TY - JOUR
T1 - The evolving role of cytoreductive nephrectomy
T2 - Incorporating genomics of metastatic renal cell carcinoma into treatment decisions
AU - Mano, Roy
AU - Gopal, Nikhil
AU - Hakimi, A. Ari
N1 - Publisher Copyright:
© 2019 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2019/9/1
Y1 - 2019/9/1
N2 - Purpose of review Recent publications evaluating cytoreductive nephrectomy in the era of targeted therapy emphasize the importance of patient selection. We reviewed the predictive role of genetic alterations in patients with metastatic renal cell carcinoma (mRCC) undergoing cytoreductive nephrectomy.Recent findingsStudies evaluating the association between genetic alterations and outcomes following systemic treatment for mRCC include mainly patients after cytoreductive nephrectomy. Expression of proangiogenic genes, single nucleotide polymorphisms involving genes of the vascular-endothelial growth factor (VEGF) pathway and somatic mutations of chromatin remodeling genes were associated with response to VEGF-targeted therapy. Outcomes following treatment with mammalian target of rapamycin (mTOR) inhibitors were initially associated with mTOR/TSC1/TSC2 mutations; however, subsequent studies did not validate these findings but rather found an association between loss of PTEN expression and PBRM1 mutations and improved outcomes. Loss of PBRM1 was initially linked to response to immunotherapy; however, larger studies question this association and showed high expression of T-effector gene signature predicted improved outcome. Primary tumors with low intratumor heterogeneity but elevated somatic copy-number alterations were associated with rapid progression at multiple sites.SummaryGenetic alterations may help select patients for cytoreductive nephrectomy and optimize timing of treatment. Intratumor heterogeneity and genetic discordance between primary and metastatic tumors may limit clinical applicability. Future studies should evaluate approaches to overcome these limitations.
AB - Purpose of review Recent publications evaluating cytoreductive nephrectomy in the era of targeted therapy emphasize the importance of patient selection. We reviewed the predictive role of genetic alterations in patients with metastatic renal cell carcinoma (mRCC) undergoing cytoreductive nephrectomy.Recent findingsStudies evaluating the association between genetic alterations and outcomes following systemic treatment for mRCC include mainly patients after cytoreductive nephrectomy. Expression of proangiogenic genes, single nucleotide polymorphisms involving genes of the vascular-endothelial growth factor (VEGF) pathway and somatic mutations of chromatin remodeling genes were associated with response to VEGF-targeted therapy. Outcomes following treatment with mammalian target of rapamycin (mTOR) inhibitors were initially associated with mTOR/TSC1/TSC2 mutations; however, subsequent studies did not validate these findings but rather found an association between loss of PTEN expression and PBRM1 mutations and improved outcomes. Loss of PBRM1 was initially linked to response to immunotherapy; however, larger studies question this association and showed high expression of T-effector gene signature predicted improved outcome. Primary tumors with low intratumor heterogeneity but elevated somatic copy-number alterations were associated with rapid progression at multiple sites.SummaryGenetic alterations may help select patients for cytoreductive nephrectomy and optimize timing of treatment. Intratumor heterogeneity and genetic discordance between primary and metastatic tumors may limit clinical applicability. Future studies should evaluate approaches to overcome these limitations.
KW - cytoreductive nephrectomy
KW - genomics
KW - metastatic renal cell carcinoma
KW - outcome
UR - http://www.scopus.com/inward/record.url?scp=85070848695&partnerID=8YFLogxK
U2 - 10.1097/MOU.0000000000000663
DO - 10.1097/MOU.0000000000000663
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C2 - 31313716
AN - SCOPUS:85070848695
SN - 0963-0643
VL - 29
SP - 531
EP - 539
JO - Current Opinion in Urology
JF - Current Opinion in Urology
IS - 5
ER -