n = 45; non-HIPEC group, n = 135), it was found that prophylactic HIPEC was associated with better DFS (HR: 0.43, 95%CI: 0.19-0.95, P = 0.037), while N2 stage correlated with worse DFS (HR: 1.97, 95%CI: 1.09-3.56, P = 0.025). Prophylactic HIPEC reduced the 3-year incidence of peritoneal seeding in cT4 patients, but the difference was not statistically significant (2.6% vs 13.8%, P = 0.070). Subgroup analysis revealed a significant DFS benefit with prophylactic HIPEC in patients with T4N0-1 disease (P = 0.045), but no difference was observed in patients with N2 disease (P = 0.370). The authors concluded that prophylactic HIPEC reduces the risk of peritoneal seeding and significantly improves DFS in patients with cT4N0-1M0 colon cancer.
Research on prophylactic HIPEC for locally advanced colon cancer is expanding. The significant heterogeneity in study results likely stems from differences in the patient selection criteria, choice of chemotherapeutic agent for perfusion, and timing and duration of HIPEC administration. COLOPEC enrolled patients with either pathological or clinical locally advanced disease or perforation, whereas HIPECT4 focused exclusively on patients with cT4N0-2M0 disease, representing a more homogeneous cohort. Differences in perfusion agents (oxaliplatin vs mitomycin C) and timing (postoperative vs intraoperative) may also contribute to outcome variability. Intraoperative HIPEC, performed before significant adhesion formation, likely allows for more uniform drug distribution and more effective reduction of residual tumor burden, potentially explaining the more favorable results observed in HIPECT4 compared to COLOPEC.
The safety profile of HIPEC is also a critical consideration. Several retrospective studies report postoperative adverse event or complication rates in HIPEC groups ranging from 41% to 58%, with grade III or higher complications in 26%-30% of patients and reoperation rates as high as 13%[39,40]. Both COLOPEC and HIPECT4 reported complications such as anastomotic leakage and paralytic ileus in the HIPEC groups, but neither study found a significant difference in overall complication rates or toxicity between HIPEC and control arms[36,37]. No evidence currently confirms a direct causal link between HIPEC and anastomotic leakage. Postoperative HIPEC may carry a higher risk of complications, anastomotic leakage, and myelosuppression, but its severe complication rates and perioperative mortality remain manageable within experienced, high-volume centers.
Consensus on the role of prophylactic HIPEC in preventing peritoneal metastases from locally advanced colon cancer is lacking, with ongoing debate regarding appropriate patient selection and drug choice, timing, duration, and safety. Prophylactic HIPEC remains one of the most promising strategies for controlling postoperative peritoneal metastases in this patient population, and further studies are needed to establish standardized protocols.
