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Re: Pathological Analysis of the Prostatic Anterior Fat Pad at Radical Prostatectomy: Insights from a Prospective Series
Urological Survey 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57
Urological Oncology: Prostate Cancer Re: Genomic Alterations in Cell-Free DNA and Enzalutamide Resistance in Castration-Resistant Prostate Cancer A. W. Wyatt, A. A. Azad, S. V. Volik, M. Annala, K. Beja, B. McConeghy, A. Haegert, E. W. Warner, F. Mo, S. Brahmbhatt, R. Shukin, S. Le Bihan, M. E. Gleave, M. Nykter, C. C. Collins and K. N. Chi Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia and Department of Medical Oncology, British Columbia Cancer Agency, Vancouver, British Columbia, Canada, School of Clinical Sciences, Monash University, Melbourne, Victoria, Australia, and Institute of Biosciences and Medical Technology, Tampere, Finland JAMA Oncol 2016; Epub ahead of print. doi: 10.1001/jamaoncol.2016.0494
Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/27148695 Editorial Comment: Determining the presence of somatic (acquired) mutations in men with metastatic castration resistant prostate cancer may have previously been of academic interest only. However, given the increasing number of targeted therapeutics in use or development, there is a growing desire to characterize individual cancers at the molecular level. In particular, identification of androgen receptor mutations, responsible for enzalutamide resistance, might influence choice of therapy. Given the genetic instability (frequent mutational rate) of advanced prostate cancer, adequate sampling of the cancer to assess mutations is a critical step in providing an accurate measure of the mutations present. For this reason direct sampling of metastatic sites may not accurately depict the number of mutations present. Recently several groups have used circulating tumor cells as a source of DNA for genomic profiling of mutations. In this study cell-free DNA was extracted from the plasma of men with metastatic castration resistant prostate cancer and targeted sequencing of specific gene regions was carried out successfully in nearly all patients. Identified mutations correlated well with risk of progression, and mutations in androgen receptor and DNA repair genes, which may influence therapeutic strategy, were identified in the majority of men at progression. Cell-free DNA would appear to be a simply derived source of genetic material of targeted genomic sequencing if these results can be duplicated in the hands of others. Samir S. Taneja, MD
Suggested Reading Todenh€ofer T, Azad A, Stewart C et al: AR-V7 transcripts in whole blood RNA of patients with metastatic castration resistant prostate cancer correlate with response to abiraterone acetate. J Urol 2017; 197: 135. Ellinger J, Albers P, Perabo FG et al: CpG island hypermethylation of cell-free circulating serum DNA in patients with testicular cancer. J Urol 2009; 182: 324. Ellinger J, El Kassem N, Heukamp LC et al: Hypermethylation of cell-free serum DNA indicates worse outcome in patients with bladder cancer. J Urol 2008; 179: 346.
Re: Pathological Analysis of the Prostatic Anterior Fat Pad at Radical Prostatectomy: Insights from a Prospective Series M. W. Ball, K. T. Harris, Z. R. Schwen, J. K. Mullins, M. Han, P. C. Walsh, A. W. Partin and J. I. Epstein
0022-5347/17/1973-0001/0 THE JOURNAL OF UROLOGY® Ó 2017 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION
AND
RESEARCH, INC.
http://dx.doi.org/10.1016/j.juro.2016.12.078 Vol. 197, 1-3, March 2017 Printed in U.S.A.
www.jurology.com Dochead: Urological Survey
LIT 5.4.0 DTD JURO14276_proof 16 December 2016 5:43 pm EO:
j
58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 1 113 114
PROSTATE CANCER
2
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
Departments of Urology, Oncology and Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland BJU Int 2016; Epub ahead of print. doi: 10.1111/bju.13654
Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/27611825 Editorial Comment: The practice of submitting for analysis the fat pad located ventral to the endopelvic fascia overlying the prostate has been popularized in performing robot-assisted radical prostatectomy. A few series have demonstrated low rates of metastatic lymph nodes identified within this “anterior fat pad.” Given the rare presence of nodes in this location, and the unlikely presence of metastasis, the value of such pathological submission and the justification of its cost are unclear. In this study the authors report the outcomes of prospective submission of the anterior fat pad in more than 2,000 consecutive radical prostatectomies. Metastasis was noted in 0.6% of patients, and the majority of these patients had anterior primary tumor location. Furthermore, metastasis was noted in only intermediate and high risk cases. Importantly anterior fat pad metastasis most often occurred independent of pelvic lymph node metastasis. The risk of biochemical relapse in short followup was 21% but outcomes were not different than those of men with pelvic lymph node metastasis. Based on this careful evaluation, it seems that excision and pathological submission of the anterior fat pad is warranted in men with high risk features and/or a large volume anterior tumor. One must exert caution when interpreting these data as the technique and rigor of fat submission may not be standardized among surgeons and individual centers. Samir S. Taneja, MD
Suggested Reading Kim IY, Modi PK, Sadimin E et al: Detailed analysis of patients with metastasis to the prostatic anterior fat pad lymph nodes: a multi-institutional study. J Urol 2013; 190: 527.
Re: Quantified Clinical Risk Change as an End Point during Prostate Cancer Active Surveillance M. S. Leapman, N. Ameli, M. R. Cooperberg, C. Chu, A. Hussein, K. Shinohara and P. R. Carroll Departments of Urology, and Epidemiology and Biostatistics, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California, and Department of Urology, Cairo University, Cairo, Egypt Eur Urol 2016; Epub ahead of print. doi: 10.1016/j.eururo.2016.04.021
Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/27157998 Editorial Comment: Active surveillance is an increasingly accepted management strategy for the men with low risk prostate cancer. Despite its increasing popularity, there remain few consensus guidelines regarding the triggers for intervention in men on surveillance. This fact is complicated by the recent inclusion of multiparametric magnetic resonance imaging in the armamentarium of followup tests at many centers. Traditionally treatment is recommended to men on surveillance when they have increasing prostate specific antigen, increasing disease volume on random sampling or an upgrade from Gleason 3 + 3 to any higher score. Whether all of these men require intervention has been a point of significant controversy. In this study men on surveillance who had undergone at least 2 biopsies were evaluated to compare the relationship of CAPRA (Cancer of the Prostate Risk Assessment) score progression and the presence of adverse disease pathology (dominant Gleason pattern 4, or pT3a disease or greater) on radical prostatectomy. The likelihood of adverse pathology increased with each unit incremental increase in CAPRA score, offering an objective framework for assessing risk during surveillance. Ultimately this observation may be useful in defining objective parameters by which to determine necessity of treatment on surveillance. Samir S. Taneja, MD
Suggested Reading Komisarenko M, Wong LM, Richard PO et al: An increase in Gleason 6 tumor volume while on active surveillance portends a greater risk of grade reclassification with further followup. J Urol 2016; 195: 307. Dochead: Urological Survey
LIT 5.4.0 DTD JURO14276_proof 16 December 2016 5:43 pm 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
Urological Oncology: Prostate Cancer Re: Genomic Alterations in Cell-Free DNA and Enzalutamide Resistance in Castration-Resistant Prostate Cancer A. W. Wyatt, A. A. Azad, S. V. Volik, M. Annala, K. Beja, B. McConeghy, A. Haegert, E. W. Warner, F. Mo, S. Brahmbhatt, R. Shukin, S. Le Bihan, M. E. Gleave, M. Nykter, C. C. Collins and K. N. Chi Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia and Department of Medical Oncology, British Columbia Cancer Agency, Vancouver, British Columbia, Canada, School of Clinical Sciences, Monash University, Melbourne, Victoria, Australia, and Institute of Biosciences and Medical Technology, Tampere, Finland JAMA Oncol 2016; Epub ahead of print. doi: 10.1001/jamaoncol.2016.0494
Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/27148695 Editorial Comment: Determining the presence of somatic (acquired) mutations in men with metastatic castration resistant prostate cancer may have previously been of academic interest only. However, given the increasing number of targeted therapeutics in use or development, there is a growing desire to characterize individual cancers at the molecular level. In particular, identification of androgen receptor mutations, responsible for enzalutamide resistance, might influence choice of therapy. Given the genetic instability (frequent mutational rate) of advanced prostate cancer, adequate sampling of the cancer to assess mutations is a critical step in providing an accurate measure of the mutations present. For this reason direct sampling of metastatic sites may not accurately depict the number of mutations present. Recently several groups have used circulating tumor cells as a source of DNA for genomic profiling of mutations. In this study cell-free DNA was extracted from the plasma of men with metastatic castration resistant prostate cancer and targeted sequencing of specific gene regions was carried out successfully in nearly all patients. Identified mutations correlated well with risk of progression, and mutations in androgen receptor and DNA repair genes, which may influence therapeutic strategy, were identified in the majority of men at progression. Cell-free DNA would appear to be a simply derived source of genetic material of targeted genomic sequencing if these results can be duplicated in the hands of others. Samir S. Taneja, MD
Suggested Reading Todenh€ofer T, Azad A, Stewart C et al: AR-V7 transcripts in whole blood RNA of patients with metastatic castration resistant prostate cancer correlate with response to abiraterone acetate. J Urol 2017; 197: 135. Ellinger J, Albers P, Perabo FG et al: CpG island hypermethylation of cell-free circulating serum DNA in patients with testicular cancer. J Urol 2009; 182: 324. Ellinger J, El Kassem N, Heukamp LC et al: Hypermethylation of cell-free serum DNA indicates worse outcome in patients with bladder cancer. J Urol 2008; 179: 346.
Re: Pathological Analysis of the Prostatic Anterior Fat Pad at Radical Prostatectomy: Insights from a Prospective Series M. W. Ball, K. T. Harris, Z. R. Schwen, J. K. Mullins, M. Han, P. C. Walsh, A. W. Partin and J. I. Epstein
0022-5347/17/1973-0001/0 THE JOURNAL OF UROLOGY® Ó 2017 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION
AND
RESEARCH, INC.
http://dx.doi.org/10.1016/j.juro.2016.12.078 Vol. 197, 1-3, March 2017 Printed in U.S.A.
www.jurology.com Dochead: Urological Survey
LIT 5.4.0 DTD JURO14276_proof 16 December 2016 5:43 pm EO:
j
58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 1 113 114
PROSTATE CANCER
2
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
Departments of Urology, Oncology and Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland BJU Int 2016; Epub ahead of print. doi: 10.1111/bju.13654
Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/27611825 Editorial Comment: The practice of submitting for analysis the fat pad located ventral to the endopelvic fascia overlying the prostate has been popularized in performing robot-assisted radical prostatectomy. A few series have demonstrated low rates of metastatic lymph nodes identified within this “anterior fat pad.” Given the rare presence of nodes in this location, and the unlikely presence of metastasis, the value of such pathological submission and the justification of its cost are unclear. In this study the authors report the outcomes of prospective submission of the anterior fat pad in more than 2,000 consecutive radical prostatectomies. Metastasis was noted in 0.6% of patients, and the majority of these patients had anterior primary tumor location. Furthermore, metastasis was noted in only intermediate and high risk cases. Importantly anterior fat pad metastasis most often occurred independent of pelvic lymph node metastasis. The risk of biochemical relapse in short followup was 21% but outcomes were not different than those of men with pelvic lymph node metastasis. Based on this careful evaluation, it seems that excision and pathological submission of the anterior fat pad is warranted in men with high risk features and/or a large volume anterior tumor. One must exert caution when interpreting these data as the technique and rigor of fat submission may not be standardized among surgeons and individual centers. Samir S. Taneja, MD
Suggested Reading Kim IY, Modi PK, Sadimin E et al: Detailed analysis of patients with metastasis to the prostatic anterior fat pad lymph nodes: a multi-institutional study. J Urol 2013; 190: 527.
Re: Quantified Clinical Risk Change as an End Point during Prostate Cancer Active Surveillance M. S. Leapman, N. Ameli, M. R. Cooperberg, C. Chu, A. Hussein, K. Shinohara and P. R. Carroll Departments of Urology, and Epidemiology and Biostatistics, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California, and Department of Urology, Cairo University, Cairo, Egypt Eur Urol 2016; Epub ahead of print. doi: 10.1016/j.eururo.2016.04.021
Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/27157998 Editorial Comment: Active surveillance is an increasingly accepted management strategy for the men with low risk prostate cancer. Despite its increasing popularity, there remain few consensus guidelines regarding the triggers for intervention in men on surveillance. This fact is complicated by the recent inclusion of multiparametric magnetic resonance imaging in the armamentarium of followup tests at many centers. Traditionally treatment is recommended to men on surveillance when they have increasing prostate specific antigen, increasing disease volume on random sampling or an upgrade from Gleason 3 + 3 to any higher score. Whether all of these men require intervention has been a point of significant controversy. In this study men on surveillance who had undergone at least 2 biopsies were evaluated to compare the relationship of CAPRA (Cancer of the Prostate Risk Assessment) score progression and the presence of adverse disease pathology (dominant Gleason pattern 4, or pT3a disease or greater) on radical prostatectomy. The likelihood of adverse pathology increased with each unit incremental increase in CAPRA score, offering an objective framework for assessing risk during surveillance. Ultimately this observation may be useful in defining objective parameters by which to determine necessity of treatment on surveillance. Samir S. Taneja, MD
Suggested Reading Komisarenko M, Wong LM, Richard PO et al: An increase in Gleason 6 tumor volume while on active surveillance portends a greater risk of grade reclassification with further followup. J Urol 2016; 195: 307. Dochead: Urological Survey
LIT 5.4.0 DTD JURO14276_proof 16 December 2016 5:43 pm 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