A 68-year-old man comes to the office for follow-up. The patient underwent radical prostatectomy for prostate adenocarcinoma 6 months ago, which decreased his serum prostate-specific antigen (PSA) level from 16 ng/mL at the time of surgery to 1 ng/mL 6 weeks after surgery. Initial staging evaluation revealed no evidence of metastatic disease. PSA level is now 8 ng/dL, and repeat imaging reveals regional lymphadenopathy. The patient is prescribed combination therapy with buserelin and bicalutamide. Which of the following is the main reason for adding bicalutamide to this patient's treatment regimen?

Question

A 68-year-old man comes to the office for follow-up.  The patient underwent radical prostatectomy for prostate adenocarcinoma 6 months ago, which decreased his serum prostate-specific antigen (PSA) level from 16 ng/mL at the time of surgery to 1 ng/mL 6 weeks after surgery.  Initial staging evaluation revealed no evidence of metastatic disease.  PSA level is now 8 ng/dL, and repeat imaging reveals regional lymphadenopathy.  The patient is prescribed combination therapy with buserelin and bicalutamide.  Which of the following is the main reason for adding bicalutamide to this patient's treatment regimen?

Quizplus · Accepted Answer

Prostate cancer is an androgen-dependent tumor early in the disease course. Because androgens in men are primarily made in the testes, patients with recurrent (eg, rising prostate-specific antigen level after prostatectomy) or disseminated (eg, regional lymphadenopathy) prostate cancer are generally treated with surgical or medical orchiectomy to reduce systemic androgen levels, thereby reducing the primary growth factor for the tumor. Androgen production in men is controlled by the hypothalamic-pituitary-testicular axis. GnRH is secreted by the hypothalamus in a pulsatile fashion, which stimulates pituitary gonadotrophs to release luteinizing hormone (LH); LH then stimulates the Leydig cells of the testes to generate and secrete androgens. Patients who undergo medical orchiectomy are often treated with a GnRH analogue (eg, buserelin), which stimulates the pituitary gland in a continuous fashion, leading to a down-regulation of the GnRH receptor. This subsequently drops LH secretion, which lowers androgen production by the testes. However, because GnRH analogues temporarily activate the GnRH receptor prior to downregulation, patients often develop a surge in androgens during the first few weeks of therapy. Therefore, androgen-receptor inhibitors (eg, bicalutamide) are usually concurrently administered during the first weeks of GnRH analogue therapy to block the activity of androgens on the tumor cells. (Choice A) Although adrenal synthesis of androgens is not an initial target in prostate cancer, patients who have progressive disease despite medical or surgical orchiectomy are often treated with abiraterone, which limits androgen production in the tumor, adrenal gland, and testes by inhibiting the enzyme 17alpha-hydroxylase. (Choice B) Chemotherapy is often administered with GnRH analogues in patients with metastatic prostate cancer to induce cancer cell death. However, bicalutamide is an androgen-receptor inhibitor, not a chemotherapy agent. (Choice C) Sexual dysfunction occurs in the majority of men given GnRH analogues due to reduced libido and erectile dysfunction. This can be managed with phosphodiesterase inhibitors. (Choice E) GnRH analogues often cause vasomotor symptoms (hot flashes) due to estrogen withdrawal. Treatment is similar to menopausal hot flashes in women; progesterone, cyproterone, and selective serotonin reuptake inhibitors are somewhat effective. Educational objective: Because prostate cancer is an androgen-dependent tumor, patients with advanced disease are generally treated with surgical or medical orchiectomy. Medical orchiectomy uses GnRH analogues to reduce LH production, which subsequently reduces androgen production in the testes. Because there is an initial surge in androgens at the start of therapy (due to stimulation of the GnRH receptor), patients prescribed GnRH therapy are usually treated with a few weeks of androgen-receptor inhibitors (eg, bicalutamide).

A 68-Year-Old Man Comes to the Office for Follow-Up