- Email: [email protected]
Re: Enzalutamide in Metastatic Prostate Cancer before Chemotherapy
PROSTATE CANCER
1419
Re: Enzalutamide in Metastatic Prostate Cancer before Chemotherapy T. M. Beer, A. J. Armstrong, D. E. Rathkopf, Y. Loriot, C. N. Sternberg, C. S. Higano, P. Iversen, S. Bhattacharya, J. Carles, S. Chowdhury, I. D. Davis, J. S. de Bono, C. P. Evans, K. Fizazi, A. M. Joshua, C. S. Kim, G. Kimura, P. Mainwaring, H. Mansbach, K. Miller, S. B. Noonberg, F. Perabo, D. Phung, F. Saad, H. I. Scher, M. E. Taplin, P. M. Venner and B. Tombal; PREVAIL Investigators Knight Cancer Institute, Oregon Health and Science University, Portland, Oregon N Engl J Med 2014; 371: 424e433.
Abstract available at http://jurology.com/ Editorial Comment: The authors report the long awaited results of PREVAIL (Safety and Efficacy Study of Oral MDV3100 in Chemotherapy-Na€ıve Patients with Progressive Metastatic Prostate Cancer), evaluating the efficacy of enzalutamide before chemotherapy in the treatment of metastatic prostate cancer progressing on androgen deprivation. The study demonstrates a delay in radiological progression and time to initiation of chemotherapy. This is the second hormonal agent to demonstrate such effects in the chemotherapy na€ıve patient, the first being abiraterone. Unlike abiraterone, an inhibitor of androgen synthesis, enzalutamide works through blockade of the androgen receptor, prevention of nuclear translocation and interference with binding of transcriptional coactivators. Clinically the major notable difference may be in the fact that enzalutamide does not require the addition of steroids, making it easier for the urologist to administer. Ultimately, given the growing number of agents available for metastatic prostate cancer, sequencing studies and guidelines will be necessary for cost containment. Samir S. Taneja, MD
Re: Indications for Intervention during Active Surveillance of Prostate Cancer: A Comparison of the Johns Hopkins and Prostate Cancer Research International Active Surveillance (PRIAS) Protocols M. Kates, J. J. Tosoian, B. J. Trock, Z. Feng, H. B. Carter and A. W. Partin James Buchanan Brady Urological Institute, Johns Hopkins Medical Institutions, Baltimore, Maryland BJU Int 2014; Epub ahead of print.
Abstract available at http://jurology.com/ Editorial Comment: In this article the authors compare cancer reclassification rates using the standard active surveillance protocol of annual biopsy with a modified regimen of biopsy at years 1, 4 and 7, or as indicated by prostate specific antigen doubling time of surveillance, as is currently being tested in the PRIAS (Prostate Cancer Research International Active Surveillance) trial. The authors conclude that use of the modified surveillance protocol would have resulted in a median 1.9-year delay in reclassification of 16% of cases. They also note that the prostate specific antigen doubling time cutoff used in PRIAS would have resulted in intervention in a subset of cases that would not have been upgraded on the next biopsy in a standard surveillance protocol. The article illustrates that more sampling will result in a higher rate of reclassification to greater risk in men with known cancer. However, the clinical significance of this finding is hard to quantify. There is no compelling evidence that a delay of 1.9 years in determination of need for therapy would greatly affect treatment efficacy. Additionally the definition of reclassification must draw some concern. In this instance it is not just upgrading, but also an increase in core disease volume in men with Gleason 3 þ 3 disease that prompts intervention. With growing suspicion that Gleason 3 þ 3 tumors rarely, if ever, metastasize, regardless of disease volume, the clinical significance of this reclassification is suspect. Most importantly, the article illustrates the need for correct baseline risk stratification to avoid repetitive biopsy. There is no doubt that our patients, and our health care system, would benefit
1419
Re: Enzalutamide in Metastatic Prostate Cancer before Chemotherapy T. M. Beer, A. J. Armstrong, D. E. Rathkopf, Y. Loriot, C. N. Sternberg, C. S. Higano, P. Iversen, S. Bhattacharya, J. Carles, S. Chowdhury, I. D. Davis, J. S. de Bono, C. P. Evans, K. Fizazi, A. M. Joshua, C. S. Kim, G. Kimura, P. Mainwaring, H. Mansbach, K. Miller, S. B. Noonberg, F. Perabo, D. Phung, F. Saad, H. I. Scher, M. E. Taplin, P. M. Venner and B. Tombal; PREVAIL Investigators Knight Cancer Institute, Oregon Health and Science University, Portland, Oregon N Engl J Med 2014; 371: 424e433.
Abstract available at http://jurology.com/ Editorial Comment: The authors report the long awaited results of PREVAIL (Safety and Efficacy Study of Oral MDV3100 in Chemotherapy-Na€ıve Patients with Progressive Metastatic Prostate Cancer), evaluating the efficacy of enzalutamide before chemotherapy in the treatment of metastatic prostate cancer progressing on androgen deprivation. The study demonstrates a delay in radiological progression and time to initiation of chemotherapy. This is the second hormonal agent to demonstrate such effects in the chemotherapy na€ıve patient, the first being abiraterone. Unlike abiraterone, an inhibitor of androgen synthesis, enzalutamide works through blockade of the androgen receptor, prevention of nuclear translocation and interference with binding of transcriptional coactivators. Clinically the major notable difference may be in the fact that enzalutamide does not require the addition of steroids, making it easier for the urologist to administer. Ultimately, given the growing number of agents available for metastatic prostate cancer, sequencing studies and guidelines will be necessary for cost containment. Samir S. Taneja, MD
Re: Indications for Intervention during Active Surveillance of Prostate Cancer: A Comparison of the Johns Hopkins and Prostate Cancer Research International Active Surveillance (PRIAS) Protocols M. Kates, J. J. Tosoian, B. J. Trock, Z. Feng, H. B. Carter and A. W. Partin James Buchanan Brady Urological Institute, Johns Hopkins Medical Institutions, Baltimore, Maryland BJU Int 2014; Epub ahead of print.
Abstract available at http://jurology.com/ Editorial Comment: In this article the authors compare cancer reclassification rates using the standard active surveillance protocol of annual biopsy with a modified regimen of biopsy at years 1, 4 and 7, or as indicated by prostate specific antigen doubling time of surveillance, as is currently being tested in the PRIAS (Prostate Cancer Research International Active Surveillance) trial. The authors conclude that use of the modified surveillance protocol would have resulted in a median 1.9-year delay in reclassification of 16% of cases. They also note that the prostate specific antigen doubling time cutoff used in PRIAS would have resulted in intervention in a subset of cases that would not have been upgraded on the next biopsy in a standard surveillance protocol. The article illustrates that more sampling will result in a higher rate of reclassification to greater risk in men with known cancer. However, the clinical significance of this finding is hard to quantify. There is no compelling evidence that a delay of 1.9 years in determination of need for therapy would greatly affect treatment efficacy. Additionally the definition of reclassification must draw some concern. In this instance it is not just upgrading, but also an increase in core disease volume in men with Gleason 3 þ 3 disease that prompts intervention. With growing suspicion that Gleason 3 þ 3 tumors rarely, if ever, metastasize, regardless of disease volume, the clinical significance of this reclassification is suspect. Most importantly, the article illustrates the need for correct baseline risk stratification to avoid repetitive biopsy. There is no doubt that our patients, and our health care system, would benefit