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. 2021 Sep 7;15(2):118–124. doi: 10.1177/1753495X211041228

Colorectal cancer during pregnancy or postpartum: Case series and literature review

Jane E Rogers 1,✉, Terri L Woodard 2, Graciela MN Gonzalez 3, Arvind Dasari 4, Benny Johnson 4, Van K Morris 4, Bryan Kee 4, Eduardo Vilar 5, Y Nancy You 6, George J Chang 6, Brian Bednarski 6, John M Skibber 6, Miguel A Rodriguez-Bigas 6, Cathy Eng 4
PMCID: PMC9277731  PMID: 35845232

Abstract

Background

Colorectal cancer in young adults is on the rise. This rise combined with delayed childbearing increases the likelihood of colorectal cancer diagnosed during pregnancy or in the postpartum period.

Methods

Electronic health records were used to identify individuals with colorectal cancer in pregnancy or the postpartum period from 1 August 2007 to 1 August 2019.

Results

Forty-two cases were identified. Median age at diagnosis was 33 years. Most (93%) were diagnosed in an advanced stage (III or IV) and had left-sided colorectal cancer tumors (81%). Molecular analysis was completed in 18 (43%) women with microsatellite status available in 40 (95%). The findings were similar to historical controls. Sixty percent were diagnosed in the postpartum period. Common presenting symptoms were rectal bleeding and abdominal pain.

Conclusion

Currently there is no consensus recommendation regarding how to manage colorectal cancer during pregnancy. Given the overlapping symptoms with pregnancy, patients often present with advanced disease. We encourage all health care professionals caring for pregnant women to fully evaluate women with persistent gastrointestinal symptoms to rule out colorectal cancer.

Keywords: Colorectal neoplasm, postpartum, pregnancy, cancer, gestational

Introduction

The American Cancer Society has recently revised colorectal cancer (CRC) screening average risk guidelines to begin at 45 years old. 1 The recommendation to begin screening at a younger age is the result of recent Surveillance, Epidemiology, and End Results reports revealing an expected increase in early age CRC onset1–3. Estimated new CRC cases in individuals younger than 50 years are expected to rise substantially by the next decade. 3 With this expected rise in early-age CRC coupled with current trends of delayed childbearing to the third and fourth decades of life, CRC diagnosed during pregnancy and in the postpartum period (within 12 months of childbearing), is likely to continue to increase in incidence.4,5

Currently, CRC in pregnancy occurs in 1 in 13,000 deliveries5–7. It is reported that less than a quarter of cases are diagnosed before delivery which could lead to a delayed CRC diagnosis. 8 A delay in diagnosis is common due to overlapping symptoms with that of normal pregnancy, complicated by the expected low incidence of early-age CRC 9 . Patients often present with rectal bleeding, abdominal cramping, iron deficiency anemia, and constipation.8,10,11 Given these overlapping symptoms, it is essential for clinicians to be aware of the early symptoms of CRC in order to distinguish between the timing and characteristics of normal pregnancy and those patients showing signs of CRC that will require further assessment.

Current treatment for localized CRC in non-pregnant individuals involves multidisciplinary management including surgical oncology, medical oncology, and/or radiation oncology (radiation oncology for primary rectal tumors).12,13 Antineoplastic agents utilized in the localized setting of CRC include 5-fluorouracil (5-FU) or capecitabine, with or without oxaliplatin. In the metastatic setting, there are 19 CRC antineoplastic agents approved for use. Some of these agents have been used in pregnancy and are described in case reports or series, however the majority have no information regarding pregnancy8,10–11,14–33. Long-term outcomes of infants exposed to these cytotoxic agents are unknown. Given the rarity of CRC during pregnancy, there is no consensus opinion on the management. Here we report the outcome of 42 women with CRC diagnosed during pregnancy or in the postpartum period to add to the literature surrounding this rare but growing problem.

Materials and methods

Our study was a single-institution retrospective analysis conducted between August 2007 and August 2019. Electronic health records were reviewed for patients <50 years old, CRC diagnosis (ICD 9 or 10) code, CRC diagnosis during pregnancy or up to one year postpartum were included. Women evaluated at any time point in their disease were included. Data collection included patient characteristics (age, ethnicity, and family history) and tumor characteristics (stage, primary tumor location, sites of metastatic disease, histological grade, and molecular analysis). Pregnancy characteristics included timing of diagnosis (gestational week or postpartum), number of pregnancies, symptoms at diagnosis and presentation, infant status at birth, method of delivery and chemotherapy given during pregnancy. Progression-free survival (PFS) was determined from the start of treatment to progression. Overall survival (OS), date of diagnosis to death or at last follow up, for the entire cohort was collected.

Statistical analysis

Descriptive statistics and frequency tables were used to summarize the data. The Kaplan–Meier product-limit method (Kaplan & Meier, 1958) was used to estimate the median survival outcomes (OS, PFS). Univariate cox proportional hazards regression was used to identify any association with each of the variables and survival outcomes. Statistical analysis was performed using Stata/SE version 16.0 statistical software (Stata Corp. LP, College Station, TX).

Results

Total cases

Forty-two women were included in this analysis. Median follow-up for the entire case series was 20 months (median follow-up of 47 months for those diagnosed with stage I-III disease; median follow-up of 12 months for those diagnosed with stage IV). Our cases were predominately Caucasian and the median age was 33 years (range: 22–42 years). Most CRC cases during pregnancy occurred during the first or second pregnancy (range: 1–5); ranging from 5 weeks of gestation to 11 months postpartum; 60% of patients were diagnosed postpartum. Presenting signs and symptoms included rectal bleeding/pain, abdominal discomfort, constipation, diarrhea, nausea/vomiting, weight loss, iron-deficiency anemia, and hematuria. Most people had reported their symptoms earlier prior to their CRC diagnosis. A comparison between the period of diagnosis (pregnancy vs. postpartum) showed no statistically or clinically significant differences (Table 1).

Table 1.

Summary statistics by diagnosis period.

Characteristic Pregnancy Postpartum p value
N % N %
Age 0.038
 N 17 25
 Median (Min–Max) 31 (24–38) 33 (24–42)
Number of presenting symptoms 0.003
 N 17 25
 Median (Min–Max) 1.00 (1–3) 2.00 (1–4)
Current pregnancy 0.802
 N 16 20
 Median (Min–Max) 2.00 (1–4) 2.00 (1–5)
Number of prior symptoms 0.447
 N 17 25
 Median (Min–Max) 1 (0–3) 1 (0–4)
Race 0.264
 Non-Caucasian 6 37.50 4 17.39
 Caucasian 10 62.50 19 82.61
Stage 0.507
 I 0 0.00 2 8.00
 II 1 5.88 0 0.00
 IIIB 6 35.29 7 28.00
 IIIC 0 0.00 2 8.00
 IV 10 58.82 14 56.00
Location 0.690
 Left 14 82.35 20 80.00
 Right 3 17.65 3 12.00
 Transverse 0 0.00 2 8.00
Current pregnancy 0.897
 1 4 25.00 7 35.00
 2 7 43.75 7 35.00
 3 4 25.00 3 15.00
 4 1 6.25 2 10.00
 5 0 0.00 1 5.00
Family history for GI tumor 0.952
 No 9 52.94 13 52.00
 Yes 8 47.06 12 48.00
Abdominal pain at presentation 0.824
 No 11 64.71 17 68.00
 Yes 6 35.29 8 32.00
Rectal pain or bleeding at presentation 0.089
 No 12 70.59 11 44.00
 Yes 5 29.41 14 56.00
Constipation/obstructive at presentation 0.477
 No 14 82.35 17 68.00
 Yes 3 17.65 8 32.00
Diarrhea at presentation 0.260
 No 17 100.00 22 88.00
 Yes 0 0.00 3 12.00
Nausea/vomiting at presentation 0.260
 No 17 100.00 22 88.00
 Yes 0 0.00 3 12.00
Weight loss at presentation 0.999
 No 15 88.24 23 92.00
 Yes 2 11.76 2 8.00
Upper quadrant pain at presentation 0.999
 No 16 94.12 23 92.00
 Yes 1 5.88 2 8.00
Iron deficiency anemia at presentation 0.066
 No 17 100.00 19 76.00
 Yes 0 0.00 6 24.00
Histology 0.738
 Well 0 0.00 2 8.00
 Moderate 12 75.00 17 68.00
 Poor 4 25.00 6 24.00
Molecular 0.126
 MSI/dMMR 5 33.33 3 12.00
 MSS/pMMR 10 66.67 22 88.00
RAS 0.638
 WT 2 33.33 6 50.00
 MT 4 66.67 6 50.00
BRAF 0.515
 WT 4 80.00 11 91.67
 MT 1 20.00 1 8.33
Symptoms prior to diagnosis 0.686
 No 4 26.67 4 16.67
 Yes 11 73.33 20 83.33
Prior diagnosis symptoms abdominal pain 0.694
 No 13 76.47 21 84.00
 Yes 4 23.53 4 16.00
Change in bowel habit 0.672
 No 14 82.35 22 88.00
 Yes 3 17.65 3 12.00
Prior to diagnosis rectal pain/bleeding 0.735
 No 10 58.82 16 64.00
 Yes 7 41.18 9 36.00
Prior to diagnosis upper quadrant 0.999
 No 17 100.00 24 96.00
 Yes 0 0.00 1 4.00
Prior to diagnosis nausea/vomiting 0.260
 No 17 100.00 22 88.00
 Yes 0 0.00 3 12.00
Prior to diagnosis iron deficiency anemia 0.506
 No 17 100.00 23 92.00
 Yes 0 0.00 2 8.00
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yo: years old; MSI/dMMR: microsatellite instability/deficient mismatch repair; MSS/pMMR: microsatellite stable/proficient mismatch repair; BRAF: serine/threonine-protein kinase B-Raf; GI: gastrointestinal; min: minimum; max: maximum.

Delivery outcomes

Thirty-seven (88%) patients proceeded to delivery. Two women did not have additional information; three terminated their pregnancy or had a miscarriage. CRC diagnosis for these three cases was at 8 weeks, 12 weeks, and 15 weeks of gestation. Only 22 (52%) women had a method of delivery documented with 13 (59%) delivering via cesarean while nine (41%) had vaginal deliveries. Eleven women had the timing of delivery reported, and the median gestational age at delivery of these women was 36 weeks (range: 33–40 weeks). The status of the infant was available in 15 (41%) cases. Thirteen (35%) infants were reported healthy; one infant was admitted to a neonatal intensive care unit (NICU) on delivery and one infant died at delivery. Information on the timing of delivery or reason for death in the case of infant death is unknown. The mother was diagnosed postpartum thereby the infant was never exposed to chemotherapy. The infant who was treated in the NICU was also chemotherapy naive as the mother was diagnosed at 34 weeks of gestation. Lack of documentation regarding the delivery method, timing of delivery, and infant status for all deliveries was not available in our records. In many cases, the women who gave birth to their infants did this at an outside institution.

Infant outcomes

Seven (19%) infants were exposed to 5-FU with or without oxaliplatin during the second or third trimester. Six cases received 5-FU plus oxaliplatin; one case received 5-FU alone. Information on five infants was available, and these infants were reported healthy at birth and/or met expected weight for the respective gestational age at the time of delivery. Chemotherapy discontinuation to timing of delivery was not reported. No radiation was given during pregnancy. Seven women had localized disease (stages I–III) diagnosed during pregnancy. Most women had primary CRC surgery following infant delivery. Two women underwent CRC surgery prior to delivery. One had an abdominal-perineal resection at 12 weeks of gestation and was eventually delivered via cesarean. No information was available regarding the infant and delivery date. The other woman had an open defunctioning loop transverse colostomy at 15 weeks of gestation with pregnancy termination as per the choice of the mother.

Molecular characteristics and family history

Forty women had microsatellite instability (MSI)-testing and 18 had next-generation sequencing (NGS) testing. NGS testing was low as 18 in our cases series had early-stage disease and NGS testing is not considered standard of care in this group. Most women with stage IV disease (75%; 18 out of 22) had NGS tumor testing. Molecular characteristics followed a similar trend to traditional CRC with 20% having MSI high/deficient mismatch repair, 56% rat sarcoma viral oncogene (RAS)-mutant CRC, and 12% had serine/threonine-protein kinase B-Raf mutant CRC.

Twenty (48%) women had a family history of gastrointestinal tumor. Four (10%) had a first-degree relative with a history of CRC. The remaining sixteen cases had gastrointestinal malignancies reported in second-degree relatives or distant relatives. Seven cases (17%) had a history of hereditary non-polyposis CRC (HNPCC, MSI-H). Information on other risk factors such as inflammatory bowel disease was not collected.

Patient outcomes

Ninety-three percent of the women were diagnosed with locally advanced stage III disease (lymph node positive) or metastatic disease. Most patients had a left-sided tumor and had a moderate or poorly differentiated adenocarcinoma. Of the 18 women diagnosed with stages I–III disease, six (33%) had disease recurrence with a median time to recurrence of 12.5 months (range: 7.5–21 months) at the time of data collection. Many women (n = 11) had not yet reached 3-year follow-up from their surgery.

Twenty-four women were diagnosed with mCRC. Seventeen (70%) had unresectable mCRC, and the other 7 had resectable mCRC at presentation. Five of these seven cases that had resectable mCRC (71%) had recurrent disease after metastatic resection. Median time to disease recurrence from metastatic disease resection was 8.6 months. Eight women in the metastatic group had died by the time of data collection. The median OS for those with stage IV surgically unresectable disease was only 17 months (95% confidence interval (CI): 8.5-not estimable) (Figure 1). Those with unresectable mCRC had a median PFS on first-line therapy of 5.2 months (95% CI: 2.3–7.7 months) and a median PFS on second-line therapy of 4.0 months (95% CI: 1.6–5.0) (Figures 2 and 3).

Figure 1.

Figure 1.

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Overall survival in the study patients for stage IV unresectable colorectal cancer.

Figure 2.

Figure 2.

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First-line therapy progression-free survival in the study patients for stage IV unresectable colorectal cancer.

Figure 3.

Figure 3.

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Second-line therapy progression-free survival in the study patients for stage IV unresectable colorectal cancer.

Discussion

Historically, the median age of an individual with CRC is 67 years. 34 The current rise in early-age CRC is alarming and will result in future challenges as current CRC management was based on a population of older age. Individuals with early-age CRC are often diagnosed with advanced-stage disease and more aggressive, poorly differentiated histology35–37. Lieu et al. demonstrated early-age onset mCRC was a poor prognostic factor in treatment naïve patients. 38 Our series of metastatic CRC women diagnosed during pregnancy or postpartum showed a poor median OS for women with a surgically unresectable disease of only 17 months and rapid progression of disease with a median PFS  =  5.2 months. This is in contrast to historical controls to what would be expected of a largely left-sided primary CRC patient population in which the median OS is reported to be ∼28–38 months with a first-line therapy PFS of ∼11–12 months39–41. Whether the outcomes of CRC therapy during pregnancy or postpartum are worse than those with early-age non-pregnant CRC individuals is a topic that warrants further exploration.

There have been similar recent reports by Kocian et al. 10 (41 cases), Aytec et al. 11 (eight cases), and Pellino et al. 8 (119 cases). We have summarized these similarities in Table 2. Many similarities were present among our cases and these three reviews including a median diagnosis age of early 30s, predominantly advanced stage at diagnosis, predominantly left-sided tumors, and most women lacked CRC risk factors. Our population, along with these reports, confirms that persistent rectal bleeding and persistent abdominal pain are symptoms that warrant CRC work-up when identified during pregnancy. Although our data carries limitations due to the retrospective nature, our evaluation adds to the literature of 5-FU ± oxaliplatin given during pregnancy. We reported on seven cases in which infants were given 5-FU ± oxaliplatin during pregnancy starting with the second trimester. The status of the infants was reported in five cases in which these infants were reported healthy. The retrospective nature of our reports and those seen in the literature creates limitations in knowledge particularly in the long-term consequences to these infants, if any, of 5-FU ± oxaliplatin exposure given in the second and third trimester. Additionally, our report highlights the need for a universal reporting system in real-time as retrospective case reports and series do not allow for a structure in reporting leading to varying details of the case, missing information, and inconsistency.

Table 2.

Gestational CRC case commonalities.8,10,11

Characteristic MDACC Kocian et al. Aytec et al. Pellino et al. et al.
Number of patients 42 41 8 119
Age of diagnosis 33 yo (range: 24–42) 32 yo (range: 24–43) 31 yo (range: 24–38) 32 yo (range: 17–46)
Stage at diagnosis Stage I (5%)
Stage II (2%)
Stage III (37%)
Stage IV (56%)		 Stage I (9.8%)
Stage II (17.1%)
Stage III (31.7%)
Stage IV (41.5%)		 Stage I (25%)
Stage II (0%)
Stage III (50%)
Stage IV (25%)		 Stage IV (48%)
Tumor location Right sided (14%)
Transverse (5%)
Left sided (81%)		 Right sided (15%)
Left sided (85%)		 Right sided (25%)
Left sided (75%)		 Colon (53.4%)
Rectum (44%)
Multiple sites (2.6%)
Presenting symptoms Rectal bleeding (45%)
Abdominal pain (33%)
Change in bowel habits (33%)
Iron deficiency anemia (14%)
Nausea/vomiting (7%)
Weight loss (10%)		 Rectal bleeding (46%)
Abdominal pain (17%)
Change in bowel habits (5%)
Weight loss (2.4%)
Abdominal mass (2.4%)
Right shoulder pain (2.4%)		 Rectal bleeding (75%)
Abdominal pain (25%)
Anemia (12.5%)		 Bleeding (47%)
Abdominal pain (37.6%)
Emergency presentation (25.9%)
CRC risk factors HNPCC (17%)
First degree CRC family history (9.5%)		 HNPCC (2.4%)
CRC family history (29.3%)		 HNPCC family history (25%)
Juvenile polyposis syndrome (12.5%)		 Increased risk for CRC (35%)
Infants exposed to chemotherapy 19% (n = 7) received chemotherapy during second and third trimester.

  • 6 patients received 5-FU plus oxaliplatin

  • 1 patient received 5-FU only


Infant outcomes: Information on 5 infants. Reported healthy/met expected birth weight		 29.3% (n = 12) received chemotherapy during second and third trimester.

  • 12 patients received 5-FU-based therapy

  • 5 patients received oxaliplatin with 5-FU-based therapy

Infant outcomes:
1 infant with leg length discrepancy
Authors mentioned more likely to have SGA when exposed to chemotherapy		 None 7% (n = 8) received chemotherapy starting after 19 weeks of gestation
Infant outcomes:
1 infant with hypothyroidism
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yo: years old; CRC: colorectal cancer; HNPCC: hereditary non-polyposis colorectal cancer; 5-FU: 5-fluorouracil; MDACC: U.T. M.D. Anderson Cancer Center; SGA: small for gestational age babies.

The lack of consensus opinion regarding treatment recommendations for women with CRC diagnosed during pregnancy or postpartum makes their management challenging. As we have identified at our center and through other reports, there are a substantial number of women who would benefit from the establishment of clear recommendations and guidelines. Additionally, given the young age and overlapping symptoms of pregnancy, these cases currently are often diagnosed late and at an advanced stage leading to poorer OS outcomes. We encourage clinicians to have a heightened awareness of persistent gastrointestinal symptoms and consider closer follow-up for women having persistent gastrointestinal symptoms postpartum. Pathogenesis for the development of CRC during pregnancy or postpartum remains unknown; however, the role of estrogen, progesterone, and cyclooxygenase enzyme have been theorized. 9 Work-up and treatment presents the challenging dilemma of balancing both maternal and fetal health.

Possible recommendations

When suspicious symptoms arise during pregnancy such as persistent rectal bleeding and abdominal pain, considerations for initial work-up should include carcinoembryonic antigen (CEA) testing and abdominal imaging. CEA appears unlikely to be increased outside the normal range during a normal pregnancy. Abdominal imaging via non-contrast magnetic resonance imaging or hepatic ultrasound is suggested as common metastatic sites are liver, lung, and peritoneal disease,42–44 and if possible a full colonoscopy. The American Society of Gastrointestinal Endoscopy (2012) published support for endoscopy in pregnancy when a strong indication exists with recommendations to delay until the second trimester if possible42,44–46. Current cases show that most tumors are left-sided giving the option for a flexible sigmoidoscopy. Postpartum testing could follow traditional CRC work-up.

General concepts for CRC management during pregnancy have been proposed, however, based on limited evidence. CRC surgery prior to 20 weeks appears to hold a similar miscarriage rate to the general population.8,44 Radiation should be avoided until postpartum and chemotherapy should be avoided until the second trimester. Agents with the most data include 5-FU with or without oxaliplatin, although data with oxaliplatin however remains limited8,10,11,14–33. Timing of fetal monitoring while receiving chemotherapy should be a multidisciplinary discussion with the treating team and the patient’s obstetrician-gynecologist dependent on the potential risks of the specific chemotherapy regimen. Vaginal deliveries can be undertaken; however, cesarean may be preferable for anterior rectal tumors.42,44 Delivery should be delayed until the fetus has adequate lung capacity. The placenta should be examined histologically in all births due metastasis to the placenta has been reported in a case.44,46 Multidisciplinary care through obstetrician-gynecologists, medical oncology, surgical oncology, and radiation oncology is of utmost importance given timing and risks of all potential therapies.

Future directions

Further reporting on infants exposed to CRC chemotherapy, particularly focused on long-term outcomes, remains warranted along with maternal CRC outcomes. With continued outcome reporting, differences present in women diagnosed with CRC during pregnancy or postpartum compared to those early-age non-pregnant individuals with CRC will hopefully be elucidated. The recognition of these cases via national treatment guidelines are needed to help establish standard recommendations similar to those for the treatment of gestational breast cancer along with long-term structured monitoring of both infants and mothers. 47

Footnotes

Declaration of conflicting interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding: The authors received no financial support for the research, authorship, and/or publication of this article.

Informed consent: A waiver of consent was granted due to minimal risk with a retrospective review.

Guarantor: Jane E Rogers.

Ethical approval: Our study was approved by the U.T. M.D. Anderson Cancer Center institutional review board.

Contributorship: JER contributed to the conceptualization, design, formal analysis, data curation, investigation, methodology, resources, supervision, manuscript writing, and final approval. TLW contributed to the conceptualization, design, investigation, methodology, supervision, manuscript writing, and final approval. GMNG contributed to the conceptualization, formal analysis, statistics, manuscript writing, and final approval. AD, BJ, BK, VKM, EV, NY, GJC, BB, JMS, and MARB contributed to the resources, provision of study materials or patients, manuscript writing, and final approval. CE contributed to the conceptualization, design, resources, provision of study materials or patients, investigation, methodology, supervision, manuscript writing, and final approval.

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