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Latest progress in molecular biology and treatment in genitourinary tumours

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Abstract

The management of genitourinary cancer, including bladder, prostate, renal and testicular cancer, has evolved dramatically in recent years due to a better understanding of tumour genetic mutations, alterations in molecular pathways, and to the development of new kinds of drugs such as targeted therapies and immunotherapies. In the field of immunotherapy, new drugs focused on stimulating, enhancing and modulating the immune system to detect and destroy cancer, have been recently discovered. Research in oncology moves quickly and new data of great relevance for clinical practice are communicated every year. For this reason, a group of experts, focused exclusively on the treatment of genitourinary tumours and who get together every year in the BestGU conference to assess the latest progress in this field have summarized the most important advances in a single review, along with a critical assessment of whether these results should alter daily clinical practice.

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References

  1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394–424.

    Article  PubMed  Google Scholar 

  2. Massari F, Di Nunno V, Comito F, Cubelli M, Ciccarese C, Iacovelli R, et al. Circulating tumor cells in genitourinary tumors. Ther Adv Urol. 2018;10:65–77.

    CAS  PubMed  Google Scholar 

  3. Mehta K, Patel K, Parikh RA. Immunotherapy in genitourinary malignancies. J Hematol Oncol. 2017;10:95.

    PubMed  PubMed Central  Google Scholar 

  4. Robertson AG, Kim J, Al-Ahmadie H, Bellmunt J, Guo G, Cherniack AD, et al. Comprehensive molecular characterization of muscle-invasive bladder cancer. Cell. 2017;171(540–56):e25.

    Google Scholar 

  5. Hurst C, Rosenberg J, Knowles M. Snapshot: bladder cancer. Cancer Cell. 2018;34:350–e1.

    CAS  PubMed  Google Scholar 

  6. Al-Ahmadie H, Iyer G. Updates on the genetics and molecular subtypes of urothelial carcinoma and select variants. Surg Pathol Clin. 2018;11:713–23.

    PubMed  PubMed Central  Google Scholar 

  7. Teo MY, Bambury RM, Zabor EC, Jordan E, Al-Ahmadie H, Boyd ME, et al. Commentary on “DNA damage response and repair gene alterations are associated with improved survival in patients with platinum-treated advanced urothelial carcinoma”. Urol Oncol. 2018;36:345–6.

    CAS  PubMed  Google Scholar 

  8. Sjodahl G, Lauss M, Lovgren K, Chebil G, Gudjonsson S, Veerla S, et al. A molecular taxonomy for urothelial carcinoma. Clin Cancer Res. 2012;18:3377–86.

    PubMed  Google Scholar 

  9. Seiler R, Ashab HAD, Erho N, van Rhijn BWG, Winters B, Douglas J, et al. Impact of molecular subtypes in muscle-invasive bladder cancer on predicting response and survival after neoadjuvant chemotherapy. Eur Urol. 2017;72:544–54.

    CAS  PubMed  Google Scholar 

  10. Bellmunt J, de Wit R, Vaughn DJ, Fradet Y, Lee JL, Fong L, et al. Pembrolizumab as second-line therapy for advanced urothelial carcinoma. N Engl J Med. 2017;376:1015–26.

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Farina MS, Lundgren KT, Bellmunt J. Immunotherapy in urothelial cancer: recent results and future perspectives. Drugs. 2017;77:1077–89.

    CAS  PubMed  Google Scholar 

  12. Stuhler V, Maas JM, Bochem J, da Costa IA, Todenhofer T, Stenzl A, et al. Molecular predictors of response to PD-1/PD-L1 inhibition in urothelial cancer. World J Urol. 2018;37:1773–844 (Epub ahead of print).

    PubMed  Google Scholar 

  13. Mariathasan S, Turley SJ, Nickles D, Castiglioni A, Yuen K, Wang Y, et al. TGFβ attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells. Nature. 2018;554:544–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Wang L, Saci A, Szabo PM, Chasalow SD, Castillo-Martín M, Domingo-Domenech J, et al. EMT- and stroma-related gene expression and resistance to PD-1 blockade in urothelial cancer. Nat Commun. 2018;9:3503.

    PubMed  PubMed Central  Google Scholar 

  15. Miao D, Margolis CA, Vokes NI, Liu D, Taylor-Weiner A, Wankowicz SM, et al. Genomic correlates of response to immune checkpoint blockade in microsatellite-stable solid tumors. Nat Genet. 2018;50:1271–81.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Bellmunt J, Lalani AA, Jacobus S, Wankowicz SA, Polacek L, Takeda DY, et al. Everolimus and pazopanib (E/P) benefit genomically selected patients with metastatic urothelial carcinoma. Br J Cancer. 2018;119:707–12.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Alfred Witjes J, Lebret T, Compérat EM, Cowan NC, De Santis M, Bruins HM, et al. Updated 2016 EAU guidelines on muscle-invasive and metastatic bladder cancer. Eur Urol. 2017;71:462–75.

    CAS  PubMed  Google Scholar 

  18. NCCN. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines: Bladder Cancer Version 1.2019. 2019. https://www.nccn.org/professionals/physician_gls/pdf/bladder.pdf. Accessed 15 Mar 2019.

  19. Burger M, Mulders P, Witjes W. Use of neoadjuvant chemotherapy for muscle-invasive bladder cancer is low among major European centres: results of a feasibility questionnaire. Eur Urol. 2012;61:1070–1.

    PubMed  Google Scholar 

  20. Necchi A, Briganti A, Raggi D, Giannatempo P, Mariani L, Messina A, et al. Interim results from PURE-01: a phase 2, open-label study of neoadjuvant pembrolizumab (pembro) before radical cystectomy for muscle-invasive urothelial bladder carcinoma (MIUC). J Clin Oncol. 2018;36:TPS533.

    Google Scholar 

  21. Powles T, Rodriguez-Vida A, Duran I, Crabb SJ, Heijden MSVD, Pous AF, et al. A phase II study investigating the safety and efficacy of neoadjuvant atezolizumab in muscle invasive bladder cancer (ABACUS). J Clin Oncol. 2018;36:4506.

    Google Scholar 

  22. de Wit R, Kulkarni GS, Uchio E, Singer EA, Krieger L, Grivas P, et al. Pembrolizumab for high-risk (HR) non–muscle invasive bladder cancer (NMIBC) unresponsive to bacillus calmette-guérin (BCG): phase 2 KEYNOTE-057 trial. Ann Oncol. 2018;29:303–31.

    Google Scholar 

  23. Bellmunt J, De Wit R, Vaughn DJ, Fradet Y, Lee JL, Fong L, et al. Two-year follow-up from the phase 3 KEYNOTE-045 trial of pembrolizumab (pembro) vs investigator’s choice (paclitaxel, docetaxel, or vinflunine) in recurrent, advanced urothelial cancer (UC). J Clin Oncol. 2018;36:410.

    Google Scholar 

  24. Powles T, Loriot Y, Ravaud A, Vogelzang NJ, Duran I, Retz M, et al. Atezolizumab (atezo) vs. chemotherapy (chemo) in platinum-treated locally advanced or metastatic urothelial carcinoma (mUC): immune biomarkers, tumor mutational burden (TMB), and clinical outcomes from the phase III IMvigor211 study. J Clin Oncol. 2018;36:409.

    Google Scholar 

  25. Sharma P, Baron A, Necchi A, Plimack ER, Pal SK, Bedke J, et al. Abstract CT178: nivolumab monotherapy in patients with advanced platinum-resistant urothelial carcinoma: efficacy and safety update and association between biomarkers and overall survival in CheckMate 275. Cancer Res. 2018;78:CT178.

    Google Scholar 

  26. Rosenberg JE, Callahan M, Brossart P, Rohrberg KS, Reguart N, Lin WH, et al. LBA32 Nivolumab (N) alone or in combination with ipilimumab (I) in patients (pts) with platinum-pretreated metastatic urothelial carcinoma (mUC), including the nivolumab 1 mg/kg + ipilimumab 3 mg/kg expansion from CheckMate 032. Ann Oncol. 2018;29:viii725.

    Google Scholar 

  27. Sharma P, Callahan MK, Bono P, Kim JW, Spiliopoulou P, Calvo E, et al. Nivolumab monotherapy in metastatic urothelial carcinoma: Longer-term efficacy and safety results from the CheckMate 032 study. J Clin Oncol. 2018;36:414.

    Google Scholar 

  28. Vuky J, Balar AV, Castellano DE, O'Donnell PH, Grivas P, Bellmunt J, et al. Updated efficacy and safety of KEYNOTE-052: A single-arm phase 2 study investigating first-line pembrolizumab (pembro) in cisplatin-ineligible advanced urothelial cancer (UC). J Clin Oncol. 2018;36:4524.

    Google Scholar 

  29. Balar AV, Dreicer R, Loriot Y, Perez-Gracia JL, Hoffman-Censits JH, Petrylak DP, et al. Atezolizumab (atezo) in first-line cisplatin-ineligible or platinum-treated locally advanced or metastatic urothelial cancer (mUC): long-term efficacy from phase 2 study IMvigor210. J Clin Oncol. 2018;36:4523.

    Google Scholar 

  30. Galsky MD, Pal SK, Mortazavi A, Milowsky MI, George S, Gupta S, et al. Randomized double-blind phase II study of maintenance pembrolizumab versus placebo after first-line chemotherapy in patients (pts) with metastatic urothelial cancer (mUC): HCRN GU14–182. J Clin Oncol. 2019;37:4504.

    Google Scholar 

  31. Rosenberg JE, Ballman KV, Halabi S, Watt C, Hahn OM, Steen PD, et al. CALGB 90601 (Alliance): randomized, double-blind, placebo-controlled phase III trial comparing gemcitabine and cisplatin with bevacizumab or placebo in patients with metastatic urothelial carcinoma. J Clin Oncol. 2019;37:4503.

    Google Scholar 

  32. Necchi A, Mariani L, Vullo SL, Raggi D, Giannatempo P, Bamias A, et al. Impact of number of cycles of platinum-based first-line chemotherapy for advanced urothelial carcinoma. J Clin Oncol. 2018;36:426.

    Google Scholar 

  33. Szabados B, van Dijk N, Tang YZ, van der Heijden MS, Wimalasingham A, de Liano AG, et al. Response rate to chemotherapy after immune checkpoint inhibition in metastatic urothelial cancer. Eur Urol. 2018;73:149–52.

    PubMed  Google Scholar 

  34. Sridhar SS, Blais N, Tran B, Reaume MN, North SA, Stockler MR, et al. Cctg BL12: randomized phase II trial comparing nab-paclitaxel (Nab-P) to paclitaxel (P) in patients (pts) with advanced urothelial cancer progressing on or after a platinum containing regimen (NCT02033993). J Clin Oncol. 2018;36:4505.

    Google Scholar 

  35. Petrylak DP, van der Heijden MS, Matsubara N, Hussain S, Flechon A, Alekseev BY, et al. 865PD RANGE, a phase III, randomized, placebo-controlled, double-blind trial of ramucirumab (RAM) and docetaxel (DOC) in platinum-refractory urothelial carcinoma (UC): overall survival results. Ann Oncol. 2018;29:viii304.

    Google Scholar 

  36. Administration TUSFaD. Guidance for industry: expedited programs for serious conditions—drugs and biologics. 2014. https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM358301.pdf. Accessed 15 Mar 2019.

  37. Ross JS, Wang K, Khaira D, Ali SM, Fisher HA, Mian B, et al. Comprehensive genomic profiling of 295 cases of clinically advanced urothelial carcinoma of the urinary bladder reveals a high frequency of clinically relevant genomic alterations. Cancer. 2016;122:702–11.

    CAS  PubMed  Google Scholar 

  38. Perera TPS, Jovcheva E, Mevellec L, Vialard J, De Lange D, Verhulst T, et al. Discovery and pharmacological characterization of JNJ-42756493 (Erdafitinib), a functionally selective small-molecule FGFR family inhibitor. Mol Cancer Ther. 2017;16:1010–20.

    CAS  PubMed  Google Scholar 

  39. Tabernero J, Bahleda R, Dienstmann R, Infante JR, Mita A, Italiano A, et al. Phase I dose-escalation study of JNJ-42756493, an oral pan-fibroblast growth factor receptor inhibitor, in patients with advanced solid tumors. J Clin Oncol. 2015;33:3401–8.

    CAS  PubMed  Google Scholar 

  40. Cervantes A, Italiano A, Spira A, Santiago-Walker AA, Zhong B, Calvo E, et al. Safety and activity of the pan–fibroblast growth factor receptor (FGFR) inhibitor erdafitinib in phase 1 study patients with advanced urothelial carcinoma. Ann Oncol. 2016;27:vi269.

    Google Scholar 

  41. Challita-Eid PM, Satpayev D, Yang P, An Z, Morrison K, Shostak Y, et al. Enfortumab vedotin antibody-drug conjugate targeting nectin-4 is a highly potent therapeutic agent in multiple preclinical cancer models. Cancer Res. 2016;76:3003–13.

    CAS  PubMed  Google Scholar 

  42. Targeting, nectin-4 in bladder cancer. Cancer Discov. 2017;7:OF3. https://doi.org/10.1158/2159-8290.CD-NB2017-095.

  43. Rosenberg JE, Sridhar SS, Zhang J, Smith DC, Ruether JD, Flaig TW, et al. Updated results from the enfortumab vedotin phase 1 (EV-101) study in patients with metastatic urothelial cancer (mUC). J Clin Oncol. 2018;36:4504.

    Google Scholar 

  44. Petrylak DP, Balar AV, O'Donnell PH, McGregor BA, Heath EI, Yu EY, et al. EV-201: Results of enfortumab vedotin monotherapy for locally advanced or metastatic urothelial cancer previously treated with platinum and immune checkpoint inhibitors. J Clin Oncol. 2019;37:4505.

    Google Scholar 

  45. Nadal R, Mortazavi A, Stein MN, Pal SK, Lee DK, Parnes HL, et al. Clinical efficacy of cabozantinib plus nivolumab (CaboNivo) and CaboNivo plus ipilimumab (CaboNivoIpi) in patients (pts) with chemotherapy-refractory metastatic urothelial carcinoma (mUC) either naïve (n) or refractory (r) to checkpoint inhibitor (CPI). J Clin Oncol. 2018;36:4528.

    Google Scholar 

  46. Espiritu SMG, Liu LY, Rubanova Y, Bhandari V, Holgersen EM, Szyca LM, et al. The evolutionary landscape of localized prostate cancers drives clinical aggression. Cell. 2018;173(1003–13):e15.

    Google Scholar 

  47. Gerhauser C, Favero F, Risch T, Simon R, Feuerbach L, Assenov Y, et al. Molecular evolution of early-onset prostate cancer identifies molecular risk markers and clinical trajectories. Cancer Cell. 2018;34(996–1011):e8.

    Google Scholar 

  48. Armenia J, Wankowicz SAM, Liu D, Gao J, Kundra R, Reznik E, et al. The long tail of oncogenic drivers in prostate cancer. Nat Genet. 2018;50:645–51.

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Wu YM, Cieslik M, Lonigro RJ, Vats P, Reimers MA, Cao X, et al. Inactivation of CDK12 delineates a distinct immunogenic class of advanced prostate cancer. Cell. 2018;173(1770–82):e14.

    Google Scholar 

  50. Viswanathan SR, Ha G, Hoff AM, Wala JA, Carrot-Zhang J, Whelan CW, et al. Structural Alterations Driving Castration-Resistant Prostate Cancer Revealed by Linked-Read Genome Sequencing. Cell. 2018;174(433–47):e19.

    Google Scholar 

  51. Quigley DA, Dang HX, Zhao SG, Lloyd P, Aggarwal R, Alumkal JJ, et al. Genomic hallmarks and structural variation in metastatic prostate cancer. Cell. 2018;175:889.

    CAS  PubMed  Google Scholar 

  52. Mishra R, Haldar S, Placencio V, Madhav A, Rohena-Rivera K, Agarwal P, et al. Stromal epigenetic alterations drive metabolic and neuroendocrine prostate cancer reprogramming. J Clin Invest. 2018;128:4472–84.

    PubMed  PubMed Central  Google Scholar 

  53. Bezzi M, Seitzer N, Ishikawa T, Reschke M, Chen M, Wang G, et al. Diverse genetic-driven immune landscapes dictate tumor progression through distinct mechanisms. Nat Med. 2018;24:165–75.

    CAS  PubMed  Google Scholar 

  54. Fizazi K, Lesaunier F, Delva R, Gravis G, Rolland F, Priou F, et al. A phase III trial of docetaxel-estramustine in high-risk localised prostate cancer: a planned analysis of response, toxicity and quality of life in the GETUG 12 trial. Eur J Cancer. 2012;48:209–17.

    CAS  PubMed  Google Scholar 

  55. Parker CC, James ND, Brawley CD, Clarke NW, Hoyle AP, Ali A, et al. Radiotherapy to the primary tumour for newly diagnosed, metastatic prostate cancer (STAMPEDE): a randomised controlled phase 3 trial. Lancet. 2018;392:2353–66.

    PubMed  PubMed Central  Google Scholar 

  56. Boeve LMS, Hulshof M, Vis AN, Zwinderman AH, Twisk JWR, Witjes WPJ, et al. Effect on survival of androgen deprivation therapy alone compared to androgen deprivation therapy combined with concurrent radiation therapy to the prostate in patients with primary bone metastatic prostate cancer in a prospective randomised clinical trial: data from the HORRAD trial. Eur Urol. 2019;75:410–8.

    PubMed  Google Scholar 

  57. Chi KN, Protheroe A, Rodriguez-Antolin A, Facchini G, Suttman H, Matsubara N, et al. Patient-reported outcomes following abiraterone acetate plus prednisone added to androgen deprivation therapy in patients with newly diagnosed metastatic castration-naive prostate cancer (LATITUDE): an international, randomised phase 3 trial. Lancet Oncol. 2018;19:194–206.

    CAS  PubMed  Google Scholar 

  58. Feyerabend S, Saad F, Li T, Ito T, Diels J, Van Sanden S, et al. Survival benefit, disease progression and quality-of-life outcomes of abiraterone acetate plus prednisone versus docetaxel in metastatic hormone-sensitive prostate cancer: a network meta-analysis. Eur J Cancer. 2018;103:78–877.

    CAS  PubMed  Google Scholar 

  59. Wallis CJD, Klaassen Z, Bhindi B, Goldberg H, Chandrasekar T, Farrell AM, et al. Comparison of abiraterone acetate and docetaxel with androgen deprivation therapy in high-risk and metastatic hormone-naive prostate cancer: a systematic review and network meta-analysis. Eur Urol. 2018;73:834–44.

    CAS  PubMed  Google Scholar 

  60. Investigators TS, Ritchie AWS, Amos C, Gilson C, Parmar MKB, Spears MR, et al. Adding abiraterone or docetaxel to long-term hormone therapy for prostate cancer: directly randomised data from the STAMPEDE multi-arm, multi-stage platform protocol. Ann Oncol. 2018;29:1235–48.

    Google Scholar 

  61. Armstrong AJ, Szmulewitz RZ, Petrylak DP, Villers A, Azad A, Alcaraz A, et al. Phase III study of androgen deprivation therapy (ADT) with enzalutamide (ENZA) or placebo (PBO) in metastatic hormone-sensitive prostate cancer (mHSPC): the ARCHES trial. J Clin Oncol. 2019;37:687.

    Google Scholar 

  62. Chi KN, Agarwal N, Bjartell A, Chung BH, de Gomes AJPS, Given R et al. Apalutamide for metastatic, castration-sensitive prostate cancer. N Engl J Med. 2019.

  63. Davis ID, Martin AJ, Stockler MR, Begbie S, Chi KN, Chowdhury S, et al. Enzalutamide with standard first-line therapy in metastatic prostate cancer. N Engl J Med. 2019;381:121–31.

    CAS  PubMed  Google Scholar 

  64. Smith MR, Zucca LE, Heidenreich A, Kakehi Y, Zhang A, Krissel H et al. LBA30ERA 223: A phase III trial of radium-223 (Ra-223) in combination with abiraterone acetate and prednisone/prednisolone for the treatment of asymptomatic or mildly symptomatic chemotherapy-naïve patients (pts) with bone-predominant metastatic castration-resistant prostate cancer (mCRPC). Ann Oncol. 2018;29.

  65. Chi KN, Azad A, Wood L, Gingerich JR, North S, Pezaro CV et al. 792O A randomized phase II study of cabazitaxel (CAB) vs (ABI) abiraterone or (ENZ) enzalutamide in poor prognosis metastatic castration-resistant prostate cancer (mCRPC). Ann Oncol. 2018;29.

  66. Clarke N, Wiechno P, Alekseev B, Sala N, Jones R, Kocak I, et al. Olaparib combined with abiraterone in patients with metastatic castration-resistant prostate cancer: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Oncol. 2018;19:975–86.

    CAS  PubMed  Google Scholar 

  67. Hussain M, Fizazi K, Saad F, Rathenborg P, Shore N, Ferreira U, et al. Enzalutamide in men with nonmetastatic, castration-resistant prostate cancer. N Engl J Med. 2018;378:2465–74.

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Smith MR, Saad F, Chowdhury S, Oudard S, Hadaschik BA, Graff JN, et al. Apalutamide treatment and metastasis-free survival in prostate cancer. N Engl J Med. 2018;378:1408–18.

    CAS  PubMed  Google Scholar 

  69. Fizazi K, Shore N, Tammela TL, Ulys A, Vjaters E, Polyakov S, et al. Darolutamide in nonmetastatic, castration-resistant prostate cancer. N Engl J Med. 2019;380:1235–46.

    CAS  PubMed  Google Scholar 

  70. Conteduca V, Jayaram A, Romero-Laorden N, Wetterskog D, Salvi S, Gurioli G, et al. Plasma androgen receptor and docetaxel for metastatic castration-resistant prostate cancer. Eur Urol. 2019;75:368–73.

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Scher HI, Graf RP, Schreiber NA, Jayaram A, Winquist E, McLaughlin B, et al. Assessment of the validity of nuclear-localized androgen receptor splice variant 7 in circulating tumor cells as a predictive biomarker for castration-resistant prostate cancer. JAMA Oncol. 2018;4:1179–86.

    PubMed  PubMed Central  Google Scholar 

  72. Romero-Laorden N, Lozano R, Jayaram A, Lopez-Campos F, Saez MI, Montesa A, et al. Phase II pilot study of the prednisone to dexamethasone switch in metastatic castration-resistant prostate cancer (mCRPC) patients with limited progression on abiraterone plus prednisone (SWITCH study). Br J Cancer. 2018;119:1052–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Antonarakis ES, Tagawa ST, Galletti G, Worroll D, Ballman K, Vanhuyse M, et al. Randomized, noncomparative, phase II trial of early switch from docetaxel to cabazitaxel or vice versa, with integrated biomarker analysis, in men with chemotherapy-naive, metastatic, castration-resistant prostate cancer. J Clin Oncol. 2017;35:3181–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Mateo J. ESMO 2018: Invited Discussant - Genomics of Prostate Cancer for Precision Medicine Based on DNA Repair Defects. 2018. https://www.urotoday.com/conference-highlights/esmo-2018/esmo-2018-prostate-cancer/107791-esmo-2018-invited-discussant-interrogating-genomics-of-prostate-cancer-for-precision-medicine-based-on-dna-repair-defects.html. Accessed 1 June 2019.

  75. Patel A, Fong L. Immunotherapy for prostate cancer: where do we go from here?-part 2: checkpoint inhibitors, immunotherapy combinations, tumor microenvironment modulation, and cellular therapies. Oncology. 2018;32:e65–e73.

    PubMed  Google Scholar 

  76. Patel A, Fong L. Immunotherapy for prostate cancer: where do we go from here?-part 1: prostate cancer vaccines. Oncology (Williston Park). 2018;32:112–20.

    PubMed  Google Scholar 

  77. Gulley JL, Borre M, Vogelzang NJ, Ng S, Agarwal N, Parker CC, et al. Phase III Trial of PROSTVAC in asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer. J Clin Oncol. 2018. https://doi.org/10.1200/JCO.18.02031.

    Article  Google Scholar 

  78. Kantoff PW, Gulley JL, Pico-Navarro C. Revised overall survival analysis of a phase II, randomized, double-blind, controlled study of PROSTVAC in men with metastatic castration-resistant prostate cancer. J Clin Oncol. 2017;35:124–5.

    PubMed  Google Scholar 

  79. Bono JS, Goh JY, Ojamaa K, Piulats-Rodriguez JM, Drake CG, Hoimes CJ, et al. KEYNOTE-199: pembrolizumab (pembro) for docetaxel-refractory metastatic castration-resistant prostate cancer (mCRPC). J Clin Oncol. 2018;36:5007.

    Google Scholar 

  80. Hansen AR, Massard C, Ott PA, Haas NB, Lopez JS, Ejadi S, et al. Pembrolizumab for advanced prostate adenocarcinoma: findings of the KEYNOTE-028 study. Ann Oncol. 2018;29:1807–13.

    CAS  PubMed  Google Scholar 

  81. Boudadi K, Suzman DL, Anagnostou V, Fu W, Luber B, Wang H, et al. Ipilimumab plus nivolumab and DNA-repair defects in AR-V7-expressing metastatic prostate cancer. Oncotarget. 2018;9:28561–71.

    PubMed  PubMed Central  Google Scholar 

  82. Yu EY, Massard C, Retz M, Tafreshi A, Galceran JC, Hammerer P, et al. Keynote-365 cohort a: pembrolizumab (pembro) plus olaparib in docetaxel-pretreated patients (pts) with metastatic castrate-resistant prostate cancer (mCRPC). J Clin Oncol. 2019;37:145.

    Google Scholar 

  83. Fong PC, Retz M, Drakaki A, Massard C, Berry WR, Romano E, et al. Keynote-365 cohort C: pembrolizumab (pembro) plus enzalutamide (enza) in abiraterone (abi)-pretreated patients (pts) with metastatic castrate resistant prostate cancer (mCRPC). J Clin Oncol. 2019;37:171.

    Google Scholar 

  84. Massard C, Retz M, Hammerer P, Quevedo F, Fong PC, Berry WR, et al. Pembrolizumab (pembro) plus docetaxel and prednisone in abiraterone (abi) or enzalutamide (enza)-pretreated patients (pts) with metastatic castrate resistant prostate cancer (mCRPC): cohort B of the phase 1b/2 KEYNOTE-365 study. J Clin Oncol. 2019;37:5029.

    Google Scholar 

  85. Karzai F, VanderWeele D, Madan RA, Owens H, Cordes LM, Hankin A, et al. Activity of durvalumab plus olaparib in metastatic castration-resistant prostate cancer in men with and without DNA damage repair mutations. J Immunother Cancer. 2018;6:141.

    PubMed  PubMed Central  Google Scholar 

  86. Abida W, Cheng ML, Armenia J, Middha S, Autio KA, Vargas HA, et al. Analysis of the prevalence of microsatellite instability in prostate cancer and response to immune checkpoint blockade. JAMA Oncol. 2018;5:471–8.

    PubMed Central  Google Scholar 

  87. Antonarakis ES, Lu C, Luber B, Liang C, Wang H, Chen Y, et al. Germline DNA-repair gene mutations and outcomes in men with metastatic castration-resistant prostate cancer receiving first-line abiraterone and enzalutamide. Eur Urol. 2018;74:218–25.

    CAS  PubMed  PubMed Central  Google Scholar 

  88. Antonarakis ES. Cyclin-dependent kinase 12, immunity, and prostate cancer. N Engl J Med. 2018;379:1087–9.

    PubMed  Google Scholar 

  89. Castro E, Romero-Laorden N, Del Pozo A, Lozano R, Medina A, Puente J, et al. PROREPAIR-B: a prospective cohort study of the impact of germline DNA repair mutations on the outcomes of patients with metastatic castration-resistant prostate cancer. J Clin Oncol. 2019;37:490–503.

    CAS  PubMed  Google Scholar 

  90. Shen H, Shih J, Hollern DP, Wang L, Bowlby R, Tickoo SK, et al. Integrated molecular characterization of testicular germ cell tumors. Cell Rep. 2018;23:3392–406.

    CAS  PubMed  PubMed Central  Google Scholar 

  91. Feldman DR, Hu J, Srinivas S, Stadler WM, Costello BA, Appleman LJ, et al. Multicenter randomized phase 2 trial of paclitaxel, ifosfamide, and cisplatin (TIP) versus bleomycin, etoposide, and cisplatin (BEP) for first-line treatment of patients (pts) with intermediate- or poor-risk germ cell tumors (GCT). J Clin Oncol. 2018;36:4508.

    Google Scholar 

  92. Bagrodia A, Lee BH, Lee W, Cha EK, Sfakianos JP, Iyer G, et al. Genetic Determinants of Cisplatin Resistance in Patients With Advanced Germ Cell Tumors. J Clin Oncol. 2016;34:4000–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  93. Adra N, Einhorn LH, Althouse SK, Ammakkanavar NR, Musapatika D, Albany C, et al. Phase II trial of pembrolizumab in patients with platinum refractory germ-cell tumors: a Hoosier Cancer Research Network Study GU14-206. Ann Oncol. 2018;29:209–14.

    CAS  PubMed  Google Scholar 

  94. Necchi A, Giannatempo P, Raggi D, Mariani L, Colecchia M, Fare E, et al. An open-label randomized phase 2 study of durvalumab alone or in combination with tremelimumab in patients with advanced germ cell tumors (APACHE): results from the first planned interim analysis. Eur Urol. 2019;75:201–3.

    CAS  PubMed  Google Scholar 

  95. Fenner M, Oing C, Dieing A, Gauler T, Oechsle K, Lorch A, et al. Everolimus in patients with multiply relapsed or cisplatin refractory germ cell tumors: results of a phase II, single-arm, open-label multicenter trial (RADIT) of the German Testicular Cancer Study Group. J Cancer Res Clin Oncol. 2019;145:717–23.

    PubMed  Google Scholar 

  96. Lubberts S, Boer H, Altena R, Meijer C, van Roon AM, Zwart N, et al. Vascular fingerprint and vascular damage markers associated with vascular events in testicular cancer patients during and after chemotherapy. Eur J Cancer. 2016;63:180–8.

    CAS  PubMed  Google Scholar 

  97. Gizzi M, Oberic L, Massard C, Poterie A, Le Teuff G, Loriot Y, et al. Predicting and preventing thromboembolic events in patients receiving cisplatin-based chemotherapy for germ cell tumours. Eur J Cancer. 2016;69:151–7.

    CAS  PubMed  Google Scholar 

  98. da Costa WH, da Cunha IW, Fares AF, Bezerra SM, Shultz L, Clavijo DA, et al. Prognostic impact of concomitant loss of PBRM1 and BAP1 protein expression in early stages of clear cell renal cell carcinoma. Urol Oncol. 2018;36(243):e1–e8.

    Google Scholar 

  99. Högner A, Krause H, Jandrig B, Kasim M, Fuller TF, Schostak M, et al. PBRM1 and VHL expression correlate in human clear cell renal cell carcinoma with differential association with patient's overall survival. Urol Oncol. 2018;36(94):e1–e14.

    Google Scholar 

  100. Espana-Agusti J, Warren A, Chew SK, Adams DJ, Matakidou A. Loss of PBRM1 rescues VHL dependent replication stress to promote renal carcinogenesis. Nat Commun. 2017;8:2026.

    PubMed  PubMed Central  Google Scholar 

  101. Pal SK, Ali SM, Yakirevich E, Geynisman DM, Karam JA, Elvin JA, et al. Characterization of clinical cases of advanced papillary renal cell carcinoma via comprehensive genomic profiling. Eur Urol. 2018;73:71–8.

    CAS  PubMed  Google Scholar 

  102. Motzer RJ, Escudier B, McDermott DF, George S, Hammers HJ, Srinivas S, et al. Nivolumab versus everolimus in advanced renal-cell carcinoma. N Engl J Med. 2015;373:1803–13.

    CAS  PubMed  PubMed Central  Google Scholar 

  103. Seeber A, Klinglmair G, Fritz J, Steinkohl F, Zimmer KC, Aigner F, et al. High IDO-1 expression in tumor endothelial cells is associated with response to immunotherapy in metastatic renal cell carcinoma. Cancer Sci. 2018;109:1583–91.

    CAS  PubMed  PubMed Central  Google Scholar 

  104. Miao D, Margolis CA, Gao W, Voss MH, Li W, Martini DJ, et al. Genomic correlates of response to immune checkpoint therapies in clear cell renal cell carcinoma. Science. 2018;359:801–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  105. Méjean A, Ravaud A, Thezenas S, Colas S, Beauval JB, Bensalah K, et al. Sunitinib alone or after nephrectomy in metastatic renal-cell carcinoma. N Engl J Med. 2018;379:417–27.

    PubMed  Google Scholar 

  106. Gross-Goupil M, Kwon TG, Eto M, Ye D, Miyake H, Seo SI, et al. Axitinib versus placebo as an adjuvant treatment of renal cell carcinoma: results from the phase III, randomized ATLAS trial. Ann Oncol. 2018;29:2371–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  107. Hanna N, Sun M, Meyer CP, Nguyen PL, Pal SK, Chang SL, et al. Survival analyses of patients with metastatic renal cancer treated with targeted therapy with or without cytoreductive nephrectomy: a National Cancer Data Base Study. J Clin Oncol. 2016;34:3267–75.

    PubMed  PubMed Central  Google Scholar 

  108. Heng DY, Wells JC, Rini BI, Beuselinck B, Lee JL, Knox JJ, et al. Cytoreductive nephrectomy in patients with synchronous metastases from renal cell carcinoma: results from the International Metastatic Renal Cell Carcinoma Database Consortium. Eur Urol. 2014;66:704–10.

    PubMed  Google Scholar 

  109. Bex A, Mulders P, Jewett M, Wagstaff J, van Thienen JV, Blank CU, et al. Comparison of immediate vs deferred cytoreductive nephrectomy in patients with synchronous metastatic renal cell carcinoma receiving sunitinib: The SURTIME randomized clinical trial. JAMA Oncol. 2018;5:164–70 (Epub ahead of print).

    PubMed Central  Google Scholar 

  110. Mejean A, Thezenas S, Chevreau C, Bensalah K, Geoffrois L, Thiery-Vuillemin A, et al. Cytoreductive nephrectomy (CN) in metastatic renal cancer (mRCC): update on Carmena trial with focus on intermediate IMDC-risk population. J Clin Oncol. 2019;37:4508.

    Google Scholar 

  111. Ravaud A, Motzer RJ, Pandha HS, George DJ, Pantuck AJ, Patel A, et al. Adjuvant sunitinib in high-risk renal-cell carcinoma after nephrectomy. N Engl J Med. 2016;375:2246–54.

    CAS  PubMed  Google Scholar 

  112. Procopio G, Cognetti F, Micelli R, Milella M, Mosca A, Chiuri VE et al. A randomized, open label, multicenter phase 2 study, to evaluate the efficacy of sorafenib (So) in patients (pts) with metastatic renal cell carcinoma (mRCC) after a radical resection of the metastases: RESORT trial. J Clin Oncol. 2018;36 (Abstract 4502)

  113. Appleman LJ, Puligandla M, Pal SK, Harris W, Agarwal N, Costello BA, et al. Randomized, double-blind phase III study of pazopanib versus placebo in patients with metastatic renal cell carcinoma who have no evidence of disease following metastasectomy: a trial of the ECOG-ACRIN cancer research group (E2810). J Clin Oncol. 2019;37:4502.

    Google Scholar 

  114. Choueiri TK, Hessel C, Halabi S, Sanford B, Michaelson MD, Hahn O, et al. Cabozantinib versus sunitinib as initial therapy for metastatic renal cell carcinoma of intermediate or poor risk (Alliance A031203 CABOSUN randomised trial): progression-free survival by independent review and overall survival update. Eur J Cancer. 2018;94:115–25.

    CAS  PubMed  PubMed Central  Google Scholar 

  115. Choueiri TK, Halabi S, Sanford BL, Hahn O, Michaelson MD, Walsh MK, et al. Cabozantinib versus sunitinib as initial targeted therapy for patients with metastatic renal cell carcinoma of poor or intermediate risk: the Alliance A031203 Cabosun Trial. J Clin Oncol. 2017;35:591–7.

    CAS  PubMed  Google Scholar 

  116. Motzer RJ, Tannir NM, McDermott DF, Arén Frontera O, Melichar B, Choueiri TK, et al. Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma. N Engl J Med. 2018;378:1277–90.

    CAS  PubMed  PubMed Central  Google Scholar 

  117. Escudier B, Tannir NM, McDermott DF, Frontera OA, Melichar B, Plimack ER et al. LBA5CheckMate 214: Efficacy and safety of nivolumab + ipilimumab (N+I) v sunitinib (S) for treatment-naïve advanced or metastatic renal cell carcinoma (mRCC), including IMDC risk and PD-L1 expression subgroups. Annals of Oncology. 2017;28.

  118. Motzer RJ, Powles T, Atkins MB, Escudier B, McDermott DF, Suárez C et al. IMmotion151: a randomized phase III study of atezolizumab plus bevacizumab vs sunitinib in untreated metastatic renal cell carcinoma (mRCC). J Clin Oncol. 2018;36 (Abstract 578)

  119. Rini BI, Powles T, Atkins MB, Escudier B, McDermott DF, Suarez C, et al. Atezolizumab plus bevacizumab versus sunitinib in patients with previously untreated metastatic renal cell carcinoma (IMmotion151): a multicentre, open-label, phase 3, randomised controlled trial. Lancet. 2019;393:2404–15.

    PubMed  Google Scholar 

  120. Motzer RJ, Penkov K, Haanen JBAG, Rini BI, Albiges L, Campbell MT et al. JAVELIN renal 101: A randomized, phase III study of avelumab + axitinib vs sunitinib as first-line treatment of advanced renal cell carcinoma (aRCC). Ann Oncol. 2018;29 (Abstract LBA6_PR)

  121. McDermott DF, Lee JL, Szczylik C, Donskov F, Malik J, Alekseev BY et al. Pembrolizumab monotherapy as first-line therapy in advanced clear cell renal cell carcinoma (accRCC): results from cohort A of KEYNOTE-427. J Clin Oncol. 2018;36 (Abstract 4500)

  122. Rini BI, Plimack ER, Stus V, Gafanov R, Hawkins R, Nosov D, et al. Pembrolizumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med. 2019;380:1116–27.

    CAS  PubMed  Google Scholar 

  123. Albiges L, Negrier S, Dalban C, Gravis G, Chevreau C, Oudard S et al. Safety and efficacy of nivolumab in metastatic renal cell carcinoma (mRCC): Results from the NIVOREN GETUG-AFU 26 study. J Clin Oncol. 2018;36 (Abstract 577)

  124. Powles T, Motzer RJ, Escudier B, Pal S, Kollmannsberger C, Pikiel J, et al. Outcomes based on prior therapy in the phase 3 METEOR trial of cabozantinib versus everolimus in advanced renal cell carcinoma. Br J Cancer. 2018;119:663–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  125. Flippot R, Escudier B, Albiges L. Immune checkpoint inhibitors: toward new paradigms in renal cell carcinoma. Drugs. 2018;78:1443–57.

    CAS  PubMed  Google Scholar 

  126. Joosten SC, Smits KM, Aarts MJ, Melotte V, Koch A, Tjan-Heijnen VC, et al. Epigenetics in renal cell cancer: mechanisms and clinical applications. Nat Rev Urol. 2018;15:430–51.

    CAS  PubMed  Google Scholar 

  127. Tannir NM, Naing A, Infante JR, Papadopoulos KP, Wong DJL, JKorn M et al. Pegilodecakin with nivolumab (nivo) or pembrolizumab (pembro) in patients (pts) with metastatic renal cell carcinoma (RCC). J Clin Oncol. 2018;36 (Abstract 4509)

  128. Vaishampayan UN, McDermott DF, Matrana MR, Rha SY, Zurita AJ, Ho TH et al. A phase 1/2 study evaluating the efficacy and safety of the oral CXCR4 inhibitor X4P-001 in combination with axitinib in patients with advanced renal cell carcinoma. J Clin Oncol. 2018;36 (Abstract 4510)

  129. Pitts D. AVEO oncology announces phase 3 TIVO-3 trial of tivozanib in renal cell carcinoma meets primary endpoint. 2019. https://investor.aveooncology.com/news-releases/news-release-details/aveo-oncology-announces-phase-3-tivo-3-trial-tivozanib-renal. Accessed 24 Mar 2019.

  130. Pant S, Spira AI, Cho BC, Goel S, Hoimes CJ, Alva AS et al. Evaluation of the spectrum selective RTK inhibitor sitravatinib in clear cell renal cell carcinoma (ccRCC) refractory to anti-angiogenic therapy (AAT). J Clin Oncol. 2018;36 (Abstract 4568)

  131. Courtney KD, Infante JR, Lam ET, Figlin RA, Rini BI, Brugarolas J, et al. Phase I dose-escalation trial of PT2385, a first-in-class hypoxia-inducible factor-2alpha antagonist in patients with previously treated advanced clear cell renal cell carcinoma. J Clin Oncol. 2018;36:867–74.

    CAS  PubMed  Google Scholar 

  132. Tannir NM, Fan AC, Lee RJ, Carthon BC, Iliopoulos O, Mier JW et al. Phase 1 study of glutaminase (GLS) inhibitor CB-839 combined with either everolimus (E) or cabozantinib (Cabo) in patients (pts) with clear cell (cc) and papillary (pap) metastatic renal cell cancer (mRCC). J Clin Oncol. 2018;36 (Abstract 603)

  133. Rini BI, Appleman LJ, Figlin RA, Merchan JR, Wang K, et al. Results from a phase I expansion cohort of the first-in-class oral HIF-2α inhibitor PT2385 in combination with nivolumab in patients with previously treated advanced RCC. J Clin Oncol. 2019;37:558.

    Google Scholar 

  134. Tannir NM, Motzer RJ, Agarwal N, Liu PY, Whiting SH, O'Keeffe B et al. CANTATA: A randomized phase 2 study of CB-839 in combination with cabozantinib vs. placebo with cabozantinib in patients with advanced/metastatic renal cell carcinoma. J Clin Oncol. 2018;36 (Abstract TPS4601)

  135. Routy B, Le Chatelier E, Derosa L, Duong CPM, Alou MT, Daillère R, et al. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science. 2018;359:91–7.

    CAS  PubMed  Google Scholar 

  136. Derosa L, Hellmann MD, Spaziano M, Halpenny D, Fidelle M, Rizvi H, et al. Negative association of antibiotics on clinical activity of immune checkpoint inhibitors in patients with advanced renal cell and non-small-cell lung cancer. Ann Oncol. 2018;29:1437–44.

    CAS  PubMed  PubMed Central  Google Scholar 

  137. Beuselinck B, Job S, Becht E, Karadimou A, Verkarre V, Couchy G, et al. Molecular subtypes of clear cell renal cell carcinoma are associated with sunitinib response in the metastatic setting. Clin Cancer Res. 2015;21:1329–39.

    CAS  PubMed  Google Scholar 

  138. Elaidi RT, Oudard S, Braychenko E, Sun CM, Sautès-Fridman C, Vano YA. A phase 2 BIOmarker driven trial with Nivolumab and Ipilimumab or VEGFR tKi in naïve metastatic Kidney cancer: the BIONIKK trial. Ann Oncol. 2017;28 (Abstract 923TiP)

  139. Albiges L, Flippot R, Rioux-Leclercq N, Choueiri TK. Non-clear cell renal cell carcinomas: from shadow to light. J Clin Oncol. 2018 (Epub ahead of print)

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Acknowledgements

The authors acknowledge the assistance of Beatriz Gil-Alberdi and Fernando Sánchez-Barbero from HealthCo (Madrid, Spain) in the preparation of the first draft of this manuscript. Astellas Pharma S.A. financially supported medical writing assistance and should also be acknowledged.

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Authors and Affiliations

  1. Medical Oncology Department, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain

    A. González-del-Alba

  2. Medical Oncology Department, Hospital Universitario Gregorio Marañón, Madrid, Spain

    J. Á. Arranz

  3. Medical Oncology Department, Dana-Farber Cancer Institute, Boston, USA

    J. Bellmunt

  4. Medical Oncology Department, Hospital Universitari Santa Creu i Sant Pau, Barcelona, Spain

    J. P. Maroto

  5. Medical Oncology Department, Complexo Hospitalario Universitario de Ourense, Orense, Spain

    O. Fernández-Calvo

  6. Medical Oncology Department, Hospital Univeristario Virgen del Rocío, Sevilla, Spain

    B. P. Valderrama

  7. Medical Oncology Department, Hospital Universitario Morales Meseguer, Murcia, Spain

    E. González-Billalabeitia

  8. Medical Oncology Department, Hospital Universitario Reina Sofía, Córdoba, Spain

    M. J. Méndez-Vidal

  9. Medical Oncology Department, Hospital Universitario de Guadalajara, Guadalajara, Spain

    J. Cassinello

  10. Medical Oncology Department, Hospital Universitario La Princesa, Madrid, Spain

    N. Romero-Laorden

  11. Medical Oncology Department, Fundación Instituto Valenciano de Oncología, Valencia, Spain

    M. Á. Climent

  12. Medical Oncology Department, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), CIBERONC, Madrid, Spain

    J. Puente

  13. Medical Oncology Department, Hospital Universitario de Cabueñes, Gijón, Spain

    I. Peláez

  14. Medical Oncology Department, Hospital Universitario Alvaro Cunqueiro, Vigo, Spain

    M. Lázaro-Quintela

  15. Medical Oncology Department, Hospital Univeristari Parc Tauli, Institut d’Investigació I Innovació Parc Taulí I3PT. Universidad Autonoma de Barcelona, Sabadell, Spain

    E. Gallardo

  16. Medical Oncology Department, Hospital Universitari Vall d’Hebron, Institute of Oncology, Universidad Autònoma de Barcelona, Barcelona, Spain

    C. Suárez

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  1. A. González-del-Alba
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Conflict of interest

A González del Alba declared honoraria from Astellas Pharma, Ipsen, Janssen-Cilag, Novartis, Pfizer, Roche and Sanofi, participated in advisory boards for Astellas Pharma, AstraZeneca, Bayer, Bristol-Myers Squibb, Eisai, EUSA Pharma, Ipsen, Janssen-Cilag, Novartis, Pfizer, Pierre Fabre, Roche and Sanofi, was compensated as speaker by Ipsen, Janssen-Cilag, Pfizer, Pierre Fabre and Roche, received research grants from Astellas Pharma, and benefitted from travel and accommodation expenses funded by Astellas Pharma, Bristol-Myers Squibb, Ipsen, Janssen-Cilag, Merck Sharp and Dohme, Pfizer, Roche and Sanofi. JA Arranz declared honoraria from Astellas Pharma, Bristol-Myers Squibb, EUSA Pharma, Janssen-Cilag and Novartis, participated in advisory boards for Astellas Pharma, Bayer, Bristol-Myers Squibb, EUSA Pharma, Janssen-Cilag, Ipsen, Merck Sharp and Dohme, Novartis and Pfizer, received research grants from Bristol-Myers Squibb, Novartis and Pierre Fabre, and benefitted from travel and accommodation expenses funded by Bristol-Myers Squibb, Janssen-Cilag, Merck Sharp & Dohme and Pfizer. J Bellmunt declared honoraria from Pfizer and Pierre Fabre, participated in advisory boards for AstraZeneca, Bayer, Bristol-Myers Squibb, Merck Sharp & Dohme, Merck, Pfizer, Roche and Sanofi, received research grants from Merck, Pfizer and Roche. JP Maroto participated in advisory boards for Astellas Pharma, AstraZeneca, Bayer, Janssen-Cilag, Ipsen, Novartis, Pfizer, Roche and Sanofi, and benefitted from travel and accommodation expenses funded by Ipsen, Pfizer and Roche. O Fernández-Calvo declared honoraria from Astellas Pharma, Eisai, Ipsen, Novartis, Pfizer, Roche and Sanofi, participated in advisory boards for Astellas Pharma, Pfizer and Sanofi, and benefitted from travel and accommodation expenses funded by Ipsen, Pfizer and Roche. B P Valderrama declared honoraria from Astellas Pharma, Bayer, Bristol-Myers Squibb, Ipsen, Novartis, Pierre Fabre and Roche, participated in advisory boards for Astellas Pharma, Bayer, Bristol-Myers Squibb, Ipsen, Merck Sharp & Dohme, Pierre Fabre, Roche and Sanofi, and benefitted from travel and accommodation expenses funded by Bristol-Myers Squibb, Janssen-Cilag and Pfizer. E González-Billalabeitia participated in advisory boards for AstraZeneca and was compensated as speaker or travel grants by Astellas Pharma, Bayer, Bristol-Myers Squibb, EUSA Pharma, Janssen-Cilag, Pfizer and Sanofi. MJ Méndez-Vidal declared honoraria from Astellas Pharma, Bayer, Bristol-Myers Squibb, Janssen-Cilag, Novartis, Pfizer, Roche and Sanofi, and benefitted from travel and accommodation expenses funded by Astellas Pharma, Bristol-Myers Squibb, Janssen-Cilag and Pfizer. J Cassinello declared honoraria from Astellas Pharma, AstraZeneca, Janssen-Cilag, Pfizer and Roche, participated in advisory boards for Novartis, Roche and Sanofi, received research grants from Astellas Pharma and Pfizer, and benefitted from travel and accommodation expenses funded by Bristol-Myers Squibb, Pfizer and Roche. N Romero Laorden declared honoraria from Astellas Pharma, Bayer, Janssen-Cilag, Pfizer, PharmaMar, Roche and Sanofi, received research grants from Astellas Pharma, Bayer, Janssen-Cilag and Sanofi, and benefitted from travel and accommodation expenses funded by Janssen-Cilag, Pfizer and Roche. MA Climent participated in advisory boards for Bristol-Myers Squibb, Ipsen, Janssen-Cilag, Merck Sharp & Dohme, Roche and Sanofi, was compensated as speaker by Bristol-Myers Squibb, Janssen-Cilag, Merck Sharp and Dohme, Novartis, Pfizer and Roche, and benefit from travel and accommodation expenses funded by Astellas Pharma, Ipsen, Janssen-Cilag, Merck Sharp and Dohme and Roche. J Puente declared honoraria from Astellas Pharma, AstraZeneca, Bayer, Bristol-Myers Squibb, Eisai, EUSA Pharma, Ipsen, Janssen-Cilag, Merck Sharp and Dohme, Pfizer, Pierre Fabre, Roche and Sanofi, participated in advisory boards for Astellas Pharma, Bayer, Bristol-Myers Squibb, Clovis, Eisai, Janssen-Cilag, Ipsen, Merck Sharp and Dohme, Pfizer, Roche and Sanofi, received research grants from Astellas Pharma and Pfizer, and benefitted from travel and accommodation expenses funded by Bristol-Myers Squibb, Janssen-Cilag, Merck Sharp and Dohme, Pfizer and Roche. I Peláez, Cabueñes declared honoraria from Astellas Pharma, AstraZeneca, Eisai, Novartis, Pfizer and Roche, participated in advisory boards for Pfizer, and benefitted from travel and accommodation expenses funded by Ipsen, Pfizer and Roche. M Lázaro-Quintela participated in advisory boards from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Esai, EUSA Pharma, Ipsen, Merck Sharp and Dohme and Roche, was compensated as speaker by AstraZeneca, Boehringer Ingelheim, Ipsen, Janssen-Cilag, Lilly, Merck Sharp and Dohme, Novartis and Roche, and benefitted from travel and accommodation expenses funded by AstraZeneca, Bristol-Myers Squibb, Lilly, Merck Sharp and Dohme, Pfizer and Roche. E Gallardo participated in advisory boards for Merck, Pfizer, Ipsen, Novartis, Eisai, EUSA Pharma, Bristol-Myers Squibb, Bayer, Roche, Sanofi, Janssen-Cilag, Astellas Pharma, Rovi, Daiichi Sankyo, Techdow, was compensated as speaker by Bayer, Ipsen, Pfizer, Bristol-Myers Squibb, Novartis, Eisai, Roche, Astellas, Janssen, Sanofi, Rovi, Daiichi Sankyo, Leo Pharma, Menarini, received research grants from Pfizer, Bayer, Ipsen, Roche, Bristol-Myers Squibb, Novartis, Merck Sharp and Dohme, Incyte, Aveo, Eisai, Calithera, Leo Pharma, Daiichi Sankyo, AstraZeneca, Sanofi, Astellas, Bavarian-Nordic, Clovis, Janssen, and benefitted from travel and accommodation expenses funded by Pfizer, Bayer, Ipsen, Roche, Novartis, Eisai, Bristol-Myers Squibb, Pierre Fabre, Astellas Pharma, Janssen-Cilag, Sanofi and Ferrer. C Suárez declared honoraria from Astellas Pharma, AstraZeneca, Bayer, Bristol-Myers Squibb, Eisai, Ipsen, Merck Sharp & Dohme, Novartis, Pfizer, Roche and Sanofi.

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González-del-Alba, A., Arranz, J.Á., Bellmunt, J. et al. Latest progress in molecular biology and treatment in genitourinary tumours. Clin Transl Oncol 22, 2175–2195 (2020). https://doi.org/10.1007/s12094-020-02373-z

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