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Re: Androgen Receptor Splice Variant 7 and Efficacy of Taxane Chemotherapy in Patients with Metastatic Castration-Resistant Prostate Cancer
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Morote J, Gomez-Caama~no A, Alvarez-Ossorio JL et al: The metabolic syndrome and its components in patients with prostate cancer on androgen deprivation therapy. J Urol 2015; 193: 1963. Cary KC, Singla N, Cowan JE et al: Impact of androgen deprivation therapy on mental and emotional well-being in men with prostate cancer: analysis from the CaPSUREÔ registry. J Urol 2014; 191: 964.
Re: Impact of a Genomic Classifier of Metastatic Risk on Postprostatectomy Treatment Recommendations by Radiation Oncologists and Urologists P. L. Nguyen, H. Shin, K. Yousefi, D. J. Thompson, J. Hornberger, A. S. Hyatt, K. K. Badani, T. M. Morgan and F. Y. Feng Department of Radiation Oncology, Dana-Farber/Brigham and Women’s Cancer Center, and Harvard Medical School, Boston, Massachusetts, Cedar Associates, Menlo Park and Department of Medicine, Stanford University, Stanford, California, Department of Urology, Columbia University Medical Center, New York, New York, Departments of Urology and Radiation Oncology, University of Michigan, Ann Arbor, Michigan, and GenomeDx Biosciences, Vancouver and EMMES Canada, Burnaby, British Columbia, Canada Urology 2015; 86: 35e40. doi: 10.1016/j.urology.2015.04.004
Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/26142578 Editorial Comment: The use of genetic biomarkers in prostate cancer risk assessment is rapidly emerging as a routine part of clinical practice. Since the commercial inception of a number of genetic risk stratification tools, clinicians have tried to figure out how best to use the tests in determining their approach to disease. I have struggled with how best to apply genetic biomarkers in my decision making. While patients are eager to try any test that might give them more information, I would argue that it is difficult for a physician, let alone a patient, to determine if a change in risk from 20% to 30% or even 35% warrants a change in plan. Patient determination of a sufficient level of risk to produce sufficient concern for intervention is highly individualized and most likely dependent on the manner in which the findings are presented to the patient. In my experience patients rarely process such information in a meaningful way. In this study the authors evaluate the influence of a genomic classifier on the decision for adjuvant radiation therapy following radical prostatectomy. This would be an ideal setting in which more accurate risk assessment could be applied. Not surprisingly, radiation oncologists were more likely to recommend radiation than urologists, although in both instances the genomic classifier strongly influenced decision making, with the urologists recommending radiation more often and the radiation oncologists recommending radiation less often, after the genomic test results were made available. Whether such an impact would be observed in determining surgery/radiation vs surveillance in men with low risk prostate cancer is an interesting question. Samir S. Taneja, MD
Suggested Reading Glass AG, Leo MC, Haddad Z et al: Validation of a genomic classifier for predicting post-prostatectomy recurrence in a community-based healthcare setting. J Urol 2015; Epub ahead of print. Karnes RJ, Bergstralh EJ, Davicioni E et al: Validation of a genomic classifier that predicts metastasis following radical prostatectomy in an at risk patient population. J Urol 2013; 190: 2047.
Re: Androgen Receptor Splice Variant 7 and Efficacy of Taxane Chemotherapy in Patients with Metastatic Castration-Resistant Prostate Cancer E. S. Antonarakis, C. Lu, B. Luber, H. Wang, Y. Chen, M. Nakazawa, R. Nadal, C. J. Paller, S. R. Denmeade, M. A. Carducci, M. A. Eisenberger and J. Luo Departments of Oncology and Urology, Johns Hopkins University School of Medicine, Baltimore, Maryland JAMA Oncol 2015; 1: 582e591. doi: 10.1001/jamaoncol.2015.1341
Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/26181238 Dochead: Urological Survey
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Editorial Comment: In this study several emerging concepts are demonstrated regarding treatment of patients with castration resistant prostate cancer. The authors test the effectiveness of taxane chemotherapy in men with and without the androgen receptor (AR) V7 splice variant. Androgen receptors encoded by the AR-V7 splice variant messenger RNA lack an androgen binding domain but are still able to activate androgen receptor gene targets (they remain constitutively active). In other words the receptor is always active, not requiring androgen binding for activation. As such, the AR-V7 variant has been postulated to be a primary mechanism of resistance to androgen receptor targeting agents such as enzalutamide and abiraterone. If androgens are not required for receptor activation and cell growth, then targeting of androgen would be of little value. In this study men were evaluated for the AR-V7 variants through extraction and analysis of circulating tumor cells. The authors found that taxanes were equally efficacious in men with and without AR-V7 variants. In men with AR-V7 positive circulating tumor cells taxanes were superior to enzalutamide and abiraterone. In men without AR-V7 the 3 treatments were equivalent. As such, the information derived from a simple blood test could determine the need for chemotherapy in this group of men, and could spare some from a treatment unlikely to work. Samir S. Taneja, MD
Suggested Reading Small AC, Gong Y, Oh WK et al: The emerging role of circulating tumor cell detection in genitourinary cancer. J Urol 2012; 188: 21. Okegawa T, Nutahara K and Higashihara E: Prognostic significance of circulating tumor cells in patients with hormone refractory prostate cancer. J Urol 2009; 181: 1091.
Dochead: Urological Survey
LIT 5.4.0 DTD JURO13312_proof 9 February 2016 11:33 am EO:
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115 116 117 118 119 120 121 122 123 124 125 126 127 128 129 130 131 132 133 134 135 136 137 138 139 140 141 142 143 144 145 146 147 148 149 150 151 152 153 154 155 156 157 158 159 160 161 162 163 164 165 166 167 168 169 170 171
Morote J, Gomez-Caama~no A, Alvarez-Ossorio JL et al: The metabolic syndrome and its components in patients with prostate cancer on androgen deprivation therapy. J Urol 2015; 193: 1963. Cary KC, Singla N, Cowan JE et al: Impact of androgen deprivation therapy on mental and emotional well-being in men with prostate cancer: analysis from the CaPSUREÔ registry. J Urol 2014; 191: 964.
Re: Impact of a Genomic Classifier of Metastatic Risk on Postprostatectomy Treatment Recommendations by Radiation Oncologists and Urologists P. L. Nguyen, H. Shin, K. Yousefi, D. J. Thompson, J. Hornberger, A. S. Hyatt, K. K. Badani, T. M. Morgan and F. Y. Feng Department of Radiation Oncology, Dana-Farber/Brigham and Women’s Cancer Center, and Harvard Medical School, Boston, Massachusetts, Cedar Associates, Menlo Park and Department of Medicine, Stanford University, Stanford, California, Department of Urology, Columbia University Medical Center, New York, New York, Departments of Urology and Radiation Oncology, University of Michigan, Ann Arbor, Michigan, and GenomeDx Biosciences, Vancouver and EMMES Canada, Burnaby, British Columbia, Canada Urology 2015; 86: 35e40. doi: 10.1016/j.urology.2015.04.004
Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/26142578 Editorial Comment: The use of genetic biomarkers in prostate cancer risk assessment is rapidly emerging as a routine part of clinical practice. Since the commercial inception of a number of genetic risk stratification tools, clinicians have tried to figure out how best to use the tests in determining their approach to disease. I have struggled with how best to apply genetic biomarkers in my decision making. While patients are eager to try any test that might give them more information, I would argue that it is difficult for a physician, let alone a patient, to determine if a change in risk from 20% to 30% or even 35% warrants a change in plan. Patient determination of a sufficient level of risk to produce sufficient concern for intervention is highly individualized and most likely dependent on the manner in which the findings are presented to the patient. In my experience patients rarely process such information in a meaningful way. In this study the authors evaluate the influence of a genomic classifier on the decision for adjuvant radiation therapy following radical prostatectomy. This would be an ideal setting in which more accurate risk assessment could be applied. Not surprisingly, radiation oncologists were more likely to recommend radiation than urologists, although in both instances the genomic classifier strongly influenced decision making, with the urologists recommending radiation more often and the radiation oncologists recommending radiation less often, after the genomic test results were made available. Whether such an impact would be observed in determining surgery/radiation vs surveillance in men with low risk prostate cancer is an interesting question. Samir S. Taneja, MD
Suggested Reading Glass AG, Leo MC, Haddad Z et al: Validation of a genomic classifier for predicting post-prostatectomy recurrence in a community-based healthcare setting. J Urol 2015; Epub ahead of print. Karnes RJ, Bergstralh EJ, Davicioni E et al: Validation of a genomic classifier that predicts metastasis following radical prostatectomy in an at risk patient population. J Urol 2013; 190: 2047.
Re: Androgen Receptor Splice Variant 7 and Efficacy of Taxane Chemotherapy in Patients with Metastatic Castration-Resistant Prostate Cancer E. S. Antonarakis, C. Lu, B. Luber, H. Wang, Y. Chen, M. Nakazawa, R. Nadal, C. J. Paller, S. R. Denmeade, M. A. Carducci, M. A. Eisenberger and J. Luo Departments of Oncology and Urology, Johns Hopkins University School of Medicine, Baltimore, Maryland JAMA Oncol 2015; 1: 582e591. doi: 10.1001/jamaoncol.2015.1341
Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/26181238 Dochead: Urological Survey
LIT 5.4.0 DTD JURO13312_proof 9 February 2016 11:33 am EO:
172 173 174 175 176 177 178 179 180 181 182 183 184 185 186 187 188 189 190 191 192 193 194 195 196 197 198 199 200 201 202 203 204 205 206 207 208 209 210 211 212 213 214 215 216 217 218 219 220 221 222 223 224 225 226 227 228
PROSTATE CANCER
229 230 231 232 233 234 235 236 237 238 239 240 241 242 243 244 245 246 247 248 249 250 251 252 253 254 255 256
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Editorial Comment: In this study several emerging concepts are demonstrated regarding treatment of patients with castration resistant prostate cancer. The authors test the effectiveness of taxane chemotherapy in men with and without the androgen receptor (AR) V7 splice variant. Androgen receptors encoded by the AR-V7 splice variant messenger RNA lack an androgen binding domain but are still able to activate androgen receptor gene targets (they remain constitutively active). In other words the receptor is always active, not requiring androgen binding for activation. As such, the AR-V7 variant has been postulated to be a primary mechanism of resistance to androgen receptor targeting agents such as enzalutamide and abiraterone. If androgens are not required for receptor activation and cell growth, then targeting of androgen would be of little value. In this study men were evaluated for the AR-V7 variants through extraction and analysis of circulating tumor cells. The authors found that taxanes were equally efficacious in men with and without AR-V7 variants. In men with AR-V7 positive circulating tumor cells taxanes were superior to enzalutamide and abiraterone. In men without AR-V7 the 3 treatments were equivalent. As such, the information derived from a simple blood test could determine the need for chemotherapy in this group of men, and could spare some from a treatment unlikely to work. Samir S. Taneja, MD
Suggested Reading Small AC, Gong Y, Oh WK et al: The emerging role of circulating tumor cell detection in genitourinary cancer. J Urol 2012; 188: 21. Okegawa T, Nutahara K and Higashihara E: Prognostic significance of circulating tumor cells in patients with hormone refractory prostate cancer. J Urol 2009; 181: 1091.
Dochead: Urological Survey
LIT 5.4.0 DTD JURO13312_proof 9 February 2016 11:33 am EO:
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