Bone metastasis in colorectal cancer: Pathophysiology, prognostic factors, survival outcomes, and treatment strategies - A comprehensive review.

Background: Colorectal cancer ranks as the third most prevalent cancer globally, with over 1.9 million new cases and 930,000 deaths in 2020. While the liver and lungs are the most common site of colorectal cancer metastases, bone metastasis is relatively rare but clinically significant. The rarity of bone metastasis in colorectal cancer, early diagnosis challenges, and the poorly understood mechanisms underlying bone metastasis have resulted in lesser research compared to other metastatic sites of colorectal cancer. Objective: The goal of this review is to summarize pathophysiology, clinical presentation, risk and prognostic factors, survival outcomes, and treatment options for bone metastasis in colorectal cancer. Results: Bone metastasis occurred in 6 to 10 % of colorectal cancer patients, with the spine and pelvis being the most common sites. Bone metastasis from colorectal cancer may result from hematogenous dissemination and retrograde venous flow through Batson's plexus. Early diagnosis can be challenging, and Positron Emission Tomography / Computed Tomography (PET/CT) provided the best accuracy for diagnosing bone metastasis in colorectal cancer. Isolated bone metastasis, low neutrophil-to-lymphocyte ratio (NLR) (high NLR with HR: 1.54), low alkaline phosphatase levels, N0 stage colorectal cancer were associated with a better prognosis and survival. High carcinoembryonic antigen (OR: 2.368, HR: 3.300), alkaline phosphatase (OR: 6.89, HR: 2.12), and CA 19-9 levels (HR: 1.5), Lactate dehydrogenase (HR: 1.961), perineural invasion (HR: 3.457), right sided location (HR: 1.84), multiples bone metastasis sites (HR: 1.452), hypercalcemia (HR: 3.75), pathologic fracture (HR:1.91) and more than two extra-bone metastatic organs (HR: 2.357) were linked to worse prognosis. The therapeutic approach for colorectal cancer patients with bone metastasis consists of a multidisciplinary strategy including systemic chemotherapy, palliative surgery, radiotherapy and bisphosphonate. Conclusion: Early diagnosis and management of bone metastasis in colorectal cancer patients is essential to improve quality of life and survival. Further research is needed to identify methods for early detection and develop tailored treatment strategies.