Local recurrence (LR) of colorectal cancer is rare. In Europe, approximately 70% of cases are considered unresectable or untreatable at the time of discovery (1). With recent improvements in standardized surgical procedures and perioperative treatment, the rate of LR after colon cancer resection has been lowered to approximately 4% (2,3) from over 10% (4-6).

The standard treatment for LR is radical resection if possible, and R0 resection has been reported to improve prognosis (7). However, surgeries for LR are complex and difficult due to the location and infiltration into surrounding tissues, resulting in a low resection rate of 13-23% (7,8). The 5-year survival rate ranges from 6% to 67%, and the re-recurrence rate ranges from 4% to 54%, showing significant variation (9,10). Due to the low incidence, few reports have examined the clinical characteristics and prognosis of LR.

The aim of multicenter study was to examine clinical characteristics of LR and survival outcome after R0 resection of LR.

Patient selection. This study retrospectively reviewed the medical records of 18 patients who underwent curative surgery for LR of colorectal cancer at four hospitals in Japan (Nagasaki University Hospital, Sasebo City General Hospital, Nagasaki Medical Center, and Ureshino Medical Center) between April 2016 and March 2024. The study was approved by the institutional review board of each participating institution, and the need to obtain informed consent was waived based on the retrospective design. The ethics approval number is 16062715-5.

LR definition and data collection. LR was defined as a histologically confirmed recurrence localized in the primary bed, in an area without peritoneum. LR was classified as high retroperitoneal recurrence above the level of the inferior mesenteric artery, incisional recurrence on the incision scar in the abdominal wall, low retroperitoneal recurrence below the level of the inferior mesenteric artery, and pelvic recurrence below the promontory.

The following data were collected: age, sex, body mass index (BMI), American Society of Anesthesiologists physical status classification, comorbidities, location of primary tumor, T factor of primary tumor, N factor of primary tumor, histological type, lymphovascular invasion, postoperative complications after primary surgery, adjuvant chemotherapy after primary surgery, interval from primary surgery to LR, neoadjuvant treatment for LR, surgical approach to LR, surgical procedure for LR, multivisceral resection, operation time, blood loss, postoperative complications after LR surgery, hospital stay, and adjuvant chemotherapy after LR surgery. Postoperative complications were defined as complications occurring within 30 days of the primary surgery and were recorded and classified according to the Clavien-Dindo classification system.

Statistical analysis. Data were analyzed using JMP software (SAS Institute, Cary, NC). Continuous data are presented as mean (range) and categorical data as counts and percentages. Overall survival (OS) and relapse-free survival (RFS) were calculated using Kaplan-Meier methods. Survival curves were compared using the log-rank test. All p-values of <0.05 were considered statistically significant.

Clinicopathological characteristics of the patients and primary tumor are shown in Table I. The 18 patients included 10 women (55.6%), and median BMI was 22.7 kg/m². Comorbidities were present in 10 patients (55.6%). The histopathological diagnosis was rectal cancer in 10 cases (55.6%) and colon cancer in 8 cases (44.4%). Clinical grade was T4 in 9 cases (50.0%), clinical N-positive status was seen in 12 cases (66.7%), and differentiation was defined as poorly differentiated adenocarcinoma/signet ring cell carcinoma in 4 cases (22.2%). Lymphovascular invasion was seen in 15 cases (83.3%) and postoperative complications after primary surgery were identified in 3 cases (16.7%). Adjuvant chemotherapy was performed in 8 patients (44.4%)

The perioperative characteristics of LR surgery are shown in Table II. The median interval from primary surgery to local recurrence was 24 months. Ten patients (55.6%) received neoadjuvant treatment for local recurrence, 11 patients (61.1%) received laparoscopic surgery and 2 (11.1%) received robotic surgery. Multivisceral resection was needed in 6 patients (33.3%), median operation time was 361 min, median blood loss was 180 ml. Postoperative complications (Clavien-Dindo grade ≥2) after LR surgery occurred in 9 patients (50.0%) and severe complication occurred one patient. The median hospital stay was 17 days, and adjuvant chemotherapy after resection of LR was given to 5 patients (27.8%). Eight patients (44.4%) experienced re-recurrence, comprising peritoneal metastasis in 5 patients, liver metastasis in one, lung metastasis in one, and adrenal gland metastasis in one.

Figure 1 shows survival analysis after LR surgery. The 5-year RFS rate was 39.4% and the 5-year OS rate was 52.2%. No significant differences between patients who received adjuvant chemotherapy after LR resection and those who did not were seen in either RFS rate (50.0% vs. 44.4%, respectively; p=0.526) or OS rate (50.0% vs. 42.8%, respectively; p=0.915).

Several reports have discussed the risks associated with LR in colorectal cancer patients (11-13). Common risk factors for colorectal cancer include pathological T factor, N factor, and lymphovascular invasion (14,15). In rectal cancer, locally advanced cancer, lower rectal cancer, and positive circumferential resection margin have been reported as a risk factors (16). In this study, T4 cases accounted for half of all LR cases. Pathological N-positive cases were also numerous. Lymphovascular invasion was observed in more than 80% of cases, and two cases (11.1%) were CRM-positive, consistent with previous reports.

Intraoperative perforation and postoperative anastomotic leakage have also been considered risk factors for LR during the perioperative period (16-20). Waldeschtdt et al. reported that 79% of patients with LR experienced intraoperative adverse events, compared to 53% of patients without LR (16). In this study, no intraoperative complications such as intestinal perforation were observed. Anastomotic leakage was noted in 2 cases (11.1%) where the primary tumor was resected at a shallow depth. Further large-scale studies are needed to clarify the impact of perioperative adverse events on LR.

Regarding the period from colorectal cancer surgery to LR, 95% of patients reportedly experienced LR within 3 years (15,21). According to Yun et al., 20% of patients experienced LR within 1 year, 60% within 2 years, and 82% within 3 years (11). In addition, Dumon et al. reported that the median period from primary surgery to LR was 24.1 months. Patients at high risk for LR thus require careful follow-up for at least 3 years.

The surgery for LR is often complex, with a resection rate of approximately 13-23% (7,8). Complete resection contributes to a favorable prognosis, but this often requires multiorgan resection, and the incidence of postoperative complications in LR surgery is also high (22). Previous reports have indicated an overall complication rate of 53.3%, with severe complications (Clavien-Dindo grade ≥3) occurring in 16% of cases (22). In addition, a mortality rate of 2.6% has been reported (22). In our study, the postoperative complication rate was 50%, similar to previous reports, but only one case (5.5%) was classified as Clavien-Dindo grade ≥3. No deaths were observed within 30 days in this study. This may be due to the absence of hyperthermic intraperitoneal chemotherapy cases with a high incidence of complications compared to previous reports (22), and the fact that more than half of the cases were treated with minimally invasive surgery.

Reports on the prognosis following R0 resection of LR have been limited. Iversen et al. reported a 3-year survival rate of 61% and a 3-year disease-free survival rate of 41%, both of which were considered favorable (23). Regarding recurrence patterns after LR, 50% of re-recurrences were distant metastases, 21% were LR, and the remaining 29% involved both local and distant metastases. Dumont et al. examined 75 patients who underwent radical resection of LR following colorectal cancer. The 5-year survival rate was 37.5%, and the 5-year local recurrence rate was 38.8% (22). In the present study, the 5-year survival rate was 52.2% and the 5-year RFS was 39.4%, representing relatively favorable results. Recurrence was observed in 44% of cases, and 62% of these cases had peritoneal metastasis. Local control was relatively good, but many cases experienced recurrence.

Previous reports have indicated recurrence rates after multimodal therapy for LR from 4% to 54% (10). In the present study, no difference in prognosis was observed between patients who received adjuvant chemotherapy after R0 resection and those who did not. However, the number of cases was small, and further large-scale trials are needed to evaluate perioperative treatment strategies.

Study limitations. First, it is a retrospective study based on the medical records of the patients. Second, although it is a multicenter study, we evaluated a small number of patients. Third, the timing of surgery for LR was left to the discretion of the surgeon.

Postoperative LR of colorectal cancer can be expected to show a relatively favorable prognosis with R0 resection. LR often occurs within 3 years, and careful follow-up is necessary for high-risk cases.

The Authors have no conflicts of interest to declare.

Keizaburo Maruyama and Tetsuro Tominaga mainly designed the study. Takashi Nonaka, Yuma Takamura, Hiroki Katayama, Shintaro Hashimoto, Mariko Yamashita, Keisuke Noda, Rika Ono, Mitsutoshi Ishii, Makoto Hisanaga, Kaido Oishi, and Fumitake Uchida performed surgery. Keitaro Matsumoto supervised this study.

No artificial intelligence (AI) tools, including large language models or machine learning software, were used in the preparation, analysis, or presentation of this manuscript.