Download PDF
Aktuelle Urol 2018; 49(02): 171-177
DOI: 10.1055/a-0573-7895
Übersicht
© Georg Thieme Verlag KG Stuttgart · New York

Die Rolle von Biomarkern in Diagnose, Prognose und Therapie von Patienten unter immunonkologischer Therapie mit urologischen Malignomen

The role of biomarkers in the diagnosis, prognosis and therapy of patients with immuno-oncological treatments of genito-urinary carcinomas
Eva Compérat
Service d’Anatomie et Cytologie Pathologiques, Hôpital Tenon
,
Caroline Eymerit
Service d’Anatomie et Cytologie Pathologiques, Hôpital Tenon
,
Julien Moroch
Service d’Anatomie et Cytologie Pathologiques, Hôpital Tenon
,
Justin Varinot
Service d’Anatomie et Cytologie Pathologiques, Hôpital Tenon
› Author Affiliations
Further Information

Publication History

Publication Date:
27 March 2018 (online)

Also available at
    Permissions and Reprints

Zusammenfassung

In den letzten Jahren haben Fortschritte in der Grundlagenforschung neue Einsichten in die Tumorbiologie gestattet, dadurch konnten neue Therapien entwickelt werden. Diese Übersichtsarbeit beleuchtet die Rolle des Pathologen und wie er anhand von Gewebemarkern helfen kann, eine Therapieentscheidung zu treffen. Wir erklären die Problematik der molekularen Blasentumoruntergruppen, die Rolle der neoadjuvanten Chemotherapie und die der Immune Checkpoint Inhibitoren, des Weiteren gehen wir auf das Nierenkarzinom und dessen Therapiemöglichkeiten ein, mit besonderem Augenmerk auf das klarzellige Nierenkarzinom als häufigsten Nierenkarzinomtyp. Wir streifen kurz das Prostatakarzinom, das als hormonabhängiger Tumor wahrscheinlich einen anderen Therapieansatz braucht. Wir versuchen, die Machbarkeit und Grenzen vom pathologischen Standpunkt her zu beleuchten.

Abstract

In recent years, fundamental research has yielded new insights into tumour biology, and new treatments have been developed. This review highlights the role of the pathologist and how he can support clinicians to find the right treatment for each patient. We explain the problems of the molecular subgroups of bladder cancer, the role of neo-adjuvant chemotherapy in the context of these findings, and show the important role of checkpoint inhibitors. Furthermore we focus on kidney cancer, with the clear cell carcinoma as the most frequent tumour type. We briefly consider prostate cancer, which as a hormone-dependent tumour probably requires different therapies. We also try to show the feasibility and the limits of pathology with the emerging tumour markers.

Schlüsselwörter

Blasenkarzinom - Nierenkarzinom - Prostatakarzinom - Immune Checkpoint Inhibitoren

Keywords

bladder cancer - kidney cancer - prostate cancer - immune checkpoint inhibitor
 

  • Literatur

  • 1 Mehta K, Patel K, Parikh RA. Immunotherapy in genitourinary malignancies. J Hematol Oncol 2017; 10: 95
    CrossrefPubMedGoogle Scholar
  • 2 Rosenberg JE, Hoffman-Censits J, Powles T. et al. Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. Lancet Lond Engl 2016; 387: 1909-1920
    PubMedGoogle Scholar
  • 3 Powles T, Eder JP, Fine GD. et al. MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer. Nature 2014; 515: 558-562
    CrossrefPubMedGoogle Scholar
  • 4 Bellmunt J, de Wit R, Vaughn DJ. et al. Pembrolizumab as Second-Line Therapy for Advanced Urothelial Carcinoma. N Engl J Med 2017; 376: 1015-1026
    CrossrefPubMedGoogle Scholar
  • 5 Cancer IA. for R on. WHO Classification of Tumours of the Urinary System and Male Genital Organs. International Agency for Research on Cancer 2016; 356
    PubMedGoogle Scholar
  • 6 Sjödahl G, Lauss M, Lövgren K. et al. A molecular taxonomy for urothelial carcinoma. Clin Cancer Res Off J Am Assoc Cancer Res 2012; 18: 3377-3386
    CrossrefPubMedGoogle Scholar
  • 7 Choi W, Porten S, Kim S. et al. Identification of distinct basal and luminal subtypes of muscle-invasive bladder cancer with different sensitivities to frontline chemotherapy. Cancer Cell 2014; 25: 152-165
    CrossrefPubMedGoogle Scholar
  • 8 Cancer Genome Atlas Research Network. Comprehensive molecular characterization of urothelial bladder carcinoma. Nature 2014; 507: 315-322
    CrossrefPubMedGoogle Scholar
  • 9 Seiler R, Ashab HAD, Erho N. et al. Impact of Molecular Subtypes in Muscle-invasive Bladder Cancer on Predicting Response and Survival after Neoadjuvant Chemotherapy. Eur Urol 2017; 72: 544-554
    CrossrefPubMedGoogle Scholar
  • 10 Dadhania V, Zhang M, Zhang L. et al. Meta-Analysis of the Luminal and Basal Subtypes of Bladder Cancer and the Identification of Signature Immunohistochemical Markers for Clinical Use. EBioMedicine 2016; 12: 105-117
    CrossrefPubMedGoogle Scholar
  • 11 McConkey DJ, Choi W, Dinney CPN. New insights into subtypes of invasive bladder cancer: considerations of the clinician. Eur Urol 2014; 66: 609-610
    CrossrefPubMedGoogle Scholar
  • 12 Sjödahl G. Molecular Subtype Profiling of Urothelial Carcinoma Using a Subtype-Specific Immunohistochemistry Panel. Methods Mol Biol Clifton NJ 2018; 1655: 53-64
    PubMedGoogle Scholar
  • 13 Lerner S, McConkey D, Hoadley K. et al. Bladder Cancer Molecular Taxonomy: Summary from aconsensus meeeting. Bladder cancer 2016; 2: 37-47
    CrossrefPubMedGoogle Scholar
  • 14 Bedwani R, Renganathan E, El Kwhsky F. et al. Schistosomiasis and the risk of bladder cancer in Alexandria, Egypt. Br J Cancer 1998; 77: 1186-1189
    CrossrefPubMedGoogle Scholar
  • 15 Phé V, Rouprêt M, Cussenot O. et al. Forkhead box protein P3 (Foxp3) expression serves as an early chronic inflammation marker of squamous cell differentiation and aggressive pathology of urothelial carcinomas in neurological patients. BJU Int 2015; 115: 28-32
    CrossrefPubMedGoogle Scholar
  • 16 Kamat AM, Briggman J, Urbauer DL. et al. Cytokine Panel for Response to Intravesical Therapy (CyPRIT): Nomogram of Changes in Urinary Cytokine Levels Predicts Patient Response to Bacillus Calmette-Guérin. Eur Urol 2016; 69: 197-200
    CrossrefPubMedGoogle Scholar
  • 17 Hirsch FR, McElhinny A, Stanforth D. et al. PD-L1 Immunohistochemistry Assays for Lung Cancer: Results from Phase 1 of the Blueprint PD-L1 IHC Assay Comparison Project. J Thorac Oncol Off Publ Int Assoc Study Lung Cancer 2017; 12: 208-222
    PubMedGoogle Scholar
  • 18 Rimm DL, Han G, Taube JM. et al. A Prospective, Multi-institutional, Pathologist-Based Assessment of 4 Immunohistochemistry Assays for PD-L1 Expression in Non-Small Cell Lung Cancer. JAMA Oncol 2017; 3: 1051-1058
    CrossrefPubMedGoogle Scholar
  • 19 Gaule P, Smithy JW, Toki M. et al. A Quantitative Comparison of Antibodies to Programmed Cell Death 1 Ligand 1. JAMA Oncol. 2016
    Google Scholar
  • 20 Ratcliffe MJ, Sharpe A, Midha A. et al. Agreement between Programmed Cell Death Ligand-1 Diagnostic Assays across Multiple Protein Expression Cutoffs in Non-Small Cell Lung Cancer. Clin Cancer Res Off J Am Assoc Cancer Res 2017; 23: 3585-3591
    CrossrefPubMedGoogle Scholar
  • 21 Hamilou Z, Lavaud P, Loriot Y. Atezolizumab in urothelial bladder carcinoma. Future Oncol Lond Engl. 2017
    Google Scholar
  • 22 Balar AV, Galsky MD, Rosenberg JE. et al. Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicentre, phase 2 trial. Lancet Lond Engl 2017; 389: 67-76
    PubMedGoogle Scholar
  • 23 Balar AV, Castellano D, O’Donnell PH. et al. First-line pembrolizumab in cisplatin-ineligible patients with locally advanced and unresectable or metastatic urothelial cancer (KEYNOTE-052): a multicentre, single-arm, phase 2 study. Lancet Oncol 2017; 18: 1483-1492
    CrossrefPubMedGoogle Scholar
  • 24 Powles T, Bellmunt J, Castellano D. et al. 170 - Pembrolizumab produces clinically meaningful responses as first-line therapy in cisplatin-ineligible advanced urothelial cancer: Results from subgroup analyses of KEYNOTE-052. Eur Urol 2017; 16: e285-e286
    CrossrefPubMedGoogle Scholar
  • 25 Remark R, Alifano M, Cremer I. et al. Characteristics and clinical impacts of the immune environments in colorectal and renal cell carcinoma lung metastases: influence of tumor origin. Clin Cancer Res Off J Am Assoc Cancer Res 2013; 19: 4079-4091
    CrossrefPubMedGoogle Scholar
  • 26 Brannon AR, Reddy A, Seiler M. et al. Molecular Stratification of Clear Cell Renal Cell Carcinoma by Consensus Clustering Reveals Distinct Subtypes and Survival Patterns. Genes Cancer 2010; 1: 152-163
    CrossrefPubMedGoogle Scholar
  • 27 Rini BI, Campbell SC, Escudier B. Renal cell carcinoma. Lancet Lond Engl 2009; 373: 1119-1132
    PubMedGoogle Scholar
  • 28 Choueiri TK, Fay AP, Gray KP. et al. PD-L1 expression in nonclear-cell renal cell carcinoma. Ann Oncol Off J Eur Soc Med Oncol 2014; 25: 2178-2184
    PubMedGoogle Scholar
  • 29 Morra L, Rechsteiner M, Casagrande S. et al. Relevance of periostin splice variants in renal cell carcinoma. Am J Pathol 2011; 179: 1513-1521
    CrossrefPubMedGoogle Scholar
  • 30 Malouf GG, Su X, Yao H. et al. Next-generation sequencing of translocation renal cell carcinoma reveals novel RNA splicing partners and frequent mutations of chromatin-remodeling genes. Clin Cancer Res Off J Am Assoc Cancer Res 2014; 20: 4129-4140
    CrossrefPubMedGoogle Scholar
  • 31 Massari F, Santoni M, Ciccarese C. et al. PD-1 blockade therapy in renal cell carcinoma: current studies and future promises. Cancer Treat Rev 2015; 41: 114-121
    CrossrefPubMedGoogle Scholar
  • 32 McDermott DF, Sosman JA, Sznol M. et al. Atezolizumab, an Anti-Programmed Death-Ligand 1 Antibody, in Metastatic Renal Cell Carcinoma: Long-Term Safety, Clinical Activity, and Immune Correlates From a Phase Ia Study. J Clin Oncol Off J Am Soc Clin Oncol 2016; 34: 833-842
    CrossrefPubMedGoogle Scholar
  • 33 Motzer RJ, Rini BI, McDermott DF. et al. Nivolumab for Metastatic Renal Cell Carcinoma: Results of a Randomized Phase II Trial. J Clin Oncol Off J Am Soc Clin Oncol 2015; 33: 1430-1437
    CrossrefPubMedGoogle Scholar
  • 34 Motzer RJ, Escudier B, McDermott DF. et al. Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma. N Engl J Med 2015; 373: 1803-1813
    CrossrefPubMedGoogle Scholar
  • 35 Abbas M, Steffens S, Bellut M. et al. Intratumoral expression of programmed death ligand 1 (PD-L1) in patients with clear cell renal cell carcinoma (ccRCC). Med Oncol Northwood Lond Engl 2016; 33: 80
    PubMedGoogle Scholar
  • 36 Zaldumbide L, Erramuzpe A, Guarch R. et al. Large (>3.8 cm) clear cell renal cell carcinomas are morphologically and immunohistochemically heterogeneous. Virchows Arch Int J Pathol 2015; 466: 61-66
    CrossrefPubMedGoogle Scholar
  • 37 Mazza C, Escudier B, Albiges L. Nivolumab in renal cell carcinoma: latest evidence and clinical potential. Ther Adv Med Oncol 2017; 9: 171-181
    CrossrefPubMedGoogle Scholar
  • 38 Sodji Q, Klein K, Sravan K. et al. Predictive role of PD-L1 expression in the response of renal medullary carcinoma to PD-1 inhibition. J Immunother Cancer 2017; 5: 62
    CrossrefPubMedGoogle Scholar
  • 39 Erlmeier F, Weichert W, Schrader AJ. et al. Prognostic impact of PD-1 and its ligands in renal cell carcinoma. Med Oncol Northwood Lond Engl 2017; 34: 99
    PubMedGoogle Scholar
  • 40 Erlmeier F, Hartmann A, Autenrieth M. et al. PD-1/PD-L1 expression in chromophobe renal cell carcinoma: An immunological exception?. Med Oncol Northwood Lond Engl 2016; 33: 120
    PubMedGoogle Scholar
  • 41 Erlmeier F, Weichert W, Autenrieth M. et al. PD-L2: A prognostic marker in chromophobe renal cell carcinoma?. Med Oncol Northwood Lond Engl 2017; 34: 71
    PubMedGoogle Scholar
  • 42 Delahunt B, Srigley JR, Egevad L. et al. International Society for Urological Pathology. International Society of Urological Pathology grading and other prognostic factors for renal neoplasia. Eur Urol 2014; 66: 795-798
    CrossrefPubMedGoogle Scholar
  • 43 Mottet N, Bellmunt J, Bolla M. et al. EAU-ESTRO-SIOG Guidelines on Prostate Cancer. Part 1: Screening, Diagnosis, and Local Treatment with Curative Intent. Eur Urol 2017; 71: 618-629
    CrossrefPubMedGoogle Scholar
  • 44 Bellmunt J, Bolla M, Briers E. et al. EAU-ESTRO-SIOG Guidelines on Prostate Cancer. Part II: Treatment of Relapsing, Metastatic, and Castration-Resistant Prostate Cancer. Eur Urol 2017; 71: 630-642
    CrossrefPubMedGoogle Scholar
  • 45 Small EJ, Schellhammer PF, Higano CS. et al. Placebo-controlled phase III trial of immunologic therapy with sipuleucel-T (APC8015) in patients with metastatic, asymptomatic hormone refractory prostate cancer. J Clin Oncol Off J Am Soc Clin Oncol 2006; 24: 3089-3094
    CrossrefPubMedGoogle Scholar
  • 46 Kantoff PW, Schuetz TJ, Blumenstein BA. et al. Overall survival analysis of a phase II randomized controlled trial of a Poxviral-based PSA-targeted immunotherapy in metastatic castration-resistant prostate cancer. J Clin Oncol Off J Am Soc Clin Oncol 2010; 28: 1099-1105
    CrossrefPubMedGoogle Scholar
  • 47 Calagua C, Russo J, Sun Y. et al. Expression of PD-L1 in Hormone-naïve and Treated Prostate Cancer Patients Receiving Neoadjuvant Abiraterone Acetate plus Prednisone and Leuprolide. Clin Cancer Res Off J Am Assoc Cancer Res 2017; 23: 6812-6822
    CrossrefPubMedGoogle Scholar
  • 48 Godin-Ethier J, Pelletier S, Hanafi L-A. et al. Human activated T lymphocytes modulate IDO expression in tumors through Th1/Th2 balance. J Immunol Baltim Md 1950 2009; 183: 7752-7760
    PubMedGoogle Scholar
  • 49 Beer TM, Kwon ED, Drake CG. et al. Randomized, Double-Blind, Phase III Trial of Ipilimumab Versus Placebo in Asymptomatic or Minimally Symptomatic Patients With Metastatic Chemotherapy-Naive Castration-Resistant Prostate Cancer. J Clin Oncol Off J Am Soc Clin Oncol 2017; 35: 40-47
    PubMedGoogle Scholar
  • 50 Kwon ED, Drake CG, Scher HI. et al. Ipilimumab versus placebo after radiotherapy in patients with metastatic castration-resistant prostate cancer that had progressed after docetaxel chemotherapy (CA184-043): a multicentre, randomised, double-blind, phase 3 trial. Lancet Oncol 2014; 15: 700-712
    CrossrefPubMedGoogle Scholar