38 results on '"Rana, R"'
Search Results
2. Outcomes for International Metastatic Renal Cell Carcinoma Database Consortium Prognostic Groups in Contemporary First-line Combination Therapies for Metastatic Renal Cell Carcinoma
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Ernst, Matthew S., Navani, Vishal, Wells, J. Connor, Donskov, Frede, Basappa, Naveen, Labaki, Chris, Pal, Sumanta K., Meza, Luis, Wood, Lori A., Ernst, D. Scott, Szabados, Bernadett, McKay, Rana R., Parnis, Francis, Suarez, Cristina, Yuasa, Takeshi, Lalani, Aly-Khan, Alva, Ajjai, Bjarnason, Georg A., Choueiri, Toni K., and Heng, Daniel Y.C.
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- 2023
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3. The Role of Stereotactic Ablative Body Radiotherapy in Renal Cell Carcinoma
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Ali, Muhammad, Mooi, Jennifer, Lawrentschuk, Nathan, McKay, Rana R., Hannan, Raquibul, Lo, Simon S., Hall, William A., and Siva, Shankar
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- 2022
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4. Outcomes of Patients with Brain Metastases from Renal Cell Carcinoma Receiving First-line Therapies: Results from the International Metastatic Renal Cell Carcinoma Database Consortium
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Takemura, Kosuke, Lemelin, Audreylie, Ernst, Matthew S., Wells, J. Connor, Saliby, Renee Maria, El Zarif, Talal, Labaki, Chris, Basappa, Naveen S., Szabados, Bernadett, Powles, Thomas, Davis, Ian D., Wood, Lori A., Lalani, Aly-Khan A., McKay, Rana R., Lee, Jae-Lyun, Meza, Luis, Pal, Sumanta K., Donskov, Frede, Yuasa, Takeshi, Beuselinck, Benoit, Gebrael, Georges, Agarwal, Neeraj, Choueiri, Toni K., and Heng, Daniel Y.C.
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- 2024
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5. Corrigendum to “Outcomes for International Metastatic Renal Cell Carcinoma Database Consortium Prognostic Groups in Contemporary First-line Combination Therapies for Metastatic Renal Cell Carcinoma” [Eur Urol 2023]
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Ernst, Matthew S., primary, Navani, Vishal, additional, Wells, J. Connor, additional, Donskov, Frede, additional, Basappa, Naveen, additional, Labaki, Chris, additional, Pal, Sumanta K., additional, Meza, Luis, additional, Wood, Lori A., additional, Ernst, D. Scott, additional, Szabados, Bernadett, additional, McKay, Rana R., additional, Parnis, Francis, additional, Suarez, Cristina, additional, Yuasa, Takeshi, additional, Lalani, Aly-Khan, additional, Alva, Ajjai, additional, Bjarnason, Georg A., additional, Choueiri, Toni K., additional, and Heng, Daniel Y.C., additional
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- 2023
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6. Primary Cytoreductive Nephrectomy: Standing the Test of Time?
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Derweesh, Ithaar H., primary, McKay, Rana R., additional, and Bagrodia, Aditya, additional
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- 2023
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7. Corrigendum to 'Outcomes for International Metastatic Renal Cell Carcinoma Database Consortium Prognostic Groups in Contemporary First-line Combination Therapies for Metastatic Renal Cell Carcinoma' [Eur Urol 2023]
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Matthew S. Ernst, Vishal Navani, J. Connor Wells, Frede Donskov, Naveen Basappa, Chris Labaki, Sumanta K. Pal, Luis Meza, Lori A. Wood, D. Scott Ernst, Bernadett Szabados, Rana R. McKay, Francis Parnis, Cristina Suarez, Takeshi Yuasa, Aly-Khan Lalani, Ajjai Alva, Georg A. Bjarnason, Toni K. Choueiri, and Daniel Y.C. Heng
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Urology - Published
- 2023
8. Corrigendum to “The Role of Stereotactic Ablative Body Radiotherapy in Renal Cell Carcinoma” [Eur Urol 2022]
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Ali, Muhammad, primary, Mooi, Jennifer, additional, Lawrentschuk, Nathan, additional, McKay, Rana R., additional, Hannan, Raquibul, additional, Lo, Simon S., additional, Hall, William A., additional, and Siva, Shankar, additional
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- 2022
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9. Primary Cytoreductive Nephrectomy: Standing the Test of Time?
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Ithaar H. Derweesh, Rana R. McKay, and Aditya Bagrodia
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Urology - Published
- 2022
10. Prognostic Significance of Bone Metastases and Bisphosphonate Therapy in Patients with Renal Cell Carcinoma
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McKay, Rana R., Lin, Xun, Perkins, Julia J., Heng, Daniel Y.C., Simantov, Ronit, and Choueiri, Toni K.
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- 2014
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11. The Role of Stereotactic Ablative Body Radiotherapy in Renal Cell Carcinoma
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Muhammad Ali, Jennifer Mooi, Nathan Lawrentschuk, Rana R. McKay, Raquibul Hannan, Simon S. Lo, William A. Hall, and Shankar Siva
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Urology ,Humans ,Prospective Studies ,Radiosurgery ,Carcinoma, Renal Cell ,Kidney Neoplasms ,Retrospective Studies - Abstract
Stereotactic ablative body radiotherapy (SABR) is an emerging treatment modality for primary and metastatic renal cell carcinoma (RCC).To review and summarise the evidence on the use of SABR in RCC in a narrative review.We performed an online search of the PubMed database from January 2000 through December 2021. Studies of SABR/stereotactic radiosurgery (SRS) targeting primary, extracranial, or intracranial metastatic RCC were included.Two meta-analyses (including 54 studies), and 13 prospective and 20 retrospective studies were included in this review. In aggregate, SABR for 589 primary RCCs in 575 patients resulted in a local control rate of above 90% with grade 3-4 toxicity of 0-9%. Similarly, the local control rate ranged between 90% and 97% with SRS in 1225 patients with intracranial metastatic RCC. SABR was able to delay systemic therapy for at least 1 yr in 70-90% of oligometastatic RCC patients with grade 3-4 toxicity of10%. As per the early data, the combination of SABR with systemic therapy for metastatic RCC, such as targeted therapy or immunotherapy, appears safe, feasible, and tolerable.We outlined data supporting SABR in the key clinical scenarios of primary and metastatic, including oligometastatic, RCC in lieu of systemic therapy, in combination with systemic therapy, and palliation of brain and spinal metastases.Stereotactic ablative body radiotherapy (SABR) is a relatively new treatment option in kidney cancer. Here, we review the published literature on the experience of using SABR in kidney cancer. The accumulated evidence demonstrates that SABR can be used safely and effectively to treat selected cases of primary or secondary kidney cancer.
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- 2022
12. Response of Primary Renal Cell Carcinoma to Systemic Therapy
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Toni K. Choueiri, Aly-Khan A. Lalani, Ronit Simantov, Ithaar Derweesh, Xun Lin, Dominick Bossé, Rana R. McKay, and Steven L. Chang
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Male ,Oncology ,medicine.medical_specialty ,Urology ,medicine.medical_treatment ,Population ,030232 urology & nephrology ,Systemic therapy ,03 medical and health sciences ,Clinical Trials, Phase II as Topic ,0302 clinical medicine ,Renal cell carcinoma ,Internal medicine ,medicine ,Humans ,Prospective Studies ,education ,Carcinoma, Renal Cell ,education.field_of_study ,business.industry ,Middle Aged ,medicine.disease ,Primary tumor ,Kidney Neoplasms ,Nephrectomy ,Clinical trial ,Treatment Outcome ,Clinical Trials, Phase III as Topic ,Response Evaluation Criteria in Solid Tumors ,030220 oncology & carcinogenesis ,Female ,business ,Kidney cancer - Abstract
Background Upfront cytoreductive nephrectomy (CRN) in renal cell carcinoma (RCC) has come into question in recent prospective clinical trials. Objective We investigated the effect of systemic therapies on primary tumor response in patients with metastatic RCC. Design, setting, and participants A pooled analysis of 12 phase II/III clinical trials of metastatic RCC patients treated with systemic therapy between 2003 and 2013 was performed. Patients with one target lesion in the kidney and no prior nephrectomy were identified as having their primary tumor in place. Outcome measurements and statistical analysis The objective response rate (ORR) of the primary tumor was defined as per the Response Evaluation Criteria in Solid Tumors (RECIST). ORR was assessed in the overall population and patient subsets based on prior treatment and International Metastatic RCC Database Consortium (IMDC) risk group. Cox’s models adjusting for baseline characteristics, treatment, line of therapy, and site of metastases were used for survival analyses. Results and limitations In total, 4736 patients were identified, of whom 565 had their primary tumor in place: 461 (82%) were treatment naive, 283 (50%) received first-line vascular endothelial growth factor (VEGF)-targeted therapy, and 222 (39%) were IMDC poor risk. The ORRs of the primary tumor were 19% (95% confidence interval 16–23) in patients treated with first-line therapy (any type), 28% (22–33) in those treated with first-line VEGF-targeted therapy, and 23% (19–28) in those treated with VEGF-targeted therapy (any line). The ORRs were 9% (5–13) and 20% (15–27) in IMDC poor- and intermediate-risk patients, respectively. Conclusions Systemic therapy reduces primary tumor size in patients with metastatic RCC. Responses in primary tumors treated with VEGF-targeted therapy were observed in upward of 28% of patients. Selection of patients for immediate CRN requires careful consideration of patient and disease characteristics. Patient summary Antiangiogenic therapy meaningfully decreases the size of primary kidney tumor. Hence, for patients with metastatic disease who are not undergoing upfront cytoreductive nephrectomy, systemic therapy can palliate both primary tumor and metastases.
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- 2019
13. Corrigendum to 'The Role of Stereotactic Ablative Body Radiotherapy in Renal Cell Carcinoma' [Eur Urol 2022]
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Muhammad Ali, Jennifer Mooi, Nathan Lawrentschuk, Rana R. McKay, Raquibul Hannan, Simon S. Lo, William A. Hall, and Shankar Siva
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Urology - Published
- 2022
14. Impact of Pathogenic Germline DNA Damage Repair alterations on Response to Intense Neoadjuvant Androgen Deprivation Therapy in High-risk Localized Prostate Cancer
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Berchuck, Jacob E., primary, Zhang, Zhenwei, additional, Silver, Rebecca, additional, Kwak, Lucia, additional, Xie, Wanling, additional, Lee, Gwo-Shu Mary, additional, Freedman, Matthew L., additional, Kibel, Adam S., additional, Van Allen, Eliezer M., additional, McKay, Rana R., additional, and Taplin, Mary-Ellen, additional
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- 2021
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15. Impact of Pathogenic Germline DNA Damage Repair alterations on Response to Intense Neoadjuvant Androgen Deprivation Therapy in High-risk Localized Prostate Cancer
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Jacob E. Berchuck, Rana R. McKay, Gwo-Shu Mary Lee, Mary-Ellen Taplin, Rebecca Silver, Eliezer M. Van Allen, Zhenwei Zhang, Adam S. Kibel, Wanling Xie, Matthew L. Freedman, and Lucia Kwak
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Biochemical recurrence ,Oncology ,Male ,medicine.medical_specialty ,DNA Repair ,medicine.drug_class ,Urology ,medicine.medical_treatment ,Genes, BRCA2 ,030232 urology & nephrology ,Androgen deprivation therapy ,03 medical and health sciences ,Prostate cancer ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Neoadjuvant therapy ,Germ-Line Mutation ,Aged ,Prostatectomy ,business.industry ,Prostatic Neoplasms ,Androgen Antagonists ,Sequence Analysis, DNA ,Middle Aged ,Androgen ,medicine.disease ,Minimal residual disease ,Neoadjuvant Therapy ,Germ Cells ,030220 oncology & carcinogenesis ,Hormone therapy ,Neoplasm Recurrence, Local ,business ,DNA Damage - Abstract
Background Intense neoadjuvant androgen deprivation therapy (ADT) before radical prostatectomy (RP) is an investigational approach to reduce recurrence rates in men with high-risk localized prostate cancer (PCa). The impact of germline DNA damage repair (gDDR) gene alterations on response to intense neoadjuvant ADT is not known. Objective To evaluate the prevalence of gDDR alterations among men with localized PCa at high risk of recurrence and evaluate their impact on response to intense neoadjuvant ADT. Design, setting, and participants We performed germline panel sequencing for 201 men with intermediate- and high-risk localized PCa from five randomized multicenter clinical trials of intense neoadjuvant ADT before RP. Intervention Intense neoadjuvant ADT followed by RP. Outcome measurements and statistical analysis The prevalence of pathogenic gDDR alterations and their association with exceptional pathologic response (complete response or minimal residual disease, defined as residual tumor with the largest cross-section dimension ≤5 mm) to intense neoadjuvant ADT and rates of post-RP biochemical recurrence. Results and limitations Pathogenic gDDR alterations were detected in 19 (9.5%) of the 201 PCa patients. The most frequently altered genes were BRCA2 (n = 6; 3.0%) and ATM (n = 4; 2.0%). Patients with gDDR alterations exhibited similar rates of exceptional pathologic response (26% vs 22%), pT3 disease (42% vs 53%), lymph node involvement (5.3% vs 10%), extraprostatic extension (35% vs 54%), and positive margins (5.3% vs 13%) to patients without gDDR alterations (all p > 0.05). The 3-yr biochemical recurrence–free survival was also similar at 45% (95% confidence interval 7.9–78%) for men with gDDR alterations and 55% (95% confidence interval 44–64%) for men without gDDR alterations. Conclusions gDDR alterations are common among men with intermediate- and high-risk localized PCa. Men with gDDR alterations appear to have a comparable response to intense neoadjuvant ADT to that among men without gDDR alterations and should not be excluded from consideration for this treatment approach. Patient summary Intense therapy to inhibit the production of androgen hormones (eg, testosterone) before surgery may minimize the risk of cancer recurrence for men with high-risk localized prostate cancer. Inherited mutations in certain DNA repair genes are associated with particularly high rates of recurrence. We found that men with these mutations respond equally well to this intense androgen inhibition before surgery as men without the mutations.
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- 2020
16. Response of Primary Renal Cell Carcinoma to Systemic Therapy
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Bossé, Dominick, primary, Lin, Xun, additional, Simantov, Ronit, additional, Lalani, Aly-Khan A., additional, Derweesh, Ithaar, additional, Chang, Steven L., additional, Choueiri, Toni K., additional, and McKay, Rana R., additional
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- 2019
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17. The Role of miRNAs in Prostate Cancer
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Philip W. Kantoff, Gwo-Shu Mary Lee, Tong Sun, and Rana R. McKay
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Male ,business.industry ,Urology ,Prostatic Neoplasms ,Disease ,Prostate-Specific Antigen ,urologic and male genital diseases ,medicine.disease ,medicine.disease_cause ,Androgen receptor ,Androgen deprivation therapy ,MicroRNAs ,Prostate-specific antigen ,Prostate cancer ,Immunology ,microRNA ,Cancer research ,Humans ,Medicine ,Biomarker (medicine) ,Kallikreins ,business ,Carcinogenesis - Abstract
Prostate cancer (PCa) is one of the leading causes of cancer morbidity and mortality in developed countries. It is a heterogeneous disease with a variable natural history. Despite standard local therapies that include surgery and radiotherapy, a proportion of patients with localized PCa develop disease progression. Androgen deprivation therapy (ADT) is an effective systemic therapy for recurrent or metastatic PCa. Among patients with advanced disease, despite initial responses to ADT, nearly all men develop resistance to primary ADT and their disease evolves to castration-resistant prostate cancer (CRPC). The emergence of CRPC heralds a lethal disease state. Molecular alterations such as chromosomal instability, epigenetic silencing, and changes in tumor-suppressor genes are associated with PCa tumorigenesis. In addition, androgen receptor signaling continues to play a critical role in PCa progression following castration. Measurement of prostate-specific antigen (PSA), a prototypical androgenregulated gene, is the current gold standard biomarker for PCa diagnosis and response to treatment, despite its wellknown limitations. The lack of sensitivity and specificity of PSA testing has contributed to controversy over the utility of PSA screening and monitoring [1]. Understanding the regulatory machinery involved in PSA synthesis, accumulation, and stability in PCa cells may help to improve the accuracy of PSA testing for PCa detection and prognostic prediction. In this issue of European Urology, Larne et al [2] identified miR-183 as a regulator of PSA expression through a gain-of-function screen. These findings offer new insights into PSA regulation and may enhance the value of PSA testing in clinical practice. miRNAs (miRs) are short noncoding RNAs, with an average length of 22 nucleotides. After their discovery in 1993, it was found that miRs function as post-transcriptional regulators that bind to complementary sequences on target mRNA, usually in the 3 0 untranslated region. Such binding usually results in mRNA degradation or translational repression, consequently reducing expression levels of encoded protein. Intriguingly, it has since been shown that miRs induce gene expression by binding to complementary promoter sequences [3]. We now recognize that the miR network is complex. Each individual miR can target hundreds of RNA transcripts, and each gene can be targeted by multiple miRs. The function of a given miR is largely determined by the relative availability of the target mRNAs [4].
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- 2015
18. Prognostic significance of bone metastases and bisphosphonate therapy in patients with renal cell carcinoma
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Rana R. McKay, Ronit Simantov, Julia J Perkins, Xun Lin, Daniel Y.C. Heng, and Toni K. Choueiri
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Oncology ,Male ,Vascular Endothelial Growth Factor A ,Indoles ,Axitinib ,Pamidronate ,Zoledronic Acid ,Renal cell carcinoma ,Sunitinib ,Renal Insufficiency ,education.field_of_study ,Bone Density Conservation Agents ,Diphosphonates ,TOR Serine-Threonine Kinases ,Imidazoles ,Middle Aged ,Sorafenib ,Prognosis ,Temsirolimus ,Kidney Neoplasms ,Survival Rate ,Bisphosphonate-Associated Osteonecrosis of the Jaw ,Female ,medicine.drug ,Niacinamide ,medicine.medical_specialty ,Indazoles ,Urology ,Population ,Antineoplastic Agents ,Bone Neoplasms ,Disease-Free Survival ,Internal medicine ,medicine ,Humans ,Pyrroles ,education ,Survival rate ,Carcinoma, Renal Cell ,Aged ,Retrospective Studies ,Sirolimus ,Bisphosphonate-associated osteonecrosis of the jaw ,Hypocalcemia ,business.industry ,Phenylurea Compounds ,Interferon-alpha ,medicine.disease ,Surgery ,business - Abstract
Bone metastases (BMs) are frequently present in patients with metastatic renal cell carcinoma (mRCC) and cause significant morbidity.The purpose of this analysis was to assess the impact of BMs and bisphosphonate therapy (BT) on outcomes in mRCC.We conducted a pooled analysis of patients with mRCC treated from 2003 to 2011 in phase 2 and 3 trials.Statistical analyses were performed using Cox regression and the Kaplan-Meier method.We identified 2749 patients treated with sunitinib (n=1059), sorafenib (n=355), axitinib (n=359), temsirolimus (n=208), temsirolimus plus interferon-α (IFN-α) (n=208), or IFN-α (n=560), with 28% (n=781) having BMs. A total of 285 patients (10.4%) received BT. The presence of BMs in patients was associated with shorter overall survival (OS) when compared with patients without BMs (13.2 vs 20.2 mo, respectively; p0.0001) and shorter progression-free survival (PFS) (5.1 vs 6.7 mo, respectively; p0.0008). When stratified by risk groups, the presence of BMs was associated with shorter OS in all risk groups. The use of BT in patients with BMs was not associated with improved OS compared with patients who did not receive BT (13.3 vs 13.1 mo, respectively; p=0.3801) or improved PFS (5.1 vs 4.9 mo, respectively; p=0.1785). Bisphosphonate users with BMs did not have a decreased rate of skeletal-related events (SREs) compared with nonusers (8.6% vs 5.8%, respectively; p=0.191). In addition, BT was associated with increased rates of hypocalcemia, renal insufficiency, and osteonecrosis of the jaw (p0.0001). Data were analyzed retrospectively.We confirm that the presence of BMs is associated with shorter survival in mRCC. BT did not affect survival or SRE prevention and was associated with increased toxicity.In this analysis, we demonstrate that bone metastases are associated with shorter survival in patients with metastatic renal cell carcinoma. In addition, we call into question the utility of bisphosphonate therapy in this population.
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- 2013
19. Depth of Remission is a Prognostic Factor for Survival in Patients with Metastatic Renal Cell Carcinoma
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Grünwald, Viktor, primary, McKay, Rana R., additional, Krajewski, Katherine M., additional, Kalanovic, Daniel, additional, Lin, Xun, additional, Perkins, Julia J., additional, Simantov, Ronit, additional, and Choueiri, Toni K., additional
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- 2015
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20. Impact of Bone and Liver Metastases on Patients with Renal Cell Carcinoma Treated with Targeted Therapy
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McKay, Rana R., primary, Kroeger, Nils, additional, Xie, Wanling, additional, Lee, Jae-Lyun, additional, Knox, Jennifer J., additional, Bjarnason, Georg A., additional, MacKenzie, Mary J., additional, Wood, Lori, additional, Srinivas, Sandy, additional, Vaishampayan, Ulka N., additional, Rha, Sun-Young, additional, Pal, Sumanta K., additional, Donskov, Frede, additional, Tantravahi, Srinivas K., additional, Rini, Brian I., additional, Heng, Daniel Y.C., additional, and Choueiri, Toni K., additional
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- 2014
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21. Radical Prostatectomy Versus Stereotactic Radiotherapy for Clinically Localised Prostate Cancer: Results of the PACE-A Randomised Trial.
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van As N, Yasar B, Griffin C, Patel J, Tree AC, Ostler P, van der Voet H, Ford D, Tolan S, Wells P, Mahmood R, Winkler M, Chan A, Thompson A, Ogden C, Naismith O, Pugh J, Manning G, Brown S, Burnett S, and Hall E
- Abstract
Background and Objective: Randomised data on patient-reported outcomes (PROs) for stereotactic body radiotherapy (SBRT) and prostatectomy in localised prostate cancer are lacking. PACE-A compared patient-reported health-related quality of life after SBRT with that after prostatectomy., Methods: PACE is a phase 3 open-label, randomised controlled trial. PACE-A randomised men with low- to intermediate-risk localised prostate cancer to SBRT or prostatectomy (1:1). Androgen deprivation therapy (ADT) was not permitted. The coprimary outcomes were the Expanded Prostate Index Composite (EPIC-26) number of absorbent urinary pads required daily and bowel domain score at 2 yr. The secondary endpoints were clinician-reported toxicity, sexual functioning, and other PROs., Key Findings and Limitations: In total, 123 men were randomised (60 undergoing prostatectomy and 63 SBRT) from August 2012 to February 2022. The median follow-up time was 60.7 mo. The median age was 65.5 yr and the median prostate-specific antigen (PSA) value 7.9 ng/ml; 92% had National Comprehensive Cancer Network (NCCN) intermediate-risk disease. Fifty participants received prostatectomy and 60 received SBRT. At 2 yr, 16/32 (50%) prostatectomy and three of 46 (6.5%) SBRT participants used one or more urinary pads daily (p < 0.001; 15 and two, respectively, used one pad daily); the estimated difference was 43% (95% confidence interval [CI]: 25%, 62%). At 2 yr, bowel scores were better for prostatectomy (median [interquartile range] 100 [100-100]) than for SBRT (87.5 [79.2-100]; p < 0.001), with an estimated mean difference of 8.9 between these (95% CI: 4.2, 13.7); sexual scores were worse for prostatectomy (18 [13.8-40.3]) than for SBRT (62.5 [32.0-87.5]). The limitations were slow recruitment and incomplete 2-yr PRO response rates., Conclusions and Clinical Implications: SBRT was associated with less patient-reported urinary incontinence and sexual dysfunction, and slightly more bowel bother than prostatectomy. These randomised data should inform treatment decision-making for patients with localised, intermediate-risk prostate cancer., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
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- 2024
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22. First-line Systemic Therapy Following Adjuvant Immunotherapy in Renal Cell Carcinoma: An International Multicenter Study.
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El Zarif T, Semaan K, Xie W, Eid M, Zarba M, Issa W, Zhang T, Nguyen CB, Alva A, Fahey CC, Beckermann KE, Karam JA, Campbell MT, Procopio G, Stellato M, Buti S, Zemankova A, Melichar B, Massari F, Mollica V, Venugopal B, Ebrahimi H, de Velasco G, Gurney HP, De Giorgi U, Parikh O, Winquist E, Master V, Garcia AR, Cutuli HJ, Ferguson TR, Gross-Goupil M, Baca SC, Pal SK, Braun DA, McKay RR, Heng DYC, and Choueiri TK
- Abstract
Background and Objective: Adjuvant pembrolizumab significantly improved overall survival (OS) in renal cell carcinoma (RCC), but real-world data on sequential treatment are scarce. We sought to evaluate the clinical outcomes of first-line (1L) systemic therapy following adjuvant immune oncology (IO)-based regimens., Methods: A retrospective study including patients with recurrent RCC following adjuvant IO across 29 international institutions was conducted. The primary endpoint was progression-free survival (PFS) on 1L systemic therapy estimated using the Kaplan-Meier method. Preplanned subanalyses of clinical outcomes by type of 1L systemic therapy, recurrence timing, and International Metastatic RCC Database Consortium (IMDC) risk groups were performed. Treatment-related adverse events leading to treatment discontinuation, dose reduction, or corticosteroid use were assessed., Key Findings and Limitations: A total of 94 patients were included. Most received adjuvant pembrolizumab (n = 37, 39%), atezolizumab (n = 28, 30%), or nivolumab + ipilimumab (n = 15, 16%). The cohort included 49 (52%) patients who had recurrence within 3 mo of the last adjuvant IO dose, whereas 45 (48%) recurred beyond 3 mo. Bone metastases were significantly higher in tumors recurring at <3 mo (10/49, 20%) than those recurring at >3 mo (1/45, 2.2%; p = 0.008). Most patients received 1L vascular endothelial growth factor-targeted therapy (VEGF-TT; n = 37, 39%), IO + VEGF-TT (n = 26, 28%), or IO + IO (n = 12, 13%). The remaining underwent local therapy. The median follow-up for the 1L systemic therapy cohort was 15 mo. The 18-mo PFS and OS rates were 45% (95% confidence interval [CI]: 34-60) and 85% (95% CI: 75-95), respectively. Treatment-related adverse events occurred in 32 (42%) patients and included skin toxicity (n = 7, 9.2%), fatigue (n = 6, 7.9%), and diarrhea/colitis (n = 4, 5.3%). Limitations included selecting patients from large academic centers and the short follow-up period., Conclusions and Clinical Implications: A subset of patients with recurrent RCC following adjuvant IO respond to systemic therapies, including VEGF-TT and IO-based regimens. Notably, patients with favorable-risk disease may derive more benefit from VEGF-TT than from IO therapies in this setting. Future approaches utilizing radiographic tools and biomarker-based liquid biopsies are warranted to detect occult metastatic disease and identify candidate patients for adjuvant IO therapy., Patient Summary: Adjuvant pembrolizumab significantly improved overall survival in renal cell carcinoma (RCC). There are limited data on clinical outcomes after the recurrence of RCC tumors following adjuvant immunotherapy. In this study, we find that patients respond to subsequent systemic therapies across different treatment options., (Copyright © 2024 European Association of Urology. Published by Elsevier B.V. All rights reserved.)
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- 2024
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23. Reply to Yaxiong Tang, Xu Hu, Kan Wu, Yanxiang Shao, and Xiang Li's Letter to the Editor re: Umberto Capitanio, Jens Bedke, Laurence Albiges, et al. A Renewal of the TNM Staging System for Patients with Renal Cancer To Comply with Current Decision-making: Proposal from the European Association of Urology Guidelines Panel. Eur Urol. 2022;83:3-5.
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Capitanio U, Bedke J, Albiges L, Volpe A, Giles RH, Hora M, Marconi L, Klatte T, Abu-Ghanem Y, Dabestani S, Fernández Pello S, Hofmann F, Kuusk T, Campi R, Tahbaz R, Powles T, Ljungberg B, and Bex A
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- Humans, Neoplasm Staging, Patients, Urology, Carcinoma, Renal Cell, Kidney Neoplasms
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- 2023
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24. European Association of Urology Guidelines Panel on Renal Cell Carcinoma Update on the New World Health Organization Classification of Kidney Tumours 2022: The Urologist's Point of View.
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Hora M, Albiges L, Bedke J, Campi R, Capitanio U, Giles RH, Ljungberg B, Marconi L, Klatte T, Volpe A, Abu-Ghanem Y, Dabestani S, Fernández-Pello S, Hofmann F, Kuusk T, Tahbaz R, Powles T, Bex A, and Trpkov K
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- Humans, Urologists, World Health Organization, Carcinoma, Renal Cell pathology, Urology, Kidney Neoplasms pathology
- Abstract
The fifth edition of the World Health Organization (WHO) classification of urogenital tumours published in 2022 will be implemented in the European Association of Urology guidelines on renal cell carcinoma for 2023. Here we provide an update summarising changes in the new WHO classification of renal tumours from a clinician perspective., (Crown Copyright © 2022. Published by Elsevier B.V. All rights reserved.)
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- 2023
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25. The 2022 Updated European Association of Urology Guidelines on the Use of Adjuvant Immune Checkpoint Inhibitor Therapy for Renal Cell Carcinoma.
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Bedke J, Albiges L, Capitanio U, Giles RH, Hora M, Ljungberg B, Marconi L, Klatte T, Volpe A, Abu-Ghanem Y, Dabestani S, Fernández-Pello S, Hofmann F, Kuusk T, Tahbaz R, Powles T, and Bex A
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- Humans, Immune Checkpoint Inhibitors therapeutic use, Neoplasm Recurrence, Local, Nivolumab therapeutic use, Carcinoma, Renal Cell therapy, Kidney Neoplasms pathology
- Abstract
In KEYNOTE-564, adjuvant pembrolizumab, a PD-1 antibody, significantly improved disease-free survival (DFS) in localised clear-cell renal cell carcinoma (ccRCC) with a high risk of relapse. In 2021, the European Association of Urology RCC Guidelines Panel issued a weak recommendation for adjuvant pembrolizumab for high-risk ccRCC as defined by the trial until final overall survival data and results from other trials were available. Meanwhile, the primary DFS endpoints were not met for adjuvant atezolizumab (PD-L1 inhibitor; IMmotion010), adjuvant nivolumab plus ipilimumab (CheckMate 914), or perioperative nivolumab (PROSPER). Owing to heterogeneity, a meta-analysis is not recommended. Pembrolizumab remains the only immune checkpoint inhibitor currently recommended in this setting. Overall survival data are immature and biomarkers to predict outcome are lacking. Uncertainty exists and overtreatment is occurring. Treatment decisions should be made with caution and with the involvement of each patient. PATIENT SUMMARY: New results from three trials of immunotherapy after surgery for kidney cancer to reduce the risk of recurrence showed no improvement with these treatments. These results are in contrast to an earlier study that showed that the antibody pembrolizumab did extend the time before kidney cancer recurrence, even though it is not yet clear if overall survival is longer. Thus, we cautiously recommend pembrolizumab as additional treatment in high-risk kidney cancer after surgery, but patient preference should be carefully considered and the risk of overtreatment should be discussed., (Copyright © 2022 European Association of Urology. Published by Elsevier B.V. All rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF
26. A Renewal of the TNM Staging System for Patients with Renal Cancer To Comply with Current Decision-making: Proposal from the European Association of Urology Guidelines Panel.
- Author
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Capitanio U, Bedke J, Albiges L, Volpe A, Giles RH, Hora M, Marconi L, Klatte T, Abu-Ghanem Y, Dabestani S, Fernández Pello S, Hofmann F, Kuusk T, Tahbaz R, Powles T, Ljungberg B, and Bex A
- Subjects
- Humans, Neoplasm Staging, Carcinoma, Renal Cell pathology, Kidney Neoplasms pathology, Urology
- Abstract
Over the past decade, only minor changes have been introduced in the TNM staging system for renal cancer. Conversely, many milestones and modifications in management of the disease have been achieved, especially for patients with locally advanced and metastatic cancers. The European Association of Urology guidelines panel proposes a new TNM classification scheme for staging of renal cell carcinoma to reflect these breakthrough clinical improvements., (Copyright © 2022 European Association of Urology. Published by Elsevier B.V. All rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF
27. European Association of Urology Guidelines on Renal Cell Carcinoma: The 2022 Update.
- Author
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Ljungberg B, Albiges L, Abu-Ghanem Y, Bedke J, Capitanio U, Dabestani S, Fernández-Pello S, Giles RH, Hofmann F, Hora M, Klatte T, Kuusk T, Lam TB, Marconi L, Powles T, Tahbaz R, Volpe A, and Bex A
- Subjects
- Humans, Carcinoma, Renal Cell therapy, Kidney Neoplasms pathology, Kidney Neoplasms therapy, Urology
- Abstract
Context: The European Association of Urology (EAU) Renal Cell Carcinoma (RCC) Guideline Panel has prepared evidence-based guidelines and recommendations for the management of RCC., Objective: To present a summary of the 2022 RCC guideline, which is based on a standardised methodology including systematic reviews (SRs) and provides transparent and reliable evidence for the management of RCC., Evidence Acquisition: For the 2022 update, a new literature search was carried out with a cutoff date of May 28, 2021, covering the Medline, EMBASE, and Cochrane databases. The data search focused on randomised controlled trials (RCTs) and retrospective or controlled comparator-arm studies, SRs, and meta-analyses. Evidence synthesis was conducted using modified GRADE criteria as outlined for all the EAU guidelines., Evidence Synthesis: All chapters of the RCC guideline were updated on the basis of a structured literature assessment, and clinical practice recommendations were developed. The majority of the studies included were retrospective with matched or unmatched cohorts and were based on single- or multi-institution data or national registries. The exception was systemic treatment of metastatic RCC, for which there are several large RCTs, resulting in recommendations that are based on higher levels of evidence., Conclusions: The 2022 RCC guidelines have been updated by a multidisciplinary panel of experts using the highest methodological standards. These guidelines provide the most reliable contemporary evidence base for the management of RCC in 2022., Patient Summary: The European Association of Urology panel for guidelines on kidney cancer has thoroughly evaluated the research data available to establish up-to-date international standards for the care of patients with kidney cancer., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2022
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28. 2021 Updated European Association of Urology Guidelines on the Use of Adjuvant Pembrolizumab for Renal Cell Carcinoma.
- Author
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Bedke J, Albiges L, Capitanio U, Giles RH, Hora M, Lam TB, Ljungberg B, Marconi L, Klatte T, Volpe A, Abu-Ghanem Y, Dabestani S, Fernández-Pello S, Hofmann F, Kuusk T, Tahbaz R, Powles T, and Bex A
- Subjects
- Antibodies, Monoclonal, Humanized, Chemotherapy, Adjuvant, Female, Humans, Immune Checkpoint Inhibitors, Male, Neoplasm Recurrence, Local drug therapy, Receptors, Death Domain, Carcinoma, Renal Cell pathology, Kidney Neoplasms pathology, Urology
- Abstract
Adjuvant treatment of nonmetastatic high-risk renal cell carcinoma is an unmet medical need. In the past, several tyrosine kinase inhibitor trials have failed to demonstrate an improvement of disease-free survival (DFS) in this setting. Only one trial (S-TRAC) provided evidence for improved DFS with sunitinib but without an overall survival (OS) signal. Keynote-564 is the first trial of an immune checkpoint inhibitor that significantly improved DFS with adjuvant pembrolizumab, a programmed death receptor-1 antibody, in clear cell renal cell carcinoma with a high risk of relapse. The intention-to-treat population, which included a group of patients after metastasectomy and no evidence of disease (M1 NED), had a significant DFS benefit. The OS data are not mature as yet. The Renal Cell Carcinoma Guideline Panel issues a weak recommendation for the adjuvant use of pembrolizumab for high-risk clear cell renal carcinoma, as defined by the trial until final OS data are available. However, the trial reilluminates the discussion on when and in whom metastasectomy should be performed. Here, caution is necessary not to perform metastasectomy in patients with poor prognostic features and rapid progressive disease, which must be excluded by a confirmatory scan of disease status prior to planned metastasectomy. PATIENT SUMMARY: New data from the adjuvant immune checkpoint inhibitor trial with pembrolizumab (a programmed death receptor-1 antibody) for the treatment of high-risk clear cell renal cell carcinoma (ccRCC) after surgery showed that the drug prolonged the period of being cancer free significantly, although whether it prolonged survival remained uncertain. Consequently, pembrolizumab is cautiously recommended as additional (ie, adjuvant) treatment in high-risk ccRCC after kidney cancer surgery., (Copyright © 2021 European Association of Urology. Published by Elsevier B.V. All rights reserved.)
- Published
- 2022
- Full Text
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29. The 2021 Updated European Association of Urology Guidelines on Renal Cell Carcinoma: Immune Checkpoint Inhibitor-based Combination Therapies for Treatment-naive Metastatic Clear-cell Renal Cell Carcinoma Are Standard of Care.
- Author
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Bedke J, Albiges L, Capitanio U, Giles RH, Hora M, Lam TB, Ljungberg B, Marconi L, Klatte T, Volpe A, Abu-Ghanem Y, Dabestani S, Pello SF, Hofmann F, Kuusk T, Tahbaz R, Powles T, and Bex A
- Subjects
- Axitinib, Humans, Immune Checkpoint Inhibitors, Ipilimumab therapeutic use, Nivolumab therapeutic use, Standard of Care, Sunitinib therapeutic use, Carcinoma, Renal Cell drug therapy, Kidney Neoplasms drug therapy, Urology
- Abstract
The recent randomized controlled phase III CLEAR trial results are the last to complement immune checkpoint inhibitor (ICI)-based doublet combination therapies for treatment-naïve metastatic clear-cell renal cell carcinoma. The CLEAR trial demonstrated an improved progression-free survival (PFS), overall survival (OS), and an objective response rate (ORR) benefit for the combination of lenvatinib plus pembrolizumab over sunitinib. The CheckMate-9ER trial update demonstrated an ongoing PFS, OS, and quality-of-life benefit for cabozantinib plus nivolumab over sunitinib as did the update of Keynote-426 for axitinib plus pembrolizumab in the intention-to-treat population, with a PFS benefit seen across all International Metastatic Database Consortium (IMDC) subgroups. In the IMDC intermediate- and poor-risk groups, the CheckMate-214 trial of ipilimumab plus nivolumab confirmed the OS benefit with a PFS plateauing after 30 months. The RCC Guidelines Panel recommends three tyrosine kinase inhibitors + ICI combinations of axitinib plus pembrolizumab, cabozantinib plus nivolumab, and lenvatinib plus pembrolizumab across all IMDC risk groups in advanced first-line RCC, and dual immunotherapy of ipilimumab and nivolumab in IMDC intermediate- and poor-risk groups. PATIENT SUMMARY: New data from combination trials with immune checkpoint inhibitors for advanced kidney cancer confirm a survival benefit for lenvatinib plus pembrolizumab, cabozantinib plus nivolumab (with improved quality-of-life), axitinib plus pembrolizumab, and ipilimumab plus nivolumab. These combination therapies are recommended as first-line treatment for advanced kidney cancer., (Copyright © 2021 European Association of Urology. Published by Elsevier B.V. All rights reserved.)
- Published
- 2021
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30. A Multicohort Open-label Phase II Trial of Bipolar Androgen Therapy in Men with Metastatic Castration-resistant Prostate Cancer (RESTORE): A Comparison of Post-abiraterone Versus Post-enzalutamide Cohorts.
- Author
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Markowski MC, Wang H, Sullivan R, Rifkind I, Sinibaldi V, Schweizer MT, Teply BA, Ngomba N, Fu W, Carducci MA, Paller CJ, Marshall CH, Eisenberger MA, Luo J, Antonarakis ES, and Denmeade SR
- Subjects
- Androgens, Androstenes therapeutic use, Benzamides therapeutic use, Humans, Male, Nitriles therapeutic use, Phenylthiohydantoin therapeutic use, Prostate-Specific Antigen, Receptors, Androgen, Testosterone administration & dosage, Prostatic Neoplasms, Castration-Resistant drug therapy, Testosterone therapeutic use
- Abstract
Background: Cyclic high-dose testosterone injections, also known as bipolar androgen therapy (BAT), is a novel treatment strategy for patients with metastatic castration-resistant prostate cancer (mCRPC). BAT has shown clinical activity in prior studies enrolling men with mCRPC and may potentially restore sensitivity to prior androgen receptor (AR)-targeted agents., Objective: To evaluate the clinical activity of BAT in patients progressing on AR-targeted therapy as well as responses to abiraterone or enzalutamide upon rechallenge after BAT., Design, Setting, and Participants: RESTORE is a multicohort phase II study enrolling asymptomatic mCRPC patients after abiraterone or enzalutamide at Johns Hopkins Hospital (NCT02090114). Participants (29 after abiraterone and 30 after enzalutamide) received 400 mg testosterone cypionate intramuscularly every 28 days, with ongoing luteinizing hormone-releasing hormone agonist/antagonist treatment (ie, BAT). Following progression on BAT, patients were rechallenged with their most recent AR-targeted therapy., Outcome Measurements and Statistical Analysis: Coprimary endpoints were >50% decline in PSA from baseline (PSA
50 ) responses to BAT and following AR-targeted therapy rechallenge. Outcomes in the post-abiraterone cohort are presented, as well as updated results from the post-enzalutamide cohort and an exploratory AR-V7 analysis., Results and Limitations: No statistically significant difference in PSA50 response rates to BAT was observed (30% [post-enzalutamide cohort] vs 17% [post-abiraterone cohort], p = 0.4). However, PSA50 responses to AR-targeted therapy rechallenge were higher in the post-enzalutamide cohort (68% vs 16%, p = 0.001). The median time from enrollment to progression following rechallenge with AR-targeted therapy (ie, progression-free survival 2; PFS2) was longer in the post-enzalutamide versus post-abiraterone patients (12.8 vs 8.1 mo, p = 0.04). Outcomes were worse in patients with detectable AR-V7 in circulating tumor cells (median PFS2: 10.3 vs 7.1 mo, p = 0.005)., Conclusions: BAT shows clinical activity in mCRPC patients and may be more effective at resensitizing to enzalutamide versus abiraterone., Patient Summary: BAT is well tolerated in metastatic castration-resistant prostate cancer patients. The type of prior AR-targeted therapy might affect response to BAT as well as AR-therapy rechallenge. BAT followed by AR-targeted therapy rechallenge did not improve outcomes in AR-V7-positive patients., (Copyright © 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.)- Published
- 2021
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- View/download PDF
31. Updated European Association of Urology Guidelines on Renal Cell Carcinoma: Nivolumab plus Cabozantinib Joins Immune Checkpoint Inhibition Combination Therapies for Treatment-naïve Metastatic Clear-Cell Renal Cell Carcinoma.
- Author
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Bedke J, Albiges L, Capitanio U, Giles RH, Hora M, Lam TB, Ljungberg B, Marconi L, Klatte T, Volpe A, Abu-Ghanem Y, Dabestani S, Fernández-Pello S, Hofmann F, Kuusk T, Tahbaz R, Powles T, and Bex A
- Subjects
- Anilides therapeutic use, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Axitinib, Humans, Immune Checkpoint Inhibitors, Ipilimumab therapeutic use, Nivolumab therapeutic use, Pyridines therapeutic use, Sunitinib therapeutic use, Carcinoma, Renal Cell drug therapy, Kidney Neoplasms drug therapy, Urology
- Abstract
Longer follow-up and new trial data from phase 3 randomised controlled trials investigating immune checkpoint blockade (PD-1 or its ligand PD-L1) in advanced clear-cell renal cell carcinoma (RCC) have recently become available. The CheckMate 9ER trial demonstrated an improved progression-free survival (PFS) and overall survival (OS) benefit for the combination of cabozantinib plus nivolumab. A Keynote-426 update demonstrated an ongoing OS benefit for pembrolizumab plus axitinib in the intention-to-treat population, with a PFS benefit seen across all International Metastatic Database Consortium (IMDC) subgroups, while an update of CheckMate 214 confirmed the long-term benefit of ipilimumab plus nivolumab in IMDC intermediate and poor risk patients. The RCC Guidelines Panel continues to recommend these tyrosine kinase inhibitors + immunotherapy (IO) combination across IMDC risk groups in advanced first-line RCC and dual immunotherapy of ipilimumab and nivolumab in IMDC intermediate and poor risk. PATIENT SUMMARY: New data from trials of immune checkpoint inhibitors for advanced kidney cancer confirm a survival benefit with the combination of cabozantinib plus nivolumab and pembrolizumab plus axitinib and ipilimumab plus nivolumab. These combination therapies are recommended as first-line treatment for advanced kidney cancer., (Copyright © 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
32. Updated European Association of Urology Guidelines on Renal Cell Carcinoma: Immune Checkpoint Inhibition Is the New Backbone in First-line Treatment of Metastatic Clear-cell Renal Cell Carcinoma.
- Author
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Albiges L, Powles T, Staehler M, Bensalah K, Giles RH, Hora M, Kuczyk MA, Lam TB, Ljungberg B, Marconi L, Merseburger AS, Volpe A, Abu-Ghanem Y, Dabestani S, Fernández-Pello S, Hofmann F, Kuusk T, Tahbaz R, and Bex A
- Subjects
- Antibodies, Monoclonal, Humanized administration & dosage, Antineoplastic Combined Chemotherapy Protocols adverse effects, Axitinib administration & dosage, Bevacizumab administration & dosage, Carcinoma, Renal Cell secondary, Humans, Ipilimumab administration & dosage, Kidney Neoplasms pathology, Nivolumab administration & dosage, Sunitinib therapeutic use, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Carcinoma, Renal Cell drug therapy, Kidney Neoplasms drug therapy
- Abstract
Recent randomised trials have demonstrated a survival benefit for a front-line ipilimumab and nivolumab combination therapy, and pembrolizumab and axitinib combination therapy in metastatic clear-cell renal cell carcinoma. The European Association of Urology Guidelines Panel has updated its recommendations based on these studies. PATIENT SUMMARY: Pembrolizumab plus axitinib is a new standard of care for patients diagnosed with kidney cancer spread outside the kidney and who did not receive any prior treatment for their cancer (treatment naïve). This applies to all risk groups as determined by the International Metastatic Renal Cell Carcinoma Database Consortium criteria., (Copyright © 2019 European Association of Urology. Published by Elsevier B.V. All rights reserved.)
- Published
- 2019
- Full Text
- View/download PDF
33. European Association of Urology Guidelines on Renal Cell Carcinoma: The 2019 Update.
- Author
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Ljungberg B, Albiges L, Abu-Ghanem Y, Bensalah K, Dabestani S, Fernández-Pello S, Giles RH, Hofmann F, Hora M, Kuczyk MA, Kuusk T, Lam TB, Marconi L, Merseburger AS, Powles T, Staehler M, Tahbaz R, Volpe A, and Bex A
- Subjects
- Antineoplastic Agents, Immunological therapeutic use, Carcinoma, Renal Cell diagnosis, Carcinoma, Renal Cell secondary, Chemotherapy, Adjuvant, Humans, Kidney Neoplasms diagnosis, Kidney Neoplasms pathology, Molecular Targeted Therapy, Watchful Waiting, Carcinoma, Renal Cell therapy, Kidney Neoplasms therapy, Nephrectomy methods
- Abstract
Context: The European Association of Urology Renal Cell Carcinoma (RCC) Guideline Panel has prepared evidence-based guidelines and recommendations for the management of RCC., Objective: To provide an updated RCC guideline based on standardised methodology including systematic reviews, which is robust, transparent, reproducible, and reliable., Evidence Acquisition: For the 2019 update, evidence synthesis was undertaken based on a comprehensive and structured literature assessment for new and relevant data. Where necessary, formal systematic reviews adhering to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were undertaken. Relevant databases (Medline, Cochrane Libraries, trial registries, conference proceedings) were searched until June 2018, including randomised controlled trials (RCTs) and retrospective or controlled studies with a comparator arm, systematic reviews, and meta-analyses. Where relevant, risk of bias (RoB) assessment, and qualitative and quantitative syntheses of the evidence were performed. The remaining sections of the document were updated following a structured literature assessment. Clinical practice recommendations were developed and issued based on the modified GRADE framework., Evidence Synthesis: All chapters of the RCC guidelines were updated based on a structured literature assessment, for prioritised topics based on the availability of robust data. For RCTs, RoB was low across studies. For most non-RCTs, clinical and methodological heterogeneity prevented pooling of data. The majority of included studies were retrospective with matched or unmatched cohorts, based on single- or multi-institutional data or national registries. The exception was for the treatment of metastatic RCC, for which there were several large RCTs, resulting in recommendations based on higher levels of evidence., Conclusions: The 2019 RCC guidelines have been updated by the multidisciplinary panel using the highest methodological standards. These guidelines provide the most reliable contemporary evidence base for the management of RCC in 2019., Patient Summary: The European Association of Urology Renal Cell Carcinoma Guideline Panel has thoroughly evaluated the available research data on kidney cancer to establish international standards for the care of kidney cancer patients., (Copyright © 2019 European Association of Urology. Published by Elsevier B.V. All rights reserved.)
- Published
- 2019
- Full Text
- View/download PDF
34. A Joint Statement from the European Association of Urology Renal Cell Cancer Guidelines Panel and the International Kidney Cancer Coalition: The Rejection of Ipilimumab and Nivolumab for Renal Cancer by the Committee for Medicinal Products for Human Use Does not Change Evidence-based Guideline Recommendations.
- Author
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Bex A, Albiges L, Staehler M, Bensalah K, Giles RH, Dabestani S, Hofmann F, Hora M, Kuczyk MA, Lam TB, Marconi L, Merseburger AS, Fernández-Pello S, Tahbaz R, Abu-Ghanem Y, Volpe A, Ljungberg B, Escudier B, and Powles T
- Subjects
- Humans, Patient Selection, Treatment Outcome, Antineoplastic Agents, Immunological adverse effects, Antineoplastic Agents, Immunological therapeutic use, Antineoplastic Combined Chemotherapy Protocols adverse effects, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Carcinoma, Renal Cell drug therapy, Carcinoma, Renal Cell mortality, Carcinoma, Renal Cell pathology, Clinical Decision-Making, Drug Approval, Evidence-Based Medicine standards, Ipilimumab adverse effects, Ipilimumab therapeutic use, Kidney Neoplasms drug therapy, Kidney Neoplasms mortality, Kidney Neoplasms pathology, Nephrology standards, Nivolumab adverse effects, Nivolumab therapeutic use, Urology standards
- Published
- 2018
- Full Text
- View/download PDF
35. Updated European Association of Urology Guidelines for Cytoreductive Nephrectomy in Patients with Synchronous Metastatic Clear-cell Renal Cell Carcinoma.
- Author
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Bex A, Albiges L, Ljungberg B, Bensalah K, Dabestani S, Giles RH, Hofmann F, Hora M, Kuczyk MA, Lam TB, Marconi L, Merseburger AS, Fernández-Pello S, Tahbaz R, Abu-Ghanem Y, Staehler M, Volpe A, and Powles T
- Subjects
- Adult, Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Chemotherapy, Adjuvant, Clinical Decision-Making, Clinical Trials, Phase III as Topic standards, Delphi Technique, Equivalence Trials as Topic, Europe, Evidence-Based Medicine standards, Patient Selection, Protein Kinase Inhibitors therapeutic use, Treatment Outcome, Carcinoma, Renal Cell secondary, Carcinoma, Renal Cell surgery, Cytoreduction Surgical Procedures methods, Cytoreduction Surgical Procedures standards, Kidney Neoplasms pathology, Kidney Neoplasms surgery, Neoplasms, Multiple Primary pathology, Neoplasms, Multiple Primary surgery, Nephrectomy methods, Nephrectomy standards, Urology standards
- Abstract
Cytoreductive nephrectomy (CN) has been the standard of care in patients with metastatic clear-cell renal cancer who present with the tumour in place. The CARMENA trial compared systemic therapy alone with CN followed by systemic therapy. This article outlines the new guidelines based on these data. PATIENT SUMMARY: The CARMENA trial demonstrates that immediate cytoreductive nephrectomy should no longer be considered the standard of care in patients diagnosed with intermediate and poor risk metastatic renal cell carcinoma when medical treatment is required. However, the psychological burden poor risk patients experience hearing that removal of their primary tumour will not be beneficial, should be carefully considered., (Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.)
- Published
- 2018
- Full Text
- View/download PDF
36. Updated European Association of Urology Guidelines: Recommendations for the Treatment of First-line Metastatic Clear Cell Renal Cancer.
- Author
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Powles T, Albiges L, Staehler M, Bensalah K, Dabestani S, Giles RH, Hofmann F, Hora M, Kuczyk MA, Lam TB, Marconi L, Merseburger AS, Fernández-Pello S, Tahbaz R, Volpe A, Ljungberg B, and Bex A
- Abstract
The randomised phase III clinical trial Checkmate-214 showed a survival superiority for the combination of ipilimumab and nivolumab when compared with the previous standard of care in first-line metastatic/advanced clear cell renal cell carcinoma (RCC) (Escudier B, Tannir NM, McDermott DF, et al. CheckMate 214: efficacy and safety of nivolumab plus ipilimumab vs sunitinib for treatment-naïve advanced or metastatic renal cell carcinoma, including IMDC risk and PD-L1 expression subgroups. LBA5, ESMO 2017, 2017). These results change the frontline standard of care for this disease and have implications for the selection of subsequent therapies. For this reason the European Association of Urology RCC guidelines have been updated. PATIENT SUMMARY: The European Association of Urology guidelines will be updated based on the results of the phase III Checkmate-214 clinical trial. The trial showed superior survival for a combination of ipilimumab and nivolumab (IN), compared with the previous standard of care, in intermediate- and poor-risk patients with metastatic clear cell renal cell carcinoma. When IN is not safe or feasible, alternative agents such as sunitinib, pazopanib, and cabozantinib should be considered. Furthermore, at present, the data from the trial are immature in favourable-risk patients. Therefore, sunitinib or pazopanib remains the favoured agent for this subgroup of patients., (Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.)
- Published
- 2018
- Full Text
- View/download PDF
37. A Systematic Review and Meta-analysis Comparing the Effectiveness and Adverse Effects of Different Systemic Treatments for Non-clear Cell Renal Cell Carcinoma.
- Author
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Fernández-Pello S, Hofmann F, Tahbaz R, Marconi L, Lam TB, Albiges L, Bensalah K, Canfield SE, Dabestani S, Giles RH, Hora M, Kuczyk MA, Merseburger AS, Powles T, Staehler M, Volpe A, Ljungberg B, and Bex A
- Subjects
- Anilides therapeutic use, Axitinib, Benzimidazoles therapeutic use, Bevacizumab therapeutic use, Carcinoma, Renal Cell pathology, Comparative Effectiveness Research, Disease-Free Survival, Erlotinib Hydrochloride therapeutic use, Everolimus therapeutic use, Humans, Imidazoles therapeutic use, Indazoles therapeutic use, Indoles therapeutic use, Interferons therapeutic use, Interleukin-2 therapeutic use, Kidney Neoplasms pathology, Niacinamide analogs & derivatives, Niacinamide therapeutic use, Phenylurea Compounds therapeutic use, Pyridines therapeutic use, Pyrimidines therapeutic use, Pyrroles therapeutic use, Pyrrolidinones therapeutic use, Quinolines therapeutic use, Quinolones therapeutic use, Sirolimus analogs & derivatives, Sirolimus therapeutic use, Sorafenib, Sulfonamides therapeutic use, Sunitinib, Antineoplastic Agents therapeutic use, Carcinoma, Renal Cell drug therapy, Kidney Neoplasms drug therapy
- Abstract
Context: While vascular endothelial growth factor-targeted therapy and mammalian target of rapamycin inhibition are effective strategies in treating clear cell renal cell carcinoma (ccRCC), the most effective therapeutic approach for patients with non-clear cell RCC (non-ccRCC) is unknown., Objective: To systematically review relevant literature comparing the oncological outcomes and adverse events of different systemic therapies for patients with metastatic non-ccRCC., Evidence Acquisition: Relevant databases including MEDLINE, Embase, and the Cochrane Library were searched up to March 24, 2016. Only comparative studies were included. Risk of bias and confounding assessments were performed. A meta-analysis was planned for and only performed if methodologically appropriate; otherwise, a narrative synthesis was undertaken., Evidence Synthesis: The literature search identified 812 potential titles and abstracts. Five randomized controlled trials, recruiting a total of 365 patients, were included. Three studies compared sunitinib against everolimus, one of which reported the results for non-ccRCC as a subgroup rather than as an entire randomized cohort. Individually, the studies showed a trend towards favoring sunitinib in terms of overall survival and progression-free survival (PFS; Everolimus versus Sunitinib in Patients with Metastatic Non-clear Cell Renal Cell Carcinoma hazard ratio [HR]: 1.41, 80% confidence interval [CI] 1.03-1.92 and 1.41, 95% CI: 0.88-2.27, Evaluation in Metastatic Non-clear Cell Renal Cell Carcinoma HR: 1.16, 95% CI: 0.67-2.01, Efficacy and Safety Comparison of RAD001 Versus Sunitinib in the First-line and Second-line Treatment of Patients with Metastatic Renal Cell Carcinoma HR: 1.5, 95% CI: 0.9-2.8), but this trend did not reach statistical significance in any study. Meta-analysis was performed on two studies which solely recruited patients with non-ccRCC reporting on PFS, the results of which were inconclusive (HR: 1.30, 95% CI: 0.91-1.86). Sunitinib was associated with more Grade 3-4 adverse events than everolimus, although this was not statistically significant., Conclusions: This systematic review and meta-analysis represent a robust summary of the evidence base for systemic treatment of metastatic non-ccRCC. The results show a trend towards favoring vascular endothelial growth factor-targeted therapy for PFS and overall survival compared with mammalian target of rapamycin inhibitors, although statistical significance was not reached. The relative benefits and harms of these treatments remain uncertain. Further research, either in the form of an individual patient data meta-analysis involving all relevant trials, or a randomized controlled trial with sufficient power to detect potential differences between treatments, is needed., Patient Summary: We examined the literature to determine the most effective treatments for advanced kidney cancer patients whose tumors are not of the clear cell subtype. The results suggest that a drug called sunitinib might be more effective than everolimus, but the statistics supporting this statement are not yet entirely reliable. Further research is required to clarify this unmet medical need., (Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.)
- Published
- 2017
- Full Text
- View/download PDF
38. The role of miRNAs in prostate cancer.
- Author
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Sun T, McKay R, Lee GS, and Kantoff P
- Subjects
- Humans, Male, Kallikreins blood, MicroRNAs metabolism, Prostate-Specific Antigen blood, Prostatic Neoplasms blood
- Published
- 2015
- Full Text
- View/download PDF
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