New developments in castrate-resistant prostate cancer

Castrate-resistant prostate cancer (CRPC) occurs when disease progresses in the presence of castrate levels of androgens and remains sensitive to further hormonal manipulation. For many years the treatment of CRPC was limited to the use of docetaxel for metastatic disease. However, this has recently changed with the approval of several new agents. Sipuleucel-T, an immunotherapeutic vaccine, is now available in the US for patients with non-metastatic CRPC and abiraterone, an oral enzyme inhibitor of androgen biosynthesis, as well as cabazitaxel, a cytotoxic chemotherapeutic, have been approved for the treatment of metastatic CRPC. Also, denosumab, a subcutaneous antibody, is now an option for the treatment of patients with CRPC with bone metastases, in addition to zoledronic acid, an intravenous bisphosphonate. Further treatment advances for metastatic CRPC therapeutics are in late stage phase III development. These include therapies affecting the androgen receptor (MDV3100) as well as additional immune-based therapeutics, PROSTVAC and ipilimumab. A broad range of agents is also emerging under the term targeted therapies. The endothelin-A receptor antagonist zibotentan, the tyrosine kinase inhibitors dasatinib, sorafenib and cabozantinib, the anti-angiogenic agent aflibercept, and the clusterin inhibitor custirsen, are all currently being tested for efficacy in metastatic CRPC. The mechanism of action of these and other promising agents are discussed alongside current therapeutic options and their potential place in the treatment landscape for CRPC is considered

Richtlijn 'prostaatcarcinoom: Diagnostiek en behandeling'

- A national, multidisciplinary practice guideline was developed concerning diagnosis and treatment of patients with prostate cancer. Because of the lack of sufficient scientific evidence at this moment no practice guideline on screening is included. - The diagnosis of prostate cancer is made by transrectal ultrasound-guided prostate biopsies. The Gleason score is used for histological grading. - In localized prostate cancer and comorbidity 'active surveillance' is advised if the life expectancy is < 10 years. In healthy patients radical prostatectomy, external and internal radiotherapy are equivalent treatment options. The final decision is made after the patient has received adequate counselling. - In locally advanced prostate cancer in a patient with a life expectancy ≥ 10 years external beam radiotherapy is the preferred treatment whether or not in combination with hormonal therapy. - In locally recurring prostate cancer following radical prostatectomy and prostate-specific antigen (PSA) < 1.0 ng/ml salvage radiotherapy can be advised. Recurrence following external beam radiotherapy may be treated by salvage radical prostatectomy or brachytherapy in selected cases. - In metastatic prostate cancer androgen deprivation therapy is advised, i.e. surgical castration, luteinizing hormone-releasing hormone (LH-RH) analogues, or parenteral estrogens. - In hormone resistant prostate cancer palliative treatment of painful metastases is advised, e.g. painkillers, local radiotherapy, or radionuclides. The role of docetaxel-based chemotherapy should be discussed. - During follow-up PSA is determined; digital rectal examination and imaging are performed whenever indicated

Practice guideline 'prostate cancer:Diagnosis and treatment'

- A national, multidisciplinary practice guideline was developed concerning diagnosis and treatment of patients with prostate cancer. Because of the lack of sufficient scientific evidence at this moment no practice guideline on screening is included. - The diagnosis of prostate cancer is made by transrectal ultrasound-guided prostate biopsies. The Gleason score is used for histological grading. - In localized prostate cancer and comorbidity 'active surveillance' is advised if the life expectancy is &lt; 10 years. In healthy patients radical prostatectomy, external and internal radiotherapy are equivalent treatment options. The final decision is made after the patient has received adequate counselling. - In locally advanced prostate cancer in a patient with a life expectancy ≥ 10 years external beam radiotherapy is the preferred treatment whether or not in combination with hormonal therapy. - In locally recurring prostate cancer following radical prostatectomy and prostate-specific antigen (PSA) &lt; 1.0 ng/ml salvage radiotherapy can be advised. Recurrence following external beam radiotherapy may be treated by salvage radical prostatectomy or brachytherapy in selected cases. - In metastatic prostate cancer androgen deprivation therapy is advised, i.e. surgical castration, luteinizing hormone-releasing hormone (LH-RH) analogues, or parenteral estrogens. - In hormone resistant prostate cancer palliative treatment of painful metastases is advised, e.g. painkillers, local radiotherapy, or radionuclides. The role of docetaxel-based chemotherapy should be discussed. - During follow-up PSA is determined; digital rectal examination and imaging are performed whenever indicated.</p