Background: The purpose of this study was to determine the direct costs associated with the management of patients with metastatic castration resistant (mCRPC), non-metastatic (nmCRPC) and metastatic hormone-sensitive (mHSPC) prostate cancer in the Colombian healthcare system. Methods: First, a literature review was carried out to identify the main clinical recommendations for the treatment and follow-up of patients with prostate cancer at local and international levels. Subsequently, a participation process was developed with clinical experts, through a modified Delphi panel, to validate the natural history of the disease, and identify treatment options, skeletal-related events management, resource utilization, and distribution of patients within stages. Based on the above, a cost analysis model was performed, using Colombian health technology assessment agency recommendations, to calculate direct cost of treatment for mCRPC, nmCRPC and mHSPC from payer’s perspective. Exchange rate used was USD $1 = COP $4,000. Finally, the results were estimated considering the cost per patient per year. Results: According to the cost analysis of each stage, in the non-metastatic castration resistant stage (nmCRPC) the associated yearly cost of a patient was lower than in the metastatic castration resistant stage (mCRPC) (USD $8,581 versus $24,590, respectively), with a difference of USD $16,008. The metastatic hormone-sensitive stage (mHSPC) had a lower yearly cost than the metastatic castration-resistant stage (mCRPC) (USD $15,030 versus $24,590, respectively), with a difference of USD $ 9,559. The event that generated the greatest impact on the cost is the incidence of skeletal-related events associated with disease metastasis (55%). The deterministic sensitivity analysis on key variables, such as the percentage of patients who responded to treatment and the incidence of skeletal-related events, showed consistency of results. Conclusions: Delaying or stopping disease progression to mCRPC could more than halve annual treatment costs for patients. Given the findings, advanced metastatic castration resistant stages demand more resource utilization associated with disease management. The Colombian healthcare system would benefit from risk management strategies that implement timely interventions associated with early diagnosis and screening. In this way, the resource utilization in health sector's institutions would be directly impacted through budget optimization, obtaining better results focused on the national follow-up indicators of the prostate cancer patient cohort.