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Erschienen in: Die Pathologie 4/2021

24.06.2021 | Prostatakarzinom | CME

Das metastasierte kastrationsresistente Prostatakarzinom

verfasst von: Dr. Vanessa Henriques, Mike Wenzel, Melanie-Christin Demes, Jens Köllermann

Erschienen in: Die Pathologie | Ausgabe 4/2021

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Zusammenfassung

Das metastasierte Prostatakarzinom im Stadium der Kastrationsresistenz (mCRPC) gilt als finales Stadium der Erkrankung mit bislang nur noch begrenzten therapeutischen Optionen. Im vorliegenden Artikel wird auf neuere histo- und molekularpathologische Befunde eingegangen, die das Krankheitsverständnis erweitern und die Grundlagen für die Entwicklung neuer und individualisierter Therapien legen können oder bereits gelegt haben. Hierzu zählt der Nachweis pathogener Mutationen in den DNA-Reparaturgenen BRCA1/2, der Androgenrezeptorspleißvariante 7 (AR-V7), der Deletion des Tumorsuppressorgens PTEN sowie der Nachweis eines unter antiandrogener Therapie entstandenen neuroendokrinen Prostatakarzinoms (t-NEPC). Die theoretischen und diagnostischen Grundlagen werden dargestellt und die zunehmende Bedeutung der Pathologie für therapeutische Weichenstellungen auch in diesem Erkrankungsstadium aufgezeigt.
Literatur
1.
Zurück zum Zitat Cornford P et al (2017) EAU-ESTRO-SIOG guidelines on prostate cancer. Part II: treatment of relapsing, metastatic, and castration-resistant prostate cancer. Eur Urol 71(4):630–642CrossRef Cornford P et al (2017) EAU-ESTRO-SIOG guidelines on prostate cancer. Part II: treatment of relapsing, metastatic, and castration-resistant prostate cancer. Eur Urol 71(4):630–642CrossRef
2.
Zurück zum Zitat Kirby M, Hirst C, Crawford ED (2011) Characterising the castration-resistant prostate cancer population: a systematic review. Int J Clin Pract 65(11):1180–1192CrossRef Kirby M, Hirst C, Crawford ED (2011) Characterising the castration-resistant prostate cancer population: a systematic review. Int J Clin Pract 65(11):1180–1192CrossRef
4.
Zurück zum Zitat Wang J et al (2019) Current trend of worsening prognosis of prostate small cell carcinoma: a population-based study. Cancer Med 8(15):6799–6806CrossRef Wang J et al (2019) Current trend of worsening prognosis of prostate small cell carcinoma: a population-based study. Cancer Med 8(15):6799–6806CrossRef
5.
Zurück zum Zitat Aggarwal R et al (2018) Clinical and genomic characterization of treatment-emergent small-cell neuroendocrine prostate cancer: a multi-institutional prospective study. J Clin Oncol 36(24):2492–2503CrossRef Aggarwal R et al (2018) Clinical and genomic characterization of treatment-emergent small-cell neuroendocrine prostate cancer: a multi-institutional prospective study. J Clin Oncol 36(24):2492–2503CrossRef
6.
Zurück zum Zitat Ku SY et al (2017) Rb1 and Trp53 cooperate to suppress prostate cancer lineage plasticity, metastasis, and antiandrogen resistance. Science 355(6320):78–83CrossRef Ku SY et al (2017) Rb1 and Trp53 cooperate to suppress prostate cancer lineage plasticity, metastasis, and antiandrogen resistance. Science 355(6320):78–83CrossRef
7.
Zurück zum Zitat Parimi V et al (2014) Neuroendocrine differentiation of prostate cancer: a review. Am J Clin Exp Urol 2(4):273–285PubMedPubMedCentral Parimi V et al (2014) Neuroendocrine differentiation of prostate cancer: a review. Am J Clin Exp Urol 2(4):273–285PubMedPubMedCentral
8.
Zurück zum Zitat Abdulfatah E et al (2021) De novo neuroendocrine transdifferentiation in primary prostate cancer—a phenotype associated with advanced clinico-pathologic features and aggressive outcome. Med Oncol 38(3):26CrossRef Abdulfatah E et al (2021) De novo neuroendocrine transdifferentiation in primary prostate cancer—a phenotype associated with advanced clinico-pathologic features and aggressive outcome. Med Oncol 38(3):26CrossRef
9.
Zurück zum Zitat National Comprehensive Cancer Network Guidelines: Prostate Cancer. 2018. National Comprehensive Cancer Network Guidelines: Prostate Cancer. 2018.
10.
Zurück zum Zitat Aggarwal RR et al (2019) Whole-genome and transcriptional analysis of treatment-emergent small-cell neuroendocrine prostate cancer demonstrates Intraclass heterogeneity. Mol Cancer Res 17(6):1235–1240CrossRef Aggarwal RR et al (2019) Whole-genome and transcriptional analysis of treatment-emergent small-cell neuroendocrine prostate cancer demonstrates Intraclass heterogeneity. Mol Cancer Res 17(6):1235–1240CrossRef
11.
Zurück zum Zitat Dardenne E et al (2016) N‑Myc induces an EZH2-mediated transcriptional program driving neuroendocrine prostate cancer. Cancer Cell 30(4):563–577CrossRef Dardenne E et al (2016) N‑Myc induces an EZH2-mediated transcriptional program driving neuroendocrine prostate cancer. Cancer Cell 30(4):563–577CrossRef
12.
Zurück zum Zitat Robinson D et al (2015) Integrative clinical genomics of advanced prostate cancer. Cell 161(5):1215–1228CrossRef Robinson D et al (2015) Integrative clinical genomics of advanced prostate cancer. Cell 161(5):1215–1228CrossRef
13.
Zurück zum Zitat de Bono J et al (2020) Olaparib for metastatic castration-resistant prostate cancer. N Engl J Med 382(22):2091–2102CrossRef de Bono J et al (2020) Olaparib for metastatic castration-resistant prostate cancer. N Engl J Med 382(22):2091–2102CrossRef
14.
Zurück zum Zitat Hussain M et al (2020) Survival with olaparib in metastatic castration-resistant prostate cancer. N Engl J Med 383(24):2345–2357CrossRef Hussain M et al (2020) Survival with olaparib in metastatic castration-resistant prostate cancer. N Engl J Med 383(24):2345–2357CrossRef
15.
Zurück zum Zitat Gallagher DJ et al (2010) Germline BRCA mutations denote a clinicopathologic subset of prostate cancer. Clin Cancer Res 16(7):2115–2121CrossRef Gallagher DJ et al (2010) Germline BRCA mutations denote a clinicopathologic subset of prostate cancer. Clin Cancer Res 16(7):2115–2121CrossRef
16.
Zurück zum Zitat Liu Y, Lu LY (2020) BRCA1 and homologous recombination: implications from mouse embryonic development. Cell Biosci 10:49CrossRef Liu Y, Lu LY (2020) BRCA1 and homologous recombination: implications from mouse embryonic development. Cell Biosci 10:49CrossRef
17.
Zurück zum Zitat Dehghani M et al (2019) Validation and clinical applications of a comprehensive next generation sequencing system for molecular characterization of solid cancer tissues. Front Mol Biosci 6:82CrossRef Dehghani M et al (2019) Validation and clinical applications of a comprehensive next generation sequencing system for molecular characterization of solid cancer tissues. Front Mol Biosci 6:82CrossRef
22.
Zurück zum Zitat Abida W et al (2019) Genomic correlates of clinical outcome in advanced prostate cancer. Proc Natl Acad Sci U S A 116(23):11428–11436CrossRef Abida W et al (2019) Genomic correlates of clinical outcome in advanced prostate cancer. Proc Natl Acad Sci U S A 116(23):11428–11436CrossRef
23.
Zurück zum Zitat Armenia J et al (2018) The long tail of oncogenic drivers in prostate cancer. Nat Genet 50(5):645–651CrossRef Armenia J et al (2018) The long tail of oncogenic drivers in prostate cancer. Nat Genet 50(5):645–651CrossRef
24.
Zurück zum Zitat Chen WS et al (2019) Genomic drivers of poor prognosis and enzalutamide resistance in metastatic castration-resistant prostate cancer. Eur Urol 76(5):562–571CrossRef Chen WS et al (2019) Genomic drivers of poor prognosis and enzalutamide resistance in metastatic castration-resistant prostate cancer. Eur Urol 76(5):562–571CrossRef
25.
Zurück zum Zitat Rossi G, Ignatiadis M (2019) Promises and pitfalls of using liquid biopsy for precision medicine. Cancer Res 79(11):2798–2804CrossRef Rossi G, Ignatiadis M (2019) Promises and pitfalls of using liquid biopsy for precision medicine. Cancer Res 79(11):2798–2804CrossRef
26.
Zurück zum Zitat Scher HI et al (2016) Association of AR-V7 on circulating tumor cells as a treatment-specific biomarker with outcomes and survival in castration-resistant prostate cancer. JAMA Oncol 2(11):1441–1449CrossRef Scher HI et al (2016) Association of AR-V7 on circulating tumor cells as a treatment-specific biomarker with outcomes and survival in castration-resistant prostate cancer. JAMA Oncol 2(11):1441–1449CrossRef
27.
Zurück zum Zitat Antonarakis ES et al (2017) Clinical significance of androgen receptor splice variant‑7 mRNA detection in circulating tumor cells of men with metastatic castration-resistant prostate cancer treated with first- and second-line Abiraterone and Enzalutamide. J Clin Oncol 35(19):2149–2156CrossRef Antonarakis ES et al (2017) Clinical significance of androgen receptor splice variant‑7 mRNA detection in circulating tumor cells of men with metastatic castration-resistant prostate cancer treated with first- and second-line Abiraterone and Enzalutamide. J Clin Oncol 35(19):2149–2156CrossRef
28.
Zurück zum Zitat Sharp A et al (2019) Clinical utility of circulating tumour cell androgen receptor splice variant‑7 status in metastatic castration-resistant prostate cancer. Eur Urol 76(5):676–685CrossRef Sharp A et al (2019) Clinical utility of circulating tumour cell androgen receptor splice variant‑7 status in metastatic castration-resistant prostate cancer. Eur Urol 76(5):676–685CrossRef
29.
Zurück zum Zitat Ferraldeschi R et al (2015) PTEN protein loss and clinical outcome from castration-resistant prostate cancer treated with abiraterone acetate. Eur Urol 67(4):795–802CrossRef Ferraldeschi R et al (2015) PTEN protein loss and clinical outcome from castration-resistant prostate cancer treated with abiraterone acetate. Eur Urol 67(4):795–802CrossRef
31.
Zurück zum Zitat de Bono JS et al (2020) LBA4 IPATential150: Phase III study of ipatasertib (ipat) plus abiraterone (abi) vs placebo (pbo) plus abi in metastatic castration-resistant prostate cancer (mCRPC). Ann Oncol 31:S1153–S1154CrossRef de Bono JS et al (2020) LBA4 IPATential150: Phase III study of ipatasertib (ipat) plus abiraterone (abi) vs placebo (pbo) plus abi in metastatic castration-resistant prostate cancer (mCRPC). Ann Oncol 31:S1153–S1154CrossRef
32.
Zurück zum Zitat Hoimes CJ et al (2020) KEYNOTE-199 cohorts (C) 4 and 5: Phase II study of pembrolizumab (pembro) plus enzalutamide (enza) for enza-resistant metastatic castration-resistant prostate cancer (mCRPC). J Clin Oncol 38(15_suppl):5543–5543CrossRef Hoimes CJ et al (2020) KEYNOTE-199 cohorts (C) 4 and 5: Phase II study of pembrolizumab (pembro) plus enzalutamide (enza) for enza-resistant metastatic castration-resistant prostate cancer (mCRPC). J Clin Oncol 38(15_suppl):5543–5543CrossRef
33.
Zurück zum Zitat Abida W et al (2019) Analysis of the prevalence of microsatellite instability in prostate cancer and response to immune checkpoint blockade. JAMA Oncol 5(4):471–478CrossRef Abida W et al (2019) Analysis of the prevalence of microsatellite instability in prostate cancer and response to immune checkpoint blockade. JAMA Oncol 5(4):471–478CrossRef
Metadaten
Titel
Das metastasierte kastrationsresistente Prostatakarzinom
verfasst von
Dr. Vanessa Henriques
Mike Wenzel
Melanie-Christin Demes
Jens Köllermann
Publikationsdatum
24.06.2021
Verlag
Springer Medizin
Erschienen in
Die Pathologie / Ausgabe 4/2021
Print ISSN: 2731-7188
Elektronische ISSN: 2731-7196
DOI
https://doi.org/10.1007/s00292-021-00956-3

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