- Email: [email protected]
Re: Active Surveillance in Younger Men with Prostate Cancer
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: Active Surveillance in Younger Men with Prostate Cancer M. S. Leapman, J. E. Cowan, H. G. Nguyen, K. K. Shinohara, N. Perez, M. R. Cooperberg, W. J. Catalona and P. R. Carroll University of California, San Francisco, California, Northwestern University, Chicago, Illinois, and Yale University School of Medicine, New Haven, Connecticut J Clin Oncol 2017; 35: 1898e1904. doi: 10.1200/JCO.2016.68.0058
Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/28346806 Editorial Comment: Active surveillance is a treatment approach growing in popularity among physicians treating prostate cancer and among patients diagnosed with prostate cancer in the United States. While there is general consensus regarding the implementation of active surveillance in men with low risk prostate cancer and there are data supporting its safety at 10 and 15 years in men with low risk disease, there is controversy over its safety in younger men and its expansion to men with low to intermediate risk disease features. In this study the authors draw on a huge surveillance experience at a single institution to address the issue of the safety of surveillance in young men. The rates of Gleason upgrade at 3 and 5-year followup were less in men younger than 60 years old compared to those 60 years or older. Also, the younger men placed on surveillance did not have an increased risk of needing or failing treatment. It is noteworthy that at baseline the younger men had lower prostate specific antigen levels, smaller glands (better sampling efficiency), fewer cancer bearing cores and a greater likelihood of Gleason 2 to 6 disease. As such, the observations regarding lower rates of pathological progression may indicate a simple function of lead time, ie younger men have earlier stage disease and progression events may occur at a more delayed interval. Most important is the suggestion that outcomes are not worse for young men on surveillance, as commonly asserted. This article is extremely important for practicing urologists as it conveys important information about a highly prevalent real-time issue that we are all confronted with in practice. I have generally counseled young men that the goals of surveillance may be distinct for them as compared to older men in that surveillance likely represents a deferral, rather than avoidance, of treatment for most, given their presumed longevity. Most important is developing adequate monitoring tools to provide safety for such deferral efforts. Samir S. Taneja, MD
Suggested Reading Cher ML, Dhir A, Auffenberg GB et al: Appropriateness criteria for active surveillance of prostate cancer. J Urol 2017; 197: 67. Anderson CB, Sternberg IA, Karen-Paz G et al: Age is associated with upgrading at confirmatory biopsy among men with prostate cancer treated with active surveillance. J Urol 2015; 194: 1607. Adolfsson J and Carstensen J: Natural course of clinically localized prostate adenocarcinoma in men less than 70 years old. J Urol 1991; 146: 96.
0022-5347/17/1984-0001/0 THE JOURNAL OF UROLOGY® Ó 2017 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION
AND
RESEARCH, INC.
http://dx.doi.org/10.1016/j.juro.2017.07.030 Vol. 198, 1-5, October 2017 Printed in U.S.A.
www.jurology.com Dochead: Urological Survey
LIT 5.5.0 DTD JURO14858_proof 17 July 2017 3:07 pm EO:
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Re: Germline Mutations in ATM and BRCA1/2 Distinguish Risk for Lethal and Indolent Prostate Cancer and are Associated with Early Age at Death R. Na, S. L. Zheng, M. Han, H. Yu, D. Jiang, S. Shah, C. M. Ewing, L. Zhang, K. Novakovic, J. Petkewicz, K. Gulukota, D. L. Helseth, Jr., M. Quinn, E. Humphries, K. E. Wiley, S. D. Isaacs, Y. Wu, X. Liu, N. Zhang, C. H. Wang, J. Khandekar, P. J. Hulick, D. H. Shevrin, K. A. Cooney, Z. Shen, A. W. Partin, H. B. Carter, M. A. Carducci, M. A. Eisenberger, S. R. Denmeade, M. McGuire, P. C. Walsh, B. T. Helfand, C. B. Brendler, Q. Ding, J. Xu and W. B. Isaacs Fudan Institute of Urology, Huashan Hospital and State Key Laboratory of Genetic Engineering, School of Life Science, Fudan University, Shanghai, China, Program for Personalized Cancer Care, Department of Surgery, Center for Molecular Medicine and Department of Medicine, NorthShore University HealthSystem, Evanston, Illinois, Department of Urology and James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine and Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, Maryland, and Department of Internal Medicine, University of Utah, Salt Lake City, Utah Eur Urol 2017; 71: 740e747. doi: 10.1016/j.eururo.2016.11.033
Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/27989354 Editorial Comment: Germline mutations in DNA repair genes, such as BRCA1, BRCA2 and ATM, have been identified as predictors, and likely causal agents, of aggressive, potentially lethal prostate cancer. In this study men with lethal prostate cancer (diagnosed at a metastatic or localized stage) were compared to men with indolent, low risk cancers identified at radical prostatectomy. The rate of BRCA1/2 or ATM mutations was higher in patients with lethal prostate cancer, and the presence of such mutations was associated with prostate cancer progression and time to progression. An increasing number of mutations in each of the 3 genes was predictive of shortened survival. Observations were independent of race. Of men evaluated the rate of mutation was 8.2% in those with metastatic disease at diagnosis, 5.3% in those with lethal cancer that was localized at diagnosis and 1.4% in those with localized disease who did not have progression to metastasis or death. As such, it appears that the rate of germline mutation in DNA repair genes among men with localized prostate is higher than initially thought but the presence of such mutations is not uniformly associated with lethality. The authors assert that BRCA1/2 and ATM germline mutation testing is warranted in men with family members dying of prostate cancer before age 75 years, and that the presence of such mutations should be considered a contraindication for surveillance of localized disease. Given the observed prevalence in men with metastatic disease, and the recent demonstration of improved survival in men with germline mutations of DNA repair genes treated with PARP inhibitors, routine testing for such mutations in men with high risk and advanced disease features would also seem logical. Samir S. Taneja, MD
Suggested Reading Williams BJ, Jones E, Zhu XL et al: Evidence for a tumor suppressor gene distal to BRCA1 in prostate cancer. J Urol 1996; 155: 720. Giri VN, Coups EJ, Ruth K et al: Prostate cancer early detection program recruitment methods and show rates in men at high risk. J Urol 2009; 182: 2212. Chen L, Ambrosone CB, Lee J et al: Association between polymorphisms in the DNA repair genes XRCC1 and APE1, and the risk of prostate cancer in white and black Americans. J Urol 2006; 175: 108.
Re: Association between Radiation Therapy, Surgery, or Observation for Localized Prostate Cancer and Patient-Reported Outcomes after 3 Years D. A. Barocas, J. Alvarez, M. J. Resnick, T. Koyama, K. E. Hoffman, M. D. Tyson, R. Conwill, D. McCollum, M. R. Cooperberg, M. Goodman, S. Greenfield, A. S. Hamilton, M. Hashibe, S. H. Kaplan, L. E. Paddock, A. M. Stroup, X. C. Wu and D. F. Penson Departments of Urologic Surgery and Biostatistics, and Vanderbilt Ingram Cancer Center, Vanderbilt University Medical Center and Tennessee Valley Veterans Administration Health System, Nashville, Tennessee, Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, Department of Urology, University of California, San Francisco Medical Center, San Francisco, Center for Health Policy Research and Department of Medicine, University of California, Irvine, Irvine, and Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia, Department of Family and Preventive Medicine, University of Utah, Salt Lake City, Utah, Rutgers Cancer Institute of New Jersey, Rutgers University, New Brunswick, New Jersey, and School of Public Health, Louisiana State University Health Sciences Center, New Orleans, Louisiana
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JAMA 2017; 317: 1126e1140. doi: 10.1001/jama.2017.1704
Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/28324093
Re: Association between Choice of Radical Prostatectomy, External Beam Radiotherapy, Brachytherapy, or Active Surveillance and Patient-Reported Quality of Life among Men with Localized Prostate Cancer R. C. Chen, R. Basak, A. M. Meyer, T. M. Kuo, W. R. Carpenter, R. P. Agans, J. R. Broughman, B. B. Reeve, M. E. Nielsen, D. S. Usinger, K. C. Spearman, S. Walden, € rmer and P. A. Godley D. Kaleel, M. Anderson, T. Stu Departments of Radiation Oncology, Urology, and Health Policy and Management, Division of Hematology and Oncology, Department of Medicine, Lineberger Comprehensive Cancer Center, Cecil G. Sheps Center for Health Services Research, Department of Epidemiology, Gillings School of Global Public Health and Carolina Survey Research Laboratory, University of North Carolina at Chapel Hill, Chapel Hill and Prostate Cancer Coalition of North Carolina, Raleigh, North Carolina JAMA 2017; 317: 1141e1150. doi: 10.1001/jama.2017.1652
Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/28324092 Editorial Comment: Historically comparisons of functional outcomes of surgery and radiation have been based on large, single institution centers of excellence, thereby decreasing the generalizability of the findings and minimizing the accuracy of the comparison owing to wide selection biases. Efforts to compare outcomes from large population data sets have similarly been limited by the inadequacy of the recorded data fields, inaccuracy of recording instruments, and wide skill sets and therapeutic approaches of the represented operators. A few things have changed with time that may allow more accurate comparison of the impact of treatment on quality of life, ie a leveling of the operative playing field (partly enabled by the robot), standardization of radiation dose and delivery method (to some extent), and efforts to prospectively record data across populations rather than single institutions. Importantly surveillance cohorts can now be used to serve as effective controls for nontreated men with prostate cancer. In these 2 studies the authors take a similar approach to comparing the short-term outcomes of active surveillance, surgery and radiation in 2 separate cohorts. Not surprisingly, during the first 2 to 3 years of followup men undergoing surgery have the worst sexual function and urinary incontinence, while those undergoing radiation tend to report urinary irritative symptoms and bowel symptoms. It is noteworthy that men treated with radiation often start with worsened sexual function, and, therefore, the magnitude of change after treatment is inherently smaller. Interestingly urinary irritative symptoms improved in operated patients compared to men on surveillance. In 1 study side effect profiles persisted at 3 years, while in another no significant differences were noted between groups by 2 years, indicating the side effect profiles continue to become comparable through time. The authors of both studies suggest the reported data can be used to counsel patients weighing treatment decisions for prostate cancer. I agree but I would caution readers that such counseling cannot occur in a vacuum. The studies for the most part do not incorporate the influence of pretreatment factors such as severity of voiding symptoms, preoperative erectile function and skill set/ experience of the treating physician. However, the trends are consistent with my experience. Longer followup would likely show continued leveling of side effect severity as radiation side effects typically increase beyond the interval reported for both of these studies. Samir S. Taneja, MD
Editorial Comment: Radiation and surgery can have negative effects on quality of life in men with localized prostate cancer. Specifically surgery can be associated with sexual dysfunction and urinary incontinence, while radiation can be associated with irritative voiding symptoms and bowel and sexual dysfunction. However, when clinicians speak to patients, they often quote data from high volume surgeons and single center series. Whether these outcomes reflect what happens in the
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community is unclear. These 2 studies inform us about current “average” community outcomes following a diagnosis of localized prostate cancer and will be useful when counseling patients regarding treatment choices. Barocas et al used data from the population based CEASAR (Comparative Effectiveness Analysis of Surgery and Radiation) study to compare outcomes following surgery, radiation and active surveillance. The study included 2,550 men identified in 5 SEER (Surveillance, Epidemiology and End Results) registries and the CaPSUREÔ database who were followed for 3 years after a new diagnosis of localized prostate cancer. At 3 years patients undergoing surgery were more likely to report sexual dysfunction and urinary incontinence than those undergoing external beam radiation therapy (EBRT) or active surveillance. Patients undergoing EBRT reported significantly more irritative voiding symptoms at 3 years than those who elected active surveillance. Chen et al reported outcomes in 1,147 men diagnosed in the state of North Carolina and followed for 2 years after diagnosis. In general the results of the latter study were similar to the former. Chen et al also included 109 men who underwent brachytherapy who had outcomes similar to those undergoing EBRT. Importantly all 3 aggressive treatment groups in their study (surgery, EBRT and brachytherapy) had worse outcomes than the active surveillance group. There are 2 important take home messages. First, these data provide further important evidence that men with low risk disease should strongly consider active surveillance and perhaps should be actively dissuaded from choosing aggressive treatments if possible. Recent data from the ProtecT (Prostate Testing for Cancer and Treatment) study demonstrate that at 10 years there are no differences in survival between patients undergoing surgery, radiation and active surveillance. Given the clear differences in quality of life, one wonders if we are doing more harm than good in these patients. In addition, low volume surgeons should be quoting impotence and incontinence rates from these larger, population based studies, that is unless they collect their own data in a rigorous manner using the proper tools. Currently many urologists counsel patients using data from high volume surgeons who either have better outcomes than the community average or select their patients better. Either way, it strikes me as somewhat disingenuous for someone who does 5 to 10 prostatectomies yearly to expect to achieve the same outcomes as someone who performs 100 or more. Better and more honest counseling will undoubtedly help patients to set reasonable expectations and ultimately improve satisfaction, if nothing else. David F. Penson, MD, MPH
Suggested Reading Feldman AS, Meyer CP, Sanchez A et al: Morbidity and mortality of locally advanced prostate cancer: a population-based analysis comparing radical prostatectomy versus external beam radiation. J Urol 2017; doi: 10.1016/j.juro.2017.05.073. Penson DF, McLerran D, Feng Z et al: 5-Year urinary and sexual outcomes after radical prostatectomy: results from the Prostate Cancer Outcomes Study. J Urol, suppl., 2008; 179: S40. Hollenbeck BK, Dunn RL, Wei JT et al: Determinants of long-term sexual health outcome after radical prostatectomy measured by a validated instrument. J Urol 2003; 169: 1453.
Re: Presence of Invasive Cribriform or Intraductal Growth at Biopsy Outperforms Percentage Grade 4 in Predicting Outcome of Gleason Score 3+4[7 Prostate Cancer € mmerlin, D. Nieboer, E. W. Steyerberg, C. H. Bangma, L. Incrocci, C. F. Kweldam, I. P. Ku T. H. van der Kwast, M. J. Roobol and G. J. van Leenders Departments of Pathology, Public Health, Urology and Radiotherapy, Josephine Nefkens Institute, Erasmus Medical Centre, Rotterdam, The Netherlands, and Laboratory Medicine Program, University Health Network, Toronto, Ontario, Canada Mod Pathol 2017; Epub ahead of print. doi: 10.1038/modpathol.2017.29
Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/28530220 Editorial Comment: We are learning that beyond Gleason grade variant prostate cancer patterns can predict outcome and distinguish patients within individual Gleason grade groups. The significance of intraductal prostate cancer on biopsy has been known for some time in that it is often associated with occult high grade invasive disease and poor clinical outcomes. Recently the literature Dochead: Urological Survey
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has revealed poor pathological and clinical outcomes for men with intraductal cancer on radical prostatectomy specimen. More recently, because intraductal cancer is generally cribriform in pattern, it has been suggested that the presence of invasive cribriform pattern (not confined to the duct) is also a poor prognostic indicator. In this study of biopsies from the ERSPC (European Randomized Study of Screening for Prostate Cancer) the authors demonstrated that the presence of invasive cribriform and/or intraductal cancer increases with increasing percentage of Gleason pattern 4 on biopsy, and that it independently predicts increased risk of biochemical relapse postoperatively. The first finding is perhaps not surprising in that cribriform patterns are Gleason grade 4, and, therefore, the more pattern 4 disease the pathologist sees, the more likely cribriform patterns are to be identified. It is noteworthy that the presence of invasive cribriform and/or intraductal cancer was a stronger predictor of relapse than percentage of Gleason grade 4 disease, suggesting that such information could be used in selecting men with Gleason 3 + 4 disease who might be suitable for surveillance. However, it is unclear why the authors did not separate invasive cribriform from intraductal patterns. In reading the article it is also unclear how overlapping these populations are. While intraductal cancer is clearly not appropriate for surveillance, whether invasive cribriform patterns require treatment uniformly and independently predict poor outcome cannot be determined from this article. Samir S. Taneja, MD
Suggested Reading Humphrey PA: Intraductal carcinoma of the prostate. J Urol 2015; 194: 1434. Robinson BD and Epstein JI: Intraductal carcinoma of the prostate without invasive carcinoma on needle biopsy: emphasis on radical prostatectomy findings. J Urol 2010; 184: 1328. Humphrey PA: Cribriform adenocarcinoma of the prostate. J Urol 2015; 193: 1655. Harding-Jackson N, Kryvenko ON, Whittington EE et al: Outcome of Gleason 3 + 5 ¼ 8 prostate cancer diagnosed on needle biopsy: prognostic comparison with Gleason 4 + 4 ¼ 8. J Urol 2016; 196: 1076.
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Urological Oncology: Prostate Cancer Re: Active Surveillance in Younger Men with Prostate Cancer M. S. Leapman, J. E. Cowan, H. G. Nguyen, K. K. Shinohara, N. Perez, M. R. Cooperberg, W. J. Catalona and P. R. Carroll University of California, San Francisco, California, Northwestern University, Chicago, Illinois, and Yale University School of Medicine, New Haven, Connecticut J Clin Oncol 2017; 35: 1898e1904. doi: 10.1200/JCO.2016.68.0058
Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/28346806 Editorial Comment: Active surveillance is a treatment approach growing in popularity among physicians treating prostate cancer and among patients diagnosed with prostate cancer in the United States. While there is general consensus regarding the implementation of active surveillance in men with low risk prostate cancer and there are data supporting its safety at 10 and 15 years in men with low risk disease, there is controversy over its safety in younger men and its expansion to men with low to intermediate risk disease features. In this study the authors draw on a huge surveillance experience at a single institution to address the issue of the safety of surveillance in young men. The rates of Gleason upgrade at 3 and 5-year followup were less in men younger than 60 years old compared to those 60 years or older. Also, the younger men placed on surveillance did not have an increased risk of needing or failing treatment. It is noteworthy that at baseline the younger men had lower prostate specific antigen levels, smaller glands (better sampling efficiency), fewer cancer bearing cores and a greater likelihood of Gleason 2 to 6 disease. As such, the observations regarding lower rates of pathological progression may indicate a simple function of lead time, ie younger men have earlier stage disease and progression events may occur at a more delayed interval. Most important is the suggestion that outcomes are not worse for young men on surveillance, as commonly asserted. This article is extremely important for practicing urologists as it conveys important information about a highly prevalent real-time issue that we are all confronted with in practice. I have generally counseled young men that the goals of surveillance may be distinct for them as compared to older men in that surveillance likely represents a deferral, rather than avoidance, of treatment for most, given their presumed longevity. Most important is developing adequate monitoring tools to provide safety for such deferral efforts. Samir S. Taneja, MD
Suggested Reading Cher ML, Dhir A, Auffenberg GB et al: Appropriateness criteria for active surveillance of prostate cancer. J Urol 2017; 197: 67. Anderson CB, Sternberg IA, Karen-Paz G et al: Age is associated with upgrading at confirmatory biopsy among men with prostate cancer treated with active surveillance. J Urol 2015; 194: 1607. Adolfsson J and Carstensen J: Natural course of clinically localized prostate adenocarcinoma in men less than 70 years old. J Urol 1991; 146: 96.
0022-5347/17/1984-0001/0 THE JOURNAL OF UROLOGY® Ó 2017 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION
AND
RESEARCH, INC.
http://dx.doi.org/10.1016/j.juro.2017.07.030 Vol. 198, 1-5, October 2017 Printed in U.S.A.
www.jurology.com Dochead: Urological Survey
LIT 5.5.0 DTD JURO14858_proof 17 July 2017 3:07 pm EO:
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Re: Germline Mutations in ATM and BRCA1/2 Distinguish Risk for Lethal and Indolent Prostate Cancer and are Associated with Early Age at Death R. Na, S. L. Zheng, M. Han, H. Yu, D. Jiang, S. Shah, C. M. Ewing, L. Zhang, K. Novakovic, J. Petkewicz, K. Gulukota, D. L. Helseth, Jr., M. Quinn, E. Humphries, K. E. Wiley, S. D. Isaacs, Y. Wu, X. Liu, N. Zhang, C. H. Wang, J. Khandekar, P. J. Hulick, D. H. Shevrin, K. A. Cooney, Z. Shen, A. W. Partin, H. B. Carter, M. A. Carducci, M. A. Eisenberger, S. R. Denmeade, M. McGuire, P. C. Walsh, B. T. Helfand, C. B. Brendler, Q. Ding, J. Xu and W. B. Isaacs Fudan Institute of Urology, Huashan Hospital and State Key Laboratory of Genetic Engineering, School of Life Science, Fudan University, Shanghai, China, Program for Personalized Cancer Care, Department of Surgery, Center for Molecular Medicine and Department of Medicine, NorthShore University HealthSystem, Evanston, Illinois, Department of Urology and James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine and Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, Maryland, and Department of Internal Medicine, University of Utah, Salt Lake City, Utah Eur Urol 2017; 71: 740e747. doi: 10.1016/j.eururo.2016.11.033
Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/27989354 Editorial Comment: Germline mutations in DNA repair genes, such as BRCA1, BRCA2 and ATM, have been identified as predictors, and likely causal agents, of aggressive, potentially lethal prostate cancer. In this study men with lethal prostate cancer (diagnosed at a metastatic or localized stage) were compared to men with indolent, low risk cancers identified at radical prostatectomy. The rate of BRCA1/2 or ATM mutations was higher in patients with lethal prostate cancer, and the presence of such mutations was associated with prostate cancer progression and time to progression. An increasing number of mutations in each of the 3 genes was predictive of shortened survival. Observations were independent of race. Of men evaluated the rate of mutation was 8.2% in those with metastatic disease at diagnosis, 5.3% in those with lethal cancer that was localized at diagnosis and 1.4% in those with localized disease who did not have progression to metastasis or death. As such, it appears that the rate of germline mutation in DNA repair genes among men with localized prostate is higher than initially thought but the presence of such mutations is not uniformly associated with lethality. The authors assert that BRCA1/2 and ATM germline mutation testing is warranted in men with family members dying of prostate cancer before age 75 years, and that the presence of such mutations should be considered a contraindication for surveillance of localized disease. Given the observed prevalence in men with metastatic disease, and the recent demonstration of improved survival in men with germline mutations of DNA repair genes treated with PARP inhibitors, routine testing for such mutations in men with high risk and advanced disease features would also seem logical. Samir S. Taneja, MD
Suggested Reading Williams BJ, Jones E, Zhu XL et al: Evidence for a tumor suppressor gene distal to BRCA1 in prostate cancer. J Urol 1996; 155: 720. Giri VN, Coups EJ, Ruth K et al: Prostate cancer early detection program recruitment methods and show rates in men at high risk. J Urol 2009; 182: 2212. Chen L, Ambrosone CB, Lee J et al: Association between polymorphisms in the DNA repair genes XRCC1 and APE1, and the risk of prostate cancer in white and black Americans. J Urol 2006; 175: 108.
Re: Association between Radiation Therapy, Surgery, or Observation for Localized Prostate Cancer and Patient-Reported Outcomes after 3 Years D. A. Barocas, J. Alvarez, M. J. Resnick, T. Koyama, K. E. Hoffman, M. D. Tyson, R. Conwill, D. McCollum, M. R. Cooperberg, M. Goodman, S. Greenfield, A. S. Hamilton, M. Hashibe, S. H. Kaplan, L. E. Paddock, A. M. Stroup, X. C. Wu and D. F. Penson Departments of Urologic Surgery and Biostatistics, and Vanderbilt Ingram Cancer Center, Vanderbilt University Medical Center and Tennessee Valley Veterans Administration Health System, Nashville, Tennessee, Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, Department of Urology, University of California, San Francisco Medical Center, San Francisco, Center for Health Policy Research and Department of Medicine, University of California, Irvine, Irvine, and Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia, Department of Family and Preventive Medicine, University of Utah, Salt Lake City, Utah, Rutgers Cancer Institute of New Jersey, Rutgers University, New Brunswick, New Jersey, and School of Public Health, Louisiana State University Health Sciences Center, New Orleans, Louisiana
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JAMA 2017; 317: 1126e1140. doi: 10.1001/jama.2017.1704
Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/28324093
Re: Association between Choice of Radical Prostatectomy, External Beam Radiotherapy, Brachytherapy, or Active Surveillance and Patient-Reported Quality of Life among Men with Localized Prostate Cancer R. C. Chen, R. Basak, A. M. Meyer, T. M. Kuo, W. R. Carpenter, R. P. Agans, J. R. Broughman, B. B. Reeve, M. E. Nielsen, D. S. Usinger, K. C. Spearman, S. Walden, € rmer and P. A. Godley D. Kaleel, M. Anderson, T. Stu Departments of Radiation Oncology, Urology, and Health Policy and Management, Division of Hematology and Oncology, Department of Medicine, Lineberger Comprehensive Cancer Center, Cecil G. Sheps Center for Health Services Research, Department of Epidemiology, Gillings School of Global Public Health and Carolina Survey Research Laboratory, University of North Carolina at Chapel Hill, Chapel Hill and Prostate Cancer Coalition of North Carolina, Raleigh, North Carolina JAMA 2017; 317: 1141e1150. doi: 10.1001/jama.2017.1652
Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/28324092 Editorial Comment: Historically comparisons of functional outcomes of surgery and radiation have been based on large, single institution centers of excellence, thereby decreasing the generalizability of the findings and minimizing the accuracy of the comparison owing to wide selection biases. Efforts to compare outcomes from large population data sets have similarly been limited by the inadequacy of the recorded data fields, inaccuracy of recording instruments, and wide skill sets and therapeutic approaches of the represented operators. A few things have changed with time that may allow more accurate comparison of the impact of treatment on quality of life, ie a leveling of the operative playing field (partly enabled by the robot), standardization of radiation dose and delivery method (to some extent), and efforts to prospectively record data across populations rather than single institutions. Importantly surveillance cohorts can now be used to serve as effective controls for nontreated men with prostate cancer. In these 2 studies the authors take a similar approach to comparing the short-term outcomes of active surveillance, surgery and radiation in 2 separate cohorts. Not surprisingly, during the first 2 to 3 years of followup men undergoing surgery have the worst sexual function and urinary incontinence, while those undergoing radiation tend to report urinary irritative symptoms and bowel symptoms. It is noteworthy that men treated with radiation often start with worsened sexual function, and, therefore, the magnitude of change after treatment is inherently smaller. Interestingly urinary irritative symptoms improved in operated patients compared to men on surveillance. In 1 study side effect profiles persisted at 3 years, while in another no significant differences were noted between groups by 2 years, indicating the side effect profiles continue to become comparable through time. The authors of both studies suggest the reported data can be used to counsel patients weighing treatment decisions for prostate cancer. I agree but I would caution readers that such counseling cannot occur in a vacuum. The studies for the most part do not incorporate the influence of pretreatment factors such as severity of voiding symptoms, preoperative erectile function and skill set/ experience of the treating physician. However, the trends are consistent with my experience. Longer followup would likely show continued leveling of side effect severity as radiation side effects typically increase beyond the interval reported for both of these studies. Samir S. Taneja, MD
Editorial Comment: Radiation and surgery can have negative effects on quality of life in men with localized prostate cancer. Specifically surgery can be associated with sexual dysfunction and urinary incontinence, while radiation can be associated with irritative voiding symptoms and bowel and sexual dysfunction. However, when clinicians speak to patients, they often quote data from high volume surgeons and single center series. Whether these outcomes reflect what happens in the
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community is unclear. These 2 studies inform us about current “average” community outcomes following a diagnosis of localized prostate cancer and will be useful when counseling patients regarding treatment choices. Barocas et al used data from the population based CEASAR (Comparative Effectiveness Analysis of Surgery and Radiation) study to compare outcomes following surgery, radiation and active surveillance. The study included 2,550 men identified in 5 SEER (Surveillance, Epidemiology and End Results) registries and the CaPSUREÔ database who were followed for 3 years after a new diagnosis of localized prostate cancer. At 3 years patients undergoing surgery were more likely to report sexual dysfunction and urinary incontinence than those undergoing external beam radiation therapy (EBRT) or active surveillance. Patients undergoing EBRT reported significantly more irritative voiding symptoms at 3 years than those who elected active surveillance. Chen et al reported outcomes in 1,147 men diagnosed in the state of North Carolina and followed for 2 years after diagnosis. In general the results of the latter study were similar to the former. Chen et al also included 109 men who underwent brachytherapy who had outcomes similar to those undergoing EBRT. Importantly all 3 aggressive treatment groups in their study (surgery, EBRT and brachytherapy) had worse outcomes than the active surveillance group. There are 2 important take home messages. First, these data provide further important evidence that men with low risk disease should strongly consider active surveillance and perhaps should be actively dissuaded from choosing aggressive treatments if possible. Recent data from the ProtecT (Prostate Testing for Cancer and Treatment) study demonstrate that at 10 years there are no differences in survival between patients undergoing surgery, radiation and active surveillance. Given the clear differences in quality of life, one wonders if we are doing more harm than good in these patients. In addition, low volume surgeons should be quoting impotence and incontinence rates from these larger, population based studies, that is unless they collect their own data in a rigorous manner using the proper tools. Currently many urologists counsel patients using data from high volume surgeons who either have better outcomes than the community average or select their patients better. Either way, it strikes me as somewhat disingenuous for someone who does 5 to 10 prostatectomies yearly to expect to achieve the same outcomes as someone who performs 100 or more. Better and more honest counseling will undoubtedly help patients to set reasonable expectations and ultimately improve satisfaction, if nothing else. David F. Penson, MD, MPH
Suggested Reading Feldman AS, Meyer CP, Sanchez A et al: Morbidity and mortality of locally advanced prostate cancer: a population-based analysis comparing radical prostatectomy versus external beam radiation. J Urol 2017; doi: 10.1016/j.juro.2017.05.073. Penson DF, McLerran D, Feng Z et al: 5-Year urinary and sexual outcomes after radical prostatectomy: results from the Prostate Cancer Outcomes Study. J Urol, suppl., 2008; 179: S40. Hollenbeck BK, Dunn RL, Wei JT et al: Determinants of long-term sexual health outcome after radical prostatectomy measured by a validated instrument. J Urol 2003; 169: 1453.
Re: Presence of Invasive Cribriform or Intraductal Growth at Biopsy Outperforms Percentage Grade 4 in Predicting Outcome of Gleason Score 3+4[7 Prostate Cancer € mmerlin, D. Nieboer, E. W. Steyerberg, C. H. Bangma, L. Incrocci, C. F. Kweldam, I. P. Ku T. H. van der Kwast, M. J. Roobol and G. J. van Leenders Departments of Pathology, Public Health, Urology and Radiotherapy, Josephine Nefkens Institute, Erasmus Medical Centre, Rotterdam, The Netherlands, and Laboratory Medicine Program, University Health Network, Toronto, Ontario, Canada Mod Pathol 2017; Epub ahead of print. doi: 10.1038/modpathol.2017.29
Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/28530220 Editorial Comment: We are learning that beyond Gleason grade variant prostate cancer patterns can predict outcome and distinguish patients within individual Gleason grade groups. The significance of intraductal prostate cancer on biopsy has been known for some time in that it is often associated with occult high grade invasive disease and poor clinical outcomes. Recently the literature Dochead: Urological Survey
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has revealed poor pathological and clinical outcomes for men with intraductal cancer on radical prostatectomy specimen. More recently, because intraductal cancer is generally cribriform in pattern, it has been suggested that the presence of invasive cribriform pattern (not confined to the duct) is also a poor prognostic indicator. In this study of biopsies from the ERSPC (European Randomized Study of Screening for Prostate Cancer) the authors demonstrated that the presence of invasive cribriform and/or intraductal cancer increases with increasing percentage of Gleason pattern 4 on biopsy, and that it independently predicts increased risk of biochemical relapse postoperatively. The first finding is perhaps not surprising in that cribriform patterns are Gleason grade 4, and, therefore, the more pattern 4 disease the pathologist sees, the more likely cribriform patterns are to be identified. It is noteworthy that the presence of invasive cribriform and/or intraductal cancer was a stronger predictor of relapse than percentage of Gleason grade 4 disease, suggesting that such information could be used in selecting men with Gleason 3 + 4 disease who might be suitable for surveillance. However, it is unclear why the authors did not separate invasive cribriform from intraductal patterns. In reading the article it is also unclear how overlapping these populations are. While intraductal cancer is clearly not appropriate for surveillance, whether invasive cribriform patterns require treatment uniformly and independently predict poor outcome cannot be determined from this article. Samir S. Taneja, MD
Suggested Reading Humphrey PA: Intraductal carcinoma of the prostate. J Urol 2015; 194: 1434. Robinson BD and Epstein JI: Intraductal carcinoma of the prostate without invasive carcinoma on needle biopsy: emphasis on radical prostatectomy findings. J Urol 2010; 184: 1328. Humphrey PA: Cribriform adenocarcinoma of the prostate. J Urol 2015; 193: 1655. Harding-Jackson N, Kryvenko ON, Whittington EE et al: Outcome of Gleason 3 + 5 ¼ 8 prostate cancer diagnosed on needle biopsy: prognostic comparison with Gleason 4 + 4 ¼ 8. J Urol 2016; 196: 1076.
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