Young adults with colon cancer: clinical features and surgical outcomes

Colon cancer is the fifth most common malignant disease, accounting for 6% of new cancer cases and 5.8% of new cancer deaths worldwide [1]. Many risk factors, such as age, race, accompanying inflammatory bowel disease, and a family history of gastrointestinal cancer, contribute to the incidence of colon cancer [2, 3]. Among them, increasing age is considered the major unchangeable risk factor for sporadic colon cancer; nearly 70% of patients are >65 years of age, and this disease is rare before the age of 40 years [4]. However, this trend has changed, and the incidence and death rates of colorectal cancer in younger individuals have been rising [5]. A population-based study [6] from England showed a six-fold increase in younger colorectal cancer patients over the past three decades, and the most sustained increase in the incidence rate was in the group aged 20–29 years. The presentation, tumor biology, and survival pattern of young-onset patients were reported to be different from those of the older population [7, 8], which might bring challenges to oncologists because of the more advanced stage, more tolerance to therapy, and longer life expectancy of young-onset patients. Previous studies [9, 10] on this topic were mainly based on public databases from Western countries and focused on the description of epidemiological or demographic data, lacking the analysis of clinicopathological features, treatment strategy, and surgical outcomes, especially in advanced tumors among Asian patients.

Given the deficiency of previous studies, here we aimed to identify the clinicopathological features and long-term survival in young-onset colon cancer patients (≤ 40 years old), which would be beneficial for providing abundant evidence for precision treatment.

Recent studies [12, 13] have emphasized an increased number of patients diagnosed with colon cancer in their 20s, 30s, and 40s. In the past, tumor biology and survival patterns were different between young colon cancer adults and the older population, which was mainly due to the more aggressive tumor biology. This would result in more intensive treatment measures because of greater tolerance to therapy and a stronger will to survive compared with older patients. However, a few retrospective studies [10, 12, 14] showed that young colon cancer patients tend to have similar surgical outcomes and OS compared to older patients. Therefore, investigations of surgical outcomes and long-term survival in young patients with colon cancer are necessary to provide abundant evidence for precision treatment. Our findings show that colon cancer in young adults is not unique. Differences in clinical features, surgical outcomes, and long-term survival were not observed in this population.

The incidence of young-onset colon cancer in adults with varies across countries and regions. A population-based study [9] that reviewed data in England from 2010 to 2014 found that among 167501 colorectal cancer patients, 3657 (2.2%) patients were 40 years old or younger, with an increasing trend in the proportion of young-onset patients (14.4% in 2010 to 23.7% in 2014, P<0.05). Another study [12] analyzed data from the Mayo Clinic Cancer Registry from 1972 to 2017 and found that the percentage of patients aged < 50 years diagnosed with rectal cancer increased linearly at a rate of 0.26% per year (P<0.001); however, a similar trend was not observed in colon cancer (P=0.296). In contrast to the Mayo Clinic, data from the Chinese Cancer Registry Annual Report showed consistent trends of average annual percent change from 2005 to 2015 in colon (0.9, 95% CI -0.6 to 2.4) and rectal (-0.5, 95% CI -2.1 to 1.1) cancer patients aged 20–34 [15]. In the present study, we also found no significant increasing trend (P=1) in young-onset colon cancer patients. Although the incidence of young-onset colon cancer is controversial, further studies should be performed to explore the potential influencing factors associated with the epidemiology of younger individuals at greater risk, and the current screening recommendations should also be reconsidered.

Conventional viewpoints treat young-onset colon cancer as a particular type with low incidence, which is always accompanied by extremely aggressive tumor biology and poor prognosis. However, a recent study [9] with the largest sample of young-onset colorectal cancer patients showed that only 16.9% of cases were poorly differentiated, and 28.7% of cases had metastatic disease. Another study [10] investigated 947 extremely young (≤25 years) colon cancer patients by reviewing the National Cancer Database and found that 29.7% of patients had poor tumor histology (mucinous, mucin-producing, or signet ring cell adenocarcinoma), and 27.5% of patients had metastatic disease. Our study had similar results, with 31.4% showing poor differentiation, 22.5% mucinous adenocarcinoma, and 27.1% metastatic disease. Thus, preconceptions about extremely aggressive tumor biology accompanied by young-onset colon cancer should be abandoned; colon cancer occurring in young adults was rare but not a particular type compared to the older ones.

Surgery is the primary treatment for non-metastatic colon cancer, and no unique surgical procedure has been proposed for patients with young-onset colon cancer. In the present study, all patients with stage I–III disease underwent complete mesocolic excision as the initial treatment. The short-term surgical outcomes, including a 3.9% surgical complication rate and 8 days of postoperative hospital stay, were acceptable and similar to previously published studies from our center [16] or others [17, 18] that performed complete mesocolic excision for all age groups. Satisfied long-term survival for early stage young-onset colon cancer patients was revealed by a recent study [9] with a large sample size, which showed 98.2% and 89.1% 5-year overall survival for stage I and II disease, respectively. In the present study, stage I and II patients also had satisfactory prognoses, with an estimated 91.5% 5-year OS and 93.5% 5-year PFS. As for stage III disease, a large sample size study [10] from the USA showed a 60.6% 5-year OS, which was inferior compared to our study of 73.9% 5-year OS and the result of 74.8% from England [9]. This might be because the USA study only included patients aged ≤ 25 years, which was much younger than our study and the England study. Second, as illustrated in the USA study, it contained a higher proportion of Black patients, and young Black patients have also been found to have worse overall survival outcomes compared to non-Hispanic Whites [10, 19]. An English study also showed that ethnicity affected the 5-year OS, with Black 63.0%, Caucasians 71.2%, and Chinese 76.2% (P<0.001).

The treatments for stage IV disease in young-onset colon cancer may vary from those in older patients in clinical practice. In most regions, more intensive treatment is applied for young adults because of greater tolerance to therapy and longer life expectancy [20]. However, a study [14] reanalyzed the Cancer and Leukemia Group B and SWOG 80405 trial and found there were no significant differences between colorectal cancer patients aged ≤ 50 years and >50 years regarding median OS (27.07 vs 26.12 months, P=0.78) and PFS (10.87 vs 10.55 months, P=0.67) during a median follow-up time of 5.98 years. In the present study, nine patients received surgery and others received conversion therapy as the initial treatment, and none received palliative treatment. The estimated 5-year OS of 51.8% was also longer than that of the England [9] (20.1%) and USA [10] (14.1%) studies. The most likely reason might be that patients with stage IV disease whose PFS was longer than 60 months were all isolated liver metastases and underwent radical surgery for primary and metastatic lesions simultaneously. Therefore, radical surgery may be the first choice for patients with colon cancer with isolated liver metastasis.

This study had some limitations. First, limited by the study design, we could not collect the data of older patients to make a comparison, which might make the conclusion less reliable. Second, the retrospective nature and small sample size could have caused bias and impacted external adaptation. Third, our study lacks the analysis of the influence of molecular mechanisms or pathway mutations in young-onset colon cancer patients which might illustrate the pathogenesis and could be the final indication of the difference between young-onset and older colon cancer. Last, the limited sample size could result in potential bias, which only large nationwide databases could address this important issue.

In summary, The differences in the clinical features, surgical outcomes, and long-term survival between young adults and elderly colon cancer patients need further investigation.