CANCER COMPLICATING PREGNANCY 0889-8545/98 $8.00 + .

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COLORECTAL CANCER
COMPLICATING PREGNANCY
Jeffrey S. Skilling, MD

Colorectal carcinoma is a rare but potentially fatal disease complicating

pregnancy. The first case of rectal cancer in a pregnant woman was reported by
Cruveilhier4 in 1842. The 32-year-old woman delivered a stillborn infant by
breech extraction. Four days postpartum she died and was diagnosed with a
colloid carcinoma of the rectum on autopsy. In 1928 Evers7 described the first
colon cancer occurring above the peritoneal reflection associated with pregnancy.
Because of an obstructing colloid carcinoma of the sigmoid, the 38-year-old
woman was delivered by cesarean section. Six days after giving birth to a
stillborn infant, the patient died of peritonitis. Since these initial reports, more
than 200 cases of colorectal cancer have been described in the literature.2Despite
improvements in the diagnosis and treatment of colorectal malignancies, mater-
nal mortality has remained high; however, neonatal survival has dramatically
improved. Stage-for-stage, the survival data for the pregnant patient with colo-
rectal cancer are equivalent to that for the nonpregnant control; however, gravid
women are more often diagnosed with more advanced disease? The poor prog-
nosis may be attributed to a delay in diagnosis as a result of pregnancy-
associated gastrointestinal symptoms masking cancer symptoms. Hormonal and
immune changes associated with pregnancy may allow a more rapid progression
of tumors?,'* The key to improved survival is early diagnosis and treatment,
which mandates a high degree of suspicion for this disease among clinicians
caring for pregnant women.

EPIDEMIOLOGY

Colorectal carcinoma is a common diagnosis in women; 66,800 new cases

were estimated to occur in the United States in 1997. A woman's lifetime risk

From the Department of Obstetrics and Gynecology, Division of Gynecologic Oncology,

University of California Davis School of Medicine, Sacramento, California

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OBSTETRICS AND GYNECOLOGY CLINICS OF NORTH AMERICA

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VOLUME 25 NUMBER 2 JUNE 1998 417
418 SKILLING

for the malignancy is 6% (1 in 17).16 Most of these cancers are diagnosed in

women aged 50 years or older; only 8% of cases occur before the age of 40
years, making it an uncommon complication in pregnancy.8Although the true
incidence of colorectal cancer in pregnancy is unknown, it is believed to range
from 1 in 50,000 to 1in 100,000 pregnancies.", l4 As more women choose to delay
childbirth until their late thirties and early forties, the incidence of this disease
in pregnancy may rise.6
Colorectal cancer is the third leading cause of cancer-related deaths in
women in the United States. Approximately 28,160 women died of colorectal
cancer in 1997 in the United States alone.I6Over the last 30 years, mortality from
colorectal malignancies has declined 29% in women.5,l 6 Unfortunately, mortality
from colorectal cancer in the pregnant patient remains high because of the
advanced stage at diagnosis and possibly other factors related to pregnancy?
Approximately 5% of colorectal cancers are inherited as autosomal domi-
nant traits. Individuals with familial adenomatous polyposis have mutation and
functional loss of the adenomatous polyposis coli (APC) gene, a tumor suppres-
sor gene on chromosome 5q2L3As a result, hundreds to thousands of adenoma-
tous polyps develop in the large bowel with the potential to undergo malignant
degeneration. The prevalence of this syndrome is estimated to be 1%of colorectal
carcinomas." Hereditary nonpolyposis colorectal carcinoma (HNPCC) is more
common, estimated to account for 3% to 8.5% of colorectal cancers.I2Lynch and
colleague^^^ have described two variants of the syndrome: (1)Lynch syndrome
I, in which colon carcinomas occur with a proximal colon predominance (70%)
and an excess of synchronous and metachronous primaries (45'/0), and (2) Lynch
syndrome 11, in which the same colon cancer characteristics are seen in addition
to an excess of other adenocarcinomas (endometrium, ovary, small bowel, biliary,
stomach, pancreas, and genitourinary). Abnormalities in the DNA mismatch
repair genes predispose individuals to HNPCC.I3Risk factors for the develop-
ment of colorectal cancer are listed in Table 1.

CLINICAL PROFILE

More than 80% of colorectal cancers in pregnant women occur in the rectum.
This rectal predominance is in contradistinction to the distribution of colorectal

Table 1. PREDISPOSING RISK FACTORS FOR COLORECTAL CANCER

Hereditary colon cancer syndromes
Familial adenomatous polyposis (FAP) and variants
Hereditary nonpolyposis colorectal carcinoma (HNPCC)
High-fat, low-fiber diet
Inflammatory bowel disease
Crohn's disease
Chronic ulcerative colitis
Pelvic radiation
Personal history of other malignancies
Colorectal cancer
Breast, ovary, or uterine cancer
Adenomatous polyps
Family history of colorectal cancer
Two or more first-degree relatives
 COLORECTAL CANCER COMPLICATING PREGNANCY 419

cancers in the general population. However, when lesions above the peritoneal
reflection are considered, the spatial distribution of the disease within the colon
seems to be similat2
A delay in diagnosis is common when the disease occurs in pregnancy.
Rectal bleeding often occurs with colorectal carcinomas and unfortunately is
frequently attributed to hemorrhoids. Other presenting complaints include ab-
dominal pain and distention, constipation, nausea, vomiting, and backache. The
symptoms of colorectal cancer are often overshadowed by the symptoms of
pregnancy, which is the major problem in diagnosis. Symptoms of the disease
are assumed to be secondary to the normal pregnancy.15

DIAGNOSIS

Clinicians need to have a high index of suspicion, especially in high-risk

patients. Persistent gastrointestinal tract symptoms, especially rectal bleeding
associated with mucoid diarrhea and tenesmus, warrants an investigation. Digi-
tal rectal examination, tests for occult blood, and flexible sigmoidoscopy fol-
lowed by colonoscopy are performed as indicated.8Barium enema is contraindi-
cated except in selected cases late in pregnancy.I5 Seidman and co-worker~’~
have described the use of MR imaging in the diagnosis of an intussuscepted
colon cancer in a pregnant patient. Van Voorhis and CruikshankZ2reported
persistent microcytic, hypochromic anemia from occult bleeding in two women
with colon cancer. Carcinoembryonic antigen (CEA) may be elevated owing to
pregnancy and is of little value as a diagnostic test8 However, CEA levels may
be useful as a follow-up marker once colorectal carcinoma has been diagr10sed.l~
Colorectal carcinoma in pregnancy has been detected by persistently elevated
maternal alpha-fetoprotein levels in a woman with hepatic metasta~es.~

MANAGEMENT

Surgical Therapy

The treatment of colorectal carcinoma in pregnancy is the same as in the

nonpregnant state. Surgical resection of the primary tumor and of regional
mesenteric lymph nodes is the only curative therapy. Classically, wide removal
of the cancer with a 5-cm margin from the gross tumor edge in the bowel wall
is described.6Several clinicians have outlined treatment guidelines based on the
gestational age of the fetus at diagnosis, as well as the patient’s desire for future
fertility,2,5. 8. 15. 20
During the first 20 weeks of pregnancy, the malignancy requires the first
consideration, and the patient should be treated as though she were not preg-
nant. The type of operation is dictated by the surgical findings and the patient.
The uterus, fallopian tubes, and ovaries may be resected, but this is not man-
dated. The gravid uterus will change the way in which the surgeon can handle
the bowel but not the surgical principles? In general, if greater access to the
rectum is needed or if the tumor involves the uterus, total abdominal hysterec-
tomy is performed.I5 Delivery is otherwise determined by obstetric indications.
After 20 weeks’ gestation, the pregnancy is usually allowed to continue
until viability. Vaginal delivery is the preferred mode of delivery; however, low-
lying rectal carcinomas may obstruct the birth canal. If cesarean section is
required, the tumor can be removed after delivery of the fetus. Alternatively,
420 SKILLING

the surgeon may choose to delay definitive colorectal surgery for several days,
which allows the uterus to involute and pelvic vascular congestion to decline.
This is the preferred practice following a vaginal deli~ery.'~Hemorrhage, colon
obstruction, or perforation may force surgical intervention"
Oophorectomy is recommended by some clinicians because of the high
incidence of metastases to the ovaries, especially from low-lying rectal cancers?
Macroscopic ovarian metastases with colorectal cancer have been reported to
occur with a frequency of 3% to 8%"; however, Pitluk and P o t i ~ k a 'reported
~ a
24% chance of concurrent ovarian metastases in women less than 40 years of
age. Nesbitt and co-worker~'~ recommend ovarian wedge biopsies with frozen
sections at the time of colorectal surgery. If the ovaries are involved or if the
uterus is to be removed, bilateral salpingo-oophorectomy is performed.

Staging

The depth of penetration into the bowel wall, the involvement of regional
lymph nodes, and the presence or absence of distant metastases determine the
stage of the colorectal carcinoma, which is the most important determinant of
survival. The tumor node metastases (TNM) classification system has replaced
the Dukes classification with its many modifications. Other prognostic variables
of lesser significance include histologic type, growth pattern, lymphatic and
blood vessel invasion, and DNA ploidy.' Recently, Rojansky and co-workers'8
reported on two pregnant women with colon carcinomas who overexpressed
the p53 protein. p53 tumor suppressor gene overexpression has been correlated
with a poorer prognosis in colorectal carcinoma.z1In addition, other variables
adversely affecting prognosis include ulceration of the primary tumor, fixation
to adjacent organs, colonic perforation or obstruction, younger age, and elevated
preoperative CEA.6

PROGNOSIS

The prognosis for the pregnant woman with colorectal cancer is stage for
stage the same as for the nonpregnant patient. Unfortunately, many pregnant
patients have advanced-staged lesions at diagnosis. Presentation with obstruc-
tion or perforation is not uncommon; prognosis is guarded in these patients. For
patients with distant metastases or unresectable disease, the fetus becomes the
primary concern. The patient should be a significant participant in the decision
process regarding termination or continuation of the pregnancy. Other than
masking colorectal cancer symptoms commonly attributed to the normal preg-
nant state, there is no evidence that pregnancy influences the usual course
of disease. Overall, the prognosis of infants born to mothers with colorectal
malignancies is good; the disease has no known effect on the fetus5The maternal
mortality rate from colorectal cancer diagnosed during pregnancy is at least
50%.''

References

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Address reprint requests to

Jeffrey S. Skilling, MD
Division of Gynecologic Oncology
Department of Obstetrics and Gynecology
University of California Davis
1621 Alhambra Boulevard, Suite 2500
Sacramento, CA 95816