Rapid drop in serum testosterone after bilateral subcapsular orchiectomy.

Bilateral subcapsular orchiectomy was performed in six patients with metastatic prostatic carcinoma. In these patients the serum levels of testosterone were determined serially up to twenty-four hours. Castrate levels of testosterone were achieved in about two and one-half hours. This is the first published report of such a rapid decrease in serum testosterone. Castrate levels of serum testosterone using the luteinizing hormone releasing hormone (LH-RH) agonists are achieved in fourteen to twenty-one days. The relative cost of orchiectomy and LH-RH agonists, for thirty-six months, was $2,042.00 and $12,780.00, respectively. LH-RH agonists may be effective for only a year. Urologists are urged to continue using bilateral subcapsular orchiectomy and not use LH-RH agonists in the management of metastatic prostatic carcinoma.     

Implementing newer agents for the management of castrate‐resistant prostate cancer: what is known and what is needed?

Men receiving androgen‐deprivation therapy will in time develop metastatic castrate‐resistant prostate cancer (mCRPC). Whilst effective treatment options for mCRPC have traditionally been limited, new agents are becoming available. Since 2010, the number and class of agents available to treat mCRPC has increased dramatically. As such, there is a need for clear guidance on the optimum treatment and sequence of treatments for mCRPC before and after chemotherapy. This evidence‐based statement, reflecting the views of the authors, provides suggestions on the continued relevance of conventional approaches to first‐ and second‐line treatment in mCRPC, the potential role of novel treatments, and factors that may influence the choice of hormonal agents and/or chemotherapy.     

PARP inhibitors for homologous recombination-deficient prostate cancer

Introduction: Prostate adenocarcinoma represents a leading cause of cancer-related mortality. Increased emphasis on understanding the molecular basis of prostate cancer has identified a substantial burden of homologous recombination (HR) pathway mutations, which are enriched in castrate-resistant disease. This discovery has yielded novel therapeutic opportunities.

Areas covered: We will discuss the treatment of castrate-resistant prostate cancer (CRPC), with a focus on the use of poly (ADP-ribose) polymerase (PARP) inhibitors in this space. Evidence for use in HR-deficient patients will be outlined with discussion of the mechanism of action for this drug class, pathways of resistance, and approaches for expanding PARP inhibitor use to non–HR-deficient prostate cancer subgroups.

Expert opinion: PARP inhibition represents an exciting tool for management of HR-inactivated CRPC. With rapid adoption of next-generation sequencing technologies and other molecular techniques, the number of patients in this category is likely to increase. Ongoing and future investigations will be critical for improved understanding of the promise and appropriate treatment sequencing of PARP inhibition and optimal options for HR-proficient and -deficient prostate cancer populations. Questions remain about the clinical significance of monoallelic vs. biallelic HR mutations, the relevance of germline vs. somatic-only mutations, and the importance of mutations in non-canonical HR genes.     

Second-line therapy for castrate-resistant prostate cancer: a literature review

Despite a survival benefit in the first-line treatment of castrate-resistant prostate cancer (CRPC) with docetaxel, the prognosis remains limited. There are increasing options available for patients with CRPC in the second-line setting, but there is currently little consensus regarding the optimal treatment. There have been numerous phase II and retrospective studies examining second-line options in CRPC, including retreatment with docetaxel, mitoxantrone, cyclophosphamide and carboplatin, which can be associated with meaningful responses in a significant minority of patients. In 2010 three randomized trials were published or presented which demonstrated a survival benefit in the second-line setting. These included cabazitaxel compared with mitoxantrone, sipuleucel-T (immunotherapy) and abiraterone acetate versus placebo. Ongoing research in the second-line setting of CRPC to optimize treatment options, with the objectives of survival prolongation, improvement in quality of life and pain management, is still needed.     

Current paradigms and evolving concepts in metastatic castration-resistant prostate cancer

Until recently, docetaxel-based therapy represented the only therapy shown to prolong survival in patients with metastatic castration-resistant prostate cancer (mCRPC). The past year and a half has been marked by unprecedented progress in treatments for this disease. Three positive phase III clinical trials have emerged, each evaluating agents (sipuleucel-T, cabazitaxel and abiraterone) with distinct mechanisms of action. Herein, the three pivotal trials are described alongside both past and current large phase III studies conducted in this mCRPC. The overall survival for patients with mCRPC treated in current clinical trials is considerably longer than noted in the past. We note that more recent trials with older agents have also shown improved survival and discuss potential non-therapeutic biases that influence this critical measure of outcome. The necessity for utilizing randomized trials when evaluating new therapeutics is emphasized given the changing prognosis in this mCRPC.