An Uncharted Path of Metastasis: A Case Report of Sigmoid Colon Cancer with Synchronous Vaginal and Urethral Spread

<b>Background and Objective:</b> Colorectal cancer (CRC) most commonly metastasizes to the liver and lungs; however, synchronous metastases to pelvic structures such as the vagina and urethra are extremely rare, posing a significant diagnostic and therapeutic challenge. This report describes an unusual case of sigmoid colon adenocarcinoma with synchronous metastases to the vagina and urethra, highlighting its diagnostic evaluation and the value of a multidisciplinary approach. <b>Methods:</b> A 59-year-old woman with a history of deep vein thrombosis treated with apixaban presented with chronic constipation and pelvic bleeding. A gynecological evaluation revealed a vaginal lesion. A colonoscopy, biopsy, pelvic magnetic resonance imaging, and molecular profiling were performed. Treatment included chemotherapy (capecitabine and oxaliplatin), panitumumab, and pelvic radiotherapy. <b>Results:</b> The biopsy confirmed a moderately differentiated invasive adenocarcinoma in the sigmoid colon with synchronous metastases to the vagina and urethra. Molecular profiling identified a <i>rat sarcoma virus oncogene</i> and <i>BRAF (B-Raf proto-oncogene</i>), allowing for the use of targeted therapy. The patient achieved a complete response according to RECIST 1.1 criteria and significant symptomatic improvement, including pain reduction, although dosages were adjusted for thrombocytopenia. She is currently continuing palliative treatment with good tolerance and durable symptomatic improvement. <b>Conclusions:</b> This case underscores the need to consider unusual metastatic sites in patients with colorectal cancer presenting with gynecological symptoms. Early diagnosis, based on imaging and histology, alongside molecular characterization, is crucial for effective personalized therapy. Multidisciplinary coordination is key to optimizing clinical outcomes in these rare metastatic presentations.