Management of Metastatic Colorectal Cancer in Pregnancy: A Systematic Review of a Multidisciplinary Challenge

Background: The global incidence of colorectal cancer (CRC) in patients under 50 years of age, also referred to as "early-onset" CRC (EO-CRC), has increased significantly in recent decades. According to current projections, CRC is expected to become the leading cause of cancer-related deaths among individuals aged 20-49 by 2030. The American Cancer Society noted a significant rise in the proportion of CRC cases in adults under 55, increasing from 11% in 1995 to 20% by 2019. Furthermore, the incidence of EO-CRC is projected to surge by over 140% by 2030. At the same time, there has been a trend in industrialized countries towards a later age at first childbirth. In 2022, the mean age of women at the birth of their first child was over 30 years in seven EU Member States. Given those trends, an increase in gestational CRC diagnoses is anticipated, but the number of reports on the treatment of CRC during pregnancy is very limited. Aim: Due to bioethical concerns and the rarity of the condition, there is a lack of clinical studies and evidence-based guidelines. In this context, we conducted a literature review of the published case reports and series on patients diagnosed with metastatic CRC during pregnancy and complemented the results with an illustrative case from our institution. We aimed to summarize the current knowledge on the treatment of CRC during pregnancy and to advance the discussion on optimal therapeutic approaches in this complex clinical situation. Methods: A comprehensive literature review was conducted using PubMed, MEDLINE, and Embase to identify studies and case reports on metastatic CRC during pregnancy, focusing on therapeutic interventions and clinical outcomes. Articles published between 1990 and 2024 were screened; studies where treatment was initiated postpartum were excluded. Data on patient characteristics, treatment, and outcomes were extracted and synthesized narratively due to heterogeneity in study designs. An anonymized illustrative case was constructed from a retrospective analysis of patient records. Results: Our literature review identified 26 cases of metastatic CRC during pregnancy, reported in both case reports and case series. The primary symptoms at diagnosis were abdominal pain, constipation, and rectal bleeding. Most cases involved hepatic metastases, with some reports noting additional pulmonary, peritoneal, or ovarian spread. Chemotherapy, including FOLFOX and FOLFIRI regimens, was administered in many cases during pregnancy, with mixed outcomes. Several reports documented normal child development and maternal survival, while others noted adverse outcomes such as stillbirth, small-for-gestational-age infants, and maternal mortality. Surgical intervention was performed in select cases, with varying maternal and fetal outcomes. Conclusion: Although data on the treatment of metastatic CRC during pregnancy are limited, it is essential to consider both the efficacy of chemotherapy and radiotherapy complementary to a surgical approach, as well as the potential for fetotoxicity. This literature review and our illustrative case demonstrate that an adapted, yet guideline-based therapy can be feasible depending on the clinical situation. Treatment in such complex cases should be multidisciplinary and conducted in specialized centers with the capacity to manage these cases effectively. This collaborative approach can ensure optimal outcomes for both the mother and the child, even in metastatic disease stage.