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Urological Oncology: Prostate Cancer Re: Adjuvant and Salvage Radiotherapy after Prostatectomy: American Society of Clinical Oncology Clinical Practice Guideline Endorsement S. J. Freedland, R. B. Rumble, A. Finelli, R. C. Chen, S. Slovin, M. N. Stein, D. S. Mendelson, C. Wackett and H. M. Sandler Duke University, Durham and University of North Carolina, Chapel Hill, North Carolina, American Society of Clinical Oncology, Alexandria, Virginia, Memorial Sloan Kettering Cancer Center, New York, New York, Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey, Pinnacle Oncology Hematology, Scottsdale, Arizona, Cedars-Sinai Medical Center, Los Angeles, California, and Princess Margaret Hospital, University Health Network, Toronto, Ontario, Canada J Clin Oncol 2014; 32: 3892e3898.
Abstract for this article http://dx.doi.org/10.1016/j.juro.2015.02.067 available at http://jurology.com/ Editorial Comment: The recently published American Urological Association/American Society for Radiation Oncology guidelines for use of adjuvant radiotherapy in men with high risk pathology findings on radical prostatectomy have been controversial. The recommendation for salvage radiation in men with extracapsular disease, Gleason grade greater than 7 and/or positive margins is supported by level I evidence from 2 randomized trials demonstrating reduction in recurrence and improved cancer specific survival. While clearly benefiting the whole cohort, I (like many others) have suspected that much of the survival benefit is derived by those patients with the most adverse pathological findings. In those patients recurrence is more likely to be associated with mortality, hence the survival benefit. In this guidelines endorsement a review panel of methodologists was assembled to offer an opinion of the guidelines and assess developmental rigor. The American Society of Clinical Oncology review panel endorsed the guidelines recommendations but cautioned that not all men with adverse pathology have the same risk of recurrence. I would add that not all have the same risk of mortality, even if they relapse. As such, the guidelines should serve as a framework for individualized assessment and treatment recommendations. Samir S. Taneja, MD
Suggested Reading Thompson IM, Valicenti RK, Albertsen P et al: Adjuvant and salvage radiotherapy after prostatectomy: AUA/ASTRO guideline. J Urol 2013; 190: 441. Spahn M, Briganti A, Capitanio U et al; European Multicenter Prostate Cancer Clinical and Translational Research Group: Outcome predictors of radical prostatectomy followed by adjuvant androgen deprivation in patients with clinical high risk prostate cancer and pT3 surgical margin positive disease. J Urol 2012; 188: 84. Thompson IM, Tangen CM, Paradelo J et al: Adjuvant radiotherapy for pathological T3N0M0 prostate cancer significantly reduces risk of metastases and improves survival: long-term followup of a randomized clinical trial. J Urol 2009; 181: 956.
Re: The Impact of Fellowship Training on Pathological Outcomes following Radical Prostatectomy: A Population Based Analysis J. G. Nayak, D. E. Drachenberg, E. Mau, D. Suderman, O. Bucher, P. Lambert and H. Quon 0022-5347/15/1935-0001/0 THE JOURNAL OF UROLOGY® © 2015 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION
AND
RESEARCH, INC.
http://dx.doi.org/10.1016/j.juro.2015.02.067 Vol. 193, 1-3, May 2015 Printed in U.S.A.
www.jurology.com Dochead: Urological Survey
LIT 5.2.0 DTD JURO12233_proof 17 February 2015 2:39 pm EO:
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CancerCare Manitoba, Winnipeg, Manitoba, Canada BMC Urol 2014; 14: 82.
Abstract available for this article http://dx.doi.org/10.1016/j.juro.2015.02.068 at http://jurology.com/ Editorial Comment: In this article from Canada the authors demonstrate that radical prostatectomy outcomes are superior among surgeons who are urooncology fellowship trained as compared to those who are not. This finding is likely a surrogate measure of case volume in training and practice. Additionally practice setting is critically important, as health care systems vary in their case distribution, quality of training and disease volume. It is difficult to determine the critical amount of experience and case volume necessary, particularly if factoring in innate surgical ability, which I consider to be important. However, it is an interesting assertion that specialized oncologic training would influence the manner in which the surgery is done, thereby decreasing positive margins. I am not convinced that is truly proved by this article. Samir S. Taneja, MD
Suggested Reading Vickers A, Bianco F, Cronin A et al: The learning curve for surgical margins after open radical prostatectomy: implications for margin status as an oncological end point. J Urol 2010; 183: 1360.
Re: Do Environmental Factors Modify the Genetic Risk of Prostate Cancer? S. Loeb, S. B. Peskoe, C. E. Joshu, W. Y. Huang, R. B. Hayes, H. B. Carter, W. B. Isaacs and E. A. Platz Department of Urology and Population Health, New York University, New York, New York, and Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, and Brady Urological Institute and Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, and Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland Cancer Epidemiol Biomarkers Prev 2015; 24: 213e220.
Abstract for this article http://dx.doi.org/10.1016/j.juro.2015.02.069 available at http://jurology.com/ Editorial Comment: In this extremely interesting article the authors explore the relationship of environmental influences and genetic risk of prostate cancer. By stratifying patients according to the presence of single nucleotide polymorphisms, which are predictive of cancer risk, the authors demonstrate that men in the high risk category carry a roughly twofold increased risk of cancer. This risk is reduced in men who report high intake of selenium in the case of advanced prostate cancer and anti-inflammatory agents in the case of localized disease. It is hard to say whether these relative risks can be separated from factors influencing detection, such as comorbid disease processes and prostate specific antigen level. For example if men taking anti-inflammatory agents were to have fewer falsepositive increased levels of serum PSA, perhaps fewer biopsies would be done. Nonetheless, the concept is provocative and warrants validation. There has long been a belief regarding the interplay between genetics and environment, and articles such as this may offer insight into how such associations can be manipulated to the benefit of the patient. Samir S. Taneja, MD
Suggested Reading Loeb S, Carter HB, Walsh PC et al: Single nucleotide polymorphisms and the likelihood of prostate cancer at a given prostate specific antigen level. J Urol 2009; 182: 101. Dos Reis ST, Pontes J Jr, Villanova FE et al: Genetic polymorphisms of matrix metalloproteinases: susceptibility and prognostic implications for prostate cancer. J Urol 2009; 181: 2320.
Dochead: Urological Survey
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Re: A Biopsy-Based 17-Gene Genomic Prostate Score Predicts Recurrence after Radical Prostatectomy and Adverse Surgical Pathology in a Racially Diverse Population of Men with Clinically Low- and Intermediate-Risk Prostate Cancer J. Cullen, I. L. Rosner, T. C. Brand, N. Zhang, A. C. Tsiatis, J. Moncur, A. Ali, Y. Chen, D. Knezevic, T. Maddala, H. J. Lawrence, P. G. Febbo, S. Srivastava, I. A. Sesterhenn and D. G. McLeod Center for Prostate Disease Research, Department of Surgery, Uniformed Services University of the Health Sciences and Walter Reed National Military Medical Center, Bethesda and Joint Pathology Center, Silver Spring, Maryland, Madigan Army Medical Center, Tacoma, Washington, and Genomic Health, Inc., Redwood City, California Eur Urol 2014; Epub ahead of print.
Abstract for this article http://dx.doi.org/10.1016/j.juro.2015.02.070 available at http://jurology.com/ Editorial Comment: Genomic prostate score (GPS), based on the tissue expression of a panel of 17 genes, has been shown to predict risk of adverse pathology on radical prostatectomy and progression on active surveillance. In this study of men undergoing radical prostatectomy preoperative GPS derived from the diagnostic biopsy was a strong predictor of the interval to biochemical relapse on univariate and multivariate analysis, with a hazard ratio of nearly 3 for every 20-unit increase in GPS. GPS was likewise predictive of adverse pathological findings at surgery. The study presents no evaluation of prostate cancer specific mortality, as the metastatic progression rate was low. As risk of relapse was 33% in men with GPS in the highest quartile, the test may serve as a means of selecting men for multimodal approaches or alternatives to radical prostatectomy. This study provides further validation of the premise of genetic measures of disease aggressiveness. Critical assessment of their application in clinical practice will be needed, as the value added to the typical clinical risk stratification tools may be modest. Samir S. Taneja, MD
Dochead: Urological Survey
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265 266 267 268 269 270 271 272 273 274 275 276 277 278 279 280 281 282 283 284 285 286 287 288 289 290 291 292 293 294 295 296 297 298 299 300
Urological Oncology: Prostate Cancer Re: Adjuvant and Salvage Radiotherapy after Prostatectomy: American Society of Clinical Oncology Clinical Practice Guideline Endorsement S. J. Freedland, R. B. Rumble, A. Finelli, R. C. Chen, S. Slovin, M. N. Stein, D. S. Mendelson, C. Wackett and H. M. Sandler Duke University, Durham and University of North Carolina, Chapel Hill, North Carolina, American Society of Clinical Oncology, Alexandria, Virginia, Memorial Sloan Kettering Cancer Center, New York, New York, Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey, Pinnacle Oncology Hematology, Scottsdale, Arizona, Cedars-Sinai Medical Center, Los Angeles, California, and Princess Margaret Hospital, University Health Network, Toronto, Ontario, Canada J Clin Oncol 2014; 32: 3892e3898.
Abstract for this article http://dx.doi.org/10.1016/j.juro.2015.02.067 available at http://jurology.com/ Editorial Comment: The recently published American Urological Association/American Society for Radiation Oncology guidelines for use of adjuvant radiotherapy in men with high risk pathology findings on radical prostatectomy have been controversial. The recommendation for salvage radiation in men with extracapsular disease, Gleason grade greater than 7 and/or positive margins is supported by level I evidence from 2 randomized trials demonstrating reduction in recurrence and improved cancer specific survival. While clearly benefiting the whole cohort, I (like many others) have suspected that much of the survival benefit is derived by those patients with the most adverse pathological findings. In those patients recurrence is more likely to be associated with mortality, hence the survival benefit. In this guidelines endorsement a review panel of methodologists was assembled to offer an opinion of the guidelines and assess developmental rigor. The American Society of Clinical Oncology review panel endorsed the guidelines recommendations but cautioned that not all men with adverse pathology have the same risk of recurrence. I would add that not all have the same risk of mortality, even if they relapse. As such, the guidelines should serve as a framework for individualized assessment and treatment recommendations. Samir S. Taneja, MD
Suggested Reading Thompson IM, Valicenti RK, Albertsen P et al: Adjuvant and salvage radiotherapy after prostatectomy: AUA/ASTRO guideline. J Urol 2013; 190: 441. Spahn M, Briganti A, Capitanio U et al; European Multicenter Prostate Cancer Clinical and Translational Research Group: Outcome predictors of radical prostatectomy followed by adjuvant androgen deprivation in patients with clinical high risk prostate cancer and pT3 surgical margin positive disease. J Urol 2012; 188: 84. Thompson IM, Tangen CM, Paradelo J et al: Adjuvant radiotherapy for pathological T3N0M0 prostate cancer significantly reduces risk of metastases and improves survival: long-term followup of a randomized clinical trial. J Urol 2009; 181: 956.
Re: The Impact of Fellowship Training on Pathological Outcomes following Radical Prostatectomy: A Population Based Analysis J. G. Nayak, D. E. Drachenberg, E. Mau, D. Suderman, O. Bucher, P. Lambert and H. Quon 0022-5347/15/1935-0001/0 THE JOURNAL OF UROLOGY® © 2015 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION
AND
RESEARCH, INC.
http://dx.doi.org/10.1016/j.juro.2015.02.067 Vol. 193, 1-3, May 2015 Printed in U.S.A.
www.jurology.com Dochead: Urological Survey
LIT 5.2.0 DTD JURO12233_proof 17 February 2015 2:39 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
CancerCare Manitoba, Winnipeg, Manitoba, Canada BMC Urol 2014; 14: 82.
Abstract available for this article http://dx.doi.org/10.1016/j.juro.2015.02.068 at http://jurology.com/ Editorial Comment: In this article from Canada the authors demonstrate that radical prostatectomy outcomes are superior among surgeons who are urooncology fellowship trained as compared to those who are not. This finding is likely a surrogate measure of case volume in training and practice. Additionally practice setting is critically important, as health care systems vary in their case distribution, quality of training and disease volume. It is difficult to determine the critical amount of experience and case volume necessary, particularly if factoring in innate surgical ability, which I consider to be important. However, it is an interesting assertion that specialized oncologic training would influence the manner in which the surgery is done, thereby decreasing positive margins. I am not convinced that is truly proved by this article. Samir S. Taneja, MD
Suggested Reading Vickers A, Bianco F, Cronin A et al: The learning curve for surgical margins after open radical prostatectomy: implications for margin status as an oncological end point. J Urol 2010; 183: 1360.
Re: Do Environmental Factors Modify the Genetic Risk of Prostate Cancer? S. Loeb, S. B. Peskoe, C. E. Joshu, W. Y. Huang, R. B. Hayes, H. B. Carter, W. B. Isaacs and E. A. Platz Department of Urology and Population Health, New York University, New York, New York, and Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, and Brady Urological Institute and Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, and Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland Cancer Epidemiol Biomarkers Prev 2015; 24: 213e220.
Abstract for this article http://dx.doi.org/10.1016/j.juro.2015.02.069 available at http://jurology.com/ Editorial Comment: In this extremely interesting article the authors explore the relationship of environmental influences and genetic risk of prostate cancer. By stratifying patients according to the presence of single nucleotide polymorphisms, which are predictive of cancer risk, the authors demonstrate that men in the high risk category carry a roughly twofold increased risk of cancer. This risk is reduced in men who report high intake of selenium in the case of advanced prostate cancer and anti-inflammatory agents in the case of localized disease. It is hard to say whether these relative risks can be separated from factors influencing detection, such as comorbid disease processes and prostate specific antigen level. For example if men taking anti-inflammatory agents were to have fewer falsepositive increased levels of serum PSA, perhaps fewer biopsies would be done. Nonetheless, the concept is provocative and warrants validation. There has long been a belief regarding the interplay between genetics and environment, and articles such as this may offer insight into how such associations can be manipulated to the benefit of the patient. Samir S. Taneja, MD
Suggested Reading Loeb S, Carter HB, Walsh PC et al: Single nucleotide polymorphisms and the likelihood of prostate cancer at a given prostate specific antigen level. J Urol 2009; 182: 101. Dos Reis ST, Pontes J Jr, Villanova FE et al: Genetic polymorphisms of matrix metalloproteinases: susceptibility and prognostic implications for prostate cancer. J Urol 2009; 181: 2320.
Dochead: Urological Survey
LIT 5.2.0 DTD JURO12233_proof 17 February 2015 2:39 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
PROSTATE CANCER
229 230 231 232 233 234 235 236 237 238 239 240 241 242 243 244 245 246 247 248 249 250 251 252 253 254 255 256 257 258 259 260 261 262 263 264
3
Re: A Biopsy-Based 17-Gene Genomic Prostate Score Predicts Recurrence after Radical Prostatectomy and Adverse Surgical Pathology in a Racially Diverse Population of Men with Clinically Low- and Intermediate-Risk Prostate Cancer J. Cullen, I. L. Rosner, T. C. Brand, N. Zhang, A. C. Tsiatis, J. Moncur, A. Ali, Y. Chen, D. Knezevic, T. Maddala, H. J. Lawrence, P. G. Febbo, S. Srivastava, I. A. Sesterhenn and D. G. McLeod Center for Prostate Disease Research, Department of Surgery, Uniformed Services University of the Health Sciences and Walter Reed National Military Medical Center, Bethesda and Joint Pathology Center, Silver Spring, Maryland, Madigan Army Medical Center, Tacoma, Washington, and Genomic Health, Inc., Redwood City, California Eur Urol 2014; Epub ahead of print.
Abstract for this article http://dx.doi.org/10.1016/j.juro.2015.02.070 available at http://jurology.com/ Editorial Comment: Genomic prostate score (GPS), based on the tissue expression of a panel of 17 genes, has been shown to predict risk of adverse pathology on radical prostatectomy and progression on active surveillance. In this study of men undergoing radical prostatectomy preoperative GPS derived from the diagnostic biopsy was a strong predictor of the interval to biochemical relapse on univariate and multivariate analysis, with a hazard ratio of nearly 3 for every 20-unit increase in GPS. GPS was likewise predictive of adverse pathological findings at surgery. The study presents no evaluation of prostate cancer specific mortality, as the metastatic progression rate was low. As risk of relapse was 33% in men with GPS in the highest quartile, the test may serve as a means of selecting men for multimodal approaches or alternatives to radical prostatectomy. This study provides further validation of the premise of genetic measures of disease aggressiveness. Critical assessment of their application in clinical practice will be needed, as the value added to the typical clinical risk stratification tools may be modest. Samir S. Taneja, MD
Dochead: Urological Survey
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