Abstract
Introduction
Colorectal cancer (CRC) is the third most common cancer worldwide, with higher rates in industrialized countries. By 2030, the number of CRC cases may rise by 60%, reaching 2.2 million new cases and 1.1 million deaths. In 2020, CRC accounted for 1.93 million new cases and 940,000 deaths, with the highest prevalence in New Zealand, Australia, and Europe, while lower rates were observed in Southern Asia and Africa. In Pakistan, CRC is the second most common cancer, accounting for 4.8% of all diagnoses. The risk factors include family history, smoking, genetic syndromes, and diet. Screening is recommended from the age of 45. Advances in immunotherapy, chemoradiotherapy, and targeted therapies have improved survival rates. This five-year study analyzed CRC cases at a Pakistani hospital to identify associations between various clinical and demographic factors and mortality.
Methods
This retrospective study, conducted at the Department of Surgery at Jinnah Post Medical Graduate Centre, Karachi, included 121 confirmed CRC patients from July 2022 to August 2024. Data from electronic medical records included diagnostic procedures and treatment histories. Tumor location and staging were determined according to the TNM staging system. Statistical analysis identified trends in tumour location, disease stage, and demographics.
Results
Among the 121 patients with CRC, the majority were middle-aged (39.7%) and male (62%). The common symptoms included abdominal pain (65.3%) and constipation (43.8%). Most patients were in Duke stage C (42.1%), with metastasis in 7.2% of cases. Open surgery was performed in 71.9% of patients. Significant associations were found between vomiting, abdominal distention, fever, and mortality, as well as between cancer type and surgical method.
Conclusion
CRC is increasingly common in middle-aged individuals, and early onset CRC is increasing in Pakistan. Targeted screening and personalized treatment are crucial, and further research is needed to address the increasing incidence, especially in younger populations.
Introduction
Colorectal cancer (CRC) is the third most common cancer worldwide. Compared to the rest of the world, industrialized affluent countries have far higher incidence rates. 1 A predicted 60% increase is anticipated by 2030, which would result in roughly 2.2 million additional cases and 1.1 million fatalities globally. This alarming trend presents a significant threat to the global public health. 2 According to global cancer burden data, CRC accounted for approximately 1.93 million new cases and 940,000 deaths worldwide in 2020. 3 At 40.6 cases per 100,000 men, New Zealand, Australia, and Europe had the highest colorectal cancer prevalence rates; numerous Southern Asian and African nations had the lowest rates, at 4.4 cases per 100,000 females. Similar patterns were seen in the mortality rates, with Southern Asia having the lowest incidence at 2.5/100,000 females and Eastern Europe having the highest rate at 20.2 per 100,000 men. 4 Based on the 28-year collective registry report from the Shaukat Khanum Memorial Cancer Hospital and Research Centre, covering the period from December 1994 to December 2022, CRC was identified as the second most prevalent cancer in Pakistan. CRC accounts for 4.8% of all newly diagnosed cancer cases, with rectal cancer accounting for 1.8%. Rectal cancer-related deaths account for 1.5% of all cancer-related fatalities in the country.3,5
CRC develops because of a combination of factors. A family or genetic history of colorectal cancer greatly increases the risk of developing the disease. Additional risk factors include smoking, alcohol use, Lynch syndrome, diabetes mellitus, hereditary nonpolyposis colorectal cancer, cholecystectomy, and inflammatory bowel disease. Moreover, certain dietary habits, such as low fibre intake, limited consumption of fruits and vegetables, and a high intake of processed red meat, further increase the likelihood of colorectal cancer. 6
Due to the rising incidence of CRC, Screening is advised for individuals at average risk beginning at 50 or 45 years of age. These individuals did not have a family history of inflammatory bowel disease, inherited syndromes, colorectal cancer, or a previous diagnosis of colon cancer. Screening methods include colonoscopy every 10 years, flexible sigmoidoscopy every five years, or annual stool tests, such as FIT or FOBT. The U.S. The Preventive Services Task Force recommends regular screening for those aged 45-75 years, with personalized screening guidelines for individuals aged 76-85 years. If abnormalities are detected, colonoscopy should be performed for further evaluation. 7
In recent decades, there have been significant advancements in the understanding and management of colorectal cancer. Key developments include immunotherapy, chemoradiotherapy, endoscopic and surgical excision, and multimodal and targeted therapies. For patients with intermediate and advanced colorectal cancer, combining these therapeutic modalities can significantly reduce Tumor development and increase survival. 8
In this retrospective study, we examined the medical records of patients with colorectal cancer (CRC) at a tertiary care hospital in Pakistan over the past five years. This study focused on collecting and analysing clinical data related to the anatomical locations of CRC tumours (such as colon and rectum segments) and the stage of disease at the time of diagnosis using standardized staging criteria. By reviewing various factors such as patient demographics, clinical presentations, diagnostic methods, and treatment outcomes, we aimed to analyze the association between these factors and mortality.
Methods
This retrospective cross-sectional study was conducted at the Department of Surgery at Jinnah Post Medical Graduate Centre, Karachi, over two years from July 2022 to August 2024. Ethical approval for this study has been granted by IRB (Institutional review board) of Jinnah Post Graduate center (NO.F.2-77/2022-GENL/212/JPMC). Requirement for obtaining informed consent was waived by the IRB of Jinnah Post Graduate center due to the retrospective nature of this study.
A non-probability sampling technique was employed for data collection. The inclusion criteria were patients with histopathologically confirmed colorectal cancer, including both primary and metastatic cases, who had undergone necessary diagnostic procedures such as colonoscopy, computed tomography (CT), and histopathological evaluation at the time of initial diagnosis. Additionally, patients with complete medical records documenting their treatment history, including surgery, chemotherapy, and radiation therapy, were included. Patients with CRC of all ages with colorectal cancer were eligible for inclusion in the study. The exclusion criteria included incomplete medical records, missing medical records, or insufficient diagnostic or treatment data. Operational definitions were established for clarity, including the anatomical location of the Tumor (right-sided, left-sided, or rectal) and disease staging based on the duke’s classification system. Data were collected by searching the hospital’s electronic medical records and PACS database to identify eligible patients. In total, 150 patients were initially identified, out of which 29 patients were excluded due to incomplete medical records, missing information, or insufficient diagnostic or treatment data, resulting in the final inclusion of 121 patients diagnosed with colorectal cancer during the study period. This study was conducted per the STROBE guidelines. 9
Statistical Analyses
Statistical analyses were performed using SPSS v26 to evaluate trends in colorectal cancer with respect to anatomical location, stage of disease, and patient demographics.
Survival status was determined from the medical records, and follow-ups were done in person or through telephone contact. Follow-up duration was variable among the participants and the survival time was recorded from the date of diagnosis till the time of death. Kaplan Meir model was used to account for the different follow-up times.
Logistic regression models and the chi-square model were used to identify the association between various clinical factors (type of cancer, mode of surgery, and different signs and symptoms) and mortality.
Result
Of the initial 150 candidates, 29 (19.3%) were excluded due to insufficient data, rendering meaningful analysis or comparison with the included participants infeasible. Limited demographic data were available for the excluded patients, showing a similar distribution of age (mean ∼50 years) and sex (approximately 60% male) compared to the included cohort. However, due to extensive missing data across clinical variables such as symptoms, tumour stage, and treatment details, formal statistical comparisons were not feasible. As a result, we were unable to robustly assess potential differences between excluded and included patients.
Data Distribution of Various Variables
Association Between Different Variables and Patient Outcomes
aChi-square Test.
bFischer Exact Test.
Discussion
Research has shown a correlation between CRC and economically developed regions. 10 Historically, affluent Western nations have exhibited the highest rates of CRC, with the incidence sharply increasing with age. However, recent trends indicate a rapid rise in CRC incidence among younger populations in both high-income and developing countries.10,11 From 1995 to 2014, Japan, South Korea, Hong Kong, and Taiwan reported a significant increase in early-onset CRC (EOCRC). 12 To address the growing CRC burden, the implementation of cost-effective screening programs, early disease detection, personalized treatment regimens, and robust preventive measures is strongly recommended. 11 Our study identified the highest CRC incidence in the middle-aged cohort (36-60 years), followed by young adults (19-35). However, among younger individuals (<18 years) and the elderly (>61 years), the incidence was comparatively lower. This contrasts with data from Oceania, Europe, and the United States, which show conflicting trends. 13 A study by Liao et al. 14 supported our findings, indicating that the middle-aged group had the highest incidence of CRC. It is important to clarify that while we refer to broader international trends to help contextualize our findings, the primary focus of this study is the patient population at a tertiary care hospital in Pakistan. All data and conclusions are drawn specifically from this institutional setting.
Globally, Karachi falls within the same category as parts of the Indian subcontinent and other underdeveloped regions, with a low incidence of colorectal cancer. 15 In terms of cases, CRC accounted for 2.8% of cancers in females and 4.4% in males, which is approximately 50% of the global estimate of 9.4% for colon and rectal cancers. 16 In our study, the CRC incidence was significantly higher in males compared than in females.
According to a meta-analysis, the percentage of young CRC patients (<40 years) among all CRC patients ranged from 0.4% to 36.5%, with most studies conducted in Europe and North America. 17 These findings suggest that sporadic early onset colon cancer is rare in affluent countries. However, developing nations exhibit significantly higher rates of early onset CRC. 18 At our institution, we observed a 50% rate of early onset colorectal cancer during the study period, 17 which is much higher than that suggested by Western data. This rate is comparable to findings from India, although it far exceeds estimates from previous Asian studies. 19
This intriguing finding can be interpreted in several ways: First, since this study was institution-based, selection bias was unavoidable. As a tertiary care facility, our institution provides greater attention to and access to superior cancer screening resources, which may not be widely available across the country. This could have resulted in the increased prevalence rate. Second, a significant portion of the population is “young”, which increases the number of “at-risk” individuals and raises the likelihood of detecting more cases within this demographic. 20
The precise causes behind the rising incidence of colorectal cancer (CRC) in individuals under 50 years of age remain unclear, but one hypothesis is the birth cohort effect. This theory suggests that those born in the second half of the 20th century may have been more exposed to modifiable behavioural risk factors such as poor diets, obesity, sedentary lifestyles, low physical activity levels, and higher smoking rates during early adulthood. However, the exact mechanisms or risk factors remain uncertain, as most of these variables have been linked to CRC, primarily in patients aged ≥50 years.21,22
In our investigation, age and survival rates did not appear to be related, and the same was true for sex, in contrast with findings from a previous study by Schreuders et al. 23 Between 1990 and 2019, the age-standardized death rate decreased significantly in high-income regions—for example, a 33.5% reduction in Australasia (95% UI −29.8 to −37.2) and a 25.3% reduction in high-income North America (95% UI −23.5 to −27.3). This decline in incidence and mortality in high-SDI (Socio-Demographic Index) regions, particularly among individuals over 50, suggests improvements in early detection through CRC screening programs, cancer registries, technological advancements, and standardization of early referrals to healthcare providers. 24
In most nations with high SDI, colorectal cancer screening is typically recommended for individuals aged 50-75 years to facilitate the early diagnosis of adenomatous polyps and adenomas. 23 The significant increase in colonoscopy screenings during the 2000s has had a notable impact on reducing CRC-related fatalities in the USA. 24 This highlights the effectiveness of early detection and intervention in lowering the mortality rates associated with colorectal cancer.
Males are more likely than females to die from colorectal cancer, with age-standardized rates for men being 1-2 times higher than for women in various Global Burden of Disease (GBD) regions, and this disparity has increased over time. Although the age-standardized incidence rate of colorectal cancer was once higher in women, it has since grown more rapidly in men, a trend observed before the first international studies on the disease were published in the 1960s. 25 Globally, males account for the majority of colorectal cancer cases, a trend linked to higher rates of alcohol consumption, visceral obesity, and smoking among men. 26
Individuals with type 2 diabetes are approximately two–three times more likely to develop colorectal cancer than those without diabetes. 27 This increased risk is thought to be linked to an inflammatory state associated with diabetes and elevated insulin levels. Hyperinsulinemia may directly and indirectly contribute to colorectal cancer development by promoting colonic cell proliferation and increasing insulin-like growth factor 1 (IGF-1) levels. IGF-1, a mitogenic factor, stimulates cell growth and inhibits cell death. 28 Additionally, chronic inflammation associated with diabetes, driven by pro-inflammatory cytokines such as tumour necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), promotes carcinogenesis, tumour growth, invasion, and metastasis. 28 In our study, 5.8% of the participants had diabetes, but no significant association between diabetes and mortality was observed.
The role of colorectal cancer (CRC) symptoms in disease identification has been evaluated in several studies, which indicate that individual symptoms have limited diagnostic value, showing low specificity and sensitivity for colorectal cancer. The positive and negative likelihood ratios (PLR and NLR) further support the notion that the likelihood of detecting CRC is not significantly influenced by the presence or absence of symptoms. 29 Nonetheless, various clinical guidelines recommend that individuals exhibiting gastrointestinal signs and symptoms indicative of potential CRC should undergo colonoscopy for further evaluation. 30
Conversely, some studies suggest that the presence of co-occurring symptoms may enhance the sensitivity and specificity of colorectal cancer diagnosis. Symptoms, such as palpation of an abdominal mass during examination, reports of dark red rectal bleeding, 29 or a combination of rectal bleeding, weight loss, and altered bowel habits, 31 can indicate a higher likelihood of CRC. Patients who are diagnosed before exhibiting symptoms (or whose symptoms are among the first signs) typically have a much better prognosis for CRC treatment. Therefore, any concerning symptoms that may suggest colorectal cancer should prompt patients to schedule an appointment with a healthcare provider immediately and undergo diagnostic testing such as colonoscopy. 32 In our study, we found no discernible correlation between symptoms, such as stomach discomfort, constipation, and mortality. However, varying degrees of significance were observed in the associations between symptoms, such as vomiting, fever, abdominal distention, and death.
CRC develops in three phases: initiation, promotion, and progression. The initiation phase involves permanent genetic damage, leading to neoplastic transformation of epithelial cells. During promotion, these altered cells proliferated, resulting in aberrant growth. Progression involves malignant transformation and metastasis. Benign precursor lesions, particularly adenomatous and serrated polyps, have a 30%-50% chance of progressing to cancer. Approximately 20% of CRC cases are linked to genetic factors, notably Lynch syndrome, which involves defects in DNA repair genes (eg, MLH1, MSH2) and familial adenomatous polyposis (FAP), associated with mutations in the APC gene. 33
Seventy to eighty-five percent of CRC cases are linked to the chromosomal instability (CIN) pathway owing to mutations in genes such as APC, p53, and K-ras. Another mechanism is microsatellite instability (MSI), often associated with methylator phenotypes (CIMP). The CRC Subtyping Consortium has identified four subtypes: CMS1 (MSI-immune), CMS2 (canonical), CMS3 (metabolic), and CMS4 (mesenchymal), which respond differently to treatments, emphasizing the molecular complexity of the disease. 34 While a small percentage of CRCs are due to genetic predispositions, most arise randomly from environmental and lifestyle factors that can damage the DNA. 35 In our study, biopsy findings indicated a significant correlation between cancer type and survival, suggesting that cancer type greatly affects patient outcomes.
Limitations
This study has several limitations that should be acknowledged. First, as a retrospective, single-centre study conducted at a tertiary care hospital, the findings may not be generalizable to the broader population, particularly in rural or underserved regions of Pakistan. The use of non-probability sampling and reliance on medical record data may have introduced selection bias and limited the ability to capture all relevant clinical variables. The exclusion of 29 participants due to insufficient data represents a potential limitation. Although basic demographic data (age and sex) of excluded patients were similar to those included, the lack of clinical and treatment information limited our ability to fully compare these groups. Therefore, the possibility of selection bias related to missing data cannot be ruled out. This limitation should be considered when interpreting the results. Variability in follow-up duration across patients also posed challenges in accurately assessing survival outcomes, despite the use of the Kaplan-Meier model. Furthermore, the study did not evaluate important lifestyle, socioeconomic, and genetic factors that may influence colorectal cancer risk and survival, limiting the depth of interpretation regarding risk associations. Finally, the relatively small sample size reduced the statistical power to detect associations for less common variables and outcomes, and future large-scale, multicentre studies are warranted to validate these findings.
Conclusion
In conclusion, our study highlights important trends in colorectal cancer (CRC), emphasizing a higher incidence in middle-aged individuals (36-60 years) and a significant occurrence of early onset CRC (EOCRC). These findings suggest that CRC is becoming more prevalent in younger populations, particularly in developing nations such as Pakistan, in contrast to Western data where EOCRC remains relatively rare. Males were found to have a higher CRC incidence than females, aligning with global patterns. Despite the presence of comorbidities, such as diabetes and hypertension, these factors did not significantly affect survival. However, certain symptoms such as vomiting, fever, and abdominal distention showed a stronger correlation with mortality. This study underscores the need for targeted CRC screening, early detection, and personalized treatment approaches, particularly for younger patients. Additionally, cancer type significantly influences patient outcomes, reinforcing the importance of molecular and genetic profiling in CRC management. Further research is essential to understand the rising EOCRC rates and refine strategies for prevention, screening, and treatment, particularly in underdeveloped regions.
Footnotes
Ethics Approval
Ethical approval has been granted from IRB (Institutional review board) of Jinnah Post Graduate center (NO.F.2-77/2022-GENL/212/JPMC), and would be provided upon request.
Author’s Contributions
All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.
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.