Tumor Characteristics and Survival Predictors in Patients With Colorectal Cancer: A Lebanese Single-Center Experience

Abstract

Background

Colorectal cancer (CRC) is a leading cause of cancer-related morbidity and mortality worldwide, with incidence rates in Lebanon among the highest in the Middle East and North Africa (MENA) region. Despite this, data on CRC epidemiology, tumor characteristics, and treatment outcomes in MENA populations remain limited. This study aimed to investigate these factors, with the goal of supporting early detection, guiding clinical decision-making, and informing personalized treatment strategies.

Methods

This retrospective cross-sectional study included patients diagnosed with CRC between 2019 and 2023 at the American University of Beirut Medical Center. Clinical data were retrieved from electronic health records and histopathological reports. Overall survival (OS), progression-free survival (PFS), and disease-free survival (DFS) were assessed using Kaplan-Meier survival analysis and multivariable Cox regression models.

Results

A total of 349 patients (mean age 61 years) were included. Most tumors were low-grade adenocarcinomas (88.1%; n=306/347), and 73.3% (n=243/331) of patients presented with advanced-stage disease (Stages III/IV). Among patients with available MMR testing (n=181/349), 5.5% (n=10/181) were mismatch repair-deficient (dMMR) by immunohistochemistry. Molecular testing revealed KRAS mutations in 42.9% (n=70/163 tested) and BRAF mutations in 7.0% (n=9/128 tested). Smoking (HR = 2.58, p = 0.007) and age ≥65 years (HR = 1.98, p = 0.050) were associated with reduced OS. Patients with inflammatory bowel disease had a significantly increased risk of progression (HR = 9.39, p = 0.032). Left-sided tumors were associated with improved OS (HR = 0.42, p = 0.018).

Conclusions

This study identifies key risk factors, including tumor location, age, IBD, and smoking, influencing survival outcomes in Lebanese patients with CRC. Findings support implementation of risk-adapted screening strategies and population-specific therapeutic approaches in Middle Eastern settings.

Keywords

colorectal neoplasms inflammatory bowel diseases epidemiology survival analysis treatment outcome risk factors middle east demography genomic instability Lebanon smoking

Introduction

Colorectal cancer (CRC) is a leading cause of cancer-related morbidity and mortality worldwide. In Lebanon CRC incidence exceeds that of most Middle Eastern and North African (MENA) countries, except for Israeli populations (both Jewish and non-Jewish), but remains lower than in Western nations.¹ From 2005 to 2016, Lebanon reported incidence rates of 21.4 cases per 100,000 for males and 18.6 cases per 100,000 for females.² Projections indicate that by 2025, male incidence will rise to 28.8 cases per 100,000 and female incidence to 26.1 cases per 100,000.² This trend is concerning as more than 80% of CRC cases in Lebanon are diagnosed at advanced stages, which significantly worsens prognosis and limits treatment options.³

CRC is a heterogeneous disease, characterized by diverse variations in tumor biology, patient demographics, and treatment outcomes across regions and populations.⁴ Understanding these complexities is essential for the development of precise and personalized therapeutic strategies.^5,6 Inflammatory bowel disease (IBD) is a well-established risk factor for CRC, and studies indicate that IBD-associated CRC demonstrates distinct tumor biology and clinical outcomes compared to sporadic cases.⁷ Additionally, factors such as tumor location, body mass index (BMI), smoking status, histopathological subtype, and stage at diagnosis significantly influence survival outcomes.^8,9 Analysis of these variables provides actionable real-world data for clinicians and supports the development of region-specific guidelines to optimize care.

Despite its growing health burden, CRC in the MENA region remains underrepresented in global research, which predominantly focuses on Western populations. This lack of regional data limits understanding of how genetic, environmental, and healthcare system factors influence CRC outcomes. This study aims to provide unique regional insights, address this gap, and offer a nuanced understanding of the CRC clinical landscape in the Middle East.

Materials & Methods

Ethical Information

This study was approved by the American University of Beirut Medical Center (AUBMC) Institutional Review Board with reference BIO-2023-0175. This approval permitted access to the AUBMC colorectal cancer database (original approval BIO-2018-0302) and extended the data collection period to include patients diagnosed through December 2023, in accordance with ethical guidelines for biomedical research. All study procedures were conducted in accordance with the Declaration of Helsinki (1975). As this was a retrospective chart review, the requirement for written informed consent was waived, as revised in 2024.

Study Design and Population

We conducted a retrospective 5-year study of patients diagnosed with CRC between January 2019 and December 2023 at the AUBMC. Patients were initially identified using the International Classification of Diseases (ICD-10) code C18, and diagnoses were further confirmed by histology. These codes were recorded when patients presented for either inpatient admission or outpatient clinic visits. Once Institutional Review Board (IRB) approval was granted, lists of medical record numbers meeting the inclusion and exclusion criteria were generated from the colorectal cancer database at AUBMC (BIO-2018-0302). Eligible patients included those diagnosed with CRC of Lebanese origin. Exclusion criteria were: non-Lebanese patients, patients with a family history of CRC, and individuals under 18 years of age. All collected data were entered into a standardized data collection sheet using Research Electronic Data Capture (REDCap) software. The reporting of this study conforms to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines for cohort studies¹⁰ [Supplementary File 2].

Studied Variables

Age was categorized into two groups: <65 and ≥65 years. Primary tumor location was categorized using a three-category anatomic classification system based on colonoscopy and histopathology reports¹: ascending colon region (including cecum, ascending colon, hepatic flexure, and transverse colon),² descending colon, and³ rectosigmoid region (including sigmoid colon, rectosigmoid junction, and rectum).¹¹ For survival analyses, ascending colon region tumors were classified as right-sided (embryologically midgut-derived), while descending colon and rectosigmoid region tumors were classified as left-sided (embryologically hindgut-derived), consistent with established molecular and prognostic differences between these tumor groups. Cancer stage at diagnosis was determined according to the 8th edition American Joint Committee on Cancer (AJCC) TNM staging system.¹¹ For descriptive purposes, stages were grouped as: localized (Stage I: T1-2, N0, M0), regional (Stage II: T3-4, N0, M0), regional with lymph nodes (Stage III: any T, N1-2, M0), and distant metastasis (Stage IV: any T, any N, M1). Tumor grade was defined using the 5th edition of the WHO classification, as follows: low-grade tumors included Grade 1 (well differentiated) and Grade 2 (moderately differentiated), while high-grade tumors included Grade 3 (poorly differentiated). Cases with insufficient data were categorized as Unknown/Not Available.¹² Histopathological subtypes of CRC include adenocarcinoma, mucinous adenocarcinoma, signet ring cell carcinoma, neuroendocrine tumor NOS, neuroendocrine carcinoma NOS, medullary adenocarcinoma, adenoma-like adenocarcinoma, and other.¹³ Mismatch repair (MMR) status was assessed by immunohistochemistry for four MMR proteins (MLH1, MSH2, MSH6, PMS2). A tumor was classified as MMR-deficient (dMMR) if there was complete loss of nuclear staining in tumor cells for one or more of the four proteins, and as MMR-proficient (pMMR) if nuclear expression was intact for all four proteins. Molecular biomarker testing included KRAS, NRAS, and BRAF mutation analysis, with results categorized as wild type or mutated. Marital status was categorized as single, married, widowed, or divorced and smoking status as current, ex-smoker, or non-smoker.

Follow up and Survival Outcomes

The primary outcomes of interest included overall survival (OS), progression-free survival (PFS), and disease-free survival (DFS). OS was defined as the duration from the date of CRC diagnosis to the date of death from any cause or the last follow-up date (for censored observations). PFS was defined as the duration from initial treatment to the date of documented disease progression or the last follow-up date in patients with stage IV CRC. DFS was defined as the duration from initial treatment to the date of documented relapse or disease progression, or the last follow-up date, in patients with stages I, II, and III CRC. The date of last follow-up was defined as the date on which the patient was last contacted or had their last documented visit to the hospital. The date of death was obtained from the medical records.

Procedures of Data Collection and Measurements

Data were collected from eligible patients’ medical records at AUBMC (n = 349). Cases with intramucosal carcinoma (carcinoma in situ, Tis) and gastrointestinal stromal tumors (GIST) were excluded from the study, as well as any records with missing key information. BMI was calculated using height and weight measurements closest to the date of CRC diagnosis. For patients with multiple cancer diagnoses, all measurements and survival time points were referenced to the index CRC diagnosis date, and each patient contributed a single primary tumor to the analysis. Ulcerative colitis (UC) and Crohn’s disease (CD) diagnoses were confirmed based on ICD-10 codes K51 and K50, respectively. The updated Charlson Comorbidity Index (uCCI) was calculated based on the disease stage at the patient’s last follow-up; no calculation was performed for deceased patients.¹⁴ Surgical procedures were counted only if they were not performed for CRC management. Only a subset of the total cohort had complete molecular profiling data available, including KRAS, NRAS, and BRAF mutation analysis. In a small subset of cases (n=8), additional molecular microsatellite instability (MSI) testing was performed to further characterize dMMR tumors as MSI-high or MSI-low based on clinical indication and test availability.

Statistical Analysis

Descriptive statistics were used to summarize patients’ characteristics, presenting mean ± standard deviation (SD) or median with interquartile range (IQR) for continuous variables, depending on normality of distribution, and frequency (percentage) for categorical variables. The χ² test or Fisher’s exact test was applied to compare categorical variables, and the Student's t-test or Mann-Whitney U test was used for comparing continuous variables between groups, as appropriate. Multivariable Cox proportional hazards regression analysis was performed to develop a prognostic model for predicting survival outcomes. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated for variables that remained significant in the final model, using backward conditional elimination with a removal threshold of p > 0.10. Variables with p < 0.05 in univariable analysis were entered into the multivariable model. The proportional hazards assumption was tested using Schoenfeld residuals. A p-value of less than 0.05 was considered statistically significant for all analyses. All statistical analyses were performed using IBM SPSS Statistics version 26.0.

Results

1. Socio-demographic and tumor characteristics

A total of 653 patients were diagnosed with CRC at AUBMC between 2019 and 2024. Of these, 124 were non-Lebanese, 137 had missing information and/or no follow-up data, and 43 had intramucosal carcinoma (carcinoma in situ, Tis) or an alternate final diagnosis. After applying these exclusions, 349 patients with CRC were included in the final analysis. Each patient contributed a single index CRC tumor to the analysis, as the study database recorded one primary CRC diagnosis per patient and patients with multiple simultaneous CRC diagnoses were addressed during data abstraction. Among the 349 patients diagnosed with CRC, 56.7% (n=204) were males and 43.3% (n=145) were females. The mean age at diagnosis was 61.50 years (SD = 14.07). Regarding smoking status, 43.3% (n=147) were non-smokers, while 28.9% (n=98) and 28.6% (n=97) were current smokers and ex-smokers, respectively. Regarding primary tumor location, 23.4% (n=82) had tumors in the ascending colon region, 8.6% (n=30) had descending colon tumors, and 67.6% (n=237) had rectosigmoid region tumors. For right/left survival analyses, 23.4% (n=82) were classified as right-sided and 76.6% (n=267) as left-sided. The stage at diagnosis was as follows: localized (7.6%, n=25), regional (20.8%, n=69), regional with lymph nodes (36.5%, n=121), and distant metastasis (36.8%, n=122). Most patients had adenocarcinoma (93.0%, n=323) during histopathological examination and had low-grade tumors (88.1%, n=306). Regarding treatment, 59.4% (n=210) of patients received fewer than 3 lines of treatment, while 40.6% (n=139) received 3 or more lines of treatment. The mean of the updated Charlson Comorbidity Index (uCCI) at last follow up was 6.02 (SD = 2.48). The median follow up duration was 17 months (SD = 28.88) [0 – 340] (Table 1 and Figure 1). Mismatch repair testing by immunohistochemistry was performed on 181 patients (51.9%), while molecular biomarker testing was performed on a subset of patients: 128 (36.7%) for BRAF and 163 (46.7%) for KRAS. Among MMR-tested patients, 94.5% (n=171/181) were pMMR and 5.5% (n=10/181) were dMMR. A small subset of dMMR tumors (n=8) underwent additional molecular MSI characterization, revealing 62.5% (n=5) as MSI-high (MSI-H) and 37.5% (n=3) as MSI-low (MSI-L). BRAF mutations were present in 7.0% (n=9 of 128 tested), and KRAS mutations in 42.9% (n=70 of 163 tested) (Table 2).

2. Treatment modalities according to tumor location

Table 1.

Socio-Demographics and Tumor Characteristics of Patients With CRC

CRC patients (n=349)
Variable	N	%
Gender
Male	204	56.7
Female	145	43.3
Age at Diagnosis
Mean (SD)	61.50 (14.07)
Smoking
Smoker	98	28.9
Non-Smoker	147	43.3
Ex-Smoker	97	28.6
NA	7
Primary Tumor Site^$
Rectosigmoid Region**	237	67.6
Ascending Colon*	82	23.4
Descending Colon	30	8.6
Stage at Diagnosis
Localized (I)	25	7.6
Regional (II)	69	20.8
Regional with Lymph Nodes (III)	121	36.5
Distant Metastasis (IV)	122	36.8
NA	12
Histopathological Classification
Adenocarcinoma	323	93
Mucinous adenocarcinoma	16	4.6
Signet ring cell carcinoma	1	0.3
Neuroendocrine tumor NOS	3	0.9
Neuroendocrine carcinoma NOS	2	0.6
Medullary adenocarcinoma	1	0.3
Adenoma-like adenocarcinoma	1	0.3
Other ^†	1	0.3
NA	1
Tumor Grade
Low grade	306	88.1
High grade	36	10.4
NA	7
Diagnosis of IBD
Yes	7	2.0
No	342	98.0
Lines of Treatment
≥ 3	139	40.6
< 3	210	59.4
uCCI at last follow-up
Mean (SD)	6.02 (2.48)
NA	29
Follow up
Median in months (SD) [Min – Max]	17.00 (28.88) [0 – 340]

NA: Not Available, denotes cases with missing data for the corresponding variable. NOS: Not Otherwise Specified; used for neuroendocrine cases where differentiation and grade could not be determined from available pathological data.

^$Primary tumor location categorized using three-category anatomic classification.

*Ascending colon region includes cecum, ascending colon, hepatic flexure, and transverse colon.

**Rectosigmoid region includes sigmoid colon, rectosigmoid junction, and rectum.

^†“Other” (n=1), refers to a case in which the pathology report used non-standard terminology that could not be mapped to a defined WHO 2019 CRC histological subtype.

Table 2.

Molecular Biomarkers in Patients With CRC

Variable	CRC (n =349)
Variable	Available	N	%
MMR Status (by IHC)	181
MMR-proficient (pMMR)		171	94.5
MMR-deficient (dMMR)*		10	5.5
NA	168
MSI Characterization (molecular)	8
MSI-High		5	62.5
MSI-Low		3	37.5
NA	341
BRAF Mutated	128
Wild type		119	93
Mutated		9	7
NA	221
KRAS Mutated	163
Wild type		93	57
Mutated		70	43
NA	186

CRC: Colorectal Cancer; IHC: Immunohistochemistry MMR: Mismatch Repair; pMMR: Proficient Mismatch Repair; dMMR: Deficient Mismatch Repair; BRAF: B-Raf proto-oncogene, serine/threonine kinase; KRAS: Kirsten rat sarcoma viral oncogene homologue. NA: Not Available, denotes cases with missing data for the corresponding variable.

*dMMR detected in 10 patients by IHC; only 8 had additional molecular MSI characterization to determine MSI-high versus MSI-low status.

Based on the primary tumor location, 89.7% of left-sided tumors received neoadjuvant chemotherapy compared with only 10.3% of right-sided tumors (p <0.001). Surgery was performed in 73.3% of left-sided tumors and 26.7% of right-sided tumors (p = 0.005). Furthermore, 66.2% of patients with left-sided tumors received adjuvant chemotherapy compared with only 33.8% of those with right-sided tumors (p <0.001). Radiotherapy was administered to 93.4% of patients with left-sided tumors while only 6.6% of those with right-sided tumors were offered radiotherapy (p <0.001). Additionally, 62.5% of patients with right-sided tumors received immunotherapy, more than patients with left-sided tumors (37.5%) (p = 0.02). (Table 3).

3. Overall, Progression-Free, and Disease-Free Survival Analysis in Colorectal Cancer Patients

Table 3.

Treatment Modalities According to Tumor Location

Variable	Colorectal Cancer (n=349)
	Primary Tumor Location
	Left-Sided (n=267)	Right-Sided (n=82)
Neoadjuvant Chemotherapy
Received	130 (89.7%)	15 (10.3%)
Did not receive
P-Value	<0.001
Adjuvant Chemotherapy
Received	86 (66.2%)	44 (33.8%)
Did not receive
P-Value	<0.001
Surgery
Received	203 (73.3%)	74 (26.7%)
Did not receive
P-Value	0.005
Radiotherapy
Received	113 (93.4%)	8 (6.6%)
Did not receive
P-Value	<0.001
Targeted Therapy
Received	65 (75.6%)	21 (24.4%)
Did not receive
P-Value	0.816
Immunotherapy
Received	3 (37.5%)	5 (62.5%)
Did not receive
P-Value	0.02
Number of Lines of Treatment
Mean (SD)	2.27 (1.08)	2.06 (1.10)
P-Value	0.129

CRC: Colorectal Cancer; IBD: Inflammatory Bowel Disease.

Patients diagnosed with CRC at age ≥65 years had an OS rate of 85.7% at 36 months following diagnosis (p = 0.072). The PFS rate was 25.8% for patients with stage IV CRC at 36 months from treatment initiation (p = 0.627). The DFS rate was 58.0% for patients with stage I, II, or III CRC at 36 months (p = 0.047). For patients with IBD-CRC, OS was 85.7% (p = 0.822) and DFS was 75.0% (p = 0.395) compared to non-IBD patients (OS: 88.2% and DFS: 62.5%, respectively). Smokers had lower OS (82.6%) compared to non-smokers (90.0%) (p = 0.028). Patients diagnosed at stage II had the highest OS (96.1%), while stage IV patients had the lowest OS (75.9%). Patients with tumors in the rectosigmoid region had higher OS (91.5%) compared to those with ascending colon region (82.9%) and descending colon (77.8%) tumors (p = 0.003) (Table 4).

Table 4.

Univariate Analysis of Demographic and Tumor Factors and Their Impact on Survival at 3 years on Patients With CRC

Variable	Levels	OS by Months, in % - Median OS in d (n=349)	PFS by days, in % - Median PFS in d (n=122)	DFS by days, in % - Median DFS in d (n=215)
Variable	Levels	All CRC	All CRC	All CRC
BMI category	< 18.50	NAV	NAV (192d)	NAV (304d)
	18.50 – 24.99	88.2 (NR)	22.4 (335d)	66.4 (NR)
	24.99 – 29.99	87.5 (NR)	13.1 (456d)	60.8 (4416d)
	> 30.00	86.5 (161m)	25.0 (217d)	69.1 (3744d)
	P -Value	0.600	0.632	0.218
Marital status	Single	94.9 (NR)	10.9 (311d)	95.8 (NR)
	Married	87.0 (161m)	20.3 (386d)	61.1 (3744d)
	P -Value	0.332	0.282	0.068
Age at diagnosis	≥ 65	85.7 (161m)	25.8 (352d)	58.0 (4416d)
	< 65	89.7 (NR)	17.0 (335d)	69.9 (1176d)
	P -Value	0.072	0.627	0.047
Diagnosis of IBD	No	88.2 (161m)	18.3 (352d)	64.2 (3744d)
	Yes	85.7 (NR)	NAV (104d)	75.0 (NR)
	P -Value	0.822	0.014	0.442
Smoking status	Smoker	82.6 (161m)	14.8 (287d)	52.3 (1127d)
	Non-Smoker	90.0 (NR)	19.7 (437d)	71.1 (3744d)
	P -Value	0.028	0.205	0.215
Stage at diagnosis	Localized (I)	94.1 (NR)	-	84.7 (NR)
	Regional (II)	96.1 (NR)	-	68.6 (3744d)
	Regional with Lymph Nodes (III)	92.9 (161m)	-	58.5 (4786d)
	Distant Metastasis (IV)	75.9 (NR)	-	-
	P -Value	0.018	-	0.096
Primary tumor site	Rectosigmoid	91.5 (NR)	20.2 (315d)	67.3 (3744d)
	Ascending	82.9 (63m)	23.5 (335d)	62.5 (1291d)
	Descending	77.8 (NR)	25.7 (891d)	50.4 (1280d)
	P -Value	0.003	0.510	0.202
Tumor grade	Grade 1 or well differentiated	84.4 (44m)	19.9 (119d)	50.0 (662d)
	Grade 2 or moderately differentiated	89.1 (NR)	21.7 (389d)	65.1 (3744d)
	Grade 3 or poorly differentiated	81.0 (NR)	NAV (220d)	64.6 (NR)
	P -Value	0.115	0.217	0.239
Histological subtype	Adenocarcinoma	88.9 (161)	17.3 (335d)	65.3 (3744d)
	Other	76.2 (NR)	NAV (611d)	50.8 (NR)
	P -Value	0.129	0.626	0.314

OS: Overall Survival, PFS: Progression-Free Survival, DFS: Disease-Free Survival, CRC: Colorectal Cancer, IBD: Inflammatory Bowel Disease, NAV: Not Available at 3 years, NR: Non Reached.

In the multivariable analysis (Table 5), patients aged ≥65 years had higher risk of mortality compared to those aged <65 years (HR = 1.98, 95% CI = 0.99-3.94, p = 0.050). Patients with IBD had significantly higher risk of disease progression (HR = 9.39, 95% CI = 1.21-72.64, p = 0.032). Primary tumor location also played a role, with left-sided tumors associated with lower risk of mortality compared to right-sided tumors (HR = 0.42, 95% CI = 0.21-0.86, p = 0.018). Smokers showed significantly higher risk of mortality compared to non-smokers (HR = 2.58, 95% CI = 1.29-5.17, p = 0.007).

Table 5.

Multivariate Cox Proportional Hazards Analysis of Factors Influencing Overall Survival (OS), Disease-free Survival (DFS), and Progression-free Survival (PFS) in Patients With CRC

Variable	Levels	OS			PFS			DFS
Variable	Levels	HR	95% CI	P-value	HR	95% CI	P-value	HR	95% CI	P-value
Age at diagnosis	Age ≥ 65 vs Age < 65	1.98	0.99-3.94	0.050 ^a	-	-	- ^g	1.83	1.07-3.13	0.026 ^d
Diagnosis of IBD	Yes vs No	3.20	0.40-25.70	0.268 ^j	10.38	1.32-81.52	0.026 ^j	0.47	0.06-3.48	0.466 ^j
Stage at diagnosis	Distant Metastasis (IV) vs Localized (I)	3.60	0.79-16.24	0.096 ^a	-	-	- ^g	-	-	- ^d
Stage at diagnosis	Regional with Lymph Nodes (III) vs Localized (I)	1.26	0.26-5.90	0.768 ^a	-	-	- ^g	4.03	1.20-13.53	0.024 ^d
Primary tumor location	Left vs Right	0.42	0.21-0.86	0.018 ^a	-	-	- ^g	-	-	- ^d
Smoking status	Smoker vs Non Smoker	2.58	1.29- 5.17	0.007 ^a	-	-	- ^g	-	-	- ^d
Cause of death	Disease Related Mortality vs non-Disease Related Mortality	0.42	0.16-1.06	0.069 ^b	-	-	- ^h	-	-	- ^e
Neoadjuvant chemotherapy	Yes vs No	0.36	0.15-0.86	0.023 ^c	-	-	- ⁱ	0.57	0.29-1.11	0.102 ^f
Adjuvant chemotherapy	Yes vs No	0.28	0.11-0.71	0.008 ^c	-	-	- ⁱ	-	-	- ^f
Surgery	Yes vs No	-	-	- ^c	-	-	- ⁱ	0.35	0.13-0.91	0.031 ^f
Targeted therapies	Yes vs No	4.49	1.98-10.18	<0.001 ^c	1.81	1.10-2.97	0.019 ⁱ	4.49	2.41-8.36	<0.001 ^f

^aAge at diagnosis, stage at diagnosis, smoking status, and primary tumor site: were retained in the final model of the backward stepwise cox regression analysis.

^bLines of treatment, cause of death, date of CRC diagnosis, and past history of GI surgeries: were retained in the final model of the backward stepwise cox regression analysis.

^cNeoadjuvant chemotherapy, adjuvant chemotherapy, targeted therapies, and date of CRC diagnosis: were retained in the final model of the backward stepwise cox regression analysis.

^dStage at diagnosis, age at diagnosis, and tumor grade: were retained in the final model of the backward stepwise cox regression analysis.

^eLines of treatment, date of CRC diagnosis, and marital status: were retained in the final model of the backward stepwise cox regression analysis.

^fTargeted therapies, and date of CRC diagnosis: were retained in the final model of the backward stepwise cox regression analysis.

^gDiagnosis of IBD, and date of CRC diagnosis: were retained in the final model of the backward stepwise cox regression analysis.

^hLines of treatment, date of CRC diagnosis: were retained in the final model of the backward stepwise cox regression analysis.

ⁱTargeted therapies, surgery, and neoadjuvant chemotherapy: were retained in the final model of the backward stepwise cox regression analysis.

^jAdjusted for date of CRC diagnosis, stage at diagnosis, age at diagnosis, and smoking status.

Discussion

Our study included 349 patients with CRC diagnosed between 2019 and 2023. Tumors in the rectosigmoid region were the most common (67.6%), followed by tumors in the ascending colon region (23.4%). Our data were collected using a three-category anatomic classification system during retrospective chart review. This classification enables the clinically and molecularly relevant distinction between right-sided and left-sided CRC, which is consistent with established prognostic differences and molecular profiles in the literature.^15,16 Additionally, most tumors were classified as grade 2, accounting for 82.8% of cases. These findings are in line with a study conducted in Libya by Elzouki et al. (2014), which reported that the majority (67.8%) of CRC tumors arose from the rectum and sigmoid colon. Tumors originating from the transverse colon, ascending colon, and cecum accounted for 20.4% of cases. However, there is a notable difference in the histological grading between the two studies. In the Libyan study, 38.8% of the patients had poorly differentiated adenocarcinoma, whereas our study found a predominance of moderately differentiated tumors (82.8%).¹⁷ This difference likely stems from a combination of genetic predispositions, environmental and lifestyle factors, and disparities in healthcare access and diagnostic practices.^18,19 Smoking was found to be significantly associated with decreased overall survival in patients with CRC, aligning with established literature on its carcinogenic effects and contribution to poor treatment response.²⁰ Given Lebanon’s high smoking prevalence, further exacerbated by the country’s economic crisis, this association is particularly concerning.²¹

A recent population-based study from the Dutch National Screening Database,²² conducted between 2014 and 2018 in asymptomatic average-risk individuals aged 55 to 75 years, showed that right-sided tumors accounted for 28.9%, left-sided tumors were the most common, representing 44.4%, and rectal tumors comprised 26.6% of the total cases. Stage I tumors were the most prevalent, accounting for 46.6%. In contrast, our study found that most CRC tumors were in the rectosigmoid region (67.6%). Staging in our study revealed that 7.6% were diagnosed at a stage I, while 20.8% at stage II. Possible explanations for these differences include variations in screening practices and population demographics. The Dutch study’s higher prevalence of stage I tumors (46.6%) compared with our study (7.6%) could be attributed to the effectiveness of their national screening program in detecting CRC at an earlier stage. In contrast, the higher proportion of advanced-stage diagnoses (stage III and IV) in our study may reflect delayed diagnosis and limited access to early screening.

A meta-analysis by Petrelli et al. (2017) analyzed 66 studies and found that the overall pooled hazard ratio (HR) for overall survival (OS) of left-sided versus right-sided CRC tumors was 0.82 (95% CI: 0.79-0.84).¹⁵ This aligns with our study, which found that left-sided tumors were associated with a lower risk of mortality compared to right-sided tumors (OS: HR = 0.42, 95% CI = 0.21-0.86, p = 0.018). Moreover, a meta-analysis by Can et al. (2022) showed that the overall pooled OS for patients with IBD-related CRC versus non-IBD CRC was 1.33 (95% CI: 1.20-1.47).²³ This is consistent with our findings, although our results were not statistically significant. In our study, IBD-related CRC versus non-IBD CRC had an OS HR of 3.20 (95% CI: 0.40-25.70, p = 0.268). Our findings align closely with studies conducted in Germany (OS, HR: 2.15, 95% CI:1 54–3.69) and Japan (OS, HR: 2.09, 95% CI: 1 59–2.72), as indicated by Can et al. (2022). This could be due to similarities in patient demographics and disease characteristics across these three eastern countries, such as age distribution, genetic predispositions, and the severity of IBD and CRC. Although regular monitoring in patients with IBD allows for timely interventions, IBD patients exhibit lower OS and PFS, raising concerns about the natural course of IBD influencing a more aggressive disease monitoring strategy. Several factors contribute to why a lesser proportion of IBD patients survive at 36 months post-diagnosis. The underlying inflammatory processes and immune dysregulation in IBD may lead to more aggressive tumor biology.²⁴ Additionally, IBD patients often have poorer baseline health and nutritional status, affecting their response to cancer treatments.²⁵ While the prevalence of IBD-associated CRC in our cohort (7/349, 2.0%) reflects typical clinical distribution, the nearly 10-fold increased risk of progression (HR = 9.39, p = 0.032) carries substantial clinical implications. These findings underscore the importance of risk-stratified management approaches for IBD patients with CRC and contribute novel regional data where Middle Eastern evidence remains scarce.

Furthermore, the study revealed that patients who did not receive neoadjuvant chemotherapy or adjuvant chemotherapy faced a higher risk of mortality. Interestingly, the absence of targeted therapies in the treatment regimen was associated with reduced mortality risk, along with PFS and DFS. These findings underscore the critical role of multimodal treatment strategies incorporating neoadjuvant, adjuvant, and targeted therapies in enhancing outcomes for patients with CRC. They also suggest that while targeted therapies may offer benefits, the use of targeted therapies in Lebanon is predominantly for advanced-stage patients and this reflects their status as a last-resort treatment due to factors such as complexity, cost, and availability in our country.²⁶

In discussing the limitations of the study, several critical considerations emerge. Firstly, the retrospective design inherently introduces potential for selection bias and incomplete data retrieval. Secondly, reliance on medical record reviews for data extraction introduces variability in data quality and consistency, impacting the accuracy of variables such as treatment histories and disease outcomes. This is a single-center study from AUBMC. While AUBMC is the largest tertiary cancer center in Lebanon with regional referrals, our findings may not be generalizable to all Middle Eastern populations, and multi-center studies are needed to validate these results across diverse healthcare settings in the region. Moreover, our study utilized a three-category anatomic classification of tumor location based on the level of detail consistently available in retrospective medical records. While this approach does not permit separate analysis of individual anatomic subsites, it enables the clinically and molecularly relevant distinction between right-sided (midgut-derived) and left-sided (hindgut-derived) CRC, which was the primary objective of our location-based analyses. This classification is consistent with embryological derivation and well-established molecular and prognostic differences between right- and left-sided tumors. Lastly, the substantial amount of missing data in the controls dataset underscores the need for more robust adjustments in the bivariate regression analysis and survival analyses, which could have strengthened the validity and reliability of our results. Additionally, MMR testing was performed in only 51.9% of the cohort (n=181/349), and the proportion of dMMR tumors among tested patients (5.5%) is consistent with expected rates in cohorts enriched for left-sided and rectal tumors. These limitations highlight areas for improvement in future research endeavors.

Conclusion

This study provides valuable insights into the distinct characteristics, treatment patterns, and their impact on survival outcomes in patients with CRC in a Lebanese cohort. Our findings showed that advanced age, smoking, a diagnosis of IBD, and right-sided tumor location were associated with decreased OS in Lebanese patients with CRC. They support personalized treatment strategies based on tumor characteristics, and targeted public health initiatives focusing on modifiable risk factors such as smoking. Future prospective studies with larger cohorts and longer follow-up periods are needed to further refine management approaches for different CRC subtypes in the Middle Eastern population.

Supplemental Material

Supplemental material - Tumor Characteristics and Survival Predictors in Patients With Colorectal Cancer: A Lebanese Single-Center Experience

Supplemental material for Tumor Characteristics and Survival Predictors in Patients With Colorectal Cancer: A Lebanese Single-Center Experience by Mustafa Saleh, Alvar Akil, Laudy Chehade, Tasnim Diab, Rani Hassan, Soltan Al Chaar, Maya Charafeddine, Monita Al Darazi, Rayan Tarnini, Pascale Salameh, Antoine Abou Rached and Ali Shamseddine in Clinical Medicine Insights: Oncology.

Supplemental Material

Supplemental material - Tumor Characteristics and Survival Predictors in Patients With Colorectal Cancer: A Lebanese Single-Center Experience

Footnotes

ORCID iDs

Mustafa Saleh

Soltan Al Chaar

Ali Shamseddine

Ethical Considerations

This study was approved by the Institutional Review Boards (IRBs) of the American University of Beirut Medical Center (AUBMC) [Reference: BIO-2023-0175].

Consent to Participate

As this was a retrospective chart review, the requirement for written informed consent was waived by the IRB.

Author Contributions

Conceptualization: M.S., A.A., P.S., A.A., S.A, and A.S. Methodology: M.S., A.A., L.C., T.D., R.H., S.A., M.C., M.AD., R.T., and P.S. Writing—original draft preparation: M.S., A.A., L.C., and T.D. Writing—review and editing: M.S., A.A., L.C., T.D., R.H., S.A., M.C., M.AD., R.T., and P.S., A.A., and A.S. Supervision: P.S., A.A., and A.S.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Declaration of Conflicting Interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Data Availability Statement

The data used and/or analyzed during the current study are available from the corresponding author on reasonable request, in accordance with institutional data sharing policies.*

Supplemental Material

Supplemental material for this article is available online.

References

Siegel

Miller

Fuchs

Jemal

. Cancer Statistics, 2021. CA Cancer J Clin. 2021;71(1):7-33.

Lakkis

El-Kibbi

Osman

. Colorectal Cancer in Lebanon: Incidence, Temporal Trends, and Comparison to Regional and Western Countries. Cancer Control. 2021;28:1073274821996869.

Dominguez

Yilmaz

Steele

. Stage IV Colorectal Cancer Management and Treatment. Journal of Clinical Medicine. 2023;12(5):2072.

Onwuzo

Boustany

Saleh

, et al. Increased Risk of Colorectal Cancer in Patients With Celiac Disease: A Population-Based Study. Cureus. 2023;15(3):e36964.

Akoko

Brand

Kotecha

, et al. Colorectal cancer in Tanzania: the current status and future directions. ecancermedicalscience. 2023;17:1564.

Bener

Moore

Ali

El Ayoubi

. Impacts of family history and lifestyle habits on colorectal cancer risk: a case-control study in Qatar. Asian Pac J Cancer Prev. 2010;11(4):963-968.

Onwuzo

Boustany

Saleh

, et al. Increased Risk of Non-Alcoholic Steatohepatitis in Patients With Inflammatory Bowel Disease: A Population-Based Study. Cureus. 2023;15(3):e35854.

Asghari-Jafarabadi

Wilkins

Plazzer

Yap

McMurrick

. Prognostic factors and survival disparities in right-sided versus left-sided colon cancer. Sci Rep. 2024;14(1):12306.

Kroenke

Neugebauer

Meyerhardt

, et al. Analysis of Body Mass Index and Mortality in Patients With Colorectal Cancer Using Causal Diagrams. JAMA Oncol. 2016;2(9):1137-1145.

10.

STROBE Initiative von Elm

Altman

Egger

Pocock

Gøtzsche

Vandenbroucke

. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. J Clin Epidemiol. 2008;61(4):344-349.

11.

Murphy

Sandler

Sanoff

Yang

Lund

Baron

. Decrease in Incidence of Colorectal Cancer Among Individuals 50 Years or Older After Recommendations for Population-based Screening. Clin Gastroenterol Hepatol. 2017;15(6):903-909.e6.

12.

Jesinghaus

Schmitt

Lang

, et al. Morphology Matters: A Critical Reappraisal of the Clinical Relevance of Morphologic Criteria From the 2019 WHO Classification in a Large Colorectal Cancer Cohort Comprising 1004 Cases. Am J Surg Pathol. 2021;45(7):969-978.

13.

Ahadi

Sokolova

Brown

Chou

Gill

. The 2019 World Health Organization Classification of appendiceal, colorectal and anal canal tumours: an update and critical assessment. Pathology. 2021;53(4):454-461.

14.

Charlson

Carrozzino

Guidi

Patierno

. Charlson Comorbidity Index: A Critical Review of Clinimetric Properties. Psychother Psychosom. 2022;91(1):8-35.

15.

Petrelli

Tomasello

Borgonovo

, et al. Prognostic Survival Associated With Left-Sided vs Right-Sided Colon Cancer: A Systematic Review and Meta-analysis. JAMA Oncol. 2017;3(2):211-219.

16.

Yahagi

Okabayashi

Hasegawa

Tsuruta

Kitagawa

. The Worse Prognosis of Right-Sided Compared with Left-Sided Colon Cancers: a Systematic Review and Meta-analysis. J Gastrointest Surg. 2016;20(3):648-655.

17.

Elzouki

Habel

Alsoaeiti

Abosedra

Khan

. Epidemiology and clinical findings of colorectal carcinoma in two tertiary care hospitals in Benghazi, Libya. Avicenna J Med. 2014;4(4):94-98.

18.

Siddiqui

Nohra

Saleh

, et al. Pediatric Oncology, Palliative Care and Low- or Middle- Income Countries: A Call for Action. Glob Pediatr Health. 2023;10:2333794X231188591.

19.

Shamseddine

Chehade

Al Mahmasani

Charafeddine

. Colorectal Cancer Screening in the Middle East: What, Why, Who, When, and How? Am Soc Clin Oncol Educ Book. 2023;43:e390520.

20.

Huang

Wei

Yeh

. Cigarette Smoking Associated with Colorectal Cancer Survival: A Nationwide, Population-Based Cohort Study. J Clin Med. 2022;11(4):913.

21.

Haddad

Aoun

Mghames

Saleh

Chahine

. Smoking Habits and Nicotine Dependence Among the General Lebanese Population Before and During Both the Economic Crisis and COVID-19 Pandemic. Tob Use Insights. 2024;17:1179173X241253962.

22.

Kooyker

de Jonge

Toes-Zoutendijk

, et al. Colorectal Cancer Stage Distribution at First and Repeat Fecal Immunochemical Test Screening. Clin Gastroenterol Hepatol. 2023;21(13):3424-3432.e2.

23.

Schardey

Zhang

, et al. Survival Outcomes and Clinicopathological Features in Inflammatory Bowel Disease-associated Colorectal Cancer: A Systematic Review and Meta-analysis. Ann Surg. 2022;276(5):e319-e330.

24.

Zhang

Shi

Lin

, et al. Overcoming cancer risk in inflammatory bowel disease: new insights into preventive strategies and pathogenesis mechanisms including interactions of immune cells, cancer signaling pathways, and gut microbiota. Front Immunol. 2024;14:1338918.

25.

Jabłońska

Mrowiec

. Nutritional Status and Its Detection in Patients with Inflammatory Bowel Diseases. Nutrients. 2023;15(8):1991.

26.

Ganesan

El Cheikh

Isidori

Kuo

Saleh

Nair

. Editorial: The management of hematologic malignancies in lower-income countries. Front Oncol. 2023;13:1218718.

Supplementary Material

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