Resistance to Luteinizing Hormone Releasing Hormone Agonist Therapy for Metastatic Prostate Cancer

Abstract

A 49-year-old man with biopsy confirmed adenocarcinoma of the prostate presented with a serum prostate specific antigen (PSA) concentration of 79 ng./ml. (normal 0 to 4) and metastatic disease on bone scan. Therapy was initiated with a 7.5 mg. depot injection of leuprolide, which was preceded by 3 days of 50 mg. bicalutamide orally per day. One month after initiation of leuprolide therapy, the patient reported impotence and a decrease in obstructive urinary frequency. Serum PSA at that time was 6.3 ng./ml. Therapy was continued with a 30 mg. injection of leuprolide once every 4 months. After approximately 6 months of hormonal therapy, the patient reported that penile erections and obstructive urinary symptoms had started to recur, similar to the symptoms at initial presentation. Laboratory values at that time showed a serum testosterone of 68 ng./dl. (normal 300 to 1,100) and a PSA of 14.3 ng./ml. The patient was started on a regimen of 1, 10.8 mg. goserelin implant every 12 weeks. It is noteworthy that at that time he reported persistent redness and skin breakdown at the depot leuprolide injection site. Upon physical examination the buttock lesion was notable for redness and induration measuring 5.75 by 3 cm. Plastic surgery with a wide excision was used to debride a necrotic sterile abscess. Seven months after starting treatment PSA was 33.9 ng./ ml. and physical examination was notable for a large firm mass replacing the prostate. The area around the goserelin injection site was erythematous, and the patient complained of hot flashes and reported occasional early morning erections. Due to the clinical symptoms of ineffective testosterone ablation, serum total testosterone, follicle-stimulating hormone and luteinizing hormone concentrations were obtained, which were 433 ng./dl., 6.6 mIU/ml. (normal 1 to 12), and 4.1 mIU/ml. (normal 2 to 12), respectively. Due to ineffective chemical castration with both forms of LH-RH agonist therapy, bilateral orchiectomy was performed on September 24, 2001. Postoperatively the patient was asymptomatic and PSA decreased to 6.7 ng./ml. DISCUSSION