Survival outcomes and prognostic factors in stage 2 and 3 colorectal cancer:Comparing elective and emergency surgical approaches

Authors

Abstract

AimThis study aimed to compare the survival outcomes of Stage 2 and Stage 3 colorectal cancer (CRC) patients undergoing emergency versus elective surgery and to identify critical prognostic factors influencing survival rates.
MethodsWe retrospectively analyzed 323 CRC patient records from January 2015 to March 2017, focusing on factors like tumor grade, lymphovascular and perineural invasion, mucinous component, perforation, tumor size, and lymph node count. Exclusions were made for incomplete data, palliative surgeries, and non-standard surgical margins. Survival analysis was performed using Kaplan Meier and logistic regression, with a p-value <0.05 indicating statistical significance.
ResultsOf the 181 patients analyzed, 60.2% were stage 2, and 39.8% were stage 3. Emergency surgery correlated with reduced survival in both stages. Notably, stage 2 emergency patients had fewer lymph nodes removed and higher incidences of tumor perforation and perineural invasion (p=0.01, 0.001, 0.014, respectively). For stage 3, vascular invasion was significantly more common in the emergency group (p=0.017). Multivariate analysis underscored lymph node count, tumor perforation, and perineural invasion as significant for stage 2 (p=0.040, 0.012, 0.002, respectively), while vascular invasion was critical for stage 3 (p=0.023).
ConclusionEmergency CRC surgery is associated with lower survival rates and more aggressive tumor features. These findings suggest that elective surgery may offer a survival advantage in CRC due to less aggressive tumor features, underlining the need for prompt diagnosis and surgical intervention. Future studies should focus on optimizing preoperative care and exploring postoperative strategies to improve outcomes for emergency surgery patients.

Keywords

Introduction

In 2022, colorectal cancer (CRC) ranks as the fourth most commonly diagnosed cancer and the second leading cause of cancer-related deaths in the USA.¹ Surgical resection remains the standard of care for non-metastatic CRC. Despite the routine treatment with radical surgery and adjuvant chemotherapy applied today, the survival outcome in CRC is heterogeneous and not satisfactory. The 5-year survival rate for patients diagnosed with local CRC is 90.1%, for those with regional lymph node involvement, it is 69.2%, while for patients with distant metastasis, the rate drops to 11.7%.² Currently, the strongest tool for assessing prognosis following potentially curative surgery is the pathological examination of the specimen. Although the depth of tumor invasion, the number of positive lymph nodes, and the presence of metastasis determine the pathological stage and are the strongest predictors of prognosis, other clinical, molecular, and histological features can independently affect the prognosis regardless of the stage. Approximately 33% of patients with CRC still present in the hospital, requiring urgent intervention due to conditions that necessitate acute care, despite widespread screening programs and endoscopic procedures.³ Obstruction, haemorrhage, and perforation are the most common indications for emergency CRC surgery, with obstruction being the most frequent at 77%.⁴ Emergency colorectal operations are associated with higher mortality and morbidity compared to elective surgery.⁵ While some studies suggest that emergency colorectal resection is associated with poor oncological outcomes, others report no difference in prognosis.^6,7,8
The Clinical Practice Guidelines Committee of the American Society of Colon and Rectal Surgeons has identified three goals that need to be addressed in the treatment of emergent cases of CRC: (1) to eliminate the adverse effects of the condition that necessitates emergency intervention; (2) to achieve the best possible tumor control; and (3) to prepare the patient for adjuvant or systemic therapy as soon as possible.⁹
In our study, we aimed to compare the survival of patients with CRC who underwent emergency or elective surgery at the same stage (stage 2 or 3) and to identify other parameters that affect survival independent of the stage.

Materials and Methods

Data from 323 patients who underwent surgery for CRC at a tertiary referral hospital between January 2015 and March 2017 were retrospectively analyzed. Factors including grade, lymphovascular invasion, perineural invasion, mucinous component presence, perforation, tumor size, the number of lymph nodes excised, and the number of metastatic lymph nodes (for stage 3 patients) were determined through pathological examination of the specimens. Pieces exhibiting any extracellular mucin were assessed as containing a mucinous component, irrespective of the amount of extracellular mucin secreted. The staging was conducted using the pathological staging criteria from the NCCN’s February 25, 2022, Version 1. 2022 publication for colon cancer. According to the College of American Pathologists Consensus Statement,¹⁰ patients were classified into two categories: well-moderately and poorly. Conventional adenocarcinoma is characterized by glandular formation, which forms the basis for histologic tumor grading: well-differentiated adenocarcinoma shows >95% gland formation; moderately differentiated adenocarcinoma has 50%-95% gland formation; and poorly differentiated adenocarcinoma is mostly solid with <50% gland formation. Patients’ survival data were accessed from a national database. Tumor localization was categorized into right colon and left colon, with tumors located in the proximal two-thirds of the transverse colon recorded as right colon and those further distal noted as left colon tumors. Patients excluded from the study were those with missing data, those who underwent palliative surgery, those who received total abdominal colectomy, those with positive surgical margins (1 cm for distal rectal cancer, 5 cm for proximal rectal cancer, 10 cm distal margin for colon cancer, and 10 cm proximal margin for all CRC), those who died perioperatively without discharge, stage I patients (due to insufficient numbers for comparison in emergency surgery), and stage IV metastatic patients.
All statistical analyses were performed using SPSS (Statistical Package for Social Sciences) for Windows version 25.0. Normality was assessed using Skewness and Kurtosis tests and graphical methods.
Ethical ApprovalThis study was approved by the Ethics Committee of Kartal Dr. Lütfi Kırdar City Hospital (Date: 29.03.2023, Decision No: 2023/514/246/24).
Statistical AnalysisData were expressed as mean ± standard deviation if normally distributed and median with min-max values if not. Additionally, data were presented as counts (n) and percentages (%). The Chi-square test was utilized for comparing two categorical variables. Fisher’s Exact Test was employed if the Chi-square test did not have a sufficient number of patients for comparison. When comparing a categorical variable with a numerical value, the Independent sample t-test was used for normally distributed numerical values, while the Mann-Whitney U test was applied for non-normally distributed numerical values. Survival comparisons between patients at the same stage were conducted using Kaplan Meier survival analysis. Logistic regression analysis was used to compare data between emergency and elective patients. Both multivariate and univariate analyses were performed using logistic regression. A p-value of <0.05 within a 95% confidence interval was considered statistically significant.
Reporting GuidelinesThe study was reported in accordance with STROBE guidelines.

Results

Our analysis covered 181 CRC patients, distinguishing 60.2% at stage 2 and 39.8% at stage 3. Notably, the age distribution and lymph node removal followed a normal distribution, contrasting with the non-normal distribution of tumor size and positive lymph node count.
Survival analysis revealed that stage 2 and 3 patients had reduced rates after emergency surgery (as depicted in Figure 1 and Figure 2).
The mean age for stage 2 was 64.72 years, with an average of 21.55 lymph nodes resected. The median tumor size for this group was 5.51 cm. Gender was nearly evenly split with a slight male predominance (51.4%), and tumors were more commonly found in the left colon (67%). Most tumors were well-moderately differentiated (91.7%), with a minority showing vascular invasion (20.2%) and perforation (9.2%). Perineural invasion was present in nearly a third of the cases (29.4%), and a mucinous component was seen in 24.8% of the stage 2 patients (Table 1).
For stage 2 patients, those undergoing emergency surgery had significantly fewer lymph nodes removed (p=0.01) and higher rates of tumor perforation (p<0.001) and perineural invasion (p=0.014). Age differences between emergency and elective surgery groups were not statistically significant (p=0.125). The presence of poorly differentiated tumors, vascular invasion, and mucinous components between the emergency and elective surgery groups showed no statistical significance, with p-values of 0.083, 0.469, and 0.522, respectively (Table 1).
Stage 3 patients had an average age of 63.21 years and an average lymph node harvest of 21.47, with a median tumor size of 4.94 cm. Gender distribution was similar to stage 2, with a slight male predominance. Vascular invasion was seen in a higher proportion (66.7%), particularly in the emergency surgery group, which was a significant finding (p=0.017). Perineural invasion was present in over half of the stage 3 patients (52.8%). The incidence of poorly differentiated tumors and the presence of a mucinous component showed no statistical difference between the emergency and elective groups (p > 0.05) (Table 1).
When comparing the emergency and elective surgery groups across various clinical and pathological factors in a multivariate framework, stage 2 patients showed significant differences in lymph node count, tumor perforation, and perineural invasion with p-values of 0.040, 0.012, and 0.002, respectively. Stage 3 analysis highlighted vascular invasion as a significant differentiating factor (p=0.017). Other variables such as age, gender, tumor size, and mucinous component presence did not demonstrate significant differences (Table 2 and Table 3).

Discussion

Our study found that in CRC patients undergoing emergency surgery, survival rates were lower at both stages compared to those operated electively. When comparing Stage 2 patients who underwent emergency and elective surgery, we observed fewer dissected lymph nodes in the emergency surgery group, while tumor perforation and perineural invasion were more common. Additionally, in the logistic regression analysis of Stage 2 patients undergoing emergency surgery, the number of dissected lymph nodes, the presence of tumor perforation, and perineural invasion were identified as independent risk factors for mortality, while age was found as a risk factor in univariate analysis.
In the Stage 3 group, vascular invasion was more frequently observed in patients undergoing emergency surgery compared to those with elective surgery. The logistic regression analysis among Stage 3 patients who had emergency surgery revealed that the presence of vascular invasion in the tumor was an independent risk factor for mortality on its own.
Emergency surgery in CRC is associated with higher morbidity, mortality, and poorer prognosis compared to elective surgery. A case-control study conducted in 2003 found that undergoing surgery in an emergency setting was an independent risk factor for both morbidity and mortality.¹¹ Another study indicated that 2-year disease-free survival was greater in patients who underwent elective surgery.¹² The lower survival rates in emergency surgical interventions are directly related to surgery generally being performed for complications such as obstruction, perforation, or haemorrhage, the biological behavior of the tumor, and the overall condition of the patient.¹³
The role of age in the management of CRC is a significant concern in general surgical practice. In univariate analyses, age has emerged as a significant determinant of mortality in CRC patients. In elderly patients, the increase in comorbidities and the decreased capacity of the body to respond to cancer and treatment can affect treatment options and outcomes. Notably, the risk of surgical interventions and the rates of postoperative complications may be higher in older patients.¹⁴ Additionally, age may influence the biological characteristics of CRC; for instance, some studies suggest that tumors may be more aggressive in older patients.¹⁵ This is a critical factor in shaping general surgeons’ approach to elderly CRC patients. Particularly, individualized treatment planning and comprehensive preoperative and postoperative assessments are necessary to achieve optimal outcomes in this population. The pronounced effect of age on mortality necessitates further development of age-specific treatment protocols and clinical decision-making processes.
It is well-known that lymph node dissection has prognostic value in CRC. The removal of a sufficient number of lymph nodes can improve patient survival rates and assist in accurately determining the stage of the disease. The consensus in the field is that at least 12 lymph nodes should be removed during CRC surgery.¹⁶ In light of this information, the threshold has been exceeded for patients operated on both emergently and electively. However, the number is higher in patients who undergo elective surgery. The reasons for this outcome can be attributed to various factors. In emergency surgical operations, the surgeon’s priority may be the hemodynamic stabilization of the patient, which could influence the extent of lymphadenectomy, and the operations are generally more complicated with a higher risk of complications, potentially altering the surgeon’s priorities.
Some studies in the literature suggest that the greater number of lymph nodes removed during elective operations could be due to the surgeon having the opportunity to perform a more meticulous and careful dissection.¹⁷ Additionally, the more planned nature of elective operations allows the surgeon to be better prepared for the surgery, enabling a more comprehensive lymphadenectomy. In our study, while there was a statistically significant difference in the number of lymph nodes removed among stage 2 patients, this difference was not observed in stage 3 patients. We attribute this to the surgeon’s ability to detect palpable lymph nodes during the operation and their diligence in performing a more extensive dissection.
The literature indicates that the need for emergency surgical intervention is often associated with more aggressive biological behavior of the tumor.³ As a consequence of this aggressive biological behavior, one would expect a higher frequency of tumor perforation, perineural, and vascular invasion. In our study, these adverse prognostic factors were more frequently observed in patients who had undergone emergency surgical intervention.
Vascular invasion is known as a bad prognostic marker of lymph node metastasis in CRC.¹⁸ This invasion is defined as the invasion of tumor cells into blood vessels. A study by Huh et al. has demonstrated that vascular invasion functions as an independent poor prognostic factor in patients with CRC.¹⁹ Emergency surgical procedures are typically applied due to severe complications such as obstruction, perforation, or haemorrhage. This could lead to a more aggressive spread of the tumor to the surrounding vascular structures. As reflected in our study, this may result in increased rates of vascular invasion in patients undergoing emergency surgery. Thus, our findings are consistent with the existing literature. However, when examining the outcomes of the study, perforation and perineural invasion were found as independent risk factors in stage 2 patients, while vascular invasion was not. In contrast, in stage 3 patients, vascular invasion was identified as an independent risk factor, but not perforation and perineural invasion, opposite to stage 2 patients. This result could be due to the small number of patients. As there is no similar study in the literature comparing patients of the same stage who underwent emergency and elective surgery, we cannot comment on this finding. Comparative evaluations of these data with similar studies with larger patient populations to be conducted in the future would be valuable.

Limitations

Our study has some limitations. We didn’t explore disease-free survival or specify the reasons for emergency surgeries like obstruction, haemorrhage, or perforation. The stress response from emergency surgeries, affecting both patients and doctors, can influence the tumor environment and potentially increase metastasis risk. Therefore, elective surgeries are preferable for better outcomes in Stage 2 and 3 CRC patients, when possible.

Conclusion

Our study shows that emergency surgery for stage 2 and 3 colorectal cancer (CRC) patients is associated with significantly bad survival outcomes compared to elective surgery. In stage 2 patients, emergency interventions were linked to a lower number of lymph nodes removed and a higher incidence of tumor perforation and perineural invasion, which are independent risk factors for poor prognosis. In stage 3 patients, vascular invasion was the primary independent risk factor affecting survival. These findings highlight the need for elective surgery whenever possible to achieve better oncological outcomes and suggest that emergency surgeries present additional challenges that affect patient prognosis.

Declarations

Abbreviations

CRC – colorectal cancer
NCCN – National Comprehensive Cancer Network
SPSS – Statistical Package for Social Sciences

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About This Article

Received:

November 20, 2024

Accepted:

December 24, 2024

Published Online:

February 20, 2025

Printed:

February 1, 2025