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SUPPLEMENT

Management of Colorectal Carcinoma in Children


and Young Adults
John Goldberg, MD* and Wayne L. Furman, MDw

year-old age group5 and has been reported in children as


Summary: Colorectal Carcinoma (CRC) is rare in patients less than young as 9 months.2
20 years of age. Although presenting symptoms are similar to In adults, CRC is more common in developed coun-
adults, this diagnosis is rarely considered in the initial differential tries. Although the cause of this disparity is not well un-
diagnosis of young patients. We will review what is published about
derstood, dietary differences have been suggested as a major
the incidence, epidemiology, and clinical presentation of CRC in
children, adolescents and young adults. Because of its rarity in this factor. Other factors reported to be associated with an in-
age group, few pediatric oncologists will have experience with creased incidence of CRC in adults include obesity,6 a high-
CRC, and clinical trials will rarely be available. The treatment of calorie diet, high consumption and/or overcooking of red
CRC in adults is evolving rapidly and consultation with medical meat, excess alcohol consumption, sedentary lifestyle, and
oncologists experience in treating adults with CRC is essential to cigarette smoking.7 However, the disparate incidence in
develop the best treatment plan for a young patient diagnosed with developed and undeveloped countries is more likely to re-
CRC. flect complex interactions among multiple factors, including
Key Words: colorectal carcinoma, children, young adults, manage- genetics, lifestyle, and environment, as well as diet.2 Most
ment guidelines of these factors are unlikely to exert a major effect in chil-
dren. Although case series offer clues about the biological
(J Pediatr Hematol Oncol 2012;34:S76–S79) nature of CRC in patients under 20 years of age,3,8 defini-
tive conclusions cannot be drawn from the small numbers
of patients studied.
In adults, most cases of CRC occur sporadically, al-
though approximately 20% to 30% have a possible genetic
OVERVIEW cause.9 Only about 5% of patients have a well-defined in-
Although colorectal carcinoma (CRC) is the third herited genetic syndrome. The most common of these (3% to
most common cancer in adults,1 it is exceptionally rare in 5% of all patients) is hereditary nonpolyposis CRC or Lynch
children, adolescents, and young adults, with an incidence syndrome; the second most common (˜1%) is familial ad-
of only about 1 per million persons below 20 years of age enomatous polyposis (FAP) or Gardner syndrome. The re-
(Fig. 1).2 Because of the extreme rarity of the tumor in this mainder are syndromes involving hamartomatous polyps,
age group, it may be difficult to develop a treatment plan such as Peutz-Jeghers syndrome and familial juvenile poly-
when CRC is diagnosed. Pediatric case series, which are posis.4 The incidence of these well-defined genetic syndromes
limited by relatively small numbers of patients and by re- in children with CRC cannot be clearly determined from
ferral bias, cannot serve as the basis of definitive treatment available pediatric series.3,4,10–20 Because nearly every patient
recommendations.3,4 Here we will briefly review what is with FAP will eventually develop CRC if left untreated, the
known about the incidence, epidemiology, and clinical standard of care is prophylactic colectomy. However, the
presentation of CRC in children, adolescents, and young optimal timing of colectomy in children with FAP is un-
adults and summarize the clinical options described in the known.13,21 Colonic polyps appear at a median age of 16
peer-reviewed literature to provide a basis for management years22 but have been seen in children as young as 5 years.23
decisions by pediatric oncologists. The majority of children with FAP who developed CRC had
a severe polyposis phenotype (more than 1000 colonic pol-
yps).12 CRC arises from the mucosal surface of the bowel; in
INTRODUCTION adults, it usually arises from preexisting adenomas that are
In 2010, approximately 142,000 patients in the United thought to progress to invasive carcinoma in a stepwise
States were diagnosed with CRC and approximately 51,000 manner over a decade or more.5,24 The applicability of this
died of CRC.1 However, fewer than 100 cases are diagnosed model to children with CRC is unknown. There are several
each year in children, adolescents, and young adults (Fig. 1).4 factors that argue for a different pathogenesis in children: (1)
CRC accounts for 2.1% of malignancies in the 15- to 29- CRC has been seen in children as young as 9 months; (2)
premalignant adenomas are rarely seen in proximity to
Received for publication January 24, 2012; accepted February 1, 2012. sporadic CRC in children; and (3) CRC in children tends to
From the *University of Miami Miller School of Medicine, Miami, FL; be of mucinous histology.2,4
and wDepartment of Oncology, St Jude Children’s Research Hos-
pital, Memphis, TN.
Supported by grants CA23099 and by the American Lebanese Syrian
Associated Charities (ALSAC). CLINICAL PRESENTATION
The authors declare no conflict of interest. Most large series suggest that children tend to present
Reprints: Wayne L. Furman, MD, Department of Oncology, St Jude
Children’s Research Hospital, 262 Danny Thomas Place, Memphis,
with late-stage disease and mucinous histology and that they
TN 38105 (e-mail: wayne.furman@stjude.org). have a relatively poor outcome.3,4,10–12,14–20,25 However, a
Copyright r 2012 by Lippincott Williams & Wilkins recent review of data from the Surveillance, Epidemiology,

S76 | www.jpho-online.com J Pediatr Hematol Oncol  Volume 34, Supplement 2, May 2012
J Pediatr Hematol Oncol  Volume 34, Supplement 2, May 2012 Management of Colorectal Carcinoma

2500
Other cancers
Colorectal cancers

Incidence per Year per Million


2000

1500

1000

500

6.3%
1.7% 2.7% 3.8% 5.0%
0.6% 1.0%
0
<5 5–9 10–14 15–19 20–24 25–29 30–34 35–39 40–44

Age at Diagnosis (Years)


FIGURE 1. Incidence of colorectal carcinoma relative to other cancers: SEER, 1975 to 2000.5 SEER indicates Surveillance, Epidemiology,
and End Results.

and End Results (SEER) program suggests that these find- tecting lesions of mucinous histology.27 Because mucinous
ings may reflect reporting bias.5 Early signs of CRC are lesions appear to predominate in children, FDG-PET scans
difficult to distinguish from common causes of abdominal may be less helpful in these patients. Other tests to consider
complaints. Anemia, vague abdominal pain, bleeding, weight include a total colonoscopy to identify other lesions or
loss, and change in bowel habits have been reported as pre- polyps, complete blood count, blood chemistry panel with
senting complaints for children with colon cancer.2–4 In a liver enzymes, and typically a carcinoembryonic antigen
recent review of 77 children with CRC who presented to (CEA) assay. Although this antigen is useful in adults28 to
St Jude Children’s Research Hospital, patients had experienced monitor disease and predict recurrence or progression, it is
symptoms for a median of 3 months and most were anemic.3 less likely to be useful in most pediatric cases. In a study by
All of the presenting complaints are so common in pediatric Rao et al,29 CEA levels in 9 of 23 pediatric patients did not
care that the possible diagnosis of CRC may be overlooked, correspond with either residual disease or disease pro-
whereas in an older adult the same complaints would prompt gression. In a follow-up study, the same group concluded
colonoscopy; this factor may be partially responsible for data that CEA is not an effective marker for monitoring most
suggesting later-stage disease at diagnosis in children. As in children with CRC.30
most other series (summarized in Saab and Furman4), 66 of Staging guidelines for adult patients should be applied
77 patients (86%) at St Jude presented with advanced-stage to children with CRC. Currently the American Joint Com-
disease, 48 (62%) had mucinous histology, 33 (43%) had mission on Cancer guidelines (http://www.cancerstaging.
>10% signet-ring cells, and the 10-year event-free survival org/staging/posters/colon8.5x11.pdf)31 provide the most widely
estimate overall was only 17.7% ± 5.1%.3 All of these pa- used staging system.
rameters are “worse” than those reported in adults with
CRC.1,26 However, while vigilance for pediatric CRC re-
mains important, adult-type screening exams (eg, colono- MANAGEMENT RECOMMENDATIONS
scopy, routine fecal occult blood testing, and sigmoidoscopy) Only 1 small prospective clinical trial has been reported
are not likely to be cost-effective and will generally identify for CRC in pediatric patients,25 and therefore treatment
many false positives in the absence of known risk factors. recommendations must be adapted from experience in adults.
Surgery is the mainstay of treatment, and patients whose
tumors cannot be completely surgically resected are rarely
DIAGNOSIS AND STAGING cured. Resection should follow guidelines established in
Histopathologic examination of tissue is required for adults. The basic surgical principles are removal of the major
diagnosis. The procedure used to obtain tissue is best de- vascular pedicle supplying the tumor along with its lym-
termined in consultation with surgical colleagues and de- phatics, and en bloc resection of any organs or structures
pends on the patient’s clinical situation. Decisions about attached to the tumor. At least a 5 cm margin of normal
how tissue is to be obtained should take into account that bowel should be obtained on either side of the tumor to
surgery is the most important component of effective minimize the possibility of an anastomotic recurrence.32
therapy. Complete evaluation of a patient with suspected Adequate lymph node resection is imperative, as some pa-
CRC should include a chest x-ray, CT of the chest, abdo- tients with stage III tumors can be cured by surgery alone. In
men, and pelvis, and a bone scan. Barium enema is some- particular, primary and secondary draining lymph node
times used to help identify areas of concern before the echelons should be removed. The number of lymph nodes
diagnosis is made. At this point, the utility of fluorodeox- examined by the pathologist is prognostic of survival,33 and
yglucose positron emission tomography (FDG-PET) scans therefore a minimum of 12 negative lymph nodes should be
is unclear. This method appears to be less useful in de- examined to define node-negative disease.34 The surgeon

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Goldberg and Furman J Pediatr Hematol Oncol  Volume 34, Supplement 2, May 2012

must also remember that the pattern of spread of mucinous current medical literature and consult with an adult on-
CRC may be intraperitoneal. Therefore, extensive explora- cologist experienced in treating CRC before recommending
tion of the peritoneal surface, including that overlying Gerota a specific regimen.
fascia and the diaphragm, should be undertaken during
laparotomy. All peritoneal nodules should be removed if FOLLOW-UP RECOMMENDATIONS
feasible. If the diagnosis was not made preoperatively and Careful observation is recommended for the child with
CRC is found in a patient being urgently explored for an sporadic CRC who completes all planned treatment. How-
acute abdomen, the surgeon should convert the procedure to ever, few data are available to predict the risk of recurrence in
a standard colon cancer resection with excision of draining such children or the risk of second malignancies later in life.
lymphatics, which may necessitate closing the original wound Because CRC is both rare in children and extremely difficult
(eg, an appendectomy incision) and using a midline to cure, the number of survivors is small. Although to date no
approach. Cases of localized recurrence may benefit from large-scale randomized trials have documented the efficacy of
reexcision. Hyperthermic perfusion of the peritoneal cavity a standard postoperative monitoring program in adults,
after colon resection and peritonectomy has been applied in young patients have a long period of latency for relapse and
only a few cases, and there are insufficient data to recom- should undergo posttreatment screening with regular colo-
mend this approach for all patients. noscopy and radiologic evaluations at least as frequently as
Unfortunately for many children, adolescents, and recommended for adults.34,48 Screening with CEA at rea-
young adults, CRC is rarely considered in the initial dif- sonable intervals could be considered for children who had
ferential diagnosis, and therefore the initial surgical ap- high CEA levels at presentation. Although the 5-year survival
proach is often inadequate. In those cases, reexploration of estimate for early-stage colon cancer is excellent at about
the abdomen, with the goals of bowel resection with ad- 90%, patients with metastatic disease have less than a 10%
equate margins and adequate lymph node sampling, should likelihood of 5-year survival. It is not clear how long relapse
be performed at a center experienced in this type of surgery. surveillance should be continued for patients who survive
Because of the rarity of CRC in children, few pediatric metastatic pediatric CRC. The child should be followed in a
oncologists will have any substantial experience with this clinic specializing in the long-term sequelae of treatment for
disease. Consultation with medical oncologists experienced childhood cancer, regardless of other follow-up plans.
in evaluating adults with CRC is essential. The treatment
for children should be adapted from current adult treat-
ment recommendations. For stage II disease, in general the CONCLUSIONS
benefit of adjuvant chemotherapy is still being studied. CRC in children, adolescents, and young adults is rare.
Currently, adjuvant chemotherapy does not appear to im- Although presenting symptoms are similar to those in
prove survival by more than 5%.34–36 Careful observation adults, CRC is often not considered in the initial evaluation
is a reasonable recommendation for most adults who have of a young patient. Because of its rarity in children, few
no evidence of disease after resection; however, adjuvant pediatric oncologists have any substantial experience with
therapy may be recommended for those with any poor CRC, and clinical trials are rarely available. The majority
prognostic features, such as poorly differentiated histology, of reported cases present with advanced-stage disease and
perforation, T4 lesion, peritumoral lymphovascular in- have mucinous or signet-ring cell carcinomas,4 whereas
volvement, or inadequate lymph node sampling.34,35 only 5% to 15% of adults present with these histologic
As noted above, most pediatric patients with CRC subtypes.49 Treatment of young patients should be adapted
present with 1 or more of the poor prognostic features. For from adult guidelines. Surgery is the mainstay of treatment,
example, in the largest available pediatric series, the 8 chil- and patients who cannot be rendered surgically free of
dren with stage II disease had only a 37.5% ± 15% 10-year disease are rarely cured. The treatment of CRC in adults is
event-free survival estimate,3 although 5-year disease-free evolving rapidly,50 and consultation with medical oncolo-
survival is 60% to 80 + % in most adult studies.35 The best gists experienced in treating adults with CRC is essential.
option for children with CRC is participation in a clinical
trial, although this opportunity is rarely available for pedia-
tric patients with CRC. The relative prevalence of 1 or more ACKNOWLEDGMENT
negative prognostic factors at diagnosis and young age by The authors thank Sharon Naron for editorial assistance.
definition suggest that adjuvant chemotherapy be strongly
considered (and carefully discussed by the oncologist with the
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