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Re: A Phase II Study of Intermittent Sunitinib in Previously Untreated Patients with Metastatic Renal Cell Carcinoma
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Urological Oncology: Adrenal, Renal, Ureteral and Retroperitoneal Tumors Re: A Phase II Study of Intermittent Sunitinib in Previously Untreated Patients with Metastatic Renal Cell Carcinoma M. C. Ornstein, L. S. Wood, P. Elson, K. D. Allman, J. Beach, A. Martin, B. R. Zanick, P. Grivas, T. Gilligan, J. A. Garcia and B. I. Rini Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio J Clin Oncol 2017; 35: 1764e1769. doi: 10.1200/JCO.2016.71.1184
Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/28113029 Editorial Comment: This phase II study investigated the feasibility, safety and clinical efficacy of first-line intermittent treatment with sunitinib in patients with metastatic renal cell carcinoma. A total of 37 patients received 4 initial cycles of sunitinib. Those with 10% or greater reduction of tumor burden were offered a treatment break. Therapy was reinitiated when there was an increase in tumor burden of 10% or more (compared to computerized tomogram findings before the break) or clinical progression. A total of 20 patients with a median decrease in tumor burden of 45% (range 13% to 86%) entered the intermittent phase. One patient withdrew at first reimaging because of progression. Objective response rate was 46%, and metastatic progression-free survival and overall survival were 22.4 and 34.8 months, respectively. Most patients in the study exhibited a stable radiological pattern, with a median increase in tumor burden of 1.6 cm during breaks and a median decrease of 1.4 cm while on treatment. Dose reduction and switch in treatment schedule were necessary in 19 and 9 patients, respectively, during the first 4 sunitinib cycles. Schedules and doses were continued during the repeat treatment periods, with only 2 patients stopping therapy because of a grade 2 to 3 adverse event. This study demonstrates the feasibility of extended treatment breaks in a selected group of patients among those with good/intermediate risk. Clinical efficacy of intermittent treatment is consistent with previous studies and overall survival as expected in this group of patients. No concerns arose regarding rapid regrowth after discontinuation of therapy, with only 1 patient requiring early resumption of treatment during the initial break. With a median of 9 cycles saved per patient, the possibility of reduced toxicity and the nonnegligible cost savings, studies such as this are encouraging. Nevertheless, confirmation is needed from larger series. The ongoing randomized controlled STAR (Study of Tamoxifen and Raloxifene) will likely yield a definitive response to intermittent therapy in terms of clinical effectiveness and, equally important, quality of life gained per year in patients with cancer. M. Pilar Laguna, MD, PhD
Suggested Reading Lenis AT, Donin NM, Johnson DC et al: Adjuvant therapy for high risk localized kidney cancer: emerging evidence and future clinical trials. J Urol 2017; doi: 10.1016/j.juro.2017.04.092. Figlin R, Sternberg C and Wood CG: Novel agents and approaches for advanced renal cell carcinoma. J Urol 2012; 188: 707. Rini BI, Garcia J, Elson P et al: The effect of sunitinib on primary renal cell carcinoma and facilitation of subsequent surgery. J Urol 2012; 187: 1548. Atkinson BJ, Kalra S, Wang X et al: Clinical outcomes for patients with metastatic renal cell carcinoma treated with alternative sunitinib schedules. J Urol 2014; 191: 611.
0022-5347/18/1991-0001/0 THE JOURNAL OF UROLOGY® Ó 2017 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION
AND
RESEARCH, INC.
https://doi.org/10.1016/j.juro.2017.09.134 Vol. 199, 1-2, January 2018 Printed in U.S.A.
www.jurology.com Dochead: Urological Survey
LIT 5.5.0 DTD JURO15034_proof 7 October 2017 7:18 pm EO:
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ADRENAL, RENAL, URETERAL AND RETROPERITONEAL TUMORS
Berkers J, Govaere O, Wolter P et al: A possible role for microRNA-141 down-regulation in sunitinib resistant metastatic clear cell renal cell carcinoma through induction of epithelial-to-mesenchymal transition and hypoxia resistance. J Urol 2013; 189: 1930. Santoni M, Conti A, Porta C et al: Sunitinib, pazopanib or sorafenib for the treatment of patients with late relapsing metastatic renal cell carcinoma. J Urol 2015; 193: 41.
Re: Surgical Histopathology for Suspected Oncocytoma on Renal Mass Biopsy: A Systematic Review and Meta-Analysis H. D. Patel, S. C. Druskin, S. P. Rowe, P. M. Pierorazio, M. A. Gorin and M. E. Allaf Department of Urology, James Buchanan Brady Urological Institute, and Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland BJU Int 2017; 119: 661e666. doi: 10.1111/bju.13763
Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/28058773 Editorial Comment: This systematic review assesses the reliability of core renal mass biopsy (RMB) in diagnosing oncocytic renal neoplasm (ORN). Overall, 205 RMBs diagnostic of ORN were evaluated. The 48 masses (22.4%) that were surgically treated provided the grounds for standard pathology comparison. Meta-analysis showed that 64.6% of tumors were oncocytoma, 12.5% chromophobe renal cell carcinoma (RCC), 12.5% other RCC, 6.3% the more indolent hybrid oncocytic/chromophobe RCC and 4.2% other benign lesions. Sensitivity and specificity could not be determined due to the low percentage of cases with definitive pathology. Positive predictive value of the RMB for diagnosis of oncocytoma was 67%. With 1 of 3 RMB diagnoses being incorrect and 1 of 4 being an RCC, the negative predictive value for diagnosis of oncocytoma is low, with the authors concluding that RMB is unreliable in definitively diagnosing a renal mass as oncocytoma. Although the methodology of this systematic review is transparent and correct, the results are hampered by the inherent limitations of the existing literature. Significant heterogeneity among studies exists and most have a high risk of bias because of the high proportion of missing reference standards. Although the positive predictive value was reproduced in the low risk bias series, when individual studies are considered the rate of confirmative surgical pathology for diagnosis of oncocytoma varies widely (25% to 100%). This finding suggests that other factors have an important role in the RMB diagnosis of ORN, including tumor heterogeneity, difficulty in differentiating eosinophilic tumors and possibly differences between pathologists in interpretation. In addition to the chances of improving diagnosis by standardization of the advised nomenclature, application of advanced immunohistochemical panels and presence of dedicated uropathologists, it should be remembered that RMB is invasive and that molecular imaging, such as the recently reported use of 99mtechnetium-sestamibi single photon emission computerized tomography for renal tumors, may offer greater sensitivity and specificity for diagnosis of oncocytoma and hybrid oncocytic/ chromophobe RCC. M. Pilar Laguna, MD, PhD
Suggested Reading Richard PO, Jewett MA, Bhatt JR et al: Active surveillance for renal neoplasms with oncocytic features is safe. J Urol 2016; 195: 581. Ginzburg S, Uzzo R, Al-Saleem T et al: Coexisting hybrid malignancy in a solitary sporadic solid benign renal mass: implications for treating patients following renal biopsy. J Urol 2014; 191: 296. Jeon HG, Seo SI, Jeong BC et al: Percutaneous kidney biopsy for a small renal mass: a critical appraisal of results. J Urol 2016; 195: 568. Kutman K, S€uer E, Bed€uk Y et al: Is there a role of the enhancement degree of the lesion on computerized tomography for the characterization of renal tumors? J Urol 2013; 189: 436. Kawaguchi S, Fernandes KA, Finelli A et al: Most renal oncocytomas appear to grow: observations of tumor kinetics with active surveillance. J Urol 2011; 186: 1218.
Dochead: Urological Survey
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Urological Oncology: Adrenal, Renal, Ureteral and Retroperitoneal Tumors Re: A Phase II Study of Intermittent Sunitinib in Previously Untreated Patients with Metastatic Renal Cell Carcinoma M. C. Ornstein, L. S. Wood, P. Elson, K. D. Allman, J. Beach, A. Martin, B. R. Zanick, P. Grivas, T. Gilligan, J. A. Garcia and B. I. Rini Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio J Clin Oncol 2017; 35: 1764e1769. doi: 10.1200/JCO.2016.71.1184
Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/28113029 Editorial Comment: This phase II study investigated the feasibility, safety and clinical efficacy of first-line intermittent treatment with sunitinib in patients with metastatic renal cell carcinoma. A total of 37 patients received 4 initial cycles of sunitinib. Those with 10% or greater reduction of tumor burden were offered a treatment break. Therapy was reinitiated when there was an increase in tumor burden of 10% or more (compared to computerized tomogram findings before the break) or clinical progression. A total of 20 patients with a median decrease in tumor burden of 45% (range 13% to 86%) entered the intermittent phase. One patient withdrew at first reimaging because of progression. Objective response rate was 46%, and metastatic progression-free survival and overall survival were 22.4 and 34.8 months, respectively. Most patients in the study exhibited a stable radiological pattern, with a median increase in tumor burden of 1.6 cm during breaks and a median decrease of 1.4 cm while on treatment. Dose reduction and switch in treatment schedule were necessary in 19 and 9 patients, respectively, during the first 4 sunitinib cycles. Schedules and doses were continued during the repeat treatment periods, with only 2 patients stopping therapy because of a grade 2 to 3 adverse event. This study demonstrates the feasibility of extended treatment breaks in a selected group of patients among those with good/intermediate risk. Clinical efficacy of intermittent treatment is consistent with previous studies and overall survival as expected in this group of patients. No concerns arose regarding rapid regrowth after discontinuation of therapy, with only 1 patient requiring early resumption of treatment during the initial break. With a median of 9 cycles saved per patient, the possibility of reduced toxicity and the nonnegligible cost savings, studies such as this are encouraging. Nevertheless, confirmation is needed from larger series. The ongoing randomized controlled STAR (Study of Tamoxifen and Raloxifene) will likely yield a definitive response to intermittent therapy in terms of clinical effectiveness and, equally important, quality of life gained per year in patients with cancer. M. Pilar Laguna, MD, PhD
Suggested Reading Lenis AT, Donin NM, Johnson DC et al: Adjuvant therapy for high risk localized kidney cancer: emerging evidence and future clinical trials. J Urol 2017; doi: 10.1016/j.juro.2017.04.092. Figlin R, Sternberg C and Wood CG: Novel agents and approaches for advanced renal cell carcinoma. J Urol 2012; 188: 707. Rini BI, Garcia J, Elson P et al: The effect of sunitinib on primary renal cell carcinoma and facilitation of subsequent surgery. J Urol 2012; 187: 1548. Atkinson BJ, Kalra S, Wang X et al: Clinical outcomes for patients with metastatic renal cell carcinoma treated with alternative sunitinib schedules. J Urol 2014; 191: 611.
0022-5347/18/1991-0001/0 THE JOURNAL OF UROLOGY® Ó 2017 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION
AND
RESEARCH, INC.
https://doi.org/10.1016/j.juro.2017.09.134 Vol. 199, 1-2, January 2018 Printed in U.S.A.
www.jurology.com Dochead: Urological Survey
LIT 5.5.0 DTD JURO15034_proof 7 October 2017 7:18 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
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115 116 117 118 119 120 121 122 123 124 125 126 127 128 129 130 131 132 133 134 135 136 137 138 139 140 141 142 143 144 145 146 147 148 149 150 151 152 153 154 155 156 157 158 159 160 161 162 163 164 165 166 167 168 169 170 171 172 173 174 175 176
ADRENAL, RENAL, URETERAL AND RETROPERITONEAL TUMORS
Berkers J, Govaere O, Wolter P et al: A possible role for microRNA-141 down-regulation in sunitinib resistant metastatic clear cell renal cell carcinoma through induction of epithelial-to-mesenchymal transition and hypoxia resistance. J Urol 2013; 189: 1930. Santoni M, Conti A, Porta C et al: Sunitinib, pazopanib or sorafenib for the treatment of patients with late relapsing metastatic renal cell carcinoma. J Urol 2015; 193: 41.
Re: Surgical Histopathology for Suspected Oncocytoma on Renal Mass Biopsy: A Systematic Review and Meta-Analysis H. D. Patel, S. C. Druskin, S. P. Rowe, P. M. Pierorazio, M. A. Gorin and M. E. Allaf Department of Urology, James Buchanan Brady Urological Institute, and Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland BJU Int 2017; 119: 661e666. doi: 10.1111/bju.13763
Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/28058773 Editorial Comment: This systematic review assesses the reliability of core renal mass biopsy (RMB) in diagnosing oncocytic renal neoplasm (ORN). Overall, 205 RMBs diagnostic of ORN were evaluated. The 48 masses (22.4%) that were surgically treated provided the grounds for standard pathology comparison. Meta-analysis showed that 64.6% of tumors were oncocytoma, 12.5% chromophobe renal cell carcinoma (RCC), 12.5% other RCC, 6.3% the more indolent hybrid oncocytic/chromophobe RCC and 4.2% other benign lesions. Sensitivity and specificity could not be determined due to the low percentage of cases with definitive pathology. Positive predictive value of the RMB for diagnosis of oncocytoma was 67%. With 1 of 3 RMB diagnoses being incorrect and 1 of 4 being an RCC, the negative predictive value for diagnosis of oncocytoma is low, with the authors concluding that RMB is unreliable in definitively diagnosing a renal mass as oncocytoma. Although the methodology of this systematic review is transparent and correct, the results are hampered by the inherent limitations of the existing literature. Significant heterogeneity among studies exists and most have a high risk of bias because of the high proportion of missing reference standards. Although the positive predictive value was reproduced in the low risk bias series, when individual studies are considered the rate of confirmative surgical pathology for diagnosis of oncocytoma varies widely (25% to 100%). This finding suggests that other factors have an important role in the RMB diagnosis of ORN, including tumor heterogeneity, difficulty in differentiating eosinophilic tumors and possibly differences between pathologists in interpretation. In addition to the chances of improving diagnosis by standardization of the advised nomenclature, application of advanced immunohistochemical panels and presence of dedicated uropathologists, it should be remembered that RMB is invasive and that molecular imaging, such as the recently reported use of 99mtechnetium-sestamibi single photon emission computerized tomography for renal tumors, may offer greater sensitivity and specificity for diagnosis of oncocytoma and hybrid oncocytic/ chromophobe RCC. M. Pilar Laguna, MD, PhD
Suggested Reading Richard PO, Jewett MA, Bhatt JR et al: Active surveillance for renal neoplasms with oncocytic features is safe. J Urol 2016; 195: 581. Ginzburg S, Uzzo R, Al-Saleem T et al: Coexisting hybrid malignancy in a solitary sporadic solid benign renal mass: implications for treating patients following renal biopsy. J Urol 2014; 191: 296. Jeon HG, Seo SI, Jeong BC et al: Percutaneous kidney biopsy for a small renal mass: a critical appraisal of results. J Urol 2016; 195: 568. Kutman K, S€uer E, Bed€uk Y et al: Is there a role of the enhancement degree of the lesion on computerized tomography for the characterization of renal tumors? J Urol 2013; 189: 436. Kawaguchi S, Fernandes KA, Finelli A et al: Most renal oncocytomas appear to grow: observations of tumor kinetics with active surveillance. J Urol 2011; 186: 1218.
Dochead: Urological Survey
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