Prognosis of Colorectal Cancer Patients with Pre-existing Obesity: An Evidence-based Case Report
Matthew Billy1, Hasna Sholihah1, Kiwah Andanni1, Margareth Ingrid Anggraeni1, Saur Maruli Evan Johannes Siregar, Listya Tresnanti Mirtha2
1Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
2Sports Medicine Division, Department of Community Medicine, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
Aim: to determine all-cause mortality and cancer-spesific mortality of colorectal cancer patient with obesity. Methods: a search was conducted on Pubmed, Proquest, Ebsco, and Scopus based on clinical query. The screening of title and abstract using inclusion and exclusion criteria, filtering double, and reading full text led to one useful article. This study, which is meta-analysis was critically appraised for its validity, importance and applicability. Results: The relative risk of colorectal cancer patient with pre-existing obesity having cancer-specific mortality and all-cause mortality is 1.22 (95% CI, 1.003-1.35) and 1.25 CI (95% CI, 1.14-1.3) respectively, when compared with non-obese colorectal cancer patient. Conclusion: Pre-existing obesity is related to increased risk of all-cause mortality and cancer-spesific mortality of in colorectal patient. Control of body weight is recommended in this patient through combination of diet, physical activity, behavior therapy, pharmacotherapy, and surgery
Key words: all-cause mortality, cancer-spesific mortality, colorectal cancer, pre-existing obesity
Colorectal cancer is the third most common cancer in the world. In Indonesia, age-standardized incidence rates of colorectal cancer are 19.1 for men and 15.6 for women per 100,000 population. Undeniably, the number of colorectal cancer cases is high because Indonesia has more than 250 million populations.1
Risk factor of colorectal cancer is multifactorial, one of which is obesity.2 In Indonesia, prevalence of obesity has increased for every age group.3 In addition, obesity as a major risk factor, has caused mortality and morbidity for degenerative disease such as cardiovascular disease, dyslipidemia or type 2 diabetes.4
Although colorectal cancer patients’ survival has improved in last decades, little is known about the prognostic factors which influence survival in colorectal cancer patients.5 The aim of this evidence-based case report (EBCR) is to critically analyze the impact of pre–exiting obesity on both all-cause mortality and cancer-spesific mortality in colorectal cancer patients.
A-52 years old women admitted to hospital with hematochezia since two days prior to admission. She also felt pain, cramp, and abdominal discomfort during defecation since six months ago which are worsen recently. There are history of alternating diarrhea and constipation since four months ago which leads to ten kilograms weight loss in four months. In addition, she easily feel tired. Last week, doctor has diagnosed her having colorectal cancer.
Patient works as an employee in private enterprise for 25 years from 8 AM until 3 PM everyday. She has four children and now lives with her two children who are still in junior high school and senior high school. Her husband passed away ten years ago by a car accident.
Patient’s height is 155 centimeters. Patient’s weight six months ago was 85 kilograms.
How are all-cause mortality and cancer-spesific mortality of CRC patient with obesity?
A search of literatures was done in December 2nd, 2015 on 4 journal databases including Pubmed, Proquest, Ebsco, and Scopus using terminology. The results obtained from 4 sites were screened by title and abstracts using inclusion and exclusion criteria, filtered double, and checked full text availability. After had read full text of those articles, we chose the suitable article for the our EBCR. Critical appraising the meta-analysis study was done by consesus of all authors using guidance for prognosis study from Center of Evidence-Based Medicine as shown in
We have 10 articles that suitable for EBCR. After had read the full text, we finally obtained one meta-analysis study. The other 9 articles were already included in this meta-analaysis study.
Meta-analysis from cohort studies done by done by Lee et al (2015).6 The result of critical appraisal of the meta-analysis is shown on table 1. From the table, we conclude that the meta-analysis study is valid, important, and relevant to our patient with level of evidence 1a.
This meta-analysis aimed to determine association between pre- and post-diagnostic body mass index (BMI) with colorectal cancer-specific mortality and all-cause mortality. He searched studies from Medline and EMBASE database that published between 1970 and September 2014.
Table 1. Critical appraisal of meta-analysis
|Article : Lee J, Meyerhardt JA, Giovannucci E, Jeon JY. Association between body mass index and prognosis of colorectal cancer: a meta-analysis of prospective cohort studies. PLoS One. 2015 Mar 26;10(3):e0120706. doi: 10.1371/journal.pone.0120706. eCollection 2015. PubMed PMID: 25811460; PubMed Central PMCID: PMC4374868.Level : 1A (meta-analysis of prospective cohort study)|
|Validity||Did the meta-analysis address a focused question?||Yes|
|Were the criteria used to select articles for inclusion appropriate?||Yes|
|Is it likely that important relevant studies were missed?||No|
|Was the validity of the included studies appraised?||Yes|
|Were the assessments of studies reproducible?||Yes|
|Were the results similar from study to study?||Yes|
|Importancy||What are the overall results of the meta-analysis?||Pre-existing obesity was associated with increased colorectal cancer-specific mortality (RR: 1.22, 95% CI: 1.003–1.35, p < 0.01) and all-cause mortality (RR: 1.25, 95% CI: 1.14–1.36, p < 0.01)|
|How precise were the results?||Precise, 95% CI interval for colorectal cancer-specific mortality and all-cause mortality is narrow|
|Applicability||Can the results be applied to my patient care?||Yes|
|Were all clinically important outcomes considered?||Yes|
|Are the benefits worth the harm and costs?||Yes|
We appraise this meta-analysis for its validity, importance, and applicability. Several reasons support validity of this study. This study addresses focused question, selects paper with inclusion criteria, appraises included study, and has similarity from study to study.
In addition, we found that this is study is important. The relative risk of patient with pre-existing obesity having cancer-specific mortality is 1.22 with a confidence interval (CI) of 1.003-1.35. Meanwhile, relative risk for all-cause mortality is 1.25 with a CI of 1.14-1.36. We can conclude that the value is precise.
This result seems biological-plausible. Although the mechanism of increased mortality in obese patients remain unclear, there are several studies which already able to synthesize possible mechanisms involved. These mechanisms mainly associated with obesity-related hormones, growth factors, modulation of energy balance and calorie restriction, multiple signaling pathways, and inflammatory processes.7 Goodwin et al. also elucidated about both direct and indirect effect of obesity-associated metabolic and adipose tissue changes and their role on cancer’s progression.8
Considering this significant role of obesity in colorectal patients’ prognosis, we recommended that in order to minimize the consequences of deteriorating prognosis, obesity’s management should be applied to all individuals with risk factor of colorectal cancer, such as family history, smoking, dietary intake, and lifestyle.9 According to NHLBI guidelines, there are multiple strategies comprised in the effective weight control, including dietary therapy, physical activity, behavioral therapy, pharmacotherapy, and surgery in addition to combination of these strategies. Recommendation of strategies used based on the obesity category and comorbidities is illustrated in Table 2.
Table 2. Recommendation of weight control strategies in obesity with comorbidities
|Diet, physical activity, and behavior therapy||With comorbidities||With comorbidities||+||+||+|
Adopted from : National Institutes of Health. The practical guide: Identification, evaluation, and treatment of overweight and obesity in adults; 2000.10
As for our patients, with BMI 35.37 kg/cm2 before the colorectal cancer diagnosis, the strategies recommendation is combination of diet, physical activity, behavior therapy, and pharmacotherapy.
Pre-existing obesity is related to increased risk of all-cause mortality and cancer-spesific mortality of in colorectal patient. Control of body weight is recommended in individuals with risk factors before diagnosis of colorectal cancer. The recommendation of weight control strategies for this patient before the colorectal cancer diagnosis is combination of diet, physical activity, behavior therapy, and pharmacotherapy
- Abdullah M, Sudoyo AW, Utomo, AR, Fauzi A, Rani AA. Molecular profile of colorectal cancer in Indonesia: is there another pathway?. Gastroenterol Hepatol Bed Bench. PMC. 2012; 5(2): 71–78
- Kokki I, Papana A, Campbell H, Theodoratou E. Estimating the incidence of colorectal cancer in South East Asia. Croat Med J. 2013; 54(6): 532 – 40
- Roemling C, Qaim M. Obesity trends and determinants in Indonesia. Pubmed. 2012; 58(3): 1005 – 13
- Parkin E, O’Reilly DA, Sherlock DJ, Manoharan P, Genehan AG. Excess adiposity and survival in patients with colorectal cancer: a systematic review. obesity reviews. 2014; 15: 434–451
- Boyle T, Fritschi L, Platell C, Heywoorth J. Lifestyle factors associated with survival after colorectal cancer diagnosis. British Journal of Cancer. 2013; 109: 814–822
- Lee J, Meyerhardt JA, Giovannucci E, Jeon JY. Association between body mass index and prognosis of colorectal cancer: a meta-analysis of prospective cohort studies. PLoS One. 2015 Mar 26;10(3):e0120706. doi: 10.1371/journal.pone.0120706. eCollection 2015. PubMed PMID: 25811460; PubMed Central PMCID: PMC4374868
- Vucenik I, Stains JP. Obesity and cancer risk: evidence, mechanisms, and recommendations. Ann N Y Acad Sci. 2012 Oct;1271:37-43.
- Goodwin PJ, Stambolic V. Impact of the obesity epidemic on cancer. Annu Rev Med. 2015;66:281-96.
- Kim D-H. Risk Factors of Colorectal Cancer. Journal of the Korean Society of Coloproctology. 2009;25(5):356.
- National Institutes of Health. The practical guide: Identification, evaluation, and treatment of overweight and obesity in adult