The present study describes the case of a 71-year-old male patient that presented with generalized lymphadenopathy and a pelvic mass, but no signs of bone and visceral metastasis. Their total prostate-specific antigen level was >100 ng/ml. A biopsy of the pelvic mass, situated near the left iliac vessels, confirmed the existence of an adenocarcinoma originating from the prostate and a subsequent prostate biopsy indicated a Gleason score of 4+5. Endocrine treatment with bicalutamide and goserelin (androgen deprivation therapy) resulted in only a partial response of the left iliac metastatic lesions to the treatment. The subsequent treatment plan of androgen deprivation therapy and abiraterone plus docetaxel did not change the progression of the disease. The patient finally developed inferior vena cava syndrome. Subsequently, the patient declined both a re-biopsy of the prostate and enlarged cervical lymph nodes, and interventions by a vascular surgeon. To the best of our knowledge, the present study is the first documented case of a natural progression of metastatic prostate cancer with inferior vena cava syndrome.