Zoledronic acid and denosumab can be used in men with mCRPC and osseous metastases to prevent skeletal-related complications .
PATIENT SUMMARY In men with a rise in their PSA levels after prior local treatment for prostate cancer only , it is important to balance overtreatment against further progression of the disease since survival and quality of life may never be affected in many of these patients .
OBJECTIVE To present a summary of the 2016 version of the European Association of Urology ( EAU ) - European Society for Radiotherapy & Oncology ( ESTRO ) - International Society of Geriatric Oncology ( SIOG ) Guidelines on the treatment of relapsing , metastatic , and castration-resistant prostate cancer ( CRPC ) .
EVIDENCE SYNTHESIS Relapse after local therapy is defined by a rising prostate-specific antigen ( PSA ) level > 0.2ng/ml following radical prostatectomy ( RP ) and > 2ng/ml above the nadir after radiation therapy ( RT ) .
And rogen deprivation therapy ( ADT ) remains the basis for treatment of men with metastatic prostate cancer ( PCa ) .
Level 1 evidence for the treatment of metastatic CRPC ( mCRPC ) includes , abiraterone acetate plus prednisone ( AA/P ) , enzalutamide , radium 223 ( Ra 223 ) , docetaxel at 75 mg/m2 every 3 wk and sipuleucel-T. Cabazitaxel , AA/P , enzalutamide , and radium are approved for second-line treatment of CRPC following docetaxel .
CONCLUSIONS The knowledge in the field of advanced and metastatic PCa and CRPC is changing rapidly .
AR-V7 and resistance to enzalutamide and abiraterone in prostate cancer.
BACKGROUND The and rogen-receptor isoform encoded by splice variant 7 lacks the lig and -binding domain , which is the target of enzalutamide and abiraterone , but remains constitutively active as a transcription factor . We hypothesized that detection of and rogen-receptor splice variant 7 messenger RNA ( AR-V7 ) in circulating tumor cells from men with advanced prostate cancer would be associated with resistance to enzalutamide and abiraterone . METHODS We used a quantitative reverse-transcriptase-polymerase-chain-reaction assay to evaluate AR-V7 in circulating tumor cells from prospect ively enrolled patients with metastatic castration-resistant prostate cancer who were initiating treatment with either enzalutamide or abiraterone .  We examined associations between AR-V7 status ( positive vs. negative ) and prostate-specific antigen ( PSA ) response rates ( the primary end point ) , freedom from PSA progression ( PSA progression-free survival ) , clinical or radiographic progression-free survival , and overall survival . RESULTS A total of 31 enzalutamide-treated patients and 31 abiraterone-treated patients were enrolled , of whom 39 % and 19 % , respectively , had detectable AR-V7 in circulating tumor cells . Among men receiving enzalutamide  , AR-V7-positive patients had lower PSA response rates than AR-V7-negative patients ( 0 % vs. 53 % , P=0.004 ) and shorter PSA progression-free survival ( median , 1.4 months vs. 6.0 months ; P<0.001 ) , clinical or radiographic progression-free survival ( median , 2.1 months vs. 6.1 months ; P<0.001 ) , and overall survival ( median , 5.5 months vs. not reached ; P=0.002 ) . Similarly , among men receiving abiraterone  , AR-V7-positive patients had lower PSA response rates than AR-V7-negative patients ( 0 % vs. 68 % , P=0.004 ) and shorter PSA progression-free survival ( median , 1.3 months vs. not reached ; P<0.001 ) , clinical or radiographic progression-free survival ( median , 2.3 months vs. not reached ; P<0.001 ) , and overall survival ( median , 10.6 months vs. not reached , P=0.006 ) . The association between AR-V7 detection and therapeutic resistance was maintained after adjustment for expression of full-length and rogen receptor messenger RNA . CONCLUSIONS Detection of AR-V7 in circulating tumor cells from patients with castration-resistant prostate cancer may be associated with resistance to enzalutamide and abiraterone . These findings require large-scale prospect i ve validation . ( Funded by the Prostate Cancer Foundation and others . )
Zoledronic acid and denosumab can be used in men with mCRPC and osseous metastases to prevent skeletal-related complications .
PATIENT SUMMARY In men with a rise in their PSA levels after prior local treatment for prostate cancer only , it is important to balance overtreatment against further progression of the disease since survival and quality of life may never be affected in many of these patients .
OBJECTIVE To present a summary of the 2016 version of the European Association of Urology ( EAU ) - European Society for Radiotherapy & Oncology ( ESTRO ) - International Society of Geriatric Oncology ( SIOG ) Guidelines on the treatment of relapsing , metastatic , and castration-resistant prostate cancer ( CRPC ) .
EVIDENCE SYNTHESIS Relapse after local therapy is defined by a rising prostate-specific antigen ( PSA ) level > 0.2ng/ml following radical prostatectomy ( RP ) and > 2ng/ml above the nadir after radiation therapy ( RT ) .
And rogen deprivation therapy ( ADT ) remains the basis for treatment of men with metastatic prostate cancer ( PCa ) .
Level 1 evidence for the treatment of metastatic CRPC ( mCRPC ) includes , abiraterone acetate plus prednisone ( AA/P ) , enzalutamide , radium 223 ( Ra 223 ) , docetaxel at 75 mg/m2 every 3 wk and sipuleucel-T. Cabazitaxel , AA/P , enzalutamide , and radium are approved for second-line treatment of CRPC following docetaxel .
CONCLUSIONS The knowledge in the field of advanced and metastatic PCa and CRPC is changing rapidly .