UroToday - Prostate cancer has been the most common visceral malignant neoplasm in U.S. men since 1984, now accounting for one third of all such cancers. Androgen-suppressing strategies have become the mainstay for the management of advanced prostate cancer. Surgical castration is still considered the 'gold standard' for androgen deprivation therapy (ADT) against which all other treatments such as oestrogens, Luteinizing hormone-releasing hormone (LHRH) agonists, LHRH antagonists, antiandrogens are rated. While orchiectomy is a very safe and cost-effective procedure, patients are increasingly not willing to undergo this simple surgery, given the medical alternatives available because it may have a negative psychological effect; some men consider it to be an unacceptable assault on their manhood.

Testicular prostheses have been shown to reduce the psychological impact resulting from loss or absence of a testicle in those patients. In 1986, the Western Section of the American Urological Association reported the indications for implantation of a testicular prosthesis over a 10-year period, demonstrating that nearly a fifth of patients undergoing insertion of a testicular prosthesis were in men undergoing bilateral orchiectomy for advanced prostate cancer [Marshall, S. Urology. 1986;28:388-90]. However, the usage of surgical castration in the management of metastatic prostate cancer has fallen dramatically since the early 1990s, after the introduction of medical castration with LHRH analogues; thus, this indication for implantation has fallen considerably [Bodiwala D et al., Ann R Coll Surg Engl. 2007;89(4):349-353].

Zoledronic acid is a third generation nitrogen-containing bisphosphonate and it is the only bisphosphonate agent demonstrated to effectively reduce skeletal related complications and delay their onset in patients with advanced renal or prostate cancer metastatic to bone. As bisphosphonates have low intestinal absorption and can cause esophageal mucosal irritation if taken orally, formulated intravenous products are available which are well absorbed and remain active in bone for some time. However, recurrent IV infusion of zoledronic acid over 15 minutes every 3 to 4 weeks may reduce the compatibility of this treatment modality. A longer duration of action for this molecule may increase the patient acceptability since it avoids the need for frequent invasive procedures.

Implants are dosage forms that are subcutaneously placed with the aid of surgery or a hypodermic needle and are designed to release drugs over a prolonged period of time. A wide variety of drugs are good candidates for formulation as implants. In their study, Raya-Rivera et al. explored the possibility of creating a hormone releasing testicular implant that could continuously supply and maintain physiologic levels of testosterone in vivo over time [Raya-Rivera et al. World J Urol 2008;26(4):351-8.23]. The authors demonstrate that engineered cartilage testis can be created in bioreactors, can be implanted in vivo, and can release testosterone for a prolonged period.

Considering the above-mentioned facts, zoledronic acid releasing testicular prostheses can be used in the treatment of prostate cancer patients with bone metastases after bilateral orchiectomy which is the most economical treatment option and still considered as the 'gold standard' for ADT. Those prostheses would reduce both the psychological impact resulting from loss of testicles after bilateral orchiectomy and the risk of experiencing SREs with those patients. In addition, placement of zoledronic acid releasing testicular prostheses can be more feasible for patients compared to recurrent intravenous infusion of this agent. This technology has the potential to become the preferred clinical management tool for prostate cancer patients with bone metasthases after bilateral orchiectomy.

Ege Can Serefoglu, MD and M. Derya Balbay, MD as part of Beyond the Abstract on UroToday

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