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Re: Urinary Collecting System Invasion is Associated with Poor Survival in Patients with Clear-Cell Renal Cell Carcinoma
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Urological Oncology: Adrenal, Renal, Ureteral and Retroperitoneal Tumors Re: Urinary Collecting System Invasion is Associated with Poor Survival in Patients with Clear-Cell Renal Cell Carcinoma G. C. Bailey, S. A. Boorjian, M. J. Ziegelmann, M. E. Westerman, C. M. Lohse, B. C. Leibovich, J. C. Cheville and R. H. Thompson Departments of Urology, Health Sciences Research and Pathology, Mayo Clinic, Rochester, Minnesota BJU Int 2017; 119: 585e590. doi: 10.1111/bju.13669
Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/27696652 Editorial Comment: In this ad hoc analysis the authors assess the prognostic significance of urinary collecting system invasion (UCSI) in renal cell carcinoma (RCC). This subject deserves attention in view of the controversial reports and the somehow neglected status of this TNM pathological feature. The performed revision of pathological slides adds value to the present work. Of 895 patients undergoing nephrectomy in this study only 6.8% presented with UCSI. At a median of 1.8 years 310 patients had died, while followup for survivors was 8.2 years. Estimated cancer specific survival at 10 years postoperatively was 17% for patients with UCSI and 60% for those without UCSI. UCSI remained independently associated with an increased risk of death (HR 1.5) in a multivariate model. A similar HR was seen when adjusting for individual components of the SSIGN (Mayo Clinic Stage, Size, Grade and Necrosis) score. Furthermore, among patients with pT3 RCC those with UCSI had survival outcomes similar to pT4 survival rates. It is recognized that pT3 stage is a heterogeneous category. The 8th edition of the AJCC Cancer Staging Manual, to be implemented in 2018, specifically describes UCSI as being in the pT3a category.1 Still multiple microscopic features coexist within the pT3a category besides UCSI, for example extension into renal or segmental veins and invasion of fat (perirenal/sinus), alone or concomitantly, providing the Gerota fascia is intact. Although scarce, some series indicate the different prognostic impacts of the presence of 1 or more of these features. A subsequent analysis of patients with pT3a disease in the present series also follows this direction, with a worse prognosis for those in the category exhibiting UCSI (HR 1.77). It is time to collaborate via multi-institutional studies that have appropriate pathological review and are sufficiently powered to establish the prognostic value of each, or concomitance of the different features that integrate the most heterogeneous RCC category. M. Pilar Laguna, MD, PhD 1. Amin MB, Greene FL, Byrd DR et al: AJCC Cancer Staging Manual. New York: Springer International 2017.
Suggested Reading Frank I, Blute ML, Cheville JC et al: An outcome prediction model for patients with clear cell renal cell carcinoma treated with radical nephrectomy based on tumor stage, size, grade and necrosis: the SSIGN score. J Urol 2002; 168: 2395. Thuret R, Ficarra V, Artibani W et al: Urinary collecting system invasion is an independent prognostic factor of organ confined renal cell carcinoma. J Urol 2009; 182: 854. Uzzo RG, Cherullo E, Myles J et al: Renal cell carcinoma invading the urinary collecting system: implications for staging. J Urol 2002; 167: 2392.
0022-5347//-0001/0 THE JOURNAL OF UROLOGY® Ó 2017 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION
AND
RESEARCH, INC.
http://dx.doi.org/10.1016/j.juro.2017.08.025 Vol. , 1-2, 20 Printed in U.S.A.
www.jurology.com Dochead: Urological Survey
LIT 5.5.0 DTD JURO14913_proof 8 August 2017 3:44 pm EO:
j
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ADRENAL, RENAL, URETERAL AND RETROPERITONEAL TUMORS
Palapattu GS, Pantuck AJ, Dorey F et al: Collecting system invasion in renal cell carcinoma: impact on prognosis and future staging strategies. J Urol 2003; 170: 768. Brookman-May S, May M, Zigeuner R et al: Collecting system invasion and Fuhrman grade but not tumor size facilitate prognostic stratification of patients with pT2 renal cell carcinoma. J Urol 2011; 186: 2175. Thompson RH, Leibovich BC, Cheville JC et al: Is renal sinus fat invasion the same as perinephric fat invasion for pT3a renal cell carcinoma? J Urol 2005; 174: 1218. Park J, Habuchi T, Arai Y et al: Reassessment of prognostic heterogeneity of pT3 renal pelvic urothelial carcinoma: analysis in terms of proposed pT3 subclassification systems. J Urol 2014; 192: 1064.
Re: Clear Cell Type A and B Molecular Subtypes in Metastatic Clear Cell Renal Cell Carcinoma: Tumor Heterogeneity and Aggressiveness D. J. Serie, R. W. Joseph, J. C. Cheville, T. H. Ho, M. Parasramka, T. Hilton, R. H. Thompson, B. C. Leibovich, A. S. Parker and J. E. Eckel-Passow Department of Health Sciences Research, Department of Cancer Biology and Division of Hematology/Oncology, Mayo Clinic, Jacksonville, Florida, Department of Laboratory Medicine and Pathology, Department of Urology, and Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota, and Division of Hematology and Medical Oncology, Mayo Clinic, Scottsdale, Arizona Eur Urol 2017; 71: 979e985. doi: 10.1016/j.eururo.2016.11.018
Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/27899233 Editorial Comment: The recently described molecular classification of clear cell (cc) renal cell carcinoma (RCC) as subtype A or B (ClearCode 34 signature) is explored in patients with metastatic ccRCC and tissue available from primary and metastatic tumors. Data presented on primary tumors confirm the association between molecular subtype B and worse cancer specific and overall survival, validating the already reported prognostic value of this molecular subclassification. However, the primary objective of the authors is to explore intratumor and intertumor heterogeneity of molecular subtypes in metastatic RCC and across the primary tumor and metastases. Intratumor heterogeneity in metastases of 9 patients showed concomitance of subtypes A and B in 22% of tumors. Intertumor subtype discordance (A or B) was found in 23% of the 30 patients with longitudinal metastasis. Metastatic pathological features were also associated with molecular subtype, with grade 3 and 4 tumors demonstrating increased odds of being cc subtype B. Also, metastases with necrosis and those to the adrenal gland, pancreas or bone exhibited a predominance of subtype B. Lung metastases were more likely subtype A. However, heterogeneity in metastases was not associated with cancer specific or overall survival. Subtypes across patient matched primary and metastatic tumors differed in 43% of the 81 patients with available primary and metastatic samples. Most cases progressed from subtype A to B. This finding strongly suggests that primary tumor is not a surrogate for genetic typing of the metastases and consequently may be inadequate to drive the treatment of metastatic tumors. The novelty of the present study is that intratumor and intertumor heterogeneity is assessed across multiple sections of resected metastatic tumors with similar pathological features, supporting the concept that if pathological review is incorporated and the most aggressive features are identified, interrogation of this unique entity should be enough to gene type the metastasis. M. Pilar Laguna, MD, PhD
Suggested Reading Ball MW, Bezerra SM, Gorin MA et al: Grade heterogeneity in small renal masses: potential implications for renal mass biopsy. J Urol 2015; 193: 36. Klatte T, Said JW, de Martino M et al: Presence of tumor necrosis is not a significant predictor of survival in clear cell renal cell carcinoma: higher prognostic accuracy of extent based rather than presence/absence classification. J Urol 2009; 181: 1558. Gowrishankar B, Przybycin CG, Ma C et al: A genomic algorithm for the molecular classification of common renal cortical neoplasms: development and validation. J Urol 2015; 193: 1479. Yang XJ, Sugimura J, Schafernak KT et al: Classification of renal neoplasms based on molecular signatures. J Urol 2006; 175: 2302. Joseph RW, Kapur P, Serie DJ et al: Clear cell renal cell carcinoma subtypes identified by BAP1 and PBRM1 expression. J Urol 2016; 195: 180. Lee RJ: Molecular determinants of metastasis in renal cell cancer: tracking down the real killer. J Urol 2015; 194: 278.
Dochead: Urological Survey
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Urological Oncology: Adrenal, Renal, Ureteral and Retroperitoneal Tumors Re: Urinary Collecting System Invasion is Associated with Poor Survival in Patients with Clear-Cell Renal Cell Carcinoma G. C. Bailey, S. A. Boorjian, M. J. Ziegelmann, M. E. Westerman, C. M. Lohse, B. C. Leibovich, J. C. Cheville and R. H. Thompson Departments of Urology, Health Sciences Research and Pathology, Mayo Clinic, Rochester, Minnesota BJU Int 2017; 119: 585e590. doi: 10.1111/bju.13669
Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/27696652 Editorial Comment: In this ad hoc analysis the authors assess the prognostic significance of urinary collecting system invasion (UCSI) in renal cell carcinoma (RCC). This subject deserves attention in view of the controversial reports and the somehow neglected status of this TNM pathological feature. The performed revision of pathological slides adds value to the present work. Of 895 patients undergoing nephrectomy in this study only 6.8% presented with UCSI. At a median of 1.8 years 310 patients had died, while followup for survivors was 8.2 years. Estimated cancer specific survival at 10 years postoperatively was 17% for patients with UCSI and 60% for those without UCSI. UCSI remained independently associated with an increased risk of death (HR 1.5) in a multivariate model. A similar HR was seen when adjusting for individual components of the SSIGN (Mayo Clinic Stage, Size, Grade and Necrosis) score. Furthermore, among patients with pT3 RCC those with UCSI had survival outcomes similar to pT4 survival rates. It is recognized that pT3 stage is a heterogeneous category. The 8th edition of the AJCC Cancer Staging Manual, to be implemented in 2018, specifically describes UCSI as being in the pT3a category.1 Still multiple microscopic features coexist within the pT3a category besides UCSI, for example extension into renal or segmental veins and invasion of fat (perirenal/sinus), alone or concomitantly, providing the Gerota fascia is intact. Although scarce, some series indicate the different prognostic impacts of the presence of 1 or more of these features. A subsequent analysis of patients with pT3a disease in the present series also follows this direction, with a worse prognosis for those in the category exhibiting UCSI (HR 1.77). It is time to collaborate via multi-institutional studies that have appropriate pathological review and are sufficiently powered to establish the prognostic value of each, or concomitance of the different features that integrate the most heterogeneous RCC category. M. Pilar Laguna, MD, PhD 1. Amin MB, Greene FL, Byrd DR et al: AJCC Cancer Staging Manual. New York: Springer International 2017.
Suggested Reading Frank I, Blute ML, Cheville JC et al: An outcome prediction model for patients with clear cell renal cell carcinoma treated with radical nephrectomy based on tumor stage, size, grade and necrosis: the SSIGN score. J Urol 2002; 168: 2395. Thuret R, Ficarra V, Artibani W et al: Urinary collecting system invasion is an independent prognostic factor of organ confined renal cell carcinoma. J Urol 2009; 182: 854. Uzzo RG, Cherullo E, Myles J et al: Renal cell carcinoma invading the urinary collecting system: implications for staging. J Urol 2002; 167: 2392.
0022-5347//-0001/0 THE JOURNAL OF UROLOGY® Ó 2017 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION
AND
RESEARCH, INC.
http://dx.doi.org/10.1016/j.juro.2017.08.025 Vol. , 1-2, 20 Printed in U.S.A.
www.jurology.com Dochead: Urological Survey
LIT 5.5.0 DTD JURO14913_proof 8 August 2017 3:44 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
2
115 116 117 118 119 120 121 122 123 124 125 126 127 128 129 130 131 132 133 134 135 136 137 138 139 140 141 142 143 144 145 146 147 148 149 150 151 152 153 154 155 156 157 158 159 160 161 162 163 164 165 166 167 168 169 170 171 172 173 174 175 176
ADRENAL, RENAL, URETERAL AND RETROPERITONEAL TUMORS
Palapattu GS, Pantuck AJ, Dorey F et al: Collecting system invasion in renal cell carcinoma: impact on prognosis and future staging strategies. J Urol 2003; 170: 768. Brookman-May S, May M, Zigeuner R et al: Collecting system invasion and Fuhrman grade but not tumor size facilitate prognostic stratification of patients with pT2 renal cell carcinoma. J Urol 2011; 186: 2175. Thompson RH, Leibovich BC, Cheville JC et al: Is renal sinus fat invasion the same as perinephric fat invasion for pT3a renal cell carcinoma? J Urol 2005; 174: 1218. Park J, Habuchi T, Arai Y et al: Reassessment of prognostic heterogeneity of pT3 renal pelvic urothelial carcinoma: analysis in terms of proposed pT3 subclassification systems. J Urol 2014; 192: 1064.
Re: Clear Cell Type A and B Molecular Subtypes in Metastatic Clear Cell Renal Cell Carcinoma: Tumor Heterogeneity and Aggressiveness D. J. Serie, R. W. Joseph, J. C. Cheville, T. H. Ho, M. Parasramka, T. Hilton, R. H. Thompson, B. C. Leibovich, A. S. Parker and J. E. Eckel-Passow Department of Health Sciences Research, Department of Cancer Biology and Division of Hematology/Oncology, Mayo Clinic, Jacksonville, Florida, Department of Laboratory Medicine and Pathology, Department of Urology, and Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota, and Division of Hematology and Medical Oncology, Mayo Clinic, Scottsdale, Arizona Eur Urol 2017; 71: 979e985. doi: 10.1016/j.eururo.2016.11.018
Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/27899233 Editorial Comment: The recently described molecular classification of clear cell (cc) renal cell carcinoma (RCC) as subtype A or B (ClearCode 34 signature) is explored in patients with metastatic ccRCC and tissue available from primary and metastatic tumors. Data presented on primary tumors confirm the association between molecular subtype B and worse cancer specific and overall survival, validating the already reported prognostic value of this molecular subclassification. However, the primary objective of the authors is to explore intratumor and intertumor heterogeneity of molecular subtypes in metastatic RCC and across the primary tumor and metastases. Intratumor heterogeneity in metastases of 9 patients showed concomitance of subtypes A and B in 22% of tumors. Intertumor subtype discordance (A or B) was found in 23% of the 30 patients with longitudinal metastasis. Metastatic pathological features were also associated with molecular subtype, with grade 3 and 4 tumors demonstrating increased odds of being cc subtype B. Also, metastases with necrosis and those to the adrenal gland, pancreas or bone exhibited a predominance of subtype B. Lung metastases were more likely subtype A. However, heterogeneity in metastases was not associated with cancer specific or overall survival. Subtypes across patient matched primary and metastatic tumors differed in 43% of the 81 patients with available primary and metastatic samples. Most cases progressed from subtype A to B. This finding strongly suggests that primary tumor is not a surrogate for genetic typing of the metastases and consequently may be inadequate to drive the treatment of metastatic tumors. The novelty of the present study is that intratumor and intertumor heterogeneity is assessed across multiple sections of resected metastatic tumors with similar pathological features, supporting the concept that if pathological review is incorporated and the most aggressive features are identified, interrogation of this unique entity should be enough to gene type the metastasis. M. Pilar Laguna, MD, PhD
Suggested Reading Ball MW, Bezerra SM, Gorin MA et al: Grade heterogeneity in small renal masses: potential implications for renal mass biopsy. J Urol 2015; 193: 36. Klatte T, Said JW, de Martino M et al: Presence of tumor necrosis is not a significant predictor of survival in clear cell renal cell carcinoma: higher prognostic accuracy of extent based rather than presence/absence classification. J Urol 2009; 181: 1558. Gowrishankar B, Przybycin CG, Ma C et al: A genomic algorithm for the molecular classification of common renal cortical neoplasms: development and validation. J Urol 2015; 193: 1479. Yang XJ, Sugimura J, Schafernak KT et al: Classification of renal neoplasms based on molecular signatures. J Urol 2006; 175: 2302. Joseph RW, Kapur P, Serie DJ et al: Clear cell renal cell carcinoma subtypes identified by BAP1 and PBRM1 expression. J Urol 2016; 195: 180. Lee RJ: Molecular determinants of metastasis in renal cell cancer: tracking down the real killer. J Urol 2015; 194: 278.
Dochead: Urological Survey
LIT 5.5.0 DTD JURO14913_proof 8 August 2017 3:44 pm EO:
177 178 179 180 181 182 183 184 185 186 187 188 189 190 191 192 193 194 195 196 197 198 199 200 201 202 203 204 205 206 207 208 209 210 211 212 213 214 215 216 217 218 219 220 221 222 223 224 225 226 227 228 229 230 231 232 233 234 235 236 237 238