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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/cdn\/css\/http\/css_Xg7z6oCTVgud_Q0huYz9x9iiD5H_2YPSJ5z2ZViSWdY.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n            \u003Cp id=\u0022p-1\u0022\u003ETreatment of advanced genitourinary cancers remains challenging. This article provides updates in genitourinary oncology addressed some important questions in the field that need answers to improve patient outcomes. Specific topics include clinical trial data for the currently approved agents, unresectable bladder cancer, as well as the treatment of metastatic renal cell carcinoma.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EReproductive Cancers\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EGastrointestinal Cancers\u003C\/li\u003E\u003C\/ul\u003E\u003Cul class=\u0022kwd-group clinical-trial\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EReproductive Cancers\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EOncology\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EGastrointestinal Cancers\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003ETreatment of advanced genitourinary cancers remains challenging. A session on updates in genitourinary oncology addressed some important questions in the field that need answers to improve patient outcomes.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EMetastatic, castration-resistant prostate cancer (mCRPC) is clinically and pathologically heterogeneous between patients as well as within a given patient. CRPC is driven by androgen receptor (AR) signaling. AR alterations are selected during therapy. Resistance can be driven by androgen production in the testis, adrenal glands, or prostate tumor; AR overexpression; AR splice variations; AR mutants; signaling cross-talk; and upregulation of AR cofactors [Hu R et al. \u003Cem\u003EExpert Rev Endocrinol Metab\u003C\/em\u003E. 2010; Heinlen C, Chang C. \u003Cem\u003EEndocr Rev.\u003C\/em\u003E 2004].\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EThe current treatment paradigm for prostate is evolving, as shown in \u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E. There are a lot of drugs available, but the optimal order in which to use them is not known, nor is the best combination or sequence known.\u003C\/p\u003E\u003Cdiv id=\u0022F1\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/36\/25\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Current Treatment Paradigm for Prostate Cancer Is Evolving\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-886805739\u0022 data-figure-caption=\u0022Current Treatment Paradigm for Prostate Cancer Is Evolving\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 1.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/36\/25\/F1.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/36\/25\/F1.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 1.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/36\/25\/F1.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/12102\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption attrib\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 1.\u003C\/span\u003E \n            \u003Cp id=\u0022p-5\u0022 class=\u0022first-child\u0022\u003ECurrent Treatment Paradigm for Prostate Cancer Is Evolving\u003C\/p\u003E\n         \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-1\u0022\u003EADT, androgen deprivation therapy; mCRPC, metastatic castration-resistant prostate cancer.\u003C\/q\u003E\u003Cq class=\u0022attrib\u0022 id=\u0022attrib-2\u0022\u003EReproduced with permission from CN Sternberg, MD.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-6\u0022\u003ECora N. Sternberg, MD, San Camillo and Forlanini Hospitals, Rome, Italy, reviewed clinical trial data for the currently approved agents. There are no prospective trial data available concerning sequencing of the newer agents. In addition, clinical or molecular predictive factors are urgently needed. Ongoing phase 3 trials, however, are beginning to address these gaps.\u003C\/p\u003E\u003Cp id=\u0022p-7\u0022\u003EOne exciting development is the discovery of AR splice variants. Of the 20 or so described, AR-V7 is the most common, and patients who express it have a 0% prostate-specific antigen (PSA) response to either abiraterone or enzalutamide [Antonarakis ES et al. \u003Cem\u003EN Engl J Med.\u003C\/em\u003E 2014]. In those patients without AR-V7, PSA responses are 68% and 53%, respectively. Splice variants were measured in circulating tumor cells in the blood so they are easier to measure than AR nuclear expression, which requires a bone marrow biopsy. If these results are validated, it may guide future treatment.\u003C\/p\u003E\u003Cp id=\u0022p-8\u0022\u003EUnlike prostate cancer, bladder cancer, particularly when unresectable or inoperable, has not been the subject of many large, randomized, controlled clinical trials despite more than half a million new cases of bladder cancer yearly worldwide. Peak incidence is around the seventh decade of life, and 20% of patients are older than 80 years, so bladder cancer will become an enormous challenge as the population ages.\u003C\/p\u003E\u003Cp id=\u0022p-9\u0022\u003EMaria De Santis, MD, Center for Oncology and Hematology, Vienna, Austria, discussed unresectable bladder cancer, calling the outcome of patients with this disease dismal, in part because there is no salvage therapy for surgery that leaves positive margins.\u003C\/p\u003E\u003Cp id=\u0022p-10\u0022\u003EOld trial data suggest it may be possible to treat inoperable bladder cancer with chemotherapy alone. Unpublished data from recent European Organization for Research and Treatment of Cancer (EORTC) subgroup analyses for patients treated with various types of combination chemotherapy demonstrated a clinical, not pathologic, complete response (CR) rate of up to 23% and an overall response rate of nearly 50%, but this involves very small numbers of patients. In addition, the relapse rate is high after CR. Therefore, chemotherapy alone is not recommended as primary therapy for localized bladder cancer, according to the European Association of Urology 2014 guidelines [Babjuk M et al. \u003Cem\u003EEur Urol\u003C\/em\u003E. 2014].\u003C\/p\u003E\u003Cp id=\u0022p-11\u0022\u003EThere has been no head-to-head comparison of radiotherapy with surgery, and trials of each modality have occurred in different patient populations. Five-year survival rates appear to be similar, however, so radiotherapy could be an alternative to radical cystectomy in patients who refuse or are unfit for surgery. Hypofractionated radiotherapy has been shown in older retrospective trials in small numbers of patients to be well tolerated and an option for palliation of pain and hematuria in muscle-invasive bladder cancer in frail elderly patients.\u003C\/p\u003E\u003Cp id=\u0022p-12\u0022\u003EChemoradiation is also feasible, and it provides a palliative benefit and, in rare instances, long-term disease-free survival. It has been studied, however, only in early-phase trials in small numbers of patients who were negatively selected because they were unfit for surgery or their tumors were not amenable to surgery, and these trials had very different end points.\u003C\/p\u003E\u003Cp id=\u0022p-13\u0022\u003EBernard Escudier, MD, Institute Gustave Roussy, Villejuif, France, discussed the treatment of metastatic renal cell carcinoma (mRCC). He pointed out that genomic classification lags behind that of other tumor types, although genomic signatures are being developed.\u003C\/p\u003E\u003Cp id=\u0022p-14\u0022\u003ERisk assessment is important in mRCC. Prof, Escudier recommended using the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) criteria for risk evaluation [Heng DYC et al. \u003Cem\u003EJ Clin Oncol\u003C\/em\u003E. 2009]. The 6 risk factors include (1) Karnofsky performance status \u0026lt; 80%, (2) hemoglobin less than the lower limit of normal, (3) time from diagnosis to treatment \u0026lt; 1 year, (4) corrected calcium greater than the upper limit of normal (ULN), (5) platelets \u0026gt; ULN, and (6) neutrophils \u0026gt; ULN. Patients with none of these factors have a favorable prognosis, those with 1 or 2 have an intermediate prognosis, and those with 3 or more have a poor prognosis.\u003C\/p\u003E\u003Cp id=\u0022p-15\u0022\u003ETreatment recommendations from the European Society For Medical Oncology (ESMO) 2014 Clinical Practice Guidelines for RCC are summarized in \u003Ca id=\u0022xref-table-wrap-1-1\u0022 class=\u0022xref-table\u0022 href=\u0022#T1\u0022\u003ETable 1\u003C\/a\u003E [Escudier B et al. \u003Cem\u003EAnn Oncol\u003C\/em\u003E. 2014].\u003C\/p\u003E\u003Cdiv id=\u0022T1\u0022 class=\u0022table pos-float\u0022\u003E\u003Cdiv class=\u0022table-inline\u0022\u003E\u003Cdiv class=\u0022callout\u0022\u003E\u003Cspan\u003EView this table:\u003C\/span\u003E\u003Cul class=\u0022callout-links\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022\/\u0022 class=\u0022table-expand-inline\u0022 data-table-url=\u0022\/highwire\/markup\/12103\/expansion?postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed\u0026amp;table-expand-inline=1\u0022 html=\u00221\u0022 fragment=\u0022#\u0022 external=\u00221\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView inline\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022\/highwire\/markup\/12103\/expansion?width=1000\u0026amp;height=500\u0026amp;iframe=true\u0026amp;postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media\u0022 class=\u0022colorbox colorbox-load table-expand-popup\u0022 rel=\u0022gallery-fragment-tables\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView popup\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/12103\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv class=\u0022table-caption\u0022\u003E\u003Cspan class=\u0022table-label\u0022\u003ETable 1.\u003C\/span\u003E \n            \u003Cp id=\u0022p-16\u0022 class=\u0022first-child\u0022\u003ERenal Cell Carcinoma: ESMO Clinical Practice Guidelines for Diagnosis, Treatment, and Follow-Up\u003C\/p\u003E\n         \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-19\u0022\u003EThe role of nephrectomy is not clear, although patients with poor IMDC risk factors should not undergo surgery.\u003C\/p\u003E\u003Cp id=\u0022p-20\u0022\u003EIf a CR is achieved, which is not common, it is not clear what should be done. Prof. Escudier recommends that if CR is achieved with systemic treatment only, that treatment should be continued for 2 to 3 months to confirm CR, then discontinued. If CR was achieved with systemic plus local treatment, treatment should stop after the local treatment. A \u201cdrug holiday\u201d is feasible, particularly in patients with indolent, stable disease. The appropriate time to switch to second-line therapy is not known. Prof. Escudier suggested that if a patient has primary refractory disease (ie, no response to a drug after 3 months of therapy), if an active second-line treatment is available, it should be used.\u003C\/p\u003E\u003Cp id=\u0022p-21\u0022\u003EThe future of RCC treatment may lie with new agents, such as checkpoint inhibitors (eg, nivolumab) that target programed death-1 (PD-1) receptors, as well as with cMet inhibitors. Other needs in RCC are the development of biomarkers to select the best therapy for patients, and determination of the best combinations of therapies.\u003C\/p\u003E\u003Cp id=\u0022p-22\u0022\u003ETo improve treatment of genitourinary cancers, more large prospective clinical trials are needed to test new and combination therapies. In addition, translational research is needed for the identification of biomarkers and establishment of prognostic genetic profiles to personalize therapy for patients with mCRPC, unresectable bladder cancer, and RCC.\u003C\/p\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2014 MD Conference Express\u00ae\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/14\/36\/25.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_figures.js?nzm0a2\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzm0a2\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_tables.js?nzm0a2\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}