Incidence

Carcinoma of the large bowel is rare in children and adolescents.[1] Colorectal cancer is seen in 0.5 cases per 100,000 people younger than 20 years in the United States annually.[2] Fewer than 100 cases are diagnosed in children each year in the United States.[3] From 1973 to 2006, the Surveillance, Epidemiology, and End Results (SEER) Program database recorded 174 cases of colorectal cancer in patients younger than 19 years.[4]

Colorectal carcinoma accounts for about 5% of all malignancies in people aged 15 to 29 years.[2] An analysis of SEER data identified 5,350 adolescents and young adults between the ages of 15 and 39 years with colorectal cancer from 2010 to 2015.[5]

References:

1. da Costa Vieira RA, Tramonte MS, Lopes LF: Colorectal carcinoma in the first decade of life: a systematic review. Int J Colorectal Dis 30 (8): 1001-6, 2015.
2. Surveillance Research Program, National Cancer Institute: SEER*Explorer: An interactive website for SEER cancer statistics. Bethesda, MD: National Cancer Institute. Available online. Last accessed March 6, 2024.
3. Saab R, Furman WL: Epidemiology and management options for colorectal cancer in children. Paediatr Drugs 10 (3): 177-92, 2008.
4. Ferrari A, Casanova M, Massimino M, et al.: Peculiar features and tailored management of adult cancers occurring in pediatric age. Expert Rev Anticancer Ther 10 (11): 1837-51, 2010.
5. Holowatyj AN, Lewis MA, Pannier ST, et al.: Clinicopathologic and Racial/Ethnic Differences of Colorectal Cancer Among Adolescents and Young Adults. Clin Transl Gastroenterol 10 (7): e00059, 2019.

Inflammatory Bowel Disease Associated With Colorectal Cancer

A register-based nationwide cohort study was conducted in Sweden and Denmark to assess the risk of colorectal cancer related to childhood-onset Crohn disease (n = 6,937) and ulcerative colitis (n = 8,514). Patients with Crohn disease were monitored until a median age of 27 years, and patients with ulcerative colitis were monitored until age 29 years.[1]

• During the follow-up period, 25 patients with Crohn disease (0.36%) were diagnosed with colorectal cancer, versus 43 reference individuals (0.06%).
• During the follow-up period, 113 patients with ulcerative colitis (1.33%) were diagnosed with colorectal cancer, versus 45 reference individuals (0.05%).
• The hazard ratio (HR) for colorectal cancer was 6.46 (95% confidence interval [CI], 3.95–10.6) in patients with Crohn disease and 32.5 (95% CI, 23.0–45.9) in patients with ulcerative colitis. The HR increased with decreasing age of diagnosis.
• The relative risk of colorectal cancer is very high in both childhood-onset Crohn disease and ulcerative colitis, and age at diagnosis is an additional risk factor.
• These factors are potentially important when implementing a colorectal cancer surveillance program for patients with inflammatory bowel disease.

References:

1. Everhov ÅH, Ludvigsson JF, Järås J, et al.: Colorectal Cancer in Childhood-onset Inflammatory Bowel Disease: A Scandinavian Register-based Cohort Study, 1969-2017. J Pediatr Gastroenterol Nutr 75 (4): 480-484, 2022.

Genetic Syndromes Associated With Colorectal Cancer

About 20% to 30% of adult patients with colorectal cancer have a significant history of familial cancer; of these, about 5% have a well-defined genetic syndrome.[1] Hereditary colorectal cancer has two well-described forms:[2,3]

• Polyposis (including familial adenomatous polyposis [FAP] and attenuated FAP, which are caused by germline pathogenic variants in the APC gene, and MUTYH-associated polyposis, which is caused by germline pathogenic variants in the MUTYH gene).

  Familial polyposis is inherited as a dominant trait, which confers a high degree of risk. Early diagnosis and surgical removal of the colon eliminates the risk of developing carcinomas of the large bowel.[4,5] Some colorectal carcinomas in young people, however, may be associated with a variant of the APC gene, which also is associated with an increased risk of brain tumors and hepatoblastoma.[6] FAP syndrome is caused by a gene variant on chromosome 5q, which normally suppresses proliferation of cells lining the intestine and later development of polyps.[7] A double-blind, placebo-controlled, randomized phase I trial in children aged 10 to 14 years with FAP reported that celecoxib at a dose of 16 mg/kg per day is safe for up to 3 months. At this dose, there was a significant decrease in the number of polyps detected by colonoscopy.[8][Level of evidence B3] The role of celecoxib in the management of FAP in children is not clear.

• Lynch syndrome (often referred to as hereditary nonpolyposis colorectal cancer), which is caused by germline pathogenic variants in DNA mismatch repair genes (MLH1, MSH2, MSH6, and PMS2) and EPCAM.

  Despite the increased risk of multiple malignancies in families with Lynch syndrome, the risk of malignant neoplasms during childhood in those families does not seem to be increased when compared with the risk in children from families with colorectal carcinoma that is not associated with Lynch syndrome.[9]

Other colorectal cancer syndromes and their associated genes include oligopolyposis (POLE, POLD1),[3]NTHL1,[10] juvenile polyposis syndrome (BMPR1A, SMAD4), Cowden syndrome (PTEN), and Peutz-Jeghers syndrome (STK11).[2] For more information about these syndromes, see Genetics of Colorectal Cancer

Another tumor suppressor gene on chromosome 18 is associated with progression of polyps to malignant tumors. Multiple colon carcinomas have been associated with neurofibromatosis type I and several other rare syndromes.[11]

In a cohort study of 201 patients with constitutional mismatch repair deficiency, 59 developed colorectal cancer at a median age of 20.1 years (range, 13.9–24.9 years). The cumulative incidence of gastrointestinal cancers by age 20 years was 42% (95% confidence interval, 30%–54%).[12]

The incidence of these genetic syndromes in children is not well defined, but several studies have examined it, as follows:

• In one review, 16% of patients younger than 40 years had a predisposing factor for the development of colorectal cancer.[13]
• A later study documented immunohistochemical evidence of mismatch repair deficiency in 31% of colorectal carcinoma samples in patients aged 30 years or younger.[14]
• A retrospective review of patients younger than 18 years in Germany identified 31 patients with colorectal carcinoma.[15] Eleven of the 26 patients who were tested for a genetic predisposition syndrome tested positive (eight cases of Lynch syndrome, one patient with FAP, and two patients with constitutional mismatch repair deficiency). When compared with the patients without a genetic predisposition syndrome, the 11 patients with a genetic predisposition syndrome presented with more localized disease, allowing complete surgical resection and improved outcome (100% survival rate).

References:

1. Gatalica Z, Torlakovic E: Pathology of the hereditary colorectal carcinoma. Fam Cancer 7 (1): 15-26, 2008.
2. Hampel H: Genetic testing for hereditary colorectal cancer. Surg Oncol Clin N Am 18 (4): 687-703, 2009.
3. Briggs S, Tomlinson I: Germline and somatic polymerase ε and δ mutations define a new class of hypermutated colorectal and endometrial cancers. J Pathol 230 (2): 148-53, 2013.
4. Erdman SH: Pediatric adenomatous polyposis syndromes: an update. Curr Gastroenterol Rep 9 (3): 237-44, 2007.
5. Vitellaro M, Piozzi G, Signoroni S, et al.: Short-term and long-term outcomes after preventive surgery in adolescent patients with familial adenomatous polyposis. Pediatr Blood Cancer 67 (3): e28110, 2020.
6. Turcot J, Despres JP, St Pierre F: Malignant tumors of the central nervous system associated with familial polyposis of the colon: report of two cases. Dis Colon Rectum 2: 465-8, 1959 Sep-Oct.
7. Vogelstein B, Fearon ER, Hamilton SR, et al.: Genetic alterations during colorectal-tumor development. N Engl J Med 319 (9): 525-32, 1988.
8. Lynch PM, Ayers GD, Hawk E, et al.: The safety and efficacy of celecoxib in children with familial adenomatous polyposis. Am J Gastroenterol 105 (6): 1437-43, 2010.
9. Heath JA, Reece JC, Buchanan DD, et al.: Childhood cancers in families with and without Lynch syndrome. Fam Cancer 14 (4): 545-51, 2015.
10. Broderick P, Dobbins SE, Chubb D, et al.: Validation of Recently Proposed Colorectal Cancer Susceptibility Gene Variants in an Analysis of Families and Patients-a Systematic Review. Gastroenterology 152 (1): 75-77.e4, 2017.
11. Pratt CB, Jane JA: Multiple colorectal carcinomas, polyposis coli, and neurofibromatosis, followed by multiple glioblastoma multiforme. J Natl Cancer Inst 83 (12): 880-1, 1991.
12. Ercan AB, Aronson M, Fernandez NR, et al.: Clinical and biological landscape of constitutional mismatch-repair deficiency syndrome: an International Replication Repair Deficiency Consortium cohort study. Lancet Oncol 25 (5): 668-682, 2024.
13. O'Connell JB, Maggard MA, Livingston EH, et al.: Colorectal cancer in the young. Am J Surg 187 (3): 343-8, 2004.
14. Goel A, Nagasaka T, Spiegel J, et al.: Low frequency of Lynch syndrome among young patients with non-familial colorectal cancer. Clin Gastroenterol Hepatol 8 (11): 966-71, 2010.
15. Weber ML, Schneider DT, Offenmüller S, et al.: Pediatric Colorectal Carcinoma is Associated With Excellent Outcome in the Context of Cancer Predisposition Syndromes. Pediatr Blood Cancer 63 (4): 611-7, 2016.

Clinical Presentation

Colorectal tumors can occur in any location in the large bowel. Large series and reviews suggest that ascending and descending colon tumors are each seen in approximately 30% of cases, with rectal tumors occurring in approximately 25% of cases.[1,2,3]

Right-sided tumors (cecum to transverse colon) were diagnosed in 28.6% of adolescent and young adult (AYA) cases. The proportion of right-sided colorectal cancers differed significantly by age group at diagnosis (38.3% of AYA patients aged 15–19 years vs. 27.3% of AYA patients aged 35–39 years). The incidence of mucinous adenocarcinoma and signet ring cell carcinoma histopathological subtypes was higher in younger patients.

Tumors of the ascending colon (right colon) may cause more subtle symptoms but are often associated with the following:

• Abdominal mass.
• Weight loss.
• Decreased appetite.
• Blood in the stool.
• Iron-deficiency anemia.

Signs and symptoms in children with descending colon tumors include the following:

• Abdominal pain (most common).
• Rectal bleeding.
• Change in bowel habits.
• Weight loss.
• Nausea and vomiting.

The median duration of symptoms before diagnosis was about 3 months in one series.[4,5]

Changes in bowel habits may be associated with tumors of the rectum or lower colon.

Any tumor that causes complete obstruction of the large bowel can cause bowel perforation and spread of the tumor cells within the abdominal cavity.

References:

1. Kaplan MA, Isikdogan A, Gumus M, et al.: Childhood, adolescents, and young adults (≤25 y) colorectal cancer: study of Anatolian Society of Medical Oncology. J Pediatr Hematol Oncol 35 (2): 83-9, 2013.
2. Kim G, Baik SH, Lee KY, et al.: Colon carcinoma in childhood: review of the literature with four case reports. Int J Colorectal Dis 28 (2): 157-64, 2013.
3. Sultan I, Rodriguez-Galindo C, El-Taani H, et al.: Distinct features of colorectal cancer in children and adolescents: a population-based study of 159 cases. Cancer 116 (3): 758-65, 2010.
4. Hill DA, Furman WL, Billups CA, et al.: Colorectal carcinoma in childhood and adolescence: a clinicopathologic review. J Clin Oncol 25 (36): 5808-14, 2007.
5. Saab R, Furman WL: Epidemiology and management options for colorectal cancer in children. Paediatr Drugs 10 (3): 177-92, 2008.

Diagnostic Evaluation

Diagnostic studies include the following:[1,2]

• Examination of the stool for blood.
• Studies of liver and kidney function.
• Measurement of carcinoembryonic antigen (CEA).
• Various medical imaging studies, including direct examination using colonoscopy to detect polyps in the large bowel. Other conventional radiographic studies include barium enema or video-capsule endoscopy followed by computed tomography of the chest and bone scans.[3]

References:

1. Pratt CB, Rao BN, Merchant TE, et al.: Treatment of colorectal carcinoma in adolescents and young adults with surgery, 5-fluorouracil/leucovorin/interferon-alpha 2a and radiation therapy. Med Pediatr Oncol 32 (6): 459-60, 1999.
2. Kauffman WM, Jenkins JJ, Helton K, et al.: Imaging features of ovarian metastases from colonic adenocarcinoma in adolescents. Pediatr Radiol 25 (4): 286-8, 1995.
3. Postgate A, Hyer W, Phillips R, et al.: Feasibility of video capsule endoscopy in the management of children with Peutz-Jeghers syndrome: a blinded comparison with barium enterography for the detection of small bowel polyps. J Pediatr Gastroenterol Nutr 49 (4): 417-23, 2009.

Histology and Genomic Alterations

There is a higher incidence of mucinous adenocarcinoma in pediatric and adolescent patients (40%–50%), with many lesions of the signet ring cell type.[1,2,3,4,5] In comparison, only about 15% of adult lesions involve this histology. Tumors with mucinous histology arise from the surface of the bowel, usually at the site of an adenomatous polyp.[5] The tumor may extend into the muscle layer surrounding the bowel, or the tumor may perforate the bowel entirely and seed through the spaces around the bowel, including intra-abdominal fat, lymph nodes, liver, ovaries, and the surface of other loops of bowel. A high incidence of metastasis involving the pelvis, ovaries, or both may be present in girls.[6]

The tumors of younger patients with the mucinous histological variant may not respond well to chemotherapy. In the adolescent and young adult (AYA) population with this histology, there is a higher incidence of signet ring cells, microsatellite instability, and variants in the mismatch repair genes.[5,7,8]

Colorectal cancers in younger patients with noninherited sporadic tumors often lack KRAS variants and other cytogenetic anomalies seen in older patients.[9] A genomic study used exome and RNA sequencing to identify variant differences in colorectal carcinomas of adults (n = 30), AYA patients (n = 30), and children (n = 2). Five of the identified genes (MYCBP2, BRCA2, PHLPP1, TOPORS, and ATR) were more frequently altered in AYA patients. These genes contained a damaging variant and were identified through whole-exome sequencing and RNA sequencing. In addition, higher variant rates in DNA mismatch and DNA repair pathways, such as MSH2, BRCA2, and RAD9B, were more prevalent in AYA samples, but the results were not validated by RNA sequencing.[10]

References:

1. Saab R, Furman WL: Epidemiology and management options for colorectal cancer in children. Paediatr Drugs 10 (3): 177-92, 2008.
2. Hill DA, Furman WL, Billups CA, et al.: Colorectal carcinoma in childhood and adolescence: a clinicopathologic review. J Clin Oncol 25 (36): 5808-14, 2007.
3. Ferrari A, Rognone A, Casanova M, et al.: Colorectal carcinoma in children and adolescents: the experience of the Istituto Nazionale Tumori of Milan, Italy. Pediatr Blood Cancer 50 (3): 588-93, 2008.
4. da Costa Vieira RA, Tramonte MS, Lopes LF: Colorectal carcinoma in the first decade of life: a systematic review. Int J Colorectal Dis 30 (8): 1001-6, 2015.
5. Poles GC, Clark DE, Mayo SW, et al.: Colorectal carcinoma in pediatric patients: A comparison with adult tumors, treatment and outcomes from the National Cancer Database. J Pediatr Surg 51 (7): 1061-6, 2016.
6. Kauffman WM, Jenkins JJ, Helton K, et al.: Imaging features of ovarian metastases from colonic adenocarcinoma in adolescents. Pediatr Radiol 25 (4): 286-8, 1995.
7. Tricoli JV, Seibel NL, Blair DG, et al.: Unique characteristics of adolescent and young adult acute lymphoblastic leukemia, breast cancer, and colon cancer. J Natl Cancer Inst 103 (8): 628-35, 2011.
8. Khan SA, Morris M, Idrees K, et al.: Colorectal cancer in the very young: a comparative study of tumor markers, pathology and survival in early onset and adult onset patients. J Pediatr Surg 51 (11): 1812-1817, 2016.
9. Bleyer A, Barr R, Hayes-Lattin B, et al.: The distinctive biology of cancer in adolescents and young adults. Nat Rev Cancer 8 (4): 288-98, 2008.
10. Tricoli JV, Boardman LA, Patidar R, et al.: A mutational comparison of adult and adolescent and young adult (AYA) colon cancer. Cancer 124 (5): 1070-1082, 2018.

Prognosis and Prognostic Factors

Several retrospective studies of adolescent and young adult (AYA) patients with colorectal cancer are summarized.

1. An analysis from the National Cancer Database, which tracks outcomes of patients with malignancies across 1,500 Commission on Cancer–accredited facilities, identified 531,462 patients with colon cancer between 2004 and 2016. There were 947 patients aged 25 years or younger.[1]
   • Compared with patients older than 25 years, younger patients had more advanced disease (stage III: 44.4% vs. 33.4%; stage IV: 27.5% vs.15.3%) and higher rates of total colectomy (8.9% vs. 2.7%) and proctocolectomy (5.0% vs. 0.0%).
   • Stage-for-stage, the 5-year survival rates were higher in patients aged 25 years or younger than in those older than 25 years.
   • This study had several limitations. The data presented in this study are registry based, and not all data points were collected for all patients. In addition, only 30% of hospitals in the United States are accredited by the Commission on Cancer.
2. A retrospective analysis of patients examined at three tertiary referral hospitals in China between September 2000 and July 2019 identified 70 patients younger than 20 years with colorectal carcinoma.[2]
   • The most common primary tumor location was the left hemicolon (35.7%).
   • The prominent pathological types were mucinous adenocarcinoma (22.9%) and signet ring cell carcinoma (22.9%).
   • Nearly one-half (47.1%) of the patients presented with distant metastasis at diagnosis.
   • Of the patients who received additional tumor testing, 23.8% (5 of 21) had deficient mismatch repair protein expression and 71.4% (5 of 7) had microsatellite instability-high disease.
3. Another study from the National Cancer Database described the features and outcomes of 918 pediatric patients (aged <21 years), 157,577 young adult patients (aged 22–50 years), and 1,303,655 older adult patients (aged >50 years) with colorectal cancer.[3]
   • Signet ring, mucinous, and poorly differentiated histology were more commonly seen in pediatric patients.
   • Children and older patients had poorer 5-year overall survival rates than early-onset adults when adjusted for other covariates, such as stage and pathology.
   • Age younger than 21 years was a significant predictor of mortality caused by colon and rectal cancer.
   • As with other publications from this group, the data presented in this study are registry based, which underestimates several variables, including outpatient therapy and predisposing factors and symptoms. This limitation may explain why a specific course for inferior outcomes in patients younger than 21 years could not be identified.
4. A single-institution retrospective review compared 94 pediatric and young adult patients (aged <25 years) with 765 older patients.[4]
   • This study reported a worse prognosis (stage-for-stage) and a higher rate of peritoneal metastasis for the younger patients.
   • Nearly 30% of the pediatric patients in the cohort were known to have a predisposing cancer susceptibility diagnosis, most commonly Lynch syndrome, familial adenomatous polyposis, or Li-Fraumeni syndrome.
5. A pediatric oncology group in the Netherlands performed a retrospective analysis of adolescents and adults aged 25 years or younger with colorectal cancer. They analyzed clinical data and molecular and genetic features of colorectal tumor tissues from 139 AYA patients (age, ≤25 years; median age, 23 years; 58% male), collected between 2000 and 2017.[5]
   • Mucinous and/or signet ring cell components were observed in 33% of tumor samples.
   • A genetic tumor-risk syndrome was confirmed in 39% of the patients.
   • Factors associated with shorter survival time included younger age at diagnosis, signet ring cell carcinoma histology, the absence of a genetic tumor-risk syndrome, and advanced stage of disease at diagnosis.

Survival is consistent with the advanced stage of disease observed in most children with colorectal cancer, with an overall mortality rate of approximately 70%. For patients with a complete surgical resection or for those with low-stage/localized disease, survival is significantly prolonged, with the potential for cure.[6]

References:

1. Akinkuotu AC, Maduekwe UN, Hayes-Jordan A: Surgical outcomes and survival rates of colon cancer in children and young adults. Am J Surg 221 (4): 718-724, 2021.
2. Zhou C, Xiao W, Wang X, et al.: Colorectal cancer under 20 years old: a retrospective analysis from three tertiary hospitals. J Cancer Res Clin Oncol 147 (4): 1145-1155, 2021.
3. Poles GC, Clark DE, Mayo SW, et al.: Colorectal carcinoma in pediatric patients: A comparison with adult tumors, treatment and outcomes from the National Cancer Database. J Pediatr Surg 51 (7): 1061-6, 2016.
4. Hayes-Jordan AA, Sandler G, Malakorn S, et al.: Colon Cancer in Patients Under 25 Years Old: A Different Disease? J Am Coll Surg 230 (4): 648-656, 2020.
5. de Voer RM, Diets IJ, van der Post RS, et al.: Clinical, Pathology, Genetic, and Molecular Features of Colorectal Tumors in Adolescents and Adults 25 Years or Younger. Clin Gastroenterol Hepatol 19 (8): 1642-1651.e8, 2021.
6. Kaplan MA, Isikdogan A, Gumus M, et al.: Childhood, adolescents, and young adults (≤25 y) colorectal cancer: study of Anatolian Society of Medical Oncology. J Pediatr Hematol Oncol 35 (2): 83-9, 2013.

Staging

Most reports suggest that children present with more advanced disease than adults, with 80% to 90% of pediatric patients presenting with Dukes stage C/D or TNM stage III/IV disease.[1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16] For more information, see the Stage Information for Colon Cancer section in Colon Cancer Treatment.

References:

1. Hill DA, Furman WL, Billups CA, et al.: Colorectal carcinoma in childhood and adolescence: a clinicopathologic review. J Clin Oncol 25 (36): 5808-14, 2007.
2. Saab R, Furman WL: Epidemiology and management options for colorectal cancer in children. Paediatr Drugs 10 (3): 177-92, 2008.
3. Chantada GL, Perelli VB, Lombardi MG, et al.: Colorectal carcinoma in children, adolescents, and young adults. J Pediatr Hematol Oncol 27 (1): 39-41, 2005.
4. Durno C, Aronson M, Bapat B, et al.: Family history and molecular features of children, adolescents, and young adults with colorectal carcinoma. Gut 54 (8): 1146-50, 2005.
5. Ferrari A, Rognone A, Casanova M, et al.: Colorectal carcinoma in children and adolescents: the experience of the Istituto Nazionale Tumori of Milan, Italy. Pediatr Blood Cancer 50 (3): 588-93, 2008.
6. Karnak I, Ciftci AO, Senocak ME, et al.: Colorectal carcinoma in children. J Pediatr Surg 34 (10): 1499-504, 1999.
7. LaQuaglia MP, Heller G, Filippa DA, et al.: Prognostic factors and outcome in patients 21 years and under with colorectal carcinoma. J Pediatr Surg 27 (8): 1085-9; discussion 1089-90, 1992.
8. Radhakrishnan CN, Bruce J: Colorectal cancers in children without any predisposing factors. A report of eight cases and review of the literature. Eur J Pediatr Surg 13 (1): 66-8, 2003.
9. Sharma AK, Gupta CR: Colorectal cancer in children: case report and review of literature. Trop Gastroenterol 22 (1): 36-9, 2001 Jan-Mar.
10. Taguchi T, Suita S, Hirata Y, et al.: Carcinoma of the colon in children: a case report and review of 41 Japanese cases. J Pediatr Gastroenterol Nutr 12 (3): 394-9, 1991.
11. Pratt CB, Rao BN, Merchant TE, et al.: Treatment of colorectal carcinoma in adolescents and young adults with surgery, 5-fluorouracil/leucovorin/interferon-alpha 2a and radiation therapy. Med Pediatr Oncol 32 (6): 459-60, 1999.
12. Sultan I, Rodriguez-Galindo C, El-Taani H, et al.: Distinct features of colorectal cancer in children and adolescents: a population-based study of 159 cases. Cancer 116 (3): 758-65, 2010.
13. Kaplan MA, Isikdogan A, Gumus M, et al.: Childhood, adolescents, and young adults (≤25 y) colorectal cancer: study of Anatolian Society of Medical Oncology. J Pediatr Hematol Oncol 35 (2): 83-9, 2013.
14. Kim G, Baik SH, Lee KY, et al.: Colon carcinoma in childhood: review of the literature with four case reports. Int J Colorectal Dis 28 (2): 157-64, 2013.
15. Poles GC, Clark DE, Mayo SW, et al.: Colorectal carcinoma in pediatric patients: A comparison with adult tumors, treatment and outcomes from the National Cancer Database. J Pediatr Surg 51 (7): 1061-6, 2016.
16. Akinkuotu AC, Maduekwe UN, Hayes-Jordan A: Surgical outcomes and survival rates of colon cancer in children and young adults. Am J Surg 221 (4): 718-724, 2021.

Special Considerations for the Treatment of Children With Cancer

Cancer in children and adolescents is rare, although the overall incidence has been slowly increasing since 1975.[1] Children and adolescents with cancer should be referred to medical centers that have a multidisciplinary team of cancer specialists with experience treating the cancers that occur during childhood and adolescence. This multidisciplinary team approach incorporates the skills of the following pediatric specialists and others to ensure that children receive treatment, supportive care, and rehabilitation that will achieve optimal survival and quality of life:

• Primary care physicians.
• Pediatric surgeons.
• Pathologists.
• Pediatric radiation oncologists.
• Pediatric medical oncologists and hematologists.
• Ophthalmologists.
• Rehabilitation specialists.
• Pediatric oncology nurses.
• Social workers.
• Child-life professionals.
• Psychologists.
• Nutritionists.

For specific information about supportive care for children and adolescents with cancer, see the summaries on Supportive and Palliative Care.

The American Academy of Pediatrics has outlined guidelines for pediatric cancer centers and their role in the treatment of children and adolescents with cancer.[2] At these centers, clinical trials are available for most types of cancer that occur in children and adolescents, and the opportunity to participate is offered to most patients and their families. Clinical trials for children and adolescents diagnosed with cancer are generally designed to compare potentially better therapy with current standard therapy. Other types of clinical trials test novel therapies when there is no standard therapy for a cancer diagnosis. Most of the progress in identifying curative therapies for childhood cancers has been achieved through clinical trials. Information about ongoing clinical trials is available from the NCI website.

Dramatic improvements in survival have been achieved for children and adolescents with cancer. Between 1975 and 2020, childhood cancer mortality decreased by more than 50%.[3,4,5] Childhood and adolescent cancer survivors require close monitoring because side effects of cancer therapy may persist or develop months or years after treatment. For information about the incidence, type, and monitoring of late effects in childhood and adolescent cancer survivors, see Late Effects of Treatment for Childhood Cancer.

Childhood cancer is a rare disease, with about 15,000 cases diagnosed annually in the United States in individuals younger than 20 years.[6] The U.S. Rare Diseases Act of 2002 defines a rare disease as one that affects populations smaller than 200,000 people in the United States. Therefore, all pediatric cancers are considered rare.

The designation of a rare tumor is not uniform among pediatric and adult groups. In adults, rare cancers are defined as those with an annual incidence of fewer than six cases per 100,000 people. They account for up to 24% of all cancers diagnosed in the European Union and about 20% of all cancers diagnosed in the United States.[7,8] In children and adolescents, the designation of a rare tumor is not uniform among international groups, as follows:

• A consensus effort between the European Union Joint Action on Rare Cancers and the European Cooperative Study Group for Rare Pediatric Cancers estimated that 11% of all cancers in patients younger than 20 years could be categorized as very rare. This consensus group defined very rare cancers as those with annual incidences of fewer than two cases per 1 million people. However, three additional histologies (thyroid carcinoma, melanoma, and testicular cancer) with incidences of more than two cases per 1 million people were also included in the very rare group due to a lack of knowledge and expertise in the management of these tumors.[9]
• The Children's Oncology Group defines rare pediatric cancers as those listed in the International Classification of Childhood Cancer subgroup XI, which includes thyroid cancers, melanomas and nonmelanoma skin cancers, and multiple types of carcinomas (e.g., adrenocortical carcinomas, nasopharyngeal carcinomas, and most adult-type carcinomas such as breast cancers and colorectal cancers).[10] These diagnoses account for about 5% of the cancers diagnosed in children aged 0 to 14 years and about 27% of the cancers diagnosed in adolescents aged 15 to 19 years.[4]

  Most cancers in subgroup XI are either melanomas or thyroid cancers, with other cancer types accounting for only 2% of the cancers diagnosed in children aged 0 to 14 years and 9.3% of the cancers diagnosed in adolescents aged 15 to 19 years.

These rare cancers are extremely challenging to study because of the relatively few patients with any individual diagnosis, the predominance of rare cancers in the adolescent population, and the low number of clinical trials for adolescents with rare cancers.

Information about these tumors may also be found in sources relevant to adults with cancer, such as Colon Cancer Treatment and Rectal Cancer Treatment.

References:

1. Smith MA, Seibel NL, Altekruse SF, et al.: Outcomes for children and adolescents with cancer: challenges for the twenty-first century. J Clin Oncol 28 (15): 2625-34, 2010.
2. American Academy of Pediatrics: Standards for pediatric cancer centers. Pediatrics 134 (2): 410-4, 2014. Also available online. Last accessed August 23, 2024.
3. Smith MA, Altekruse SF, Adamson PC, et al.: Declining childhood and adolescent cancer mortality. Cancer 120 (16): 2497-506, 2014.
4. National Cancer Institute: NCCR*Explorer: An interactive website for NCCR cancer statistics. Bethesda, MD: National Cancer Institute. Available online. Last accessed August 23, 2024.
5. Surveillance Research Program, National Cancer Institute: SEER*Explorer: An interactive website for SEER cancer statistics. Bethesda, MD: National Cancer Institute. Available online. Last accessed March 6, 2024.
6. Ward E, DeSantis C, Robbins A, et al.: Childhood and adolescent cancer statistics, 2014. CA Cancer J Clin 64 (2): 83-103, 2014 Mar-Apr.
7. Gatta G, Capocaccia R, Botta L, et al.: Burden and centralised treatment in Europe of rare tumours: results of RARECAREnet-a population-based study. Lancet Oncol 18 (8): 1022-1039, 2017.
8. DeSantis CE, Kramer JL, Jemal A: The burden of rare cancers in the United States. CA Cancer J Clin 67 (4): 261-272, 2017.
9. Ferrari A, Brecht IB, Gatta G, et al.: Defining and listing very rare cancers of paediatric age: consensus of the Joint Action on Rare Cancers in cooperation with the European Cooperative Study Group for Pediatric Rare Tumors. Eur J Cancer 110: 120-126, 2019.
10. Pappo AS, Krailo M, Chen Z, et al.: Infrequent tumor initiative of the Children's Oncology Group: initial lessons learned and their impact on future plans. J Clin Oncol 28 (33): 5011-6, 2010.

Treatment of Childhood Colorectal Cancer

Most pediatric patients with colorectal cancer present with evidence of metastatic disease,[1] either as gross tumor or as microscopic deposits in lymph nodes, on the surface of the bowel, or on intra-abdominal organs.[2,3]

Treatment options for childhood colorectal cancer include the following:

1. Surgery.
2. Radiation therapy and chemotherapy.
3. Other agents.

Surgery

Complete surgical excision is the most important prognostic factor and the primary goal of surgery, but it is often impossible. Removal of large portions of tumor provides little benefit for those with extensive metastatic disease.[4] Most patients with microscopic metastatic disease generally develop gross metastatic disease. Few individuals with metastatic disease at diagnosis become long-term survivors.

Radiation Therapy and Chemotherapy

Current therapy includes the use of radiation for rectal and lower colon tumors, in conjunction with chemotherapy using fluorouracil (5-FU) with leucovorin.[5] Other agents, including irinotecan, may be of value.[1][Level of evidence C1]

A review of nine clinical trials involving 138 patients younger than 40 years demonstrated that the use of combination chemotherapy improved progression-free survival and overall survival (OS) in these patients. Furthermore, OS and response rates to chemotherapy were similar to those observed in older patients.[6][Level of evidence B4]

No significant benefit has been determined for interferon-alfa given in conjunction with 5-FU/leucovorin.[7]

Other Agents

No prospective pediatric clinical trials have been conducted using checkpoint inhibitors. However, the U.S. Food and Drug Administration has granted accelerated approval to nivolumab for patients aged 12 years and older with microsatellite instability-high (MSI-H) or mismatch repair deficient metastatic colorectal cancer that has progressed following treatment with combination fluoropyrimidine, oxaliplatin, and irinotecan. This approval was based on extrapolation of the results of the CheckMate 142 trial. The trial showed an objective response rate of 31% and a disease control rate of 69% in patients with MSI-H or mismatch repair deficient colorectal cancers that had progressed after a regimen of fluoropyrimidine, oxaliplatin, and irinotecan.[8]

Pembrolizumab has also been approved for adult and pediatric patients with unresectable or metastatic MSI-H or mismatch repair deficient cancer, including colorectal cancer that has progressed after fluoropyrimidine, oxaliplatin, and irinotecan therapy. This approval was based on the KEYNOTE-164 trial, which demonstrated an objective response rate of 33% in patients with MSI-H or mismatch repair deficient metastatic colorectal cancer.[9] The approval was also based on the results of the KEYNOTE-117 trial, which included 307 treatment-naive patients with MSI-H or mismatch repair deficient colorectal cancer who were randomly assigned to receive pembrolizumab or a 5-FU–containing regimen. The trial showed that pembrolizumab was superior to chemotherapy, with respect to progression-free survival (median, 16.5 vs. 8.2 months; hazard ratio, 0.60; 95% confidence interval, 0.45–0.80; P = .0002).[10]

Other active agents used in adults include oxaliplatin, bevacizumab, panitumumab, cetuximab, aflibercept, and regorafenib.[11,12,13,14]

References:

1. Hill DA, Furman WL, Billups CA, et al.: Colorectal carcinoma in childhood and adolescence: a clinicopathologic review. J Clin Oncol 25 (36): 5808-14, 2007.
2. Ferrari A, Rognone A, Casanova M, et al.: Colorectal carcinoma in children and adolescents: the experience of the Istituto Nazionale Tumori of Milan, Italy. Pediatr Blood Cancer 50 (3): 588-93, 2008.
3. Chantada GL, Perelli VB, Lombardi MG, et al.: Colorectal carcinoma in children, adolescents, and young adults. J Pediatr Hematol Oncol 27 (1): 39-41, 2005.
4. Saab R, Furman WL: Epidemiology and management options for colorectal cancer in children. Paediatr Drugs 10 (3): 177-92, 2008.
5. Madajewicz S, Petrelli N, Rustum YM, et al.: Phase I-II trial of high-dose calcium leucovorin and 5-fluorouracil in advanced colorectal cancer. Cancer Res 44 (10): 4667-9, 1984.
6. Blanke CD, Bot BM, Thomas DM, et al.: Impact of young age on treatment efficacy and safety in advanced colorectal cancer: a pooled analysis of patients from nine first-line phase III chemotherapy trials. J Clin Oncol 29 (20): 2781-6, 2011.
7. Wolmark N, Bryant J, Smith R, et al.: Adjuvant 5-fluorouracil and leucovorin with or without interferon alfa-2a in colon carcinoma: National Surgical Adjuvant Breast and Bowel Project protocol C-05. J Natl Cancer Inst 90 (23): 1810-6, 1998.
8. Overman MJ, McDermott R, Leach JL, et al.: Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142): an open-label, multicentre, phase 2 study. Lancet Oncol 18 (9): 1182-1191, 2017.
9. Le DT, Kim TW, Van Cutsem E, et al.: Phase II Open-Label Study of Pembrolizumab in Treatment-Refractory, Microsatellite Instability-High/Mismatch Repair-Deficient Metastatic Colorectal Cancer: KEYNOTE-164. J Clin Oncol 38 (1): 11-19, 2020.
10. André T, Shiu KK, Kim TW, et al.: Pembrolizumab in Microsatellite-Instability-High Advanced Colorectal Cancer. N Engl J Med 383 (23): 2207-2218, 2020.
11. Saltz LB, Clarke S, Díaz-Rubio E, et al.: Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol 26 (12): 2013-9, 2008.
12. Heinemann V, von Weikersthal LF, Decker T, et al.: FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3): a randomised, open-label, phase 3 trial. Lancet Oncol 15 (10): 1065-75, 2014.
13. Van Cutsem E, Tabernero J, Lakomy R, et al.: Addition of aflibercept to fluorouracil, leucovorin, and irinotecan improves survival in a phase III randomized trial in patients with metastatic colorectal cancer previously treated with an oxaliplatin-based regimen. J Clin Oncol 30 (28): 3499-506, 2012.
14. Grothey A, Van Cutsem E, Sobrero A, et al.: Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet 381 (9863): 303-12, 2013.

Treatment Options Under Clinical Evaluation for Childhood Colorectal Cancer

Information about National Cancer Institute (NCI)–supported clinical trials can be found on the NCI website. For information about clinical trials sponsored by other organizations, see the ClinicalTrials.gov website.

Latest Updates to This Summary (08 / 27 / 2024)

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

This summary was comprehensively reviewed.

This summary is written and maintained by the PDQ Pediatric Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® Cancer Information for Health Professionals pages.

About This PDQ Summary

Purpose of This Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of pediatric colorectal cancer. It is intended as a resource to inform and assist clinicians in the care of their patients. It does not provide formal guidelines or recommendations for making health care decisions.

Reviewers and Updates

This summary is reviewed regularly and updated as necessary by the PDQ Pediatric Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).

Board members review recently published articles each month to determine whether an article should:

• be discussed at a meeting,
• be cited with text, or
• replace or update an existing article that is already cited.

Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.

The lead reviewers for Childhood Colorectal Cancer Treatment are:

• Denise Adams, MD (Children's Hospital Boston)
• Karen J. Marcus, MD, FACR (Dana-Farber Cancer Institute/Boston Children's Hospital)
• William H. Meyer, MD
• Paul A. Meyers, MD (Memorial Sloan-Kettering Cancer Center)
• Thomas A. Olson, MD (Aflac Cancer and Blood Disorders Center of Children's Healthcare of Atlanta - Egleston Campus)
• Alberto S. Pappo, MD (St. Jude Children's Research Hospital)
• D. Williams Parsons, MD, PhD (Texas Children's Hospital)
• Arthur Kim Ritchey, MD (Children's Hospital of Pittsburgh of UPMC)
• Carlos Rodriguez-Galindo, MD (St. Jude Children's Research Hospital)
• Stephen J. Shochat, MD (St. Jude Children's Research Hospital)

Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website's Email Us. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.

Levels of Evidence

Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Pediatric Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.

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The preferred citation for this PDQ summary is:

PDQ® Pediatric Treatment Editorial Board. PDQ Childhood Colorectal Cancer Treatment. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/types/colorectal/hp/child-colorectal-treatment-pdq. Accessed <MM/DD/YYYY>. [PMID: 31661210]

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Last Revised: 2024-08-27