Comparative Study of Colorectal Cancer Based on Tumor Location in Adolescent and Young Adult Population in Nepal

Introduction: Colorectal cancer in the Adolescent and Young Adult population are increasing and are characterized by a more advanced stage at diagnosis, poorer cell differentiation, higher signet ring histology, and left-sided colon location of the primary tumor. This study aims to compare colorectal cancer data in the Adolescent and Young Adult population-based on tumor location. Materials and Methods: This is a retrospective cross-sectional study of colorectal cancer in the Adolescent and Young Adult population from April 2017 to September 2020 in Shree Birendra Hospital. Data were collected for age, sex, clinical features, histology, TNM stage, colonoscopy finding, radiologic features, treatment, and follow-up status based on tumor location. Data were analyzed using Excel 2010 and SPSS v 17. Results: The total number of patients was 61 with the mean age of 32.36 ± 6.24 years. There was a male preponderance of 63.93%. Right-sided colorectal cancer was 24.59% while left-sided colorectal cancer was 75.41%. For right-sided colorectal cancers, the most common symptoms were pain abdomen (73.3%) and diarrhea (53.3%) while for left-sided colorectal cancers, it was pain abdomen (80.4%) and bleeding per rectum (45.7%). The most common histology was adenocarcinoma (95.08%) with moderately differentiated being most common in both locations. Surgery, radiation and chemotherapy for right-sided and left-sided colorectal cancer were 86.66%, 0.0%, 86.66% and 58.67%, 28.26%, 89.13% respectively. Conclusions: Left-sided colorectal cancer was more common in the Adolescent and Young Adult population in our study. There were significant differences in the clinical presentation of colorectal cancer as per the tumor location.


INTRODUCTION
Adolescent and Young Adult (AYA) with cancer are distinguished by physiological, developmental, and societal characteristics that set them apart from younger and older age groups. 1 Adolescent and Young Adult Oncology Progress Review Group, with consensus from National Cancer Institute (NCI) and the European Network for Cancer Research in Children and Adolescents (ENCCA), agree in defining the AYA population as comprising individuals aged 15 through 39 years at cancer diagnosis, with 15 to 19 years being Adolescents. 1 The global cancer burden among 20-39 yearolds differs from that in younger or older ages but also varies substantially by age, sex, development level, and geographical region. 2 Over the last 30 years, AYA oncology patients have not shared the improvement of cure rate obtained for the children with cancer. 3 Cancer occurring between the ages of 15 and 39 years is 4 times less rare than cancer occurring during the first 15 years of life. 4 Colorectal cancer (CRC) incidence in the AYA population has been increasing by 2% per year. The surge in CRC incidence in young adults is particularly alarming as the overall CRC frequency has been decreasing. 5 CRC in the AYA population are characterized by a more advanced stage at diagnosis, poorer cell differentiation, higher prevalence of signet ring cell histology, and left-sided colon location of the primary tumor. 5 Young patients with colorectal cancer have several distinct clinic-pathological and molecular biological features. 6 Though initial signs and symptoms of CRC are similar in pediatric and adult patients, the strikingly higher frequency of mucinous histology suggests that the biology of CRC differs in pediatric and adult patients and may contribute to poor outcomes. 7 CRC in young adults presents more frequently with stage 3 or 4 diseases, underscoring its relevance in this population. The prognosis of the CRC is similar when matched for the stage of disease at presentation however the survival is lower for the youngest subgroups. 8 This study aims to compare colorectal cancer in the AYA population-based on tumor location and describe age & sex distribution, clinical features, histology, TNM stage, radiologic features, treatment, and follow-up status based on tumor location. Cancers proximal or distal of the splenic flexure were classified as right-sided or left-sided, respectively. 9

MATERIALS AND METHODS
This is a retrospective cross-sectional study of patients diagnosed with Colorectal Cancer (CRC) in the Adolescent and Young Adult (AYA) population (defined as patients in the age group 15 to 39 years) attending Shree Birendra Hospital. The study was approved by Institutional Review Committee.
The data were collected from the Oncology Unit registry. Data of patients diagnosed with CRC were collected from April 2017 to September 2020. All AYA patients diagnosed with CRC during this period were included in the study. Those patients whose diagnoses were uncertain or have inadequate records were excluded. Diagnosis of CRC was based on colonoscopy findings, CT scan imaging, and tissue biopsy. Tumors located in the caecum, ascending colon, hepatic flexure, and transverse colon was considered right-sided CRC while tumors located in splenic flexure, descending colon, sigmoid, recto-sigmoid, and rectum are considered left-sided CRC. The staging was done using TNM classification. Data were collected for age, sex, clinical features, histology, TNM stage, colonoscopy finding, radiologic features, treatment, and follow-up status based on tumor location. Continuous variables were expressed as mean ± standard deviation (SD) and categorical variables as numbers and frequencies. Categorical variables were compared using the χ2 test and continuous variables with the independent t-test. Data were analyzed using Excel 2010 and SPSS v 17.
The most common clinical presentation in our study was the pain abdomen followed by bleeding per rectum. This was in contrast with the study from Nepal where bleeding per rectum (70.6%) was more common than abdominal pain (57.1%). 10 In a study done across all ages in one of the teaching hospitals of Nepal, pain abdomen (86%) and bleeding per rectum (55%) were common symptoms at presentation. 12 Our study showed more left-sided tumors compared to right-sided. The left-sided tumor was more common in metastatic CRC in a study with a large sample size 9 while in a large data of patients across all ages, 67.03% of patients had right-sided CRC while 32.96% patients had left-sided CRC. 13 In another study, there were 47.9% patients with right-sided CRC and 52.1% patients with left-sided CRC. 14 Thus the site of the tumor is not consistent in various studies. The most common site of the tumor was the rectum (49.18%) in our study and other studies also showed a similar distribution of tumor site. 10,12,15 The most common histology was adenocarcinoma (95.08%). The most common histologic subtypes in right-sided CRC were moderately differentiated followed by mucinous, poorly differentiated, and welldifferentiated. For left-sided CRC, common histologic subtypes were moderately differentiated, mucinous, and well-differentiated. This finding was similar to another Nepalese data of patients across all ages, where moderately differentiated (70%) was the most common histology, followed by mucinous (20%) 12 whereas, in another study of childhood and adolescence patients, mucinous (62%) was most common histology. 7,16 The various subtypes within the histology group were compared as per the tumor location however the difference was not significant.
For right-sided CRC, the most common symptoms were pain abdomen and diarrhea while for left-sided CRC; the most common symptoms were pain abdomen and bleeding per rectum. When the clinical features were compared in right vs. left-sided CRC, the left-sided tumor was more likely to present with bleeding per rectum (p=0.001) and constipation (p=0.019) whereas diarrhea (p=0.003) was more common in right-sided tumor and the differences observed were statistically significant. Pain abdomen was a predominant feature in all CRC and was not different within the tumor location (p=0.68). The relatively narrow anatomical space explains more symptoms in the left-sided tumor which can lead to early presentation and tumor diagnosis. Studies have shown that the overall survival is better in left-sided cancer 14 however survival data were not available for our study.
Deo et al.
Both right and left-sided CRC presented late with a stage of presentation. Stage III was most common for both. There was no significant difference in the stages as per tumor location (p=0.70). In another study, stage III (40.3%) was the most common stage of presentation in CRC in AYA less than 25 years. 11 In a study by Weiss JM  In right-sided CRC, surgery was the most common modality of treatment with the majority undergoing right hemicolectomy. The rate of surgery done for right-sided CRC was comparable with another study (86.66 vs. 96%) while for left-sided CRC rate of surgery was lower in our study (58.7% vs. 95.4%). 14 In left-sided CRC, 28.26% of the patients received radiation and most of them received LV+5FU infusion as chemo-sensitizer.
The rate of radiation was comparable on both sides. 14 Chemotherapy regimens used for both sides varied in different studies with FOLFOX, FOLFIRI, and CAPEOX being the most common regimens. 7,9,14