|Ahead of print publication
A 10-year registry-based incidence, mortality, and survival analysis of colorectal cancer in Northern Malaysia
Ibtisam Ismail, Huan Keat Chan, Soelar Shahrul Aiman, Abu Hassan Muhammad Radzi
Clinical Research Centre, Sultanah Bahiyah Hospital, Kedah, Malaysia
|Date of Submission||28-Apr-2020|
|Date of Decision||08-Jun-2020|
|Date of Acceptance||10-Sep-2020|
|Date of Web Publication||30-Jul-2021|
Clinical Research Centre, Sultanah Bahiyah Hospital, KM 6, Jalan Langgar, 05460 Alor Setar, Kedah
Source of Support: None, Conflict of Interest: None
Introduction: Colorectal cancer (CRC) is the third most common cancer globally. This study aimed to determine the incidence, mortality, and survival rates of CRC in northern Malaysia over the last decade.
Materials and Methods: This was a registry-based, cross-sectional study. All the CRC patients seeking treatment from any of the 21 hospitals located in northern Malaysia between 2008 and 2017 were included in this study. Both the incidence and mortality rates were expressed as the number of cases per 100,000. The time series analysis was performed to assess the changes in the age-standardized incidence and mortality rates (ASIR and ASMR) of CRC, while the Cox regression analysis was used to detect the differences in the mortality risk between subgroups of CRC patients.
Results: Of the 5746 CRC patients identified, approximately 40% were diagnosed only at Stages III and IV of the disease. Although the ASIR of CRC was stable and narrowly ranged from 17.03 to 20.01 per 100,000 (P = 0.775), the ASMR of CRC significantly reduced from 12.73 per 100,000 in 2008 to 2.99 per 100,000 in 2017 (P < 0.001). Besides increasing with age and the severity of the disease, the mortality risk was significantly higher in men (adjusted hazard ratio [HR]: 1.18; 95% confidence interval [CI]: 1.02, 1.17) and the Malay ethnic group (adjusted HR: 1.33; 95% CI, 1.08, 1.64).
Conclusion: While efforts had been made to promote the timely treatment of CRC, it is encouraging to note a downtrend in its mortality rate. However, there is still a need to upscale the CRC screening going forward.
Keywords: Colorectal cancer, incidence, Malaysia, mortality, survival
|How to cite this URL:|
Ismail I, Chan HK, Aiman SS, Muhammad Radzi AH. A 10-year registry-based incidence, mortality, and survival analysis of colorectal cancer in Northern Malaysia. J Can Res Ther [Epub ahead of print] [cited 2022 Jul 1]. Available from: https://www.cancerjournal.net/preprintarticle.asp?id=322709
| > Introduction|| |
Colorectal cancer (CRC) is one of the major noncommunicable diseases (NCDs) globally. According to the latest GLOBOCAN-based estimates, it is currently the third most common cancer in the world. Over 1.8 million new CRC cases and approximately 880,792 CRC-related deaths were recorded in 2018 alone. Asian countries such as China, Japan, Korea, and Turkey are all reported to have the highest 5-year prevalence in Asia, recording more than 46.5 cases per 100,000.
It is well known that CRC is multifactorial in etiology, resulting from interactions between environmental, genetic,,, lifestyle, and socioeconomic factors. The great variations in the geographical distribution of CRC incidence are also evident. In general, the incidence of CRC is higher in rapidly growing and developed countries such as Hungary, Slovenia, Australia, and New Zealand and lower in less developed regions such as Africa. A similar trend was also observed in Asia. Although the CRC incidence in Japan and Singapore has been plateauing since the 1990s, an upward trend is witnessed in China. Meanwhile, CRC remains the second most common and the third most fatal cancer in Malaysia, incurring an additional health-care cost of MYR 1.07 million yearly.
Mounting evidence also suggests a biological correlation between CRC and metabolic syndromes., While the three northernmost states, namely Perlis, Kedah, and Penang, were collectively reported to have a relatively high prevalence of several NCDs, including diabetes mellitus, hypertension, and hypercholesterolemia, the region-specific information regarding cancer is still scarce. With the aim to fill this gap, this present study was designed to determine the incidence, mortality, and survival rates of CRC in northern Malaysia over the last 10 years.
| > Materials and Methods|| |
This was a cross-sectional study based on the National Cancer Patient Registry-Colorectal Cancer (NCPR-CC). Since its inception back in 2008, the NCPR-CC has been used as the platform to gather all the reports on CRC cases electronically submitted from both public and private hospitals across the country. It is currently maintained by the Clinical Research Centre, one of the public research institutions under the Ministry of Health. The NCPR-CC was periodically cross-checked with the cancer database of the State Health of Department and updated to ensure its data completeness. This study was registered with the National Medical Research Registry and approved by the Medical Research Ethical Committee (NMRR-07-49-242).
This study focused on three states (Perlis, Kedah, and Penang) in northern Malaysia. The data were obtained from which all the 21 public and private hospitals providing oncology services. All of them were appointed as source data providers for the NCPR-CC since 2008. All the CRC cases included in this study were histologically confirmed between January 2008 and December 2018 and were reported to the NCPR-CC by trained medical staff, including surgeons, physicians, pathologists, and nurses.
The individual information gathered from the NCPR-CC ranged from age, gender, ethnicity, and the stage of cancer at the time of diagnosis to survival status. The collection of the data regarding the treatment received by patients is still ongoing and is not reported in this study. The survival status of patients was also cross-checked with the records of the National Registration Department.
The data cleaning, management, and analyses were performed using the R Software for Windows version 3.5.11. The findings of the descriptive analysis were summarized as frequencies and percentages. Both the incidence and mortality rates were expressed as the number of cases per 100,000. The age-standardized incidence and mortality rates (ASIR and ASMR) of CRC were also computed based on the standard proportion of individuals from each age class as recommended by the WHO and the proportion of individuals from each age class in the three selected states as estimated by the Department of Statistics.
Furthermore, the time series analysis was performed to assess the changes in the ASIR and ASMR of CRC over the years. The survival of CRC patients was summarized as medians and 95% confidence intervals (CIs). The differences in the mortality risk between subgroups of CRC patients were also demonstrated through the Cox regression analysis using the “enter” method, with the results summarized as hazard ratios (HRs) and 95% CI.
| > Results|| |
A total of 5746 CRC cases were reported to the NCPR-CC during the period from January 2008 to December 2017. Most of the CRC patients were above 55 years of age (75.9%), yielding a mean age of 63.1 (standard deviation: 13.0) years. They were mainly male (54.3%) and of Chinese ethnicity (56.2%) as compared to other ethnicities. Over 40% of the patients were diagnosed only at Stages III and IV of the disease, and slightly more than half had died at the time of the study [Table 1].
Most of the patients diagnosed at Stage I of the disease were of Chinese ethnicity (60.3%), followed by Malay (21.5%) and Indian (7.2%). On the other hand, nearly half of the patients diagnosed at Stage IV of the disease were of Malay ethnicity [Table 2].
|Table 2: Correlation between ethnicity and tumor-node- metastasis staging|
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The ASIR of CRC demonstrated no significant changes, narrowly ranging from 17.05 to 20.01 per 100,000 over the years. Despite the stable trend in the ASIR of CRC shown by the population under 50 years of age, an uptrend was evident in those aged between 60 and 69 years. The ASIR of CRC of the Malay ethnic group also significantly increased from 7.49 per 100,000 in 2008 to 10.32 per 100,000 in 2017 (P = 0.029) [Table 3].
|Table 3: Incidence rate (per 100,000) by age groups, gender, and ethnicity of colorectal cancer patients in northern Malaysia: National Cancer Patient Registry- Colorectal Cancer, 2008-2017|
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In contrast, after reaching its peak (13.34 per 100,000) in 2009, the ASMR of CRC constantly decreased over the years and reached its all-time low (2.99 per 100,000) in 2017 (P < 0.001). A similar trend was seen in both genders and all the ethnic groups. It was also found that a decline in the ASMR of CRC took place in all the populations above 50 years of age, except for the 60–64 years' group [Table 4].
|Table 4: Mortality rate (per 100,000) by age groups, gender, and ethnicity of colorectal cancer patients in northern Malaysia: National Cancer Patient Registry-Colorectal Cancer, 2008-2017|
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The patients below 30 years of age demonstrated the longest median survival (5.3 years) [Table 5]. In comparison with the patients in the age range between 40 and 44 years, those aged above 55 years were found to have a significantly higher mortality risk, ranging from 1.33 to 2.69 times. The male patients were also shown to have 1.18 times higher mortality risk (95% CI: 1.08, 1.30) than women. Malay was the only ethnic group showing a higher mortality risk as compared with Indian (HR: 1.33; 95% CI: 1.08, 1.64). The median survival time was considerably lower in those patients who were diagnosed at Stages III (4.6 years) and IV (1.3 years) of the disease. As compared with the patients diagnosed at Stage II, those diagnosed at Stages III (HR: 1.84; 95% CI: 1.52, 2.23) and IV (HR: 4.71; 95% CI: 3.90, 5.68) were shown to have a higher mortality risk [Table 5].
|Table 5: Survival of colorectal cancer patients in northern Malaysia: National Cancer Patient Registry-Colorectal Cancer, 2008-2017|
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| > Discussion|| |
CRC has become one of the major global public health concerns, and Malaysia is no exception. To the best of our knowledge, this is the first region-specific, large-scale study exploring the epidemiology of CRC in Malaysia. Its strength lies in the engagement of all the 21 public and private hospitals located in the three selected states, and thus, the findings are expected to provide a whole picture of the disease for this region.
It is found that the ASIR of CRC in northern Malaysia fell between 17.57 and 20.01 per 100,000 over the last 10 years, consistent with the GLOBOCAN-based estimate made for the Western Pacific Region (18.31 per 100,000). Meantime, Onyoh et al. also reported a similar estimate of the ASIR of CRC for Malaysia (19.9 per 100,000 persons), putting it in the same leagues as Thailand (15.5 per 100,000 persons) and the Philippines (18.9 per 100,000 persons). It was also reported that Malaysia still had a relatively low ASIR of CRC as compared with Brunei (35 per 100,000 persons) and Singapore (36.8 per 100,000 persons), its two neighboring countries which share a similar ethnic composition.
However, it is noteworthy that the ASIR of CRC in this study could be underestimated, as an organized CRC screening program is still not in place in Malaysia. Even though the stool-based CRC test has been made available in public health institutions across the country since 2013, the screening remains opportunistic and is only recommended for the average-risk population between 50 and 75 years of age.
Although colonoscopy could prevent approximately 65% of CRC cases, its uptake is still suboptimal in the high-risk population, including the younger individuals with a family history of CRC. This could also explain why early-onset cancer did not demonstrate an increasing trend in this study as it did in most developing countries. Furthermore, this study reveals that nearly half of the CRC patients in northern Malaysia only presented for medical care at advanced stages of the disease, suggesting that the diagnosis of CRC has been mainly driven by the presence of symptoms.
Different from other notification-based cancer registries in Malaysia, NCPR-CC has been applying a longitudinal cross-sectional design, which allows its database to be updated periodically. Nevertheless, the Chinese ethnic group was shown to have the highest ASIR of CRC among all the ethnic groups, followed by Indian and Malay, consistent with the previous findings. A population-based survey from Singapore reported a similar observation that CRC predominates in the Chinese ethnic group. Meanwhile, in Brunei, the risk of CRC in Chinese was shown to be two times higher than of the other groups. As genetic factors again prove to be important in shaping the epidemiology of CRC in Malaysia, it is important for the stakeholders to start a more focus and targeted CRC screening, particularly among the Chinese ethnic group as they possessed a higher risk of developing CRC, as well as offering the same chance to other ethnicities. Nevertheless, northern Malaysia also witnessed an uptrend in CRC in the population aged between 60 and 69 years, particularly those of Malay ethnicity. Such findings would be expected, as this population forms the majority of the patients commonly seeking care from public health institutions and has a higher chance to be offered a stool-based screening test in general.
While the Ministry of Health Malaysia has been pushing for the early detection and timely treatment of cancer over the last decade, it is also encouraging to note a decline in the mortality rate of CRC. In addition to the opportunistic CRC screening program, this is attributable to the improved accessibility of health-care facilities in the country, as well as to the advancement of the cancer treatment. The patients of Malay ethnicity were shown to be have the tendency of being diagnosed at late stages of CRC in relative to other ethnic groups, even though they were reported to equally good, if not better, knowledge about the disease. This suggests that the awareness of a disease does not necessarily translate into health-seeking behavior.
Nonetheless, the overall median survival rate reported in this study was only 3.1 years, still much lower than that reported for the whole country. This was likely due to the delayed presentation of most of the CRC patients in this region, who were generally of a lower socioeconomic status and likely had poorer awareness of the disease. In fact, delayed presentation of cancer patients is not a new issue in Malaysia, mainly due to the poor public awareness of the disease and suboptimal screening uptake., Given that the cost of illness for the late-stage CRC (RM24,972 for Stage 3 and RM27,377 for Stage 4) was also shown to be nearly twice as much as that of the early-stage CRC (MYR13,622 for Stage 1 and MYR19,752 for Stage 2) in Malaysia, there is a clear need to upscale the CRC screening in Malaysia. In addition, while early onset has increasingly become a public health concern worldwide, it is time for policymakers to consider lower the recommended age for CRC screening.
Prior studies conducted had suggested some associations between the early onsets of CRC in young patients with more aggressive histopathologic characteristics, adverse pathological features as well as less responsive to the treatment given in which negatively impact the survival outcome, of the patients. However, our result did not conform to these findings. Our survival analysis demonstrated that there is no significant change in survival time among the younger population. The reason behind this pretty unclear, however, we postulated that most of our young patients captured in this study were presented with early-stage cancer, which allows them to get better access and treatment options.
Although the NCPR-CC covers all the hospitals in northern Malaysia, the study is limited to the CRC patients seeking care from public and private hospitals. Further investigation into the patients who opted for alternatives or did not receive any form of treatment is, therefore, required. On top of that, this study was retrospective in design, the incomplete information, especially regarding the CRC staging at the time of diagnosis, restricting a more comprehensive survival analysis.
| > Conclusion|| |
A stable trend in the incidence of CRC in Malaysia was shown between 2008 and 2017. A downtrend in the CRC mortality over the years was also witnessed. As young-onset CRC did not demonstrate an increasing trend as it did in other developing countries, a concern is raised over the possibility of underscreening in the young population. Hence, efforts to upscale the CRC screening and promote the public awareness of the disease are warranted.
The authors would like to thank the Director-General of Health Malaysia for permission to publish this paper. We also acknowledged the contribution of all the 21 hospitals in Northern Region Malaysia to the NCPR-CC over the years.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]