Aggressive Colorectal Cancer in the Young

Abstract

Despite the steady decline in the incidence of colorectal cancer (CRC) and cancer-related mortality in Americans of 50 years and older over the last few decades, there has been a disturbing trend of steadily rising incidence in early-onset colorectal cancer (EOCRC), defined as CRC in those younger than 50 years. With the incidence of EOCRC increasing from 4.8 per 100,000 in 1988 to 8.0 per 100,000 in 2015, and with the decreased rates in those older than 50 years largely attributed to improved screening in the older population, new screening recommendations have recently lowered the age for screening average-risk individuals from 50 to 45. EOCRC has been found to present differently from late-onset CRC, with a higher proportion of patients presenting with left-sided and rectal cancer, more aggressive histological features, and more advanced stage at the time of diagnosis. This article reviews the most recent evidence from population-based studies and institutional series, as well as the newest screening guidelines, and provides an up-to-date summary of our current understanding of EOCRC, from clinical presentation to tumor biology and prognosis, and future directions in treatment and prevention.

The rising incidence of aggressive colorectal cancers (CRCs) in people younger than 50 years has been a disturbing trend surgeons and practitioners have been increasingly noticing for some time. CRC is historically thought to be a disease of the elderly, and remains the third most commonly diagnosed cancer among both men and women in the United States. ¹ Over the past four decades, there has been an encouraging decline in CRC incidence and CRC-related mortality across all age groups in the U.S. population ( Fig. 1A ), with an overall U.S. incidence of 37.2 per 100,000 in 2015, down from a peak of 66.3 per 100,000 in 1985, ² and overall U.S. mortality from CRC at 14.0 per 100,000 in 2015 from a peak of 28.6 per 100,000 in 1976. ³ These trends are undoubtedly due in part to the continued improvement in screening rates in those older than 50 years. ¹

Fig. 1.

(A, B) National Cancer Institute data derived from https://statecancerprofiles.cancer.gov/historicaltrend/ .

However, the rising incidence of early-onset colorectal cancer (EOCRC), defined as CRCs in those younger than 50 years, demands a careful and thorough investigation, as the incidence in the United States has steadily increased in this population from a nadir of 4.8 per 100,000 persons in 1988 to 8.0 per 100,000 in 2015 ⁴ ( Fig. 1B ). Large U.S. population-based cancer registry data have further delineated that this increased incidence has been attributed solely to rising rates of early-onset tumors in the distal colon and rectum. ¹ The recognition of rising incidence of EOCRC has been most thoroughly documented in the United States, and while recent trends in population-based incidence of CRC in Europe are largely unknown, emerging population-based studies in Australia ⁵ and Canada ⁶ have shown similar alarming trends over the past two decades. CRC screening programs for individuals younger than 50 years have not yet been widely implemented, but with an increasingly affected subset of the general population being too young for the traditional screening paradigm, there exists an opportunity for earlier identification, treatment, and prevention. The American Cancer Society was the first to change its recommendations regarding CRC screening for average-risk individuals to start at the age of 45 years instead of 50 years in May 2018. ⁷

There are several well-described hereditary syndromes, such as familial adenomatous polyposis (FAP) and Lynch's syndrome, and familial syndromes that have traditionally been associated with increased CRC risk in young patients. There is no evidence, however, that these rare hereditary syndromes have become significantly more prevalent, and as such they do not explain the overall increased incidence of EOCRC. If the rising incidence is mostly attributed to increasing rates of nonhereditary cancers, the potential contribution of known risk factors for CRC such as diabetes mellitus, obesity, a sedentary lifestyle, and the impact of the western diet and specific environmental exposures on the incidence of EOCRC must be further explored.

In addition, differences in tumor biology and host factors between CRC and EOCRC may account for variations in clinical presentation and overall prognosis. A deeper understanding of those differences may lead to improved diagnostics, targeted therapies, and overall improved outcomes.

This article will review the epidemiological trends, clinical presentation, tumor characteristics, predisposing factors, and cancer-specific outcomes of EOCRC, as well as the latest CRC screening recommendations for patients younger than 50 years. It will also address topics ripe for additional research and future treatment strategies to address the disturbing rise in the incidence of EOCRC.

Epidemiology

In American men and women younger than 50 years, CRC is the second most common cancer overall, and the third leading cause of cancer-related mortality, ⁸ after breast and lung cancers. Based on a recent review of the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database and the Centers for Disease Control National Program of Cancer Registries, Siegel et al ¹ reported that while the incidence of CRC in U.S. adults older than 50 years declined by 32% (from 175.4 to 119.3 per 100,000) between 2000 and 2013, CRC incidence in adults younger than 50 years increased by 22% (from 5.9 to 7.2 per 100,000) over the same time frame. This study ¹ further elucidated that tumors in the distal colon and rectum, with incidence rate ratios of 1.24 and 1.22, respectively, were solely responsible for the increased incidence during this time period in this age group.

Overall, 10% of CRCs in women and 11% of CRCs in men occur under the age of 50 years. ¹ Data from the National Cancer Database (NCDB) between 1998 and 2007 demonstrated that 75.2% of EOCRCs occurred between ages 40 and 49 years, with a median age of 44 years. ⁹ Men and women have similar incidence patterns of EOCRCs, though males demonstrate slightly increased incidence compared with women across age groups younger than 50 years: ages 30 to 34 years (men 4.9 vs. women 4.2 cases per 100,000), ages 35 to 39 years (men 9.0 vs. women 7.6 cases per 100,000), ages 40 to 44 years (men 16.4 vs. women 15.3 cases per 100,000), and ages 45 to 49 years (men 30.8 vs. women 25.9 cases per 100,000). ⁸

The overall incidence of CRC in individuals between ages 20 and 49 years increased 1.5% per year in men and 1.6% per year in women between 1992 and 2005. ¹⁰

Similar to incidence, mortality rates from CRC have declined in those older than 50 years, while they have risen in those with EOCRC. Between 2000 and 2014, the ≥50 years old age group saw a 34% decrease in mortality rates from CRC (from 70.5 to 46.4 per 100,000 ¹¹ ), while the death rate in those <50 increased by 13% ¹ (from 1.6 per 100,000 to 1.8 per 100,000 ¹² ).

There are significant differences in the demographics of EOCRC among racial and socioeconomic groups. Relative to CRC in patients of 50 years and older, EOCRCs are more prevalent in nonwhite ethnicities (29.5 vs. 17.6%) and those who were either not insured or insured by Medicaid (16.5 vs. 4.7%). ⁹ Across all age groups, non-Hispanic blacks (NHBs) have the highest rates of CRC incidence and mortality; Siegel et al revealed that during 2009 to 2013, NHBs had CRC incidence rates ∼20% higher than non-Hispanic whites (49.2 per 100,000 vs. 40.2), and mortality rates nearly 40% higher (20.5 per 100,000 vs. 14.6 during 2010 to 2014). ¹ A study from Howard University ¹³ investigated whether this general finding that African Americans have the highest overall incidence of CRC and the highest CRC-related mortality also applied to the younger African American population. ¹⁴ Based on the SEER-18 registry data collected between 2000 and 2012, African Americans of 20 to 44 years of age had higher CRC incidence rates (7.9 per 100,000) than non-Hispanic whites (6.7 per 100,000) or Asian-Pacific Islanders (6.3 per 100,000) of the same age. African Americans also had the highest rate of stage IV disease (18.26%) compared with non-Hispanic whites (16.49%) and Asian-Pacific Islanders (17.65%).

EOCRC: Clinical Presentation

The vast majority of individuals younger than 50 years have not undergone screening for CRC; therefore, incidental discovery of an EOCRC is less likely to occur than in the older cohort. The diagnosis of EOCRC is most commonly made after the onset of symptoms.

A 2008 retrospective cohort study from the Mayo Clinic ¹⁵ by Dozois et al evaluated the clinical presentation of patients with EOCRC. After excluding patients with inflammatory bowel disease (IBD), polyposis, or other familial syndromes, 1,025 patients of 50 years or younger were diagnosed with primary CRC at a single institution between 1976 and 2002. At the time of diagnosis, 86% had symptoms, including rectal bleeding (51%), abdominal pain (32%), change in bowel habits (18%), and weight loss (13%).

Several studies have attempted to further characterize the clinical presentation of EOCRC by evaluating the time interval between the onset of symptoms and diagnosis. A retrospective, single-institution cohort study from Stanford ¹⁶ by Chen et al compared 232 patients of 50 years and older diagnosed with CRC to 253 patients with EOCRC, all diagnosed after onset of symptoms, between 2008 and 2014. Patients with EOCRC had a significantly longer median time to diagnosis (128 vs. 79 days), symptom duration (60 vs. 30 days), and duration of diagnostic work-up (31 vs. 22 days).

Scott et al ¹⁷ published a case–control study further evaluating this delay in diagnosis in early-onset rectal cancers at a single academic medical center between 1997 and 2007. Fifty-six patients under age 50 years diagnosed with rectal adenocarcinoma were matched to 56 patients over age 50 years with the same diagnosis. Overall, 96% of the study's patients with rectal cancer under age 50 years presented with symptoms (vs. 80% in the over age 50 group), and the time interval from onset of symptoms to initial presentation to a health care provider was six times longer in the under age 50 years group (121 vs. 21 days). Furthermore, the time from onset of symptoms to treatment was 217 versus 58 days for those under versus over age 50 years, respectively.

EOCRC: Clinical Staging

Multiple studies have shown that EOCRC is more likely to present at more advanced stages at the time of diagnosis. A structured meta-analysis ¹⁸ of 55 studies published before 2004, which compared patients younger than 40 years with those older than 40 years, found 66 to 68% of the younger cohort presented with Dukes' C or D tumors, compared with 32 to 49% in the older age group. By capturing individuals in the NCDB diagnosed with invasive adenocarcinoma of the colon and rectum between 1998 and 2007, You et al found that 59.4% of young patients with rectal cancer presented with stage III or IV disease, compared with 46.4% in the older cohort. ¹⁹ In the previously mentioned Chen et al's study, ¹⁶ which did not include patients diagnosed upon asymptomatic screening, those with EOCRC were significantly more likely to be at an advanced stage (stage III or IV) than those diagnosed at 50 years or older. When compared with the age >50 years group, Abdelsattar et al ²⁰ utilized SEER CRC data from 1998 to 2011 and found that individuals with EOCRC were significantly more likely than older patients to present with regional as opposed to localized disease (relative risk ratio [RRR]: 1.37, p  < 0.001) and distant as opposed to localized disease (RRR: 1.58, p  < 0.001).

EOCRC: Tumor Characteristics

There has been mounting evidence that a preponderance of EOCRCs is left-sided tumors located at or distal to the splenic flexure. Among women and men younger than 50 years, Siegel et al ¹ found that tumors are most commonly diagnosed in the rectum (36 and 41%, respectively), while just 25% of EOCRCs in women and 26% of EOCRCs in men occur in the proximal colon. Rho et al found that in their multinational retrospective study from six international tertiary cancer centers comparing “young-onset” colorectal adenocarcinomas to “late-onset” diagnosed between 2003 and 2014, 45.5% (102 of 224) of the young-onset group had rectal cancer versus 31.3% (86 of 274) in the older cohort. ²¹

In a retrospective study of 734 patients with EOCRC (and not known to have IBD, FAP, or Lynch's syndrome) treated at the Cleveland Clinic between 2000 and 2016, tumors were located in the rectum in 484 (66%), sigmoid in 105 (14%), descending colon in 19 (3%), and right or transverse colon in 126 (17%). ²² While acknowledging their center's referral bias for rectal cancer, 83% of the EOCRCs identified were distal to the splenic flexure and therefore theoretically within the range of flexible sigmoidoscopy; Segev et al suggested that screening with this platform would be an effective tool to screen individuals younger than 50 years.

Patients with CRC diagnosed before 50 years of age have also been found to have higher rates of synchronous tumors relative to the late-onset group. A 2003 study from National Taiwan University Hospital by Liang et al ²³ found that when compared with 339 patients with CRC diagnosed after the age of 60 years, 138 patients with CRC diagnosed younger than 40 years were significantly more likely to have synchronous lesions (in 5.8% of younger patients vs. 1.2% of older patients) and metachronous lesions (in 4.0 vs. 1.6%).

EOCRC: Tumor Biology

A somewhat controversial topic in understanding the distinctive characteristics of EOCRC is whether or not tumors demonstrate more aggressive histological features and invasive behavior than tumors found in older patients. Aggressive histological subtypes of CRCs, such as those bearing mucinous, poorly differentiated, or signet ring cell features, have been associated with a worse prognosis. ^{24 25} While some studies have argued against it, ^{26 27} there is a growing consensus in the literature that these aggressive tumors occur more frequently in the young. ^{9 24 28 29}

Though these studies have shown EOCRCs to present with more advanced disease and have more aggressive features when compared with the late-onset cohort, Abdelsattar et al demonstrated that survival rates, stage-for-stage, were actually improved in the younger cohort. ²⁰ Their SEER-based study, utilizing CRC data between 1998 and 2011, concluded that the 5-year cancer-specific survival rate for localized disease was 95.1 versus 91.9%, 76 versus 70.3% for regional disease, and 21.3 versus 14.1% for distant disease in the <50 years age group versus the ≥50 years age group, respectively.

EOCRC: Genetic Alterations

While the hereditary forms of CRC such as FAP and Lynch's syndrome are associated with well-described germline mutations leading to tumorigenesis in young patients, a burgeoning field of study is in understanding the various molecular biological pathways of sporadic CRCs in the young and potential differences in their molecular profiles from late-onset CRCs. ³⁰

It has been proposed that sporadic tumors may result from a large number of common genetic variations of variable penetrance, each exerting a small but cumulative influence on risk for tumor development. ³¹ Microsatellite instability (MSI) is uncommon in sporadic EOCRC, as the majority of these tumors are microsatellite stable (MSS) and have intact DNA repair mechanisms. ³² Young CRC patients with MSI are most commonly related to Lynch's syndrome, and are distinct from MSI tumors in the older onset groups because of their association with MSH2 inactivation (vs. MLH1 inactivation or promoter methylation in the older age groups). ³³ MSS tumors in the young, which are typically left sided and associated with a family history of CRC, ³⁴ vary greatly from those in the late-onset group, which tend to be right sided and less likely to have synchronous or metachronous lesions. ²⁸

The silencing of genes in CRCs by way of methylation of CpG islands has been implicated in up to 40% of CRCs, ³⁴ but more so in the late-onset group than the young. CpG island methylator phenotype (CIMP) CRCs tend to be right sided and harbor MSI. While most EOCRCs are CIMP low, the young-onset CIMP-high tumors are associated with Lynch's syndrome. ³⁴

Microsatellite and chromosome stable tumors comprise up to 30% of sporadic CRCs, and are more frequently identified in the early-onset group. These tumors, which tend to be CIMP low, are more common in the distal colon and rectum, and harbor aggressive characteristics, with earlier disease recurrence and higher propensity to present with metastasis at the time of diagnosis. ³⁵

Some young-onset CRCs have also been shown to uniquely demonstrate LINE-1 hypomethylation, which reflects genome-wide hypomethylation and chromosomal instability. ³⁶ The degree of LINE-1 hypomethylation has been shown to have a linear association with colon cancer-specific mortality, such that it is recognized as an independent risk factor for reduced survival. ³⁷

EOCRC: Risk Factors

While hereditary cancer syndromes, such as FAP and Lynch's syndrome, have been reported to account for just 2 to 5% of CRCs in the general population, ³⁸ they contribute to a greater percentage in the young, with up to approximately one in five EOCRCs attributed to hereditary cancer syndrome germline mutations. ³⁹ Interestingly, though, Stoffel et al ³⁹ found that in their retrospective, single-institution study of 430 young CRC cases diagnosed between 1998 and 2015, half of the EOCRCs with a known germline mutation were in patients who did not otherwise exhibit a family history typical of a hereditary cancer syndrome. This finding has significant implications since there may be a significant portion of individuals at high risk for developing early-onset disease that would not otherwise meet clinical criteria to undergo early screening based on a family history of CRC. With the overall higher rates of germline mutations in early- compared with late-onset disease, and with many of these discovered genetic mutations occurring in an otherwise unsuspecting cohort of young individuals without a family history, all individuals with EOCRC should be considered for genetic evaluation.

There is, however, no published evidence demonstrating that the rates of hereditary cancer syndromes are rising, and as Patel and Ahnen summarized in their recent comprehensive review on EOCRC, they are not thought to be a significant contributor to the overall rising incidence of CRCs in those younger than 50 years. ⁴⁰ Furthermore, while Siegel et al defined that tumors in the distal colon and rectum were solely responsible for the increased incidence of EOCRCs ¹ and You et al described EOCRCs as having much higher rates of later stage disease, ¹⁹ tumors discovered to have germline mutations were significantly more likely to be found proximal to the splenic flexure and less likely to have an advanced stage of disease. ³⁹ Early targeted screening of patients with a germline mutation for a hereditary cancer syndrome could impact the timeliness of diagnosis, treatment, and outcomes of a significant portion of CRCs in the young. Ultimately, determining the cause for the rising incidence of CRCs in the young demands an investigation into factors driving the rise of sporadic cancers.

EOCRC: Nonhereditary Risk Factors

Obesity, diabetes mellitus, and decreased physical activity are nonhereditary risk factors that have been associated with CRCs, and there is evidence that each is more prevalent than in previous generations. Between 1980 and 2014, the incidence of diabetes in the United States almost doubled from 3.5 to 6.6 per 1,000 people, ⁴¹ and it has been observed that having diabetes independently confers an absolute risk increase of ∼30% for developing CRC. ⁴² Obesity rates have been climbing steadily as well; between 2007 to 2008 and 2015 to 2016, the prevalence of U.S. adults being either obese (body mass index [BMI] ≥30) or severely obese (BMI ≥40) rose from 33.7 to 39.6% and 5.7 to 7.7%, respectively. ⁴³ A meta-analysis of studies on the topic found that with each 5 kg/m ² increase in BMI, men and women had a 30 and 12% higher risk of colon cancer, respectively. ⁴⁴ Sedentary behaviors have been shown to increase the risk of colon cancer, ranging from 24% for occupational sitting to 54% for time spent watching TV, ⁴⁵ while physical activity has been found to decrease the risk of colon cancer in a dose–response manner by 20 to 25%. ⁴⁶

While the incidence of EOCRC has increased in tandem with the aforementioned risk factors, there is an argument against this relationship being causative. Obesity, diabetes, and low activity levels have become more prevalent across all age groups, not just those younger than 50 years, and yet, CRC rates have been steadily decreasing in those older than 50 years. One explanation for this discrepancy is earlier screening of older cohorts that have been similarly exposed. ⁴⁰

The role of dietary factors, such as red meat, processed foods, or low fiber diets, lifestyle choices, such as smoking and alcohol intake, as well as environmental toxin exposure all may play a role in CRC development. In the absence of definitive evidence, population-based studies are needed to evaluate the potential role of each of these factors.

EOCRC: The Role of Screening

The observation of the rising incidence of CRCs in an age group younger than the average age at which screening routinely starts has brought to light the question of whether or not it would be beneficial and cost-effective to begin screening at an earlier age.

CRC screening in average-risk individuals has generally been recommended to occur between 50 and 74 years of age, with the U.S. Preventive Services Task Force's CISNET (Cancer Intervention and Surveillance Modeling Network) model estimating that strict adherence to a regular colonoscopic screening regimen would reduce incidence of CRC by 62 to 88% and mortality by 79 to 90%. ⁴⁷ Adherence to recommendations has improved in recent years. The National Center for Health Statistics reported that between 2000 and 2013, the percentage of individuals who received a colonoscopy increased across all age groups within the recommended screening cohort, from 14 to 41% in those who are 50 to 54 years of age, from 16 to 52% in those 55 to 59 years of age, and from 25 to 63% in those older than 65 years. ⁴⁸ Despite this overall improved compliance in screening, with just 41% of the age 50 to 54 years bracket undergoing colonoscopy, there is still a wide swath of an at-risk population not bearing the benefits of the screening program. This is of particular concern because while the greatest delineation in Siegel et al's landmark SEER study ¹ described the increasing incidence of colon and rectal cancers in the <50 years age group and decreasing incidence in those age ≥50 years, further subgroup analysis actually shows that trend of rising incidence actually extends into the 50 to 54 years age group as well. ⁴⁹

The American Cancer Society's Guideline Development Group (GDG) took this finding of increasing colorectal incidence in those younger than 55 years into careful consideration when recently re-evaluating the optimal age to begin screening for CRC in average-risk individuals. ⁵⁰ Citing evidence that the prevalence of large polyps (≥9 mm) is similar in adults younger than 50 years (4.2% in whites, 6.2% in blacks) to those between 50 and 59 years of age (5.3% in whites, 6.1% in blacks), ⁵¹ the GDG posited that there was substantial disease prevention potential in beginning screening at the age of 45 years. Additionally, when weighing updated CRC risk modeling microsimulations that reflected the observed increased incidence in the younger population, ⁵² the American Cancer Society was further supported in their conclusion that CRC screening for the general population should start at the age of 45 years. ⁵⁰

Specific earlier screening recommendations for high-risk individuals include those with IBD affecting the colon, a hereditary cancer syndrome such as Lynch's syndrome or FAP, a family history of CRC in at least one first-degree relative diagnosed before 60 years of age, and a prior personal history of CRC.

With a two- to fourfold increase in lifetime risk for developing CRC, ⁵³ individuals with a strong family history of one or more first-degree relatives with CRC before 60 years of age have long been recommended to undergo earlier screening than their average-risk counterparts. The current consensus for screening this high-risk population has been to start screening at either age 40 or 10 years earlier than the age at diagnosis for the youngest affected family member. ⁵⁴ Overall, 15% of individuals of 40 to 49 years of age undergoing early screening for a family history of CRC are found to have adenomas. ⁵⁵ Unfortunately, despite their increased risk, only 62.9% of patients with this familial risk factor undergo screening as recommended. ⁵⁶ Improving CRC screening compliance in light of both new recommendations for the general population and established recommendations for high-risk population demands increased awareness among health care providers and patients.

EOCRC: Treatment and Prognosis

Given that EOCRC tends to present at more advanced stages and may exhibit more aggressive histological characteristics, it is essential to evaluate the most appropriate therapeutic strategy to achieve the best possible outcomes. In a retrospective review ⁵⁷ of 582 patients with rectal cancer treated with an R0 resection at Massachusetts General Hospital between 2004 and 2015, the 125 patients younger than 50 years were more likely to have stage III or IV disease, positive lymph nodes, perineural invasion, small vessel invasion, and high-grade disease. Despite these differences in stage and tumor characteristics, there were no statistically significant differences in oncologic outcomes stage for stage between those younger and older than 50 years. Overall mortality was lower in the age <50 years cohort, at 19.2 versus 26.9%, and overall survival was greater in the younger age group, at 44.2 versus 35.4 months, though neither of these reached statistical significance. Kneuertz et al ⁵⁸ conducted a nationwide cohort study comparing 13,102 patients with EOCRC to 37,007 patients with late-onset CRC undergoing surgical treatment between 2003 and 2005 to examine age-related differences in the adjuvant treatment regimens and any relative survival gains. They found that young patients were two to four times more likely to receive systemic chemotherapy after resection than older patients in each stage, and more likely to be overtreated, as 5.7% of young-onset patients (vs. 1.8% of older onset patients) with stage I disease and 50.5% (vs. 19.1%) with stage II low-risk disease received systemic chemotherapy. These aggressive adjuvant regimens with potential long-term toxicity did not impact survival, as the 5-year relative survival of the young-onset group versus the older onset group was 91.1 versus 90.2% for stage II disease overall.

Future Directions

EOCRC has, in recent years, been increasingly recognized as a growing threat, with its steadily rising incidence, ¹ more aggressive features, ⁹ and its propensity to present at more advanced stages. ¹⁹ The recently published updated guidelines from the American Cancer Society ⁵⁰ to begin colorectal screening at the age of 45 years to help combat the rising wave of young people with aggressive, advanced colorectal tumors is an important step, but much research remains to be done.

The new screening recommendations must be diffused, enforced, and implemented. This will require increased societal awareness of the changing demographics of CRC, increased risk in the younger population, patient and provider education on the topic, and appropriate coverage of screening tests and procedures by insurance companies. The cost-effectiveness of the updated screening protocols studies will need to be evaluated.

In addition, more research on the biological and molecular differences of young- versus older onset CRCs could lead to novel and targeted therapeutic strategies.

With rising numbers of young individuals being diagnosed with CRC, there is also a growing need to understand the impact of EOCRC on both the patient and provider alike. Younger patients may have an increased willingness to tolerate more aggressive treatment strategies that may not at present be the standard of care, and also compel the multidisciplinary treatment team to make greater attempts at organ preservation, with total neoadjuvant chemoradiation or transanal total mesorectal excision being two emerging examples to approach this goal.

How standard or innovative treatment approaches affect those with EOCRC also remains a fertile ground for study, as there is a paucity of data on quality of life, stoma rates, surgical complications, and other clinical factors specific to the younger population. Further studies on all the issues earlier would help guide physicians and patients in making informed decisions regarding treatment strategies.

Funding Statement

Funding No financial support was received for the authoring of this article.