|Year : 2020 | Volume
| Issue : 2 | Page : 62-65
Indeterminate pulmonary nodules among patients with new diagnosis of colorectal cancer: Prevalence and significance assessment
Nidal H Bokhary1, Abdulrahman A Alghamdi1, Faisal A Alfaidi1, Khaled A Alfaidi1, Naif H Aljohani1, Fahad K Alshammari1, Omar Iskandrani2, Hanaa Tashkandi3, Atlal Abusanad4
1 Faculty of Medicine, King Abdulaziz University (KAU) and Hospital, Jeddah, Saudi Arabia
2 Department of Radiation Oncology, King Abdulaziz University (KAU), Jeddah, Saudi Arabia
3 Department of General Surgery, King Abdulaziz University (KAU) and Hospital, Jeddah, Saudi Arabia
4 Department of Internal Medicine and Medical Oncology, Faculty of Medicine, King Abdulaziz University (KAU) and Hospital, Jeddah, Saudi Arabia
|Date of Submission||21-Aug-2020|
|Date of Acceptance||09-Oct-2020|
|Date of Web Publication||31-Dec-2020|
Dr. Nidal H Bokhary
Faculty of Medicine, King Abdulaziz University (KAU) and Hospital, Al Ehtifalat St, Jeddah 21589.
Source of Support: None, Conflict of Interest: None
Background: In Saudi Arabia, colorectal cancer (CRC) accounts for 11.5% of cancer incidence, where nearly one-third is metastatic. Global guidelines recommend accurate pretreatment staging to determine resectability and stage-directed treatment. Computed tomography (CT) scan is among the widely used imaging for staging. However, at times, the characterization of abnormalities detected by CT scan is perplexing. Indeterminate pulmonary nodules (IPNs) are nodules that are neither benign nor malignant, which are incidentally detected on baseline staging chest CT. We aimed to estimate the prevalence of IPN that were identified among CRC patients. Materials and Methods: We conducted a retrospective record review of all newly diagnosed CRC patients between June 2013 and June 2018 from an academic hospital in Jeddah, Kingdom of Saudi Arabia (KSA). Demographics and certain prespecified variables were collected. The presence of IPN on staging chest CT as per consultant radiologist report was documented, and the ability of other modalities to identify the nature of IPN was compared. Data were analyzed using SPSS and a P value < 0.05 was considered significant. Results: Of 283 CRC patients, 208 (73.5%) underwent chest CT, and the mean age was 57.4 years (±SD 13.1). The prevalence of IPN among CRC patients is 17.7%. Thirty IPN patients had a follow-up chest CT for IPN, which identified IPN nature in 18(60%) of them. The likelihood of IPN to be CRC-related metastasis was significantly associated with the presence of synchronous liver metastasis (P = 0.0005), younger age (P = 0.022), and colon cancer (P = 0.011). Conclusion: The prevalence of IPN was 17.7%, which is different in comparison to other studies from different countries. There is a vital need for unified guidelines describing IPN to accurately stage CRC patients, decrease unnecessary follow-ups, and acquire the exact prevalence of IPN.
Keywords: Colorectal cancer (CRC), computed tomography, indeterminate, prevalence, pulmonary nodules
|How to cite this article:|
Bokhary NH, Alghamdi AA, Alfaidi FA, Alfaidi KA, Aljohani NH, Alshammari FK, Iskandrani O, Tashkandi H, Abusanad A. Indeterminate pulmonary nodules among patients with new diagnosis of colorectal cancer: Prevalence and significance assessment. J Curr Oncol 2020;3:62-5
|How to cite this URL:|
Bokhary NH, Alghamdi AA, Alfaidi FA, Alfaidi KA, Aljohani NH, Alshammari FK, Iskandrani O, Tashkandi H, Abusanad A. Indeterminate pulmonary nodules among patients with new diagnosis of colorectal cancer: Prevalence and significance assessment. J Curr Oncol [serial online] 2020 [cited 2021 Apr 23];3:62-5. Available from: https://www.journalofcurrentoncology.org/text.asp?2020/3/2/62/305850
| Introduction|| |
One of the leading causes of cancer mortality and morbidity is colorectal cancer (CRC). It accounts for 9% of all cancers, being the third most common cancer worldwide and the fourth most common cause of cancer deaths. In Saudi Arabia, CRC is the most common cancer in males, and the third most common in females, with a total incidence of 11.5% in 2014, of which 29.1% is metastatic disease. Lungs are one of the most common sites for metastasis. This distant metastatic spread can be present at the time of diagnosis. Hence, the staging of CRC is essential. Treatment differs according to whether the disease is metastatic or not. The National Institute for Health and Care Excellence (NICE) guidelines recommends that computed tomography (CT) is to be used as the primary modality for staging. With increasing CT sensitivity, characterization of findings can be at times challenging. Occasionally, pulmonary findings can neither be classified as benign nor malignant; such findings are referred to as indeterminate pulmonary nodules (IPNs) that are detected by the staging chest CT.
A retrospective study done in the United Kingdom in 2011 found that the prevalence of IPN among CRC patients was 25.3%. Another retrospective study done in Turkey in 2012 reported that the prevalence of IPN among CRC patients was 4.09%. A systematic review in 2013 reported that the prevalence of IPN among CRC patients was 9%. Another study from Koege university hospital, Denmark in January 2014 found that the IPN prevalence among CRC patients was 20%. Noticeably, the frequency of IPN varies among different populations and there is no report on the prevalence of IPN among CRC patients from Saudi Arabia. Consequently, this study aims to measure the prevalence of IPN that were identified on baseline staging chest CT and the significance of CRC-related variables that may predict their nature among CRC patients in King Abdulaziz University Hospital (KAUH), Jeddah, Kingdom of Saudi Arabia (KSA) between June 2013 and June 2018.
| Materials and Methods|| |
A retrospective review was conducted on all newly diagnosed CRC patients in KAUH, Jeddah, KSA from June 2013 to June 2018. The study proposal has satisfied the hospital legal and ethical requirements and granted approval by the Institutional Review Board (IRB) of KAUH. All newly diagnosed CRC patients of 18 years old and above who had biopsy-proven CRC were included. Patients were sub-classified into two groups according to whether they underwent pretreatment staging chest CT or not. The study included 283 patients. Patients’ demographics, primary tumor site, presence of liver metastases, and smoking status were documented.
The presence of IPN on staging chest CT as per consultant radiologist report was documented, and the ability of other modalities to identify the nature of IPN was compared. Statistical analysis was performed using IBM SPSS software package, version 21.0. Frequencies were calculated for the qualitative variables. Chi-square test was used to compare follow-up modalities. A value of P < 0.05 was considered significant. The datasets generated during this study are available from the corresponding author on reasonable request.
| Results|| |
A total of 283 patients with CRC were included from June 2013 to 2018. The mean age was 57.36 years (±SD 13.096). The majority was males 171 (60.4%) and 47 (16.6%) were smokers. Other demographic data are summarized in [Table 1].
A total of 208 patients (73%) underwent baseline staging chest CT, of which 50 had IPN and 158 had no IPN, whereas 75 (26.5%) did not undergo chest CT. Thirty-one patients with IPN (62%) were followed up. Thirty had follow-up chest CT, and the nature of the nodules was identified in 18 (60%) of them. Only one patient had a biopsy, and the nature of IPN was identified [Table 2].
|Table 2: Follow-up modalities and the ability to identify the nature of IPN|
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Liver metastases were present in 147(51.9%) of the total patients, whereas 136 patients (48.1%) had no evidence of metastasis. Twenty-six patients (17.7%) with liver metastasis had IPN. A significant association between liver metastasis and the likelihood of IPN to be CRC metastases was shown (P = 0.0005) [Table 3].
Colon was the primary tumor site in 195 patients (68.9%), of those 33 (16.9%) had IPN, whereas rectum was the primary tumor site in 67 (23.7%), of those 10 (14.9%) had IPN and rectosigmoid junction was the primary tumor site in 21 (7.4%), of those 7 (33.3%) had IPN. There was a significant association between the primary tumor site and the likelihood of IPN to be CRC-related metastasis [Table 4]. Tumors arising from colon are more likely to be associated with metastatic pulmonary nodules (P = 0.011).
Age groups and IPN nature showed a signiﬁcant association (P = 0.022), the younger the age, the more likely that IPN is malignant [Table 5]. On the contrary, gender and smoking status showed no significant association with IPN presence (P = 0.174 and 0.249), respectively.
| Discussion|| |
In this study, we aimed to measure the prevalence of IPNs discovered on baseline staging chest CT of newly diagnosed CRC in KAUH, Jeddah, KSA between June 2013 and June 2018.
The prevalence of IPN in CRC patients in our study is 17.7% on baseline CT, which appears different from other studies in the UK (25%) and Turkey (4.09%)., The lack of a unanimously recognized definition of IPN in the CRC setting may contribute to the apparent discrepancy. Generally, it is those nodules that are too small to evaluate for radiological characterization such as density and shape. Therefore, different radiologists may interpret CT finding differently. Unlike other studies, the measurement of IPN prevalence in our study was based on baseline staging chest CT at diagnosis time excluding any IPN on follow-up CTs.
Thirty patients underwent follow-up CT, in which 18 (60%) had IPN nature identified (15 benign vs. 3 CRC-related metastasis). Only one patient had a biopsy. The study from Turkey reported that 30 patients underwent follow-up CT and IPN turned to be malignant in 5 (16%), whereas no biopsies were done. Unlike our study where we report the result of all IPN whether turned to be benign or malignant on follow-ups, that study reported only the malignant progression of IPN identified on baseline CT. CT operated in all studies as the preferred modality for follow-up due to its ability to detect smaller lesions in the lungs, whereas biopsy was not performed frequently due to the limited yield with small nodules and the potential risks of invasive procedure.
A total of 147 patients had liver metastasis, of whom 26 (17.7) had IPN, and we found that the likelihood of IPN to be malignant is increased in the presence of liver metastasis (P = 0.0005). This signiﬁcant association is explained by the typical anatomic spread of CRC having the liver as the most common site for secondaries in CRC patients, followed by the lungs. Some suggest that chest X-ray may suffice for staging in the absence of liver metastasis. Although the absence of synchronous liver metastasis may reduce the potential of IPN to be malignant, it does not exclude it strictly.
Generally, in Saudi Arabia, the age of CRC diagnosis is younger than what is reported from western countries supported by the higher number of CRC patients <60 years old in this cohort. Therefore, IPN was more frequent among patients aged 44–58 years. Being younger than 58 years old is shown to be associated with increased malignant potential of IPN. Such findings might be related to the observation that early-onset CRC presents with more aggressive features and increased potential to metastasize earlier. A recent study from MD Anderson investigating the clinical and molecular characterization of early-onset CRC showed that early-onset patients were more likely to have synchronous metastatic disease. Nonetheless, other histologic and molecular variables reported to be distinctive among early-onset CRC patients such as predilection for the distal colon, signet ring cell differentiation, venous invasion, and perineural invasion. All together may explain the likelihood of IPN to be malignant in younger age group vs. older patients. We were faced with limited documentation regarding smoking status and missing radiology reports on some patients who referred from outside hospitals to receive chemotherapy only in KAUH, whereas others died before performing any follow-up modalities to verify IPN nature.
| Conclusion|| |
This study showed that the overall IPN prevalence in CRC patients from Saudi Arabia is 17.7%, which is different from other studies in different populations. There is a need for a standardized protocol for IPN identification to accurately stage CRC patients, decrease unnecessary follow-ups, and acquire an exact prevalence of IPN. We also recommend that other comparative studies are to be considered among other national health care centers.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
All authors contributed to the data collection, analysis, and interpretation of data and in writing the manuscript.
Data availability statement
The datasets generated during this study are available from the corresponding author on reasonable request (Dr. Nidal Bokhary, e-mail: [email protected]).
| References|| |
Haggar FA, Boushey RP Colorectal cancer epidemiology: Incidence, mortality, survival, and risk factors. Clin Colon Rectal Surg 2009;22:191-7.
Saudi Cancer Registry. Available from: http://www.chs.gov.sa/Ar/HealthCenters/NCC/CancerRegistry/CancerRegistryReports/2013.pdf.
Mitry E, Guiu B, Cosconea S, Jooste V, Faivre J, Bouvier AM Epidemiology, management and prognosis of colorectal cancer with lung metastases: A 30-year population-based study. Gut 2010;59:1383-8.
Manfredi S, Lepage C, Hatem C, Coatmeur O, Faivre J, Bouvier AM Epidemiology and management of liver metastases from colorectal cancer. Ann Surg 2006;244:254-9.
Colorectal Cancer: The Diagnosis and Management of Colorectal Cancer. Cardiff: National Institute for Health and Clinical Excellence: Guidance; 2011.
Rubin GD Lung nodule and cancer detection in computed tomography screening. J Thorac Imaging 2015;30:130-8.
Nordholm-Carstensen A Pulmonary nodules and metastases in colorectal cancer. Dan Med J 2016;63:B5190.
McQueen AS, Scott J CT staging of colorectal cancer: What do you find in the chest? Clin Radiol 2012;67:352-8.
Varol Y, Varol U, Karaca B, Karabulut B, Sezgin C, Uslu R The frequency and significance of radiologically detected indeterminate pulmonary nodules in patients with colorectal cancer. Med Princ Pract 2012;21:457-61.
Nordholm-Carstensen A, Wille-Jørgensen PA, Jorgensen LN, Harling H Indeterminate pulmonary nodules at colorectal cancer staging: A systematic review of predictive parameters for malignancy. Ann Surg Oncol 2013;20:4022-30.
Christoffersen MW, Bulut O, Jess P The diagnostic value of indeterminate lung lesions on staging chest computed tomographies in patients with colorectal cancer. Dan Med Bull 2010;57:A4093.
Jess P, Seiersen M, Ovesen H, Sandstrøm H, Maltbæk N, Buhl AA, et al
. Has PET/CT a role in the characterization of indeterminate lung lesions on staging CT in colorectal cancer? A prospective study. Eur J Surg Oncol 2014;40:719-22.
Cantarini R, Covotta F, Aucello A, Montalto G, Procacciante F, Marcheggiani A, et al
. Surgical treatment of isolated lung and adrenal metastasis from colorectal cancer. Case report. Ann Ital Chir 2012;83:337-42.
Quyn AJ, Matthews A, Daniel T, Amin AI, Yalamarthi S The clinical significance of radiologically detected indeterminate pulmonary nodules in colorectal cancer. Colorectal Dis 2012;14:828-31.
Willauer AN, Liu Y, Pereira AAL, Lam M, Morris JS, Raghav KPS, et al
. Clinical and molecular characterization of early-onset colorectal cancer. Cancer 2019;125:2002-10.
Chang DT, Pai RK, Rybicki LA, Dimaio MA, Limaye M, Jayachandran P, et al
. Clinicopathologic and molecular features of sporadic early-onset colorectal adenocarcinoma: An adenocarcinoma with frequent signet ring cell differentiation, rectal and sigmoid involvement, and adverse morphologic features. Mod Pathol 2012;25:1128-39.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]