Abstract
Background/Aim: The aim of our study was to investigate the outcome of colon cancer with bladder invasion after surgical intervention. Patients and Methods: Between 2011 and 2022, a total of 41 patients diagnosed with colon cancer and bladder invasion underwent surgical procedures at Taichung Veterans General Hospital. The impact of various risk factors on overall survival (OS) was assessed using Kaplan-Meier analyses and Cox proportional hazards models. Results: Among the enrolled patients, 21 underwent radical cystectomy, while 20 underwent partial cystectomy. Twelve had tumors located in the rectum, 19 in the sigmoid colon, and 10 in both the rectum and sigmoid colon. The median OS was 71.8 months in stage 2, 50.8 months in stage 3, and 11.2 months in stage 4 (p=0.061). Median OS was 71.8 months in patients with negative surgical margins and 10.5 months in those with positive surgical margins (p=0.003). In multivariate regression analysis, positive surgical margins [hazard ratio (HR)=3.64, 95% confidence interval (CI)=1.28-10.34, p=0.015] and emergency operations (HR=4.57, 95%CI=1.34-15.55, p=0.015) significantly impacted OS. Conclusion: Complete resection of colon cancer with bladder invasion can yield excellent oncologic outcomes. The decision between partial and radical cystectomy should balance surgical margin clearance and the preservation of quality of life. Both surgical margin involvement and emergency operations are independent risk factors for OS.
Colon cancer ranks among the most prevalent cancers and is a leading cause of cancer-related deaths worldwide (1). Approximately 20% of primary colorectal cancers extend to adjacent organs, with approximately 30% of these cases involving the urinary tract (2-5). Despite advances in diagnostic tools such as computed tomography (CT) and cystoscopy, preoperative identification of true bladder invasion remains challenging, with varying degrees of sensitivity and specificity (6-8). In most cases, bladder invasion is identified during surgery. However, intraoperative biopsy of the affected organ or adjacent tissue carries significant risks, including sampling error and the potential for tumor spillage (9, 10). Consequently, the gold standard treatment involves en bloc resection of the primary colonic tumor along with either partial or radical cystectomy, followed by adjuvant systemic chemotherapy (11, 12). Decisions between partial and total cystectomy must weigh the need for clear margins, the risk of local recurrence, and the patient’s quality of life. Pathological bladder invasion and the completeness of resection have been proposed as critical factors influencing local recurrence and survival (13). Additionally, the method of urinary tract reconstruction can potentially impact renal function deterioration post-surgery (14, 15). The aim of our study was to investigate the prognosis of advanced colon cancer cases with suspected bladder invasion, focusing on surgical and oncological outcomes.
Patients and Methods
This retrospective chart review study was approved by the Institutional Review Board of Taichung Veterans General Hospital (IRB No. CE13240A-3). From 2011 to 2022, a total of 41 patients with advanced colon cancer suspected of bladder invasion underwent surgical intervention at Taichung Veterans General Hospital. Patients with missing data, incomplete follow-up, or non-colorectal cancer pathology reports were excluded from the study. The patients were categorized into two groups: radical cystectomy and partial cystectomy. Patient characteristics, including age, sex, Eastern Cooperative Oncology Group (ECOG) performance status, comorbidities, body mass index (BMI), tumor location, tumor stage, pathological characteristics, tumor markers, colorectal surgery methods, and bladder surgery methods, were recorded. A negative surgical margin was defined as no tumor involvement in the pathological specimen, either at the metastatic or primary tumor site. Renal function changes were evaluated by the estimated glomerular filtration rate (eGFR) according to the different reconstruction methods, including primary bladder repair, ureterostomy, and ileal conduit.
The primary endpoint of the study was overall survival (OS) following colorectal surgery. Continuous variables were analyzed using the Mann-Whitney U-test, while categorical variables were assessed using Pearson’s Chi-squared test. Survival outcomes were evaluated with Kaplan-Meier analysis. To explore the association between various factors, hazard ratios (HR) and 95% confidence intervals (CIs) were calculated using univariate and multivariate Cox regression models. All statistical analyses were conducted using version 22.0 of the Statistical Package for the Social Sciences (SPSS) software (IBM, Armonk, NY, USA).
Results
The characteristics of patients with colon cancer suspected of bladder invasion are summarized in Table I. Among the 41 patients, 21 underwent radical cystectomy and 20 underwent partial cystectomy. There were no significant differences between the two groups in terms of age, sex, ECOG performance status, comorbidities, or BMI. A greater number of patients with rectal tumors underwent radical cystectomy (n=12), while more patients with sigmoid tumors underwent partial cystectomy (n=16). Consequently, a higher proportion of patients in the radical cystectomy group underwent abdominoperineal resection (n=15), compared to those who underwent anterior resection (n=10) and low anterior resection (n=7) in the partial cystectomy group. Additionally, high-grade hydronephrosis was more prevalent in the radical cystectomy group compared to the partial cystectomy group (p=0.013). Pathological staging revealed a higher number of stage III and stage IV tumors in the radical cystectomy group compared to the partial cystectomy group (p=0.021). There was also a higher incidence of surgical margin involvement in the radical cystectomy group compared to the partial cystectomy group (p=0.002). The median follow-up time was 10.55 months for the radical cystectomy group and 31.15 months for the partial cystectomy group (p=0.064).
Colon cancer with bladder invasion (n=41).
Table II presents the estimated renal function deterioration based on different urinary tract reconstruction methods. In the partial cystectomy group, 20 patients underwent primary bladder repair. In the radical cystectomy group, 10 patients received ureterostomy reconstruction, and 11 patients underwent ileal conduit reconstruction. There were no significant differences in renal function, as measured by serum creatinine levels or eGFR, between the different reconstruction methods.
Renal function change among different bladder surgery.
OS and recurrence-free survival (RFS) were evaluated using Kaplan-Meier survival curves across different comparison groups. There was no significant difference in OS and RFS between the radical cystectomy and partial cystectomy groups, although there was a trend toward better survival outcomes in the partial cystectomy group. Figure 1A shows that the median OS was 50.8 months in the partial cystectomy group compared to 16.7 months in the radical cystectomy group (p=0.244). Figure 1B illustrates that the median RFS was not reached in the partial cystectomy group compared to 5.2 months in the radical cystectomy group (p=0.110).
Overall survival and recurrence-free survival between partial cystectomy and radical cystectomy. A) Kaplan-Meier curve comparing overall survival between partial cystectomy and radical cystectomy in patients with colon cancer involving bladder invasion. The median overall survival was 50.8 months in the partial cystectomy group compared to 16.7 months in the radical cystectomy group, p=0.244. B) Kaplan-Meier curve comparing recurrence-free survival between partial cystectomy and radical cystectomy in patients with colon cancer involving bladder invasion. The median recurrence-free survival was non-reached in the partial cystectomy group compared to 5.2 months in the radical cystectomy group, p=0.110.
Figure 2 illustrates the OS and RFS across different pathological stages. The median OS was 71.8 months for stage II, 50.8 months for stage III, and 11.2 months for stage IV (Figure 2A, p=0.064). The median RFS was 49.6 months for stage III and 3.2 months for stage IV (Figure 2B, p<0.001). Figure 3 demonstrates the impact of surgical margin involvement on both OS and RFS. Patients with surgical margin involvement had significantly worse OS (10.5 months vs. 71.8 months, p=0.003, Figure 3A) and RFS (4.7 months vs. not reached, p=0.003, Figure 3B) compared to those without margin involvement. Figure 4 indicates that tumors located in the rectum were associated with poorer OS and RFS compared to those located in the sigmoid colon.
Overall survival and recurrence-free survival between different pathologic stages. A) Kaplan-Meier curve comparing overall survival among different pathologic stages in patients with colon cancer involving bladder invasion. The median overall survival was 71.8 months in stage 2, 50.8 months in stage 3 and 11.2 months in stage 4, p=0.064. B) Kaplan-Meier curve comparing recurrence-free survival among different pathologic stages in patients with colon cancer involving bladder invasion. The median recurrence-free survival was non-reached in stage 2, 49.6 months in stage 3 and 3.2 months in stage 4, p<0.001.
Overall survival and recurrence-free survival between surgical margin positive and negative. A) Kaplan-Meier curve comparing overall survival among surgical margin positive and negative patients with colon cancer involving bladder invasion. The median overall survival was 71.8 months in the surgical margin negative group and 10.5 months in the surgical margin positive group, p=0.003. B) Kaplan-Meier curve comparing recurrence-free survival between surgical margin positive and negative patients with colon cancer involving bladder invasion. The median recurrence-free survival was non-reached in the surgical margin negative group and 4.7 months in the surgical margin positive group, p=0.003.
Overall survival and recurrence-free survival between different tumor locations. Kaplan-Meier curve comparing overall survival based on different tumor location (rectum, sigmoid or rectum plus sigmoid) in patients with colon cancer involving bladder invasion. The median overall survival was 50.8 months in the sigmoid, 19.7 months in the rectum plus sigmoid and 10.5 months in the rectum, p=0.181. B) Kaplan- Meier curve comparing recurrence-free survival based on different tumor location (rectum, sigmoid or rectum plus sigmoid) in patients with colon cancer involving bladder invasion. The median recurrence free survival was 49.6 months in the sigmoid, non-reached in the rectum plus sigmoid and 4.7 months in the rectum, p=0.112.
In the univariate and multivariate analyses of OS, Table III shows that positive surgical margins (HR=3.64, 95%CI=1.28-10.34, p=0.015) and emergency operations (HR=4.57, 95%CI=1.34-15.55, p=0.015) are independent risk factors for patients with colon cancer and bladder invasion undergoing radical excision.
Uni-multivariant for overall survival.
Discussion
Advanced colon cancer has the potential to invade adjacent visceral organs, presenting serious clinical conditions and therapeutic challenges for both patients and colorectal surgeons. Due to the urinary bladder’s close proximity to the colon, it is one of the most commonly affected organs by locally advanced colon cancer (4, 16). Patients may present with lower urinary tract symptoms or gross hematuria; however, the majority do not experience urinary tract symptoms, and these may only become evident during colorectal surgery (17). In reality, the presence of urinary symptoms does not reliably indicate the severity of bladder invasion, and previous studies have shown inconsistent results regarding the reliability of urinary symptoms as indicators of bladder infiltration (7). When urinary bladder involvement is discovered during colorectal surgery, a urologist is consulted for tumor excision and potential reconstruction. However, patients remain at high risk for tumor recurrence or disease progression (18).
When patients present with gross hematuria, cystoscopy is the standard diagnostic tool, which may reveal a submucosal tumor on the posterior wall of the bladder. If a biopsy result indicates adenocarcinoma, it is potentially indicative of colorectal adenocarcinoma as the primary origin (19). However, cystoscopy revealed a mass in only one-third of our patients and the reported sensitivity in predicting true bladder invasion ranges from 57% to 87%, with specificity reported to be as low as 25% (7, 20). Preoperative CT scans demonstrate high sensitivity in detecting colon cancer invasion of the bladder. It may reveal gross tumor invasion, abnormal enhancing masses on the bladder wall, irregular bladder mucosa, and loss of the perivesical fat plane (21). Additionally, CT urography may reveal a colovesical fistula, indicating advanced bladder invasion by the cancer (22). In our study, all patients underwent preoperative CT scans. Prior to surgery, 85% of the patients were classified as clinical T4 colon cancer. However, the pathological findings revealed that 26.8% of the cases were pT3, while 73.2% were pT4. All patients had tumors originating from the sigmoid colon or rectum. These results suggest that rectal or sigmoid colon cancers classified as T4 on CT scans warrant careful consideration for potential bladder invasion.
Neoadjuvant chemotherapy and/or radiation therapy in advanced colon cancer have demonstrated promising prognostic outcomes, including significant tumor regression, improved pathological tumor response, and prolonged overall survival (23-26). In our study population, 85.7% of patients in the radical cystectomy group had tumors originating from the rectum, and 42.86% of these patients had received neoadjuvant therapy. In contrast, among patients in the partial cystectomy group, only 20.0% had rectal-origin tumors, and only 5.0% had received neoadjuvant therapy. Neoadjuvant therapy achieved a significant survival benefit for locally advanced colon cancer (27, 28). However, this result was not observed in our cohort. Several factors may contribute to this discrepancy, including potential selection bias and the fact that more than half of the patients did not have rectal-origin tumors. Additionally, the presence of 26.8% of patients with pT3 tumors and 46.3% with tumors originating from the sigmoid colon may have influenced the outcomes. These variables could have impacted the observed results and contributed to the differences noted in our study.
The decision between partial and total cystectomy during colorectal surgery should be carefully balanced, taking into account factors, such as surgical margin clearance, the risk of local recurrence, and the patient’s life expectancy and quality of life (13). In our study population, the radical cystectomy group exhibited poorer clinical outcomes in terms of overall survival and recurrence-free survival compared to the partial cystectomy group. This discrepancy may be attributed to the more advanced pathological stages, higher prevalence of rectal tumors, and involvement of surgical margins in the radical cystectomy group. These factors reflect the more challenging clinical conditions faced by patients undergoing radical cystectomy and highlight the complex decision-making process required by surgeons. Our results also indicate that a positive surgical margin is associated with worse overall survival and recurrence-free survival. Moreover, it appears to be an independent risk factor for overall survival, even after adjusting for other risk factors.
A study conducted by the Federation de Recherche EN CHirurgie (FRENCH) Group, which included 117 patients, reported a 3-year disease-free survival (DFS) rate of 82.9% and a 3-year OS rate of 59.5% (2). The R0 resection rate in the study was reported as 87.2%, which is significantly higher than that observed in our population. It is important to note that mid and low rectal cancers were excluded from that study. In contrast, our cohort, which included these cases, experienced worse survival outcomes. This discrepancy may be attributed to a higher rate of positive surgical margins and a greater prevalence of rectal tumors in our population. Another study involving 90 patients documented a 5-year relapse-free survival rate of 62.9% and a 5-year OS rate of 62.5% (29). This study also suggested that patients undergoing en bloc total cystectomy for locally advanced colorectal cancers experience worse postoperative and oncologic outcomes compared to those undergoing partial cystectomy. These findings are consistent with the results observed in our study. In summary, achieving a negative surgical margin is a crucial factor for long-term outcomes. The decision between partial or radical cystectomy should ideally be guided by the potential for R0 resection, as this significantly impacts patient prognosis (13).
Emergency surgery for colorectal cancer is recognized as an independent risk factor influencing prognosis, accounting for 17.1% of cases in our population. Many colorectal carcinomas present emergently due to complications, such as obstruction, perforation, and hemorrhage. Such emergency interventions are correlated with poor short- and long-term outcomes (30). Though most colorectal cancer cases are identified through elective diagnosis, a significant fraction, approximately 10% to 30%, presents in emergency situations (31, 32). A large prospective study indicated that in patients with stage III colon cancer undergoing adjuvant chemotherapy, the presence of obstruction was linked to increased recurrence rates and decreased survival (33). Furthermore, a systematic review and meta-analysis of stage II and stage III colorectal cancer revealed that emergency surgery independently affected DFS (34). Patients presenting with emergent colorectal cancer in conjunction with bladder invasion are at heightened risk for locally advanced disease and potential distal metastasis, contributing to a poorer prognosis.
This study has several limitations. Primarily, the small sample size is a significant constraint, which stems from the fact that colonic tumor invasion into the bladder is a relatively rare condition. Conducting a randomized controlled trial in this context poses considerable challenges, including slow patient recruitment due to the rarity of the disease, as well as ethical concerns related to the feasibility of randomization and intervention. Additionally, the high proportion of emergency surgeries, the inconsistent protocols for neoadjuvant therapy, and the high incidence of rectal cancer contribute to outcomes that may be inferior compared to those reported in existing studies. Nevertheless, our results present real-world experiences of colorectal cancer with bladder invasion, reflecting conditions outside the context of randomized trials
Conclusion
Complete resection of colon cancer with bladder invasion can yield excellent oncologic outcomes. The decision between partial and radical cystectomy should balance surgical margin clearance and the preservation of quality of life. Both surgical margin involvement and emergency operations are independent risk factors for overall survival.
Footnotes
Authors’ Contributions
Study design and protocol development: TWC and SCH. Manuscript writing and editing: TWC and SCH. Statistical analysis: LWC and SCH. Data collection and patient management: TWC, LWC, FFC, JRL, and SCH.
Conflicts of Interest
None of the contributing Authors have any conflicts of interest, including specific financial interests or relationships and affiliations relevant to the subject matter or materials discussed in the manuscript.
- Received August 6, 2024.
- Revision received August 27, 2024.
- Accepted August 29, 2024.
- Copyright © 2024 The Author(s). Published by the International Institute of Anticancer Research.
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY-NC-ND) 4.0 international license (https://creativecommons.org/licenses/by-nc-nd/4.0).
