Supplementary Material for: Management of Metastatic Colorectal Cancer in Pregnancy - A Systematic Review of a Multidisciplinary Challenge

The global incidence of early-onset colorectal cancer (EO-CRC) has increased significantly, with CRC projected to be the leading cause of cancer-related deaths among individuals aged 20-49 by 2030. Concurrently, a trend towards later age at first childbirth has been observed in industrialized countries, indicating a potential rise in CRC diagnoses during pregnancy. However, reports on managing metastatic CRC during pregnancy are limited. Bioethical concerns and the rarity of this condition contribute to the lack of clinical studies and evidence-based guidelines. This literature review, complemented by an illustrative case from our institution, aims to summarize existing knowledge and discuss optimal therapeutic approaches for this complex clinical scenario.

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, excluding studies where treatment was initiated postpartum. Data on patient characteristics, treatment, and outcomes were extracted and synthesized narratively due to heterogeneity in study designs. An anonymized illustrative case was constructed through a retrospective analysis of patient records.

Results
We identified 26 cases of metastatic CRC during pregnancy in the literature. Primary symptoms at diagnosis included abdominal pain, constipation, and rectal bleeding. Most cases involved hepatic metastases, with additional pulmonary, peritoneal, or ovarian spread noted in some. Chemotherapy regimens like FOLFOX and FOLFIRI were administered in many cases during pregnancy, with varying outcomes. Some 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 interventions were performed selectively, with maternal and fetal outcomes differing based on the clinical context.

Conclusion
Despite limited data on metastatic CRC treatment during pregnancy, a multidisciplinary approach that includes chemotherapy, radiotherapy, and surgical interventions, when appropriate, appears feasible. Guideline-based therapy adapted to individual clinical scenarios is crucial. Treatment in such complex cases should be managed in specialized centers equipped to address the unique challenges, ensuring optimal outcomes for both the mother and the child, even in advanced disease stages.