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New advances in genitourinary cancer: evidence gathered in 2014

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Abstract

This review provides updated information published in 2014 regarding advances and major achievements in genitourinary cancer. Sections include the best in prostate cancer, renal cancer, bladder cancer, and germ cell tumors. In the field of prostate cancer, data related to treatment approach of hormone-sensitive disease, castrate-resistant prostate cancer, mechanisms of resistance, new drugs, and molecular research are presented. In relation to renal cancer, relevant aspects in the treatment of advanced renal cell carcinoma, immunotherapy, and molecular research, including angiogenesis and von Hippel-Lindau gene, molecular biology of non-clear cell histologies, and epigenetics of clear renal cell cancer are described. New strategies in the management of muscle-invasive localized bladder cancer and metastatic disease are reported as well as salient findings of biomolecular research in urothelial cancer. Some approaches intended to improve outcomes in poor prognosis patients with metastatic germ cell cancer are also reported. Results of clinical trials in these areas are discussed.

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References

  1. Siegel, R., Ma, J., Zou, Z., & Jemal, A. (2014). Cancer statistics, 2014. CA: A Cancer Journal for Clinicians. doi:10.3322/caac.21208.

    Google Scholar 

  2. James, N. D., Spears, M. R., Clarke, N. W., Dearnaley, D. P., De Bono, J. S., Gale, J., et al. (2014). Survival with newly diagnosed metastatic prostate cancer in the “docetaxel era”: data from 917 patients in the control arm of the STAMPEDE Trial (MRC PR08, CRUK/06/019). European Urology. doi:10.1016/j.eururo.2014.09.032.

    Google Scholar 

  3. Klotz, L., Miller, K., Crawford, E. D., Shore, N., Tombal, B., Karup, C., et al. (2014). Disease control outcomes from analysis of pooled individual patient data from five comparative randomised clinical trials of degarelix versus luteinising hormone-releasing hormone agonists. European Urology, 66, 1101–1108. doi:10.1016/j.eururo.2013.12.063.

    Article  CAS  PubMed  Google Scholar 

  4. Crawford, E. D., Shore, N. D., Moul, J. W., Tombal, B., Schröder, F. H., Miller, K., et al. (2014). Long-term tolerability and efficacy of degarelix: 5-year results from a phase III extension trial with a 1-arm crossover from leuprolide to degarelix. Urology, 83, 1122–1128. doi:10.1016/j.urology.2014.01.013.

    Article  PubMed  Google Scholar 

  5. Garcia-Albeniz, X., Chan, J. M., Paciorek, A. T., Logan, R. W., Kenfield, S. A., Cooperberg, R. M., et al. (2014). Immediate versus deferred initiation of androgen deprivation therapy in prostate cancer patients with PSA-only relapse. Journal of Clinical Oncology, 32, 5s (suppl; abstr 5003).

    Article  CAS  Google Scholar 

  6. Tombal, B., Borre, M., Rathenborg, P., Werbrouck, P., Van Poppel, H., Heidenreich, A., et al. (2014). Enzalutamide monotherapy in hormone-naive prostate cancer: primary analysis of an open-label, single-arm, phase 2 study. Lancet Oncology, 15, 592–600. doi:10.1016/S1470-2045(14)70129-9.

    Article  CAS  PubMed  Google Scholar 

  7. Fizazi, K., Laplanche, A., Lesaunier, F., Delva, R., Gravis, G., Rolland, F., et al. (2014). Docetaxel-estramustine in localized high-risk prostate cancer: results of the French Genito-Urinary Tumor Group GETUG 12 phase III trial. Journal of Clinical Oncology, 32, 5s (suppl; abstr 5005).

    Article  CAS  Google Scholar 

  8. Asangani, I. A., Dommeti, V. L., Wang, X., Malik, R., Cieslik, M., Yang, R., et al. (2014). Therapeutic targeting of BET bromodomain proteins in castration-resistant prostate cancer. Nature, 510, 278–282. doi:10.1038/nature13229.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Li, L., Chang, W., Yang, G., Ren, C., Park, S., Karantanos, T., et al. (2014). Targeting poly(ADP-ribose) polymerase and the c-Myb-regulated DNA damage response pathway in castration-resistant prostate cancer. Science Signaling, 7, ra47. doi:10.1126/scisignal.2005070.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  10. Lohr, J. G., Adalsteinsson, V. A., Cibulskis, K., Choudhury, A. D., Rosenberg, M., Cruz-Gordillo, P., et al. (2014). Whole-exome sequencing of circulating tumor cells provides a window into metastatic prostate cancer. Nature Biotcehnology, 32, 479–484. doi:10.1038/nbt.2892.

    Article  CAS  Google Scholar 

  11. Carreira, S., Romanel, A., Goodall, J., Grist, E., Ferraldeschi, R., Miranda, S., et al. (2014). Tumor clone dynamics in lethal prostate cancer. Science Translational Medicine, 6, 254ra125. doi:10.1126/scitranslmed.3009448.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  12. Gao, D., Vela, I., Sboner, A., Iaquinta, P. J., Karthaus, W. R., Gopalan, A., et al. (2014). Organoid cultures derived from patients with advanced prostate cancer. Cell, 159, 176–187. doi:10.1016/j.cell.2014.08.016.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Castro, E., Goh, C., Leongamornlert, D., Saunders, E., Tymrakiewicz, M., Dadaev, T., et al. (2014). Effect of BRCA mutations on metastatic relapse and cause-specific survival after radical treatment for localised prostate cancer. European Urology. doi:10.1016/j.eururo.2014.10.022.

    PubMed Central  Google Scholar 

  14. Motzer, R. J., Hutson, T. E., Cella, D., Reeves, J., Hawkins, R., Guo, J., et al. (2013). Pazopanib versus sunitinib in metastatic renal-cell carcinoma. New England Journal of Medicine, 369, 722–731. doi:10.1056/NEJMoa1303989.

    Article  CAS  PubMed  Google Scholar 

  15. Motzer, E. J., Hudson, T. E., McCann, L., & Choueiri, T. K. (2014). Overall survival in renal-cell carcinoma with pazopanib versus sunitinib. New England Journal of Medicine, 370, 1769–1770. doi:10.1056/NEJMc1400731.

    Article  CAS  PubMed  Google Scholar 

  16. Rini, B. I., Bellmunt, J., Clancy, J., Wang, K., Niethammer, A. G., Hariharan, S., et al. (2014). Randomized phase III trial of temsirolimus and bevacizumab versus interferon alfa and bevacizumab in metastatic renal cell carcinoma: INTORACT trial. Journal of Clinical Oncology, 32, 752–759. doi:10.1200/JCO.2013.50.5305.

    Article  CAS  PubMed  Google Scholar 

  17. Motzer, R. J., Barrios, C. H., Kim, T. M., Falcon, S., Cosgriff, T., Harker, W. G., et al. (2014). Phase II randomized trial comparing sequential first-line everolimus and second-line sunitinib versus first-line sunitinib and second-line everolimus in patients with metastatic renal cell carcinoma. Journal of Clinical Oncology, 32, 2765–2772. doi:10.1200/JCO.2013.54.6911.

    Article  CAS  PubMed  Google Scholar 

  18. Michel, M.S., Vervenne, W., Santis, M., von Weikersthal, L.F., Goebell, P.J., Juergen Lerchenmueller, J., et al. (2014). SWITCH: a randomized sequential open-label study to evaluate efficacy and safety of sorafenib (SO)/sunitinib (SU) versus SU/SO in the treatment of metastatic renal cell cancer (mRCC). Journal of Clinical Oncology,32. (suppl 4; abstr 393).

  19. Hutson, T. E., Escudier, B., Esteban, E., Bjarnason, G. A., Lim, H. Y., Pittman, K. B., et al. (2014). Randomized phase III trial of temsirolimus versus sorafenib as second-line therapy after sunitinib in patients with metastatic renal cell carcinoma. Journal of Clinical Oncology, 32, 760–767. doi:10.1200/JCO.2013.50.3961.

    Article  CAS  PubMed  Google Scholar 

  20. Motzer, R. J., Porta, C., Vogelzang, N. J., Sternberg, C. N., Szczylik, C., Zolnierek, J., et al. (2014). Dovitinib versus sorafenib for third-line targeted treatment of patients with metastatic renal cell carcinoma: an open-label, randomised phase 3 trial. Lancet Oncology, 15, 286–296.

  21. Heng, D. Y., Wells, J. C., Rini, B. I., Beuselinck, B., Lee, J. L., Knox, J. J., et al. (2014). Cytoreductive nephrectomy in patients with synchronous metastases from renal cell carcinoma: results from the International Metastatic Renal Cell Carcinoma Database Consortium. European Urology, 66, 704–710. doi:10.1016/j.eururo.2014.05.034.

    Article  PubMed  Google Scholar 

  22. Tannir, N. M., Jonasch, E., Altinmakas, E., Ng, C. S., Qiao, W., Tamboli, P., et al. (2014). Everolimus versus sunitinib prospective evaluation in metastatic non-clear cell renal cell carcinoma (The ESPN Trial): a multicenter randomized phase 2 trial. Journal of Clinical Oncology, 32, 5s (suppl; abstr 4505).

    Article  CAS  Google Scholar 

  23. A proof of concept study of maintenance therapy with tasquinimod in patients with metastatic castrate-resistant prostate cancer who are not progressing after a first line docetaxel based chemotherapy. Available at: http://clinicaltrials.gov/ct2/show/NCT01732549. Accessed June 6, 2014.

  24. Ojemuyinwa, M.A., Karzai, F.H., Shah, A.A., Theoret, M.R., Harold, N., Chun, G., et al. (2014). A safety study of trebananib (AMG 386) and abiraterone in metastatic castration-resistant prostate cancer. Journal of Clinical Oncology, 32. (suppl; abstr 218).

  25. Kwon, E. D., Drake, C. G., Scher, H. I., Fizazi, K., Bossi, A., van den Eertwegh, A. J., et al. (2014). Ipilimumab versus placebo after radiotherapy in patients with metastatic castration-resistant prostate cancer that had progressed after docetaxel chemotherapy (CA184-043): a multi- centre, randomised, double-blind, phase 3 trial. Lancet Oncology, 15, 700–712. doi:10.1016/S1470-2045(14)70189-5.

    Article  CAS  PubMed  Google Scholar 

  26. Drake, C.G., Kwon, E.D., Fizazi, K., Bossi, A., van den Eertwegh, A.J., Logothetis, C. (2014). Results of subset analyses on overall survival (OS) from the study CA184-043: ipilimumab versus placebo in post-docetaxel metastatic castration-resistant prostate cancer. Journal of Clinical Oncology, 32. (suppl 4; abstr 2).

  27. Schweizer, M.T., Drake, C.G. (2014). Immunotherapy for prostate cancer: recent developments and future challenges. Cancer Metastasis Reviews: 33641–55.

  28. Miyahira, A. K., Kissick, H. T., Bishop, J. L., Takeda, E. Y., Barbieri, C. E., Simons, J. W., et al. (2014). Beyond immune checkpoint blockade: new approaches to targeting host-tumor interactions in prostate cancer: report from the 2014 Coffey-Holden Prostate Cancer Academy meeting. Prostate, 75, 337–347. doi:10.1002/pros.22920.

    Article  PubMed  Google Scholar 

  29. Olson, B. M., Johnson, L. E., & McNeel, D. G. (2013). The androgen receptor: a biologically relevant vaccine target for the treatment of prostate cancer. Cancer Immunology, Immunotherapy, 62, 585–596. doi:10.1007/s00262-012-1363-9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  30. Lucas, J. M., Heinlein, C., Kim, T., Hernandez, S. A., Malik, M. S., True, L. D., et al. (2014). The androgen-regulated protease TMPRSS2 activates a proteolytic cascade involving components of the tumor microenvironment and promotes prostate cancer metastasis. Cancer Discovery, 4, 1310–1325. doi:10.1158/2159-8290.CD-13-1010.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  31. Theurillat, J. P., Udeshi, N. D., Errington, W. J., Svinkina, T., Baca, S. C., Pop, M., et al. (2014). Prostate cancer. Ubiquitylome analysis identifies dysregulation of effector substrates in SPOP-mutant prostate cancer. Science, 346, 85–89. doi:10.1126/science.1250255.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  32. Hussong, M., Börno, S. T., Kerick, M., Wunderlich, A., Franz, A., Sültmann, H., et al. (2014). The bromodomain protein BRD4 regulates the KEAP1/NRF2-dependent oxidative stress response. Cell Death Diseases, 5, e1195. doi:10.1038/cddis.2014.157.

    Article  CAS  Google Scholar 

  33. Tannock, I. F., de Wit, R., Berry, W. R., Horti, J., Pluzanska, A., Chi, K. N., et al. (2004). Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. New England Journal of Medicine, 351, 1502–1512.

    Article  CAS  PubMed  Google Scholar 

  34. Petrylak, D. P., Tangen, C. M., Hussain, M. H., Lara, P. N., Jr., Jones, J. A., Taplin, M. E., et al. (2004). Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. New England Journal of Medicine, 351, 1513–1520.

    Article  CAS  PubMed  Google Scholar 

  35. Berthold, D. R., Pond, G. R., Soban, F., de Wit, R., Eisenberger, M., & Tannock, I. F. (2008). Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer: updated survival in the TAX 327 study. Journal of Clinical Oncology, 26, 242–245. doi:10.1200/JCO.2007.12.4008.

    Article  CAS  PubMed  Google Scholar 

  36. Clarke, J. M., & Armstrong, A. J. (2013). Novel therapies for the treatment of advanced prostate cancer. Current Treatment Options in Oncology, 14, 109–126. doi:10.1007/s11864-012-0222-4.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  37. Sweeney, C., Chen, Y. H., Carducci, M. A., Liu, G., Jarrard, D. F., Eisenberger, M. A., et al. (2014). Impact on overall survival (OS) with chemohormonal therapy versus hormonal therapy for hormone-sensitive newly metastatic prostate cancer (mPrCa): an ECOG-led phase III randomized trial. Journal of Clinical Oncology, 32, 5s (suppl; abstr LBA2).

    Article  CAS  Google Scholar 

  38. Gravis, G., Fizazi, K., Joly, F., Oudard, S., Priou, F., Esterni, B., et al. (2013). Androgen-deprivation therapy alone or with docetaxel in non-castrate metastatic prostate cancer (GETUG-AFU 15): a randomised, open-label, phase 3 trial. Lancet Oncology, 14, 149–158. doi:10.1016/S1470-2045(12)70560-0.

    Article  CAS  PubMed  Google Scholar 

  39. James, N. D., Sydes, M. R., Mason, M.D., et al. (2015). Docetaxel and/or zoledronic acid for hormone-naïve prostate cancer: first overall survival results from STAMPEDE. Journal of Clinical Oncology, 33. (suppl; abstr 5001)

  40. Dreicer, R., Jones, R., Oudard, S., Efstathiou, E., Saad, F., de Wit, R., et al. (2014). Results from a phase 3, randomized, double-blind, multicenter, placebo-controlled trial of orteronel (TAK-700) plus prednisone in patients with metastatic castration-resistant prostate cancer (mCRPC) that has progressed during or following docetaxel-based therapy (ELM-PC 5 trial). Journal of Clinical Oncology, 32. (suppl 4; abstr 7˄).

  41. de Wit, R., Fizazi, K., Jinga, V., Efstathiou, E., Fong, P., Wirth, M., et al. (2014). Phase 3, randomized, placebo-controlled trial of orteronel (TAK-700) plus prednisone in patients (pts) with chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC) (ELM-PC 4 trial). Journal of Clinical Oncology, 32, 5s (suppl; abstr 5008).

    Article  CAS  Google Scholar 

  42. Efstathiou, E. Enzalutamide (ENZA) in combination with abiraterone acetate (AA) in bone metastatic castration resistant prostate cancer (mCRPC). Available at: http://meetinglibrary.asco.org/content/94606

  43. Scher, H. I., Fizazi, K., Saad, F., Taplin, M. E., Sternberg, C. N., Miller, K., et al. (2012). Increased survival with enzalutamide in prostate cancer after chemotherapy. New England Journal of Medicine, 367, 1187–1197.

    Article  CAS  PubMed  Google Scholar 

  44. Beer, T.M., Armstrong, A.J., Sternberg, C.N., Higano, C.S., Iversen, P., Loriot, Y., et al. (2014). Enzalutamide in men with chemotherapy-naive metastatic prostate cancer (mCRPC): results of phase III PREVAIL study. Journal of Clinical Oncology, 32. (suppl 4; abstr LBA1^).

  45. Parker, C., Vogelzang, N. J., Sartor, A. O., Bottomley, D., Coleman, R. E., Skjorestad, I., et al. (2014). 1.5-year post-treatment follow-up of radium-223 dichloride (Ra-223) safety in patients with castration-resistant prostate cancer (CRPC) and symptomatic bone metastases from the phase 3 ALSYMPCA study. Journal of Clinical Oncology, 32, 5s (suppl; abstr 5070).

    Article  CAS  Google Scholar 

  46. Ryan, C.J., Smith, M.R., Fizazi, K., Miller, K., Muders, P.F.A., Sternberg, C.N., et al. Final overall survival analysis of COU-AA-302, a randomized phase 3 study of abiraterone acetate in metastatic castration-resistant prostate cancer patients without prior chemotherapy. Available at: http://www.ascopost.com/ViewNews.aspx?nid=18643

  47. Zong, Y., & Goldstein, A. S. (2013). Adaptation or selection—mechanisms of castration-resistant prostate cancer. Nature Reviews. Urology, 10, 90–98. doi:10.1007/s11427-013-4522-0.

    Article  CAS  PubMed  Google Scholar 

  48. Karantanos, T., Evans, C. P., Tombal, B., Thompson, T. C., Montironi, R., & Isaacs, W. B. (2014). Understanding the mechanisms of androgen deprivation resistance in prostate cancer at the molecular level. European Urology. doi:10.1016/j.eururo.2014.09.049.

    PubMed  Google Scholar 

  49. Mills, I. G. (2014). Maintaining and reprogramming genomic androgen receptor activity in prostate cancer. Nature Reviews Cancer, 14, 187–198. doi:10.1038/nrc3678.

    Article  CAS  PubMed  Google Scholar 

  50. Li, P., Yang, R., & Gao, W. Q. (2014). Contributions of epithelial-mesenchymal transition and cancer stem cells to the development of castration resistance of prostate cancer. Molecular Cancer, 13, 55. doi:10.1186/1476-4598-13-55.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  51. Fleischmann, A., Rocha, C., Schobinger, S., Seiler, R., Wiese, B., & Thalmann, G. N. (2011). Androgen receptors are differentially expressed in Gleason patterns of prostate cancer and down-regulated in matched lymph node metastases. Prostate, 71, 453–460. doi:10.1002/pros.21259.

    Article  CAS  PubMed  Google Scholar 

  52. Terry, S., & Beltran, H. (2014). The many faces of neuroendocrine differentiation in prostate cancer progression. Frontiers in Oncology, 4, 60. doi:10.3389/fonc.2014.00060.

    Article  PubMed Central  PubMed  Google Scholar 

  53. Efstathiou, E., Titus, M., Tsavachidou, D., Tzelepi, V., Wen, S., Hoang, A., et al. (2012). Effects of abiraterone acetate on androgen signaling in castrate-resistant prostate cancer in bone. Journal of Clinical Oncology, 30, 637–643. doi:10.1200/JCO.2010.33.7675.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  54. Efstathiou, E., Titus, M., Wen, S., Hoang, A., Karlou, M., Ashe, R., et al. (2015). Molecular characterization of enzalutamide-treated bone metastatic castration-resistant prostate cancer. European Urology, 67, 53–60. doi:10.1016/j.eururo.2014.05.005.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Rathkopf, D., & Scher, H. I. (2013). Androgen receptor antagonists in castration-resistant prostate cancer. Cancer Journal, 19, 43–49. doi:10.1097/PPO.0b013e318282635a.

    Article  CAS  Google Scholar 

  56. Powell, K.A., Seeman, L., Maddipati, K.R., et al. (2014). ERG regulation of intracrine androgen production and castration-resistant prostate cancer progression [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5–9; San Diego, CA. Philadelphia (PA): AACR. Abstract nr 456.

  57. Mateo, J., Hall, E., Sandhu, S., Omlin, A.G., Miranda, S., Carreira, S., et al. (2014). Antitumour activity of the PARP inhibitor olaparib in unselected sporadic castration-resistant prostate cancer (CRPC) in the TOPARP trial. Annals of Oncology, 251–41. doi: 10.1093/annonc/mdu438.

  58. Conteduca, V., Salvi, S., Casadio, V., Burgio, S. L., Menna, C., Rossi, L., et al. (2014). AR and CYP17A1 copy number variations may predict clinical outcome of patients with metastatic castration-resistant prostate cancer treated with abiraterone. Annals of Oncology, 25(suppl 4), iv257–iv258. doi:10.1093/annonc/mdu336.7. Abstract 759PD.

    Google Scholar 

  59. Bremmer, F., Jarry, H., Strauß, A., Behnes, C. L., Trojan, L., & Thelen, P. (2014). Increased expression of CYP17A1 indicates an effective targeting of the androgen receptor axis in castration resistant prostate cancer (CRPC). Springerplus, 3, 574. doi:10.1186/2193-1801-3-574. eCollection 2014.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  60. Wang, H. T., Yao, Y. H., Li, B. G., Tang, Y., Chang, J. W., & Zhang, J. (2014). Neuroendocrine prostate cancer (NEPC) progressing from conventional prostatic adenocarcinoma: factors associated with time to development of NEPC and survival from NEPC diagnosis—a systematic review and pooled analysis. Journal of Clinical Oncology, 32(30), 3383–3390. doi:10.1200/JCO.2013.54.3553.

    Article  PubMed  Google Scholar 

  61. Small, E. J., Youngren, J., Alumkal, J., et al. (2014). Neuroendocrine prostate cancer (NEPC) in patients (pts) with metastatic castration resistant prostate cancer (MCRPC) resistant to abiraterone (ABI) or enzalutamide (ENZ): preliminary results from the SU2C/PCF/AACR West Coast Prostate Cancer Dream Team (WCDT). Annals of Oncology, 25(suppl 4), iv258. doi:10.1093/annonc/mdu336.8. Abstract 760PD.

    Google Scholar 

  62. Mulholland, D.J. (2014). Persistent androgen ablation promotes enhanced neuroendocrine features in Pten-deficient prostate cancer [abstract]. Proceeding of the American Association for Cancer Research; 2014 Apr 5–9; San Diego, CA. Philadelphia (PA): AACR. Abstract nr LB-44.

  63. Ware, K. E., Garcia-Blanco, M. A., Armstrong, A. J., & Dehm, S. M. (2014). Biologic and clinical significance of androgen receptor variants in castration resistant prostate cancer. Endocrine-Related Cancer, 21, T87–T103. doi:10.1158/1078-0432.CCR-13-1863.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  64. Antonarakis, E. S., Lu, C., Wang, H., Luber, B., Nakazawa, M., Roeser, J. C., et al. (2014). AR-V7 and resistance to enzalutamide and abiraterone in prostate cancer. New England Journal of Medicine, 371, 1028–1038. doi:10.1056/NEJMoa1315815.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  65. Yu, Z., Chen, S., Sowalsky, A. G., Voznesensky, O. S., Mostaghel, E. A., Nelson, P. S., et al. (2014). Rapid induction of androgen receptor splice variants by androgen deprivation in prostate cancer. Clinical Cancer Research, 20, 1590–1600. doi:10.1158/1078-0432.CCR-13-1863.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  66. Arora, V. K., Schenkein, E., Murali, R., et al. (2013). Glucocorticoid receptor confers resistance to antiandrogens by bypassing androgen receptor blockade. Cell, 155, 1309–1322. doi:10.1016/j.cell.2013.11.012.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  67. Bishop, J. L., Sio, A., Angeles, A., Roberts, M. E., Azad, A. A., Chi, K. N., et al. (2015). PD-L1 is highly expressed in enzalutamide resistant prostate cancer. Oncotarget, 6, 232–242.

    Article  Google Scholar 

  68. Nguyen, H. G., Yang, J. C., Kung, H. J., Shi, X. B., Tilki, D., Lara, P. N., Jr., et al. (2014). Targeting autophagy overcomes enzalutamide resistance in castration-resistant prostate cancer cells and improves therapeutic response in a xenograft model. Oncogene, 33, 4521–4530. doi:10.1038/onc.2014.25.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  69. Chi, K. N., Higano, C., Reeves, J., Feyerabend, S., Gravis, G., Ferrero, J., et al. (2014). A randomized phase 3 study comparing first-line docetaxel/prednisone (DP) to DP plus custirsen in men with metastatic castration-resistant prostate cancer (mCRPC). Annals of Oncology, 25(suppl 4), iv256. doi:10.1093/annonc/mdu336.3.

    Google Scholar 

  70. Haas, N.B., Manola, J., Uzzo, R.G., Atkins, M.B., Wilding, G., Pins, M., et al. (2015) Initial results from ASSURE (E2805): adjuvant sorafenib or sunitinib for unfavorable renal carcinoma, an ECOG-ACRIN-led, NCTN phase III trial. Journal of Clinical Oncology, 33. (suppl 7; abstr 403).

  71. Melero, I., Grimaldi, A. M., Perez-Gracia, J. L., & Ascierto, P. A. (2013). Clinical development of immunostimulatory monoclonal antibodies and opportunities for combination. Cancer Clinical Research, 29, 997–1008. doi:10.1158/1078-0432.CCR-12-2214.

    Article  CAS  Google Scholar 

  72. Chen, D. S., & Mellman, I. (2013). Oncology meets immunology: the cancer-immunity cycle. Immunity, 39, 1–10. doi:10.1016/j.immuni.2013.07.012.

    Article  PubMed  CAS  Google Scholar 

  73. Morse, M., McDermott, D. F., Daniels, G. A., Kaufman, H., Wong, M. K. K., Aung, S., et al. (2014). High-dose (HD) IL-2 for metastatic renal cell carcinoma (mRCC) in the targeted therapy era: extension of OS benefits beyond complete response (CR) and partial response (PR). Journal of Clinical Oncology, 32, 5s (suppl; abstr 4523).

    Article  CAS  Google Scholar 

  74. Choueiri, T. K., Fishman, M. N., Escudier, B. J., Kim, J. J., Kluger, H. M., Stadler, W. M., et al. (2014). Immunomodulatory activity of nivolumab in previously treated and untreated metastatic renal cell carcinoma (mRCC): biomarker-based results from a randomized clinical trial. Journal of Clinical Oncology, 32, 5s (suppl; abstr 5012).

    Article  CAS  Google Scholar 

  75. Choueiri, T.K., Fishman, M.N., Escudier, B.J., Kim, J.J., Kluger, H.M., Stadler, W.M., et al. (2014). Exploratory study to investigate the immunomodulatory activity of nivolumab antibody in subjects with metastatic clear cell renal carcinoma (RCC) (CA209-009(NCT01358721. Annals of Oncology, 25. (suppl 4, abstr 1051).

  76. Motzer, R.J., Rini, B.I., McDermott, D.F., Redman, B.G., Kuzel, T.M., Harrison, M.R., et al. (2014). Nivolumab for metastatic renal cell carcinoma: results of a randomized phase II trial. Journal of Clinical Oncology.

  77. McDermott, D. F., Sznol, M., Sosman, J. A., Soria, J., Gordon, M. S., Hamid, O., et al. (2014). Immune correlates and long term follow up of a phase Ia study of MPDL3280A, an engineered PD-L1 antibody, in patients with metastatic renal cell carcinoma (mRCC). Annals of Oncology, 25(suppl_4), iv280–iv304. doi:10.1093/annonc/mdu337.

    Google Scholar 

  78. Pardoll, D. M. (2012). The blockade of immune check-points in cancer immunotherapy. Nature Reviews Cancer, 12, 252–264.

    Article  CAS  PubMed  Google Scholar 

  79. Hammers, H., Plimack, E.R., Infante, J.R., Ernstoff, M.S., Rini, B.I., McDermott, D.F., et al. (2014). Phase I of nivolumab in combination with ipilimumab in metastatic renal cell carcinoma (mRCC). Journal of Clinical Oncology, 32. (Suppl 15s, abstr 4504).

  80. Amin, S., Plimack, E.R., Infante, J.R., Ernstoff, M.S., Rini, B.I., McDermott, D.F., et al. (2014). Nivolumab (anti-PD-1; BMS-936558, ONO-4538) in combination with sunitinib or pazopanib in patients (pts) with metastatic renal cell carcinoma (mRCC). Journal of Clinical Oncology, 32. (suppl, abstr 5010).

  81. Amin, S., Plimack, E. R., Infante, J. R., Ernstoff, M. S., Rini, B. I., McDermott, D. F., et al. (2014). Nivolumab (N) (anti-PD-1; BMS-936558, ONO-4538) in combination with sunitinib (S) or pazopanib (P) in patients (pts) with metastatic renal cell carcinoma (mRCC). Annals of Oncology, 25(suppl_4), iv361–iv372. doi:10.1093/annonc/mdu342.

    Google Scholar 

  82. Choueri, T.K. (2014). Phase 1/2 study of pembrolizumab (MK-3475) in combination with pegylated interferon alfa-2b or ipilimumab in patients with advanced melanoma or renal cell carcinoma. Annals of Oncology, 25. (suppl 4, abstr 1075).

  83. McDermott, D. F., Infante, J. R., Voss, M. H., Motzer, R. J., Haanen, J. B. A. G., Chowdhury, S., et al. (2014). A phase I/II study to assess the safety and efficacy of pazopanib and MK-3475 in subjects with advanced renal cell carcinoma. Journal of Clinical Oncology, 32, 5s (suppl; abstr TPS4604^).

    Article  CAS  Google Scholar 

  84. Lieu, C., Bendell, J., Powderly, J. D., Pishvaian, M. J., Hochster, H., Eckhardt, S. G., et al. (2014). Safety and efficacy of MPDL3280A (anti-PDL1) in combination with bevacizumab (bev) and/or chemotherapy (chemo) in patients (pts) with locally advanced or metastatic solid tumors. Annals of Oncology, 25(suppl_4), iv361–iv372. doi:10.1093/annonc/mdu342.

    Google Scholar 

  85. Callahan, M. K., Ott, P. A., Odunsi, K., Bertolini, S. V., Pan, L. S., Venhaus, R. R., et al. (2014). A phase 1 study to evaluate the safety and tolerability of MEDI4736, an anti-PD-L1 antibody, in combination with tremelimumab in patients with advanced solid tumors. Journal of Clinical Oncology, 32, 5s (suppl; abstr TPS3120^).

    Article  CAS  Google Scholar 

  86. Amin, A., Dudek, A. Z., Logan, T. F., Lance, R. S., Holzbeierlein, J. M., Master, V. A., et al. (2014). Long-term survival in unfavorable-risk mRCC patients treated with a combination of autologous immunotherapy (AGS-003) plus sunitinib. Journal of Clinical Oncology, 32, 5s (suppl; abstr 4524^).

    Article  CAS  Google Scholar 

  87. Khleif, S., Munn, D., Nyak-Kapoor, A., Mautino, M. R., Kennedy, E., Vahanian, N. V., et al. (2014). First-in-human phase 1 study of the novel indoleamine-2,3-dioxygenase (IDO) inhibitor NLG-919. Journal of Clinical Oncology, 32, 5s (suppl; abstr TPS3121).

    Article  CAS  Google Scholar 

  88. Infante, J. R., Burris, H. A., III, Ansell, S. M., Nemunaltis, J. J., Weiss, G. R., Villalobos, V. M., et al. (2014). Immunologic activity of an activating anti-CD27 antibody (CDX-1127) in patients (pts) with solid tumors. Journal of Clinical Oncology, 32, 5s (suppl; abstr 3027).

    Article  CAS  Google Scholar 

  89. Bellmunt, J., Fougeray, R., Rosenberg, J. E., von der Maase, H., Schutz, F. A., Salhi, Y., et al. (2013). Long-term survival results of a randomized phase III trial of vinflunine plus best supportive care versus best supportive care alone in advanced urothelial carcinoma patients after failure of platinum-based chemotherapy. Annals of Oncology, 24, 1466–1472. doi:10.1093/annonc/mdt007.

    Article  CAS  PubMed  Google Scholar 

  90. Hagenkord, J. M., Gatalica, Z., Jonasch, E., & Monzon, F. A. (2011). Clinical genomics of renal epithelial tumors. Cancer Genetics, 204, 285–297. doi:10.1016/j.cancergen.2011.06.001.

    Article  CAS  PubMed  Google Scholar 

  91. Maher, E. R. (2013). Genomics and epigenomics of renal cell carcinoma. Seminars in Cancer Biology, 23, 10–17. doi:10.1016/j.semcancer.2012.06.003.

    Article  CAS  PubMed  Google Scholar 

  92. Cohen, H. T., & McGovern, F. J. (2005). Renal-cell carcinoma. New England Journal of Medicine, 353, 2477–2490.

    Article  CAS  PubMed  Google Scholar 

  93. Moserle, L., Jiménez-Valerio, G., & Casanovas, O. (2014). Antiangiogenic therapies: going beyond their limits. Cancer Discovery, 4, 31–41. doi:10.1158/2159-8290.CD-13-0199.

    Article  CAS  PubMed  Google Scholar 

  94. Jäger, W., Thomas, C., Fazli, L., Hurtado-Coll, A., Li, E., Janssen, C., et al. (2014). DHH is an independent prognosticator of oncologic outcome of clear cell renal cell carcinoma. Journal of Urology, 192, 1842–1848. doi:10.1016/j.juro.2014.07.013.

    Article  PubMed  Google Scholar 

  95. Miles, K. M., Seshadri, M., Ciamporcero, E., Adelaiye, R., Gillard, B., Sotomayor, P., et al. (2014). Dll4 blockade potentiates the anti-tumor effects of VEGF inhibition in renal cell carcinoma patient-derived xenografts. PLoS One, 9, e112371. doi:10.1371/journal.pone.0112371.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  96. Graham, D. K., DeRyckere, D., Davies, K. D., & Earp, H. S. (2014). The TAM family: phosphatidylserine sensing receptor tyrosine kinases gone awry in cancer. Nature Reviews Cancer, 14, 769–785.

    Article  CAS  PubMed  Google Scholar 

  97. Cancer Genome Atlas Research Network. (2013). Comprehensive molecular characterization of clear cell renal cell carcinoma. Nature, 499, 43–49. doi:10.1038/nature12222.

    Article  CAS  Google Scholar 

  98. Li, S., Kong, Y., Si, L., Chi, Z., Cui, C., Sheng, X., & Guo, J. (2014). Phosphorylation of mTOR and S6RP predicts the efficacy of everolimus in patients with metastatic renal cell carcinoma. BMC Cancer, 14, 376. doi:10.1186/1471-2407-14-376.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  99. Kwiatkowski, D. J., & Manning, B. D. (2014). Molecular basis of giant cells in tuberous sclerosis complex. New England Journal of Medicine, 371, 778–780.

    Article  PubMed  CAS  Google Scholar 

  100. Pal, S. K., He, M., Tong, T., Wu, H., Liu, X., Lau, C., et al. (2014). RNA-seq reveals aurora kinase-driven mTOR pathway activation in patients with sarcomatoid metastatic renal cell carcinoma. Molecular Cancer Research. doi:10.1158/1541-7786.MCR-14-0352.

    Google Scholar 

  101. Davis, C. F., Ricketts, C. J., Wang, M., Yang, L., Cherniack, A. D., Shen, H., et al. (2014). The somatic genomic landscape of chromophobe renal cell carcinoma. Cancer Cell, 26, 319–330. doi:10.1016/j.ccr.2014.07.014.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  102. Scelo, G., Riazalhosseini, Y., Greger, L., Letourneau, L., Gonzàlez-Porta, M., Wozniak, M. B., et al. (2014). Variation in genomic landscape of clear cell renal cell carcinoma across Europe. Nature Communications, 5, 5135. doi:10.1038/ncomms6135.

    Article  CAS  PubMed  Google Scholar 

  103. Brugarolas, J. (2014). Molecular genetics of clear-cell renal cell carcinoma. Journal of Clinical Oncology, 32, 1968–1976. doi:10.1200/JCO.2012.45.2003.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  104. Juengel, E., Nowaz, S., Makarevi, J., Natsheh, I., Werner, I., Nelson, K., et al. (2014). HDAC-inhibition counteracts everolimus resistance in renal cell carcinoma in vitro by diminishing cdk2 and cyclin A. Molecular Cancer, 13, 152. doi:10.1186/1476-4598-13-152.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  105. Gerlinger, M., Rowan, A. J., Horswell, S., Larkin, J., Endesfelder, D., Gronroos, E., et al. (2012). Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. New England Journal of Medicine, 366, 883–889. doi:10.1056/NEJMoa1113205.

    Article  CAS  PubMed  Google Scholar 

  106. Greaves, M., & Maley, C. C. (2012). Clonal evolution in cancer. Nature, 481, 306–313. doi:10.1038/nature10762.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  107. Hiley, C. T., & Swanton, C. (2014). Spatial and temporal cancer evolution: causes and consequences of tumour diversity. Clinical Medicine, 14(Suppl 6), s33–s37. doi:10.7861/clinmedicine.14-6-s33.

    Article  PubMed  Google Scholar 

  108. Gerlinger, M., Horswell, S., Larkin, J., Rowan, A. J., Salm, M. P., Varela, I., et al. (2014). Genomic architecture and evolution of clear cell renal cell carcinomas defined by multiregion sequencing. Nature Genetics, 46, 225–233. doi:10.1038/ng.2891.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Burrell, R. A., & Swanton, C. (2014). Tumour heterogeneity and the evolution of polyclonal drug resistance. Molecular Oncology, 8, 1095–1111. doi:10.1016/j.molonc.2014.06.005.

    Article  CAS  PubMed  Google Scholar 

  110. Gulati, S., Martinez, P., Joshi, T., Birkbak, N. J., Santos, C. R., Rowan, A. J., et al. (2014). Systematic evaluation of the prognostic impact and intratumour heterogeneity of clear cell renal cell carcinoma biomarkers. European Urology. doi:10.1016/j.eururo.2014.06.053.

    PubMed Central  PubMed  Google Scholar 

  111. Prior, C., Perez-Gracia, J. L., Garcia-Donas, J., Rodriguez-Antona, C., Guruceaga, E., Esteban, E., et al. (2014). Identification of tissue microRNAs predictive of sunitinib activity in patients with metastatic renal cell carcinoma. PLoS One, 9, e86263. doi:10.1371/journal.pone.0086263.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  112. Grossman, H. B., Natale, R. B., Tangen, C. M., Speights, V. O., Vogelzang, N. J., Trump, D. L., et al. (2003). Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer. New England Journal of Medicine, 28, 859–866.

    Article  Google Scholar 

  113. International Collaboration Trialists. (2011). International phase III trial assessing neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer: long- term results of the BA06 30894 trial. Journal of Clinical Oncology, 29, 2171–2177.

  114. Petrelli, F., Coinu, A., Cabiddu, M., Ghilardi, M., Vavassori, I., & Barni, S. (2014). Correlation of pathologic complete response with survival after neoadjuvant chemotherapy in bladder cancer treated with cystectomy: a meta-analysis. European Urology, 65, 350–357.

    Article  PubMed  Google Scholar 

  115. Zargar, H., Espiritu, P. N., Fairey, A. S., Mertens, L. S., Dinney, C. P., Mir, M. C., et al. (2014). Multicenter assessment of neoadjuvant chemotherapy for muscle-invasive bladder cancer. European Urology. doi:10.1016/j.eururo.2014.09.007.

    Google Scholar 

  116. Choueiri, T. K., Jacobus, S., Bellmunt, J., Qu, A., Appleman, L. J., Tretter, C., et al. (2014). Neoadjuvant dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin with pegfilgrastim support in muscle-invasive urothelial cancer: pathologic, radiologic, and biomarker correlates. Journal of Clinical Oncology, 32, 1889–1894. doi:10.1200/JCO.2013.52.4785.

    Article  CAS  PubMed  Google Scholar 

  117. Sternberg, C. N., Skoneczna, I. A., Kerst, J. M., Fossa, S. D., Albers, P., Agerbaek, M., et al. (2015). Immediate versus deferred chemotherapy after radical cystectomy in patients with pT3-pT4 or N+ M0 urothelial carcinoma of the bladder (EORTC 30994): an intergroup, open-label, randomised phase 3 trial. Lancet Oncology, 16, 76–86. doi:10.1016/S1470-2045(14)71160-X.

    Article  PubMed  Google Scholar 

  118. Leow, J. J., Martin-Doyle, W., Rajagopal, P. S., Patel, C. G., Anderson, E. M., Rothman, A. T., et al. (2014). Adjuvant chemotherapy for invasive bladder cancer: a 2013 updated systematic review and meta-analysis of randomized trials. European Urology, 66, 42–54. doi:10.1016/j.eururo.2013.08.033.

    Article  CAS  PubMed  Google Scholar 

  119. Mak, R. H., Hunt, D., Shipley, W. U., Efstathiou, J. A., Tester, W. J., Hagan, M. P., et al. (2014). Long-term outcomes in patients with muscle-invasive bladder cancer after selective bladder-preserving combined-modality therapy: a pooled analysis of Radiation Therapy Oncology Group protocols 8802, 8903, 9506, 9706, 9906, and 0233. Journal of Clinical Oncology, 32, 3801–3809. doi:10.1200/JCO.2014.57.5548.

    Article  PubMed  PubMed Central  Google Scholar 

  120. Castellano, D. E., Bellmunt, J., Maroto, J. P., Font-Pous, A., Morales-Barrera, R., Ghanem, I., et al. (2014). Phase II clinical trial of PM00104 (Zalypsis(®)) in urothelial carcinoma patients progressing after first-line platinum-based regimen. Cancer Chemotherapy and Pharmacology, 73, 857–867. doi:10.1007/s00280-014-2419-7.

    Article  CAS  PubMed  Google Scholar 

  121. Hoffman-Censits, J.H., Vaughn, D.J., Lin, J., Keefe, S.M., Haas, N.B. (2014). A phase II study of cabazitaxel in patients with urothelial carcinoma who have disease progression following platinum-based chemotherapy. Journal of Clinical Oncology, 32. (suppl; abstr e15519).

  122. Alva, A., Daignault, S., Smith, D. C., & Hussain, M. (2014). Phase II trial of combination nab-paclitaxel, carboplatin and gemcitabine in first line therapy of advanced urothelial carcinoma. Investigational New Drugs, 32, 188–194. doi:10.1007/s10637-013-0054-5.

    Article  CAS  PubMed  Google Scholar 

  123. De Santis, M., Wiechno, P. J., Lucas, C., Lin, C., Su, W., Bellmunt, J., et al. (2014). Mature survival (OS) data of a randomised international phase II trial (JASINT1): vinflunine (VFL) gemcitabine (GEM) vs. VFL-CBDCA in CDDP-unfit patients (pts) with advanced urothelial carcinoma (UC). Annals of Oncology, 25(suppl_4), iv280–iv304. doi:10.1093/annonc/mdu337.

    Google Scholar 

  124. Hussain, M., Daignault, S., Agarwal, N., Grivas, P. D., Siefker-Radtke, A. O., Puzanov, I., et al. (2014). A randomized phase 2 trial of gemcitabine/cisplatin with or without cetuximab in patients with advanced urothelial carcinoma. Cancer, 120, 2684–2693. doi:10.1002/cncr.28767.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  125. Oudard, S., Culine, S., Vano, Y., Goldwasser, F., Théodore, C., Nguyen, T., et al. (2015). Multicentre randomised phase II trial of gemcitabine+platinum, with or without trastuzumab, in advanced or metastatic urothelial carcinoma overexpressing Her2. European Journal of Cancer, 51, 45–54. doi:10.1016/j.ejca.2014.10.009.

    Article  CAS  PubMed  Google Scholar 

  126. Milowsky, M. I., Dittrich, C., Durán, I., Jagdev, S., Millard, F. E., Sweeney, C. J., et al. (2014). Phase 2 trial of dovitinib in patients with progressive FGFR3-mutated or FGFR3 wild-type advanced urothelial carcinoma. European Journal of Cancer, 50, 3145–3152. doi:10.1016/j.ejca.2014.10.013.

    Article  CAS  PubMed  Google Scholar 

  127. Kilgour, E., Ferry, D., Saggese, M., Arkenau, H. T., Rooney, C., Smith, N. R., et al. (2014). Exploratory biomarker analysis of a phase I study of AZD4547, an inhibitor of fibroblast growth factor receptor (FGFR), in patients with advanced solid tumors. Journal of Clinical Oncology, 32, 5 (suppl; abstr 11010).

    Article  CAS  Google Scholar 

  128. Grivas, P. D., Daignault, S., Tagawa, S. T., Nanus, D. M., Stadler, W. M., Dreicer, R., et al. (2014). Double-blind, randomized, phase 2 trial of maintenance sunitinib versus placebo after response to chemotherapy in patients with advanced urothelial carcinoma. Cancer, 120, 692–701. doi:10.1002/cncr.28477.

    Article  CAS  PubMed  Google Scholar 

  129. Krege, S., Rexer, H., von Dorp, F., de Geeter, P., Klotz, T., Retz, M., et al. (2014). Prospective randomized double-blind multicentre phase II study comparing gemcitabine and cisplatin plus sorafenib chemotherapy with gemcitabine and cisplatin plus placebo in locally advanced and/or metastasized urothelial cancer: SUSE (AUO-AB 31/05). BJU International, 113, 429–436. doi:10.1111/bju.12437.

    Article  CAS  PubMed  Google Scholar 

  130. Srinivas, S., Narayanan, S., Harshman, L.C., Lam, A.P., Vaishampayan, U.K., Haas, D., et al. Phase II trial of pazopanib and weekly paclitaxel in metastatic urothelial cancer (UC). Journal of Clinical Oncology, 32. (suppl 4; abstr 299).

  131. Apolo, A.B..., Parnes, H.L., Madan, R.A., Gulley, J.L., Wright, J.J, Hoffman-Censits, J.H., et al. (2014). A phase II study of cabozantinib in patients (pts) with relapsed or refractory metastatic urothelial carcinoma (mUC). Journal of Clinical Oncology, 32. (suppl 4; abstr 307).

  132. Powles, T., Eder, J. P., Fine, G. D., Braiteh, F. S., Loriot, Y., Cruz, C., et al. (2014). MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer. Nature, 515, 558–562.

    Article  CAS  PubMed  Google Scholar 

  133. The Cancer Genome Atlas Research Network. (2014). Comprehensive molecular characterization of urothelial bladder carcinoma. Nature, 507, 315–322.

    Article  PubMed Central  CAS  Google Scholar 

  134. Iyer, G., Al-Ahmadie, H., Schultz, N., Hanrahan, A. J., Ostrovnaya, I., Balar, A. V., et al. (2013). Prevalence and co-occurrence of actionable genomic alterations in high-grade bladder cancer. Journal of Clinical Oncology, 31, 3133–3140. doi:10.1200/JCO.2012.46.5740.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  135. Sjodahl, G., Lauss, M., Lovgren, K., Chebil, G., Gudjonsson, S., Veerla, S., et al. (2012). A molecular taxonomy for urothelial carcinoma. Clinical Cancer Research, 18, 3377–3386. doi:10.1158/1078-0432.CCR-12-0077-T.

    Article  PubMed  CAS  Google Scholar 

  136. Choi, W., Porten, S., Kim, S. H., Willis, D., Plimack, E. R., Hoffman-Censits, J., et al. (2014). Identification of distinct basal and luminal subtypes of muscle-invasive bladder cancer with different sensitivities to frontline chemotherapy. Cancer Cell, 25, 152–165. doi:10.1016/j.ccr.2014.01.009.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  137. Damrauer, J. S., Hoadley, K. A., Chism, D. D., Fan, C., Tiganelli, C. J., Wobker, S. E., et al. (2014). Intrinsic subtypes of high-grade bladder cancer reflect the hallmarks of breast cancer biology. Proceedings of the National Academy of Sciences of the United States of America, 111, 3110–3115. doi:10.1073/pnas.1318376111.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  138. Hussain, M. H., MacVicar, G. R., Petrylak, D. P., Dunn, R. L., Vaishampayan, U., Lara, P. N., Jr., et al. (2007). Trastuzumab, paclitaxel, carboplatin, and gemcitabine in advanced human epidermal growth factor receptor-2/neu-positive urothelial carcinoma: results of a multicenter phase II National Cancer Institute trial. Journal of Clinical Oncology, 25, 2218–2224.

    Article  CAS  PubMed  Google Scholar 

  139. Vaughn, D. J., Broome, C. M., Hussain, M., Gutheil, J. C., & Markowitz, A. B. (2002). Phase II trial of weekly paclitaxel in patients with previously treated advanced urothelial cancer. Journal of Clinical Oncology, 20, 937–940.

    Article  CAS  PubMed  Google Scholar 

  140. Rebouissou, S., Bernard-Pierrot, I., de Reynies, A., Lepage, M. L., Krucker, C., Chapeaublanc, E., et al. (2014). EGFR as a potential therapeutic target for a subset of muscle-invasive bladder cancers presenting a basal-like phenotype. Science Translational Medicine, 6, 244ra291. doi:10.1126/scitranslmed.3008970.

    Article  CAS  Google Scholar 

  141. Guo, G., Sun, X., Chen, C., Wu, S., Huang, P., Li, Z., et al. (2013). Whole-genome and whole-exome sequencing of bladder cancer identifies frequent alterations in genes involved in sister chromatid cohesion and segregation. Nature Genetics, 45, 1459–1463. doi:10.1038/ng.2798.

    Article  CAS  PubMed  Google Scholar 

  142. Iyer, G., Hanrahan, A. J., Milowsky, M. I., Al-Ahmadie, H., Scott, S. N., Janakiraman, M., et al. (2012). Genome sequencing identifies a basis for everolimus sensitivity. Science, 338, 221. doi:10.1126/science.1226344.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  143. Wagle, N., Grabiner, B. C., Van Allen, E. M., Hodis, E., Jacobus, S., Supko, J. G., et al. (2014). Activating mTOR mutations in a patient with an extraordinary response on a phase I trial of everolimus and pazopanib. Cancer Discovery, 4, 546–553.

    Article  PubMed Central  PubMed  Google Scholar 

  144. Gui, Y., Guo, G., Huang, Y., Hu, X., Tang, A., Gao, S., et al. (2011). Frequent mutations of chromatin remodeling genes in transitional cell carcinoma of the bladder. Nature Genetics, 43, 875–878. doi:10.1038/ng.907.

    Article  CAS  PubMed  Google Scholar 

  145. Lehmann, A. R. (2001). The xeroderma pigmentosum group D (XPD) gene: one gene, two functions, three diseases. Genes and Development, 15, 15–23.

    Article  CAS  PubMed  Google Scholar 

  146. Van Allen, E. M., Mouw, K. W., Kim, P., Iyer, G., Wagle, N., Al-Ahmadie, H., et al. (2014). Somatic ERCC2 mutations correlate with cisplatin sensitivity in muscle-invasive urothelial carcinoma. Cancer Discovery, 4, 1140–1153. doi:10.1158/2159-8290.CD-14-0623.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  147. Blaveri, E., Simko, J. P., Korkola, J. E., Brewer, J. L., Baehner, F., Mehta, K., et al. (2005). Bladder cancer outcome and subtype classification by gene expression. Clinical Cancer Research, 11, 4044–4055.

    Article  CAS  PubMed  Google Scholar 

  148. Powles, T. N. J. V., Fine, G. D., Eder, J. P., Braiteh, F. S., Loriot, Y., & Zambrano, C. Z. (2014). Inhibition of PD-L1 by MPDL3280A and clinical activity in pts with metastatic urothelial bladder cancer (UBC). Journal of Clinical Oncology, 32, 5s (suppl; abstr 5011)

    Article  CAS  Google Scholar 

  149. International Germ Cell Cancer Collaborative Group. (1997). International germ cell consensus classification: a prognostic factor-based staging system for metastatic germ cell cancers. Journal of Clinical Oncology, 15, 594–603.

    Google Scholar 

  150. Einhorn, L. H., Williams, S. D., Loehrer, P. J., Birch, R., Drasga, R., Omura, G., et al. (1989). Evaluation of optimal duration of chemotherapy in favorable-prognosis disseminated germ cell tumors: a Southeastern Cancer Study Group protocol. Journal of Clinical Oncology, 7, 387–391.

    CAS  PubMed  Google Scholar 

  151. Kondagunta, G. V., Bacik, J., Donadio, A., Bajorin, D., Marion, S., Sheinfeld, J., et al. (2005). Combination of paclitaxel, ifosfamide, and cisplatin is an effective second-line therapy for patients with relapsed testicular germ cell tumors. Journal of Clinical Oncology, 23, 6549–6555.

    Article  CAS  PubMed  Google Scholar 

  152. Motzer, R. J., Nichols, C. J., Margolin, K. A., Bacik, J., Richardson, P. G., Vogelzang, N. J., et al. (2007). Phase III randomized trial of conventional-dose chemotherapy with or without high-dose chemotherapy and autologous hematopoietic stem-cell rescue as first-line treatment for patients with poor-prognosis metastatic germ cell tumors. Journal of Clinical Oncology, 25, 247–256.

    Article  CAS  PubMed  Google Scholar 

  153. Daugaard, G., Skoneczna, I., Aass, N., De Wit, R., De Santis, M., Dumez, H., et al. (2011). A randomized phase III study comparing standard dose BEP with sequential high-dose cisplatin, etoposide, and ifosfamide (VIP) plus stem-cell support in males with poor-prognosis germ-cell cancer. An intergroup study of EORTC, GTCSG, and Grupo Germinal (EORTC 30974). Annals of Oncology, 22, 1054.61. doi:10.1093/annonc/mdq575.

    Article  PubMed  Google Scholar 

  154. Fizazi, K., Culine, S., Kramar, A., Amato, R. J., Bouzy, J., Chen, I., et al. (2004). Early predicted time to normalization of tumor markers predicts outcome in poor-prognosis nonseminomatous germ cell tumors. Journal of Clinical Oncology, 22, 3868–3876.

    Article  PubMed  Google Scholar 

  155. Massard, C., Kramar, A., Beyer, J., Hartmann, J. T., Lorch, A., Pico, J. L., et al. (2013). Tumor marker kinetics predict outcome in patients with relapsed disseminated non-seminomatous germ-cell tumors. Annals of Oncology, 24, 322–328. doi:10.1093/annonc/mds504.

    Article  CAS  PubMed  Google Scholar 

  156. Fizazi, K., Pagliaro, L.C., Flechon, A., Mardiak, J., Geoffrois, L., Kerbrat, P., et al. (2013). A phase III trial of personalized chemotherapy based on serum tumor marker decline in poor-prognosis germ-cell tumors: results of GETUG 13. Journal of Clinical Oncology, 31. (suppl; abstr LBA4500).

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Acknowledgments

The authors thank Marta Pulido, MD, PhD, freelance author’s editor for assistance in writing of the manuscript and Content Ed Net Communications, Madrid (Spain) for editorial assistance with funding from Astellas.

Conflict of interest

C. Suárez has participated in advisory boards for Janssen, Astellas, Sanofi, and Bayer.

J. Puente has participated in advisory boards for Astellas, Sanofi, and Janssen.

E. Gallardo has been a member of advisory boards for Astellas, Janssen, Sanofi, and Bayer and has received travel or meeting funding by Astellas, Janssen, and Sanofi.

M.J. Méndez-Vidal has served as an advisor and a speaker for Janssen, Astellas, and Sanofi.

L. León has received honoraria as a speaker from Astellas.

D. Olmos have received research funding from Astellas, Janssen, Sanofi, Bayer, and Veridex.

X. García del Muro has served as an advisor and a speaker for Pfizer, Bayer, and Novartis.

E. González-Billalabeitia has been a member of the advisory boards of Astellas, Janssen, and Sanofi at the time of writing of the manuscript.

E. Grande has received financial support for research from Astellas, GSK, and Pfizer and served as an advisor and a speaker for Pfizer, Novartis, Pierre-Fabre, and Janssen.

A. González del Alba has participated in advisory boards for Janssen, Astellas, Sanofi, GSK and Bayer at the time of writing of the manuscript.

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Authors and Affiliations

  1. Vall d’Hebron University Hospital and Institute of Oncology, Universitat Autònoma de Barcelona, Barcelona, Spain

    C. Suárez

  2. Medical Oncology Department, Hospital Clínico Universitario San Carlos, Madrid, Spain

    J. Puente

  3. Medical Oncology Department, Hospital Universitari Parc Taulí, Sabadell, Barcelona, Spain

    E. Gallardo

  4. Medical Oncology Department, Instituto Maimónides de Investigación Biomédica (IMIBIC), Hospital Universitario Reina Sofía, Córdoba, Spain

    M. J. Méndez-Vidal

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

    M. A. Climent

  6. Medical Oncology Department, Hospital Clínico, Santiago de Compostela, A Coruña, Spain

    L. León

  7. Prostate Cancer Clinical Research Unit, Spanish National Cancer Research Centre (CNIO), Madrid, Spain

    D. Olmos

  8. CNIO-IBIMA Genitourinary Cancer Research Unit, Hospitales Universitarios Virgen de la Victoria & Regional de Málaga, Madrid, Spain

    D. Olmos

  9. Centro Integral Oncológico Clara Campal, Madrid, Spain

    D. Olmos

  10. Institut Català d’Oncologia L’Hospitalet, Barcelona, Spain

    X. García del Muro

  11. Medical Oncology and Hematology Department, Hospital G. U. Morales Meseguer, Murcia, Spain

    E. González-Billalabeitia

  12. Medical Oncology Department, GI, Endocrine and Translational Research Unit, Early Drug Development Unit-IRYCIS, Ramon y Cajal University Hospital, Madrid, Spain

    E. Grande

  13. Bladder Cancer Center, Dana-Farber Cancer Institute, Dana-Farber/Brigham and Women’s Cancer Center, Harvard Medical School, Boston, MA, USA

    J. Bellmunt

  14. Medical Oncology Department, Hospital Clinic, Barcelona, Spain

    B. Mellado

  15. Medical Oncology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

    P. Maroto

  16. Medical Oncology Department, Hospital Universitario Son Espases, Carretera de Valldemosa 79, 07010, Palma de Mallorca, Spain

    A. González del Alba

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  1. C. Suárez
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  2. J. Puente
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  3. E. Gallardo
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  7. D. Olmos
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  9. E. González-Billalabeitia
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  14. A. González del Alba
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Corresponding author

Correspondence to A. González del Alba.

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Suárez, C., Puente, J., Gallardo, E. et al. New advances in genitourinary cancer: evidence gathered in 2014. Cancer Metastasis Rev 34, 443–464 (2015). https://doi.org/10.1007/s10555-015-9577-x

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