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CUP-Syndrom – die neue ESMO-Leitlinie

Cancer of unknown primary—The new ESMO guidelines

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Zusammenfassung

Hintergrund

Als CUP-Syndrom („cancer of unknown primary“) bezeichnet man eine Krebserkrankung, die histologisch aus Metastasengewebe gesichert ist, bei der aber trotz ausführlicher Diagnostik kein Primärtumor nachgewiesen werden kann. Damit handelt es sich beim CUP-Syndrom um eine Ausschlussdiagnose.

Relevante Aktualisierungen

Aktuell hat die European Society of Medical Oncology (ESMO) stark überarbeitete Leitlinien zum CUP-Syndrom herausgegeben. Folgende relevante Aktualisierungen sind vorgenommen worden: Bei der Diagnose des CUP-Syndroms zielen die neuen Leitlinien darauf ab, die Erkrankung präziser zu definieren und die Diagnose anhand von Algorithmen besser zu standardisieren. Auch wird die molekulare Diagnostik am Tumorgewebe in den neuen Empfehlungen verankert. Die Klassifikation des CUP-Syndroms wurde ebenfalls überarbeitet. Zum einen wurde bei der Neudefinition der günstigen Untergruppen, für die eine spezifische Behandlung indiziert ist, das Karzinom mit nierenzellkarzinomtypischer Immunhistochemie („renal-like CUP“) neu aufgenommen. Zum anderen wurde eine lokal mittels Operation und/oder Strahlentherapie potenziell kurativ behandelbare Subgruppe basierend auf einer neu definierten oligometastasierten Situation in die CUP-Klassifikation eingeführt. Bezüglich der Therapie der CUP-Syndrome zeigen die aktuellen Leitlinien auf, in welchen Indikationen jenseits der empirischen Chemotherapie, die immer noch den therapeutischen Goldstandard darstellt, auch Immuntherapien und zielgerichtete Therapien zum Einsatz kommen können.

Schlussfolgerung

Ziel dieser Übersichtsarbeit ist es, den aktuellen Stand der Diagnostik, Klassifikation und Therapie des CUP-Syndroms aufzuzeigen und dabei insbesondere die aktuellen Entwicklungen und die in den revidierten ESMO-Leitlinien vorgenommenen Änderungen darzustellen.

Abstract

Background

The European Society of Medical Oncology (ESMO) recently published extensively revised guidelines on cancer of unknown primary (CUP). The new version contains the following relevant amendments: with respect to diagnostics of CUP, the current guidelines aim for a more precise and standardized definition of CUP by establishing diagnostic algorithms. Recommendations for molecular diagnostics of cancer tissue have also been implemented. With respect to CUP classification, the favorable category has been revised. A carcinoma with immunohistochemistry typical for renal cell carcinoma (renal-like CUP) was introduced in the new definition of favorable subtypes, for which a specific treatment is indicated. Based on a newly defined oligometastatic situation a subgroup with localized cancer potentially curatively treatable with surgery and/or radiotherapy was introduced into the CUP classification. With respect to treatment of CUP, the current guidelines present options beyond empirical chemotherapy, which is still the standard of care treatment, and pinpoint indications and predictive biomarkers for targeted and immune checkpoint inhibitor treatment.

Relevant updates

The European Society of Medical Oncology (ESMO) recently published extensively revised guidelines on the CUP syndrome. The new version contains the following relevant amendments: the current guidelines aim for a more precise and standardized definition of CUP by establishing diagnostic algorithms with respect to the diagnostics of CUP syndrome. Recommendations for molecular diagnostics of cancer tissue have also been implemented. The classification of the CUP syndrome has also been revised. A carcinoma with immunohistochemistry typical for renal cell carcinoma (renal-like CUP) was introduced in the new definition of favorable subtypes, for which a specific treatment is indicated. Based on a newly defined oligometastatic situation a local potentially curatively treatable with surgery and/or radiotherapy subgroup was introduced into the CUP classification. With respect to treatment of the CUP syndrome, the current guidelines present options beyond empirical chemotherapy, which is still the gold standard treatment, and pinpoint indications and predictive biomarkers for targeted and immune checkpoint inhibitor treatment.

Schlussfolgerung

The aim of this review is to present the current state of diagnostics, classification and treatment of CUP syndrome, with a focus on recent developments and revisions implemented in the current ESMO guidelines.

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Literatur

  1. Fizazi K et al (2015) Cancers of unknown primary site: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 26(Suppl 5):v133–v138

    Article  PubMed  Google Scholar 

  2. Kramer A et al (2022) Cancer of unknown primary: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. https://doi.org/10.1016/j.annonc.2022.11.013

    Article  PubMed  Google Scholar 

  3. Kwee TC, Kwee RM (2009) Combined FDG-PET/CT for the detection of unknown primary tumors: systematic review and meta-analysis. Eur Radiol 19(3):731–744

    Article  PubMed  Google Scholar 

  4. Albertson M et al (2019) PET/CT evaluation of head and neck cancer of unknown primary. Semin Ultrasound CT MR 40(5):414–423

    Article  PubMed  Google Scholar 

  5. Maghami E et al (2020) Diagnosis and management of squamous cell carcinoma of unknown primary in the head and neck: ASCO guideline. J Clin Oncol 38(22):2570–2596

    Article  PubMed  Google Scholar 

  6. Lievens Y et al (2020) Defining oligometastatic disease from a radiation oncology perspective: an ESTRO-ASTRO consensus document. Radiother Oncol 148:157–166

    Article  PubMed  Google Scholar 

  7. Pauli C et al (2021) A challenging task: identifying patients with cancer of unknown primary (CUP) according to ESMO guidelines: the CUPISCO trial experience. Oncologist 26(5):e769–e779

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Bochtler T et al (2019) Comparative genetic profiling aids diagnosis and clinical decision making in challenging cases of CUP syndrome. Int J Cancer 145(11):2963–2973

    Article  CAS  PubMed  Google Scholar 

  9. Pouyiourou M et al (2021) Local ablative treatment with surgery and/or radiotherapy in single-site and oligometastatic carcinoma of unknown primary. Eur J Cancer 157:179–189

    Article  PubMed  Google Scholar 

  10. Varadhachary GR et al (2008) Carcinoma of unknown primary with a colon-cancer profile-changing paradigm and emerging definitions. Lancet Oncol 9(6):596–599

    Article  PubMed  Google Scholar 

  11. Hainsworth JD et al (2012) A retrospective study of treatment outcomes in patients with carcinoma of unknown primary site and a colorectal cancer molecular profile. Clin Colorectal Cancer 11(2):112–118

    Article  PubMed  Google Scholar 

  12. Greco FA, Hainsworth JD (2018) Renal cell carcinoma presenting as carcinoma of unknown primary site: recognition of a treatable patient subset. Clin Genitourin Cancer 16(4):e893–e898

    Article  PubMed  Google Scholar 

  13. Overby A et al (2019) Carcinoma of Unknown Primary Site (CUP) With Metastatic Renal-Cell Carcinoma (mRCC) Histologic and Immunohistochemical Characteristics (CUP-mRCC): Results From Consecutive Patients Treated With Targeted Therapy and Review of Literature. Clin Genitourin Cancer 17(1):e32–e37

    Article  PubMed  Google Scholar 

  14. Golfinopoulos V et al (2009) Comparative survival with diverse chemotherapy regimens for cancer of unknown primary site: multiple-treatments meta-analysis. Cancer Treat Rev 35(7):570–573

    Article  CAS  PubMed  Google Scholar 

  15. Lee J et al (2013) Evaluation of survival benefits by platinums and taxanes for an unfavourable subset of carcinoma of unknown primary: a systematic review and meta-analysis. Br J Cancer 108(1):39–48

    Article  PubMed  Google Scholar 

  16. Huebner G et al (2009) Paclitaxel and carboplatin vs gemcitabine and vinorelbine in patients with adeno- or undifferentiated carcinoma of unknown primary: a randomised prospective phase II trial. Br J Cancer 100(1):44–49

    Article  CAS  PubMed  Google Scholar 

  17. Gross-Goupil M et al (2012) Cisplatin alone or combined with gemcitabine in carcinomas of unknown primary: results of the randomised GEFCAPI 02 trial. Eur J Cancer 48(5):721–727

    Article  CAS  PubMed  Google Scholar 

  18. Culine S et al (2003) Cisplatin in combination with either gemcitabine or irinotecan in carcinomas of unknown primary site: results of a randomized phase II study—trial for the French Study Group on Carcinomas of Unknown Primary (GEFCAPI 01). J Clin Oncol 21(18):3479–3482

    Article  CAS  PubMed  Google Scholar 

  19. Fizazi K et al (2019) A phase 3 trial of empiric chemotherapy with cisplatin and gemcitabine or systemic treatment tailored by molecular gene expression analysis in patients with carcinomas of an unknown primary (CUP) site (GEFCAPI 04). Ann Oncol 30(suppl_5):v851–v934

    Article  Google Scholar 

  20. Hayashi H et al (2019) Randomized phase II trial comparing site-specific treatment based on gene expression profiling with carboplatin and paclitaxel for patients with cancer of unknown primary site. J Clin Oncol. https://doi.org/10.1200/JCO.18.00771

    Article  PubMed  PubMed Central  Google Scholar 

  21. Ross JS et al (2015) Comprehensive genomic profiling of carcinoma of unknown primary site: new routes to targeted therapies. JAMA Oncol 1(1):40–49

    Article  PubMed  Google Scholar 

  22. Bochtler T et al (2020) Integrated clinicomolecular characterization identifies RAS activation and CDKN2A deletion as independent adverse prognostic factors in cancer of unknown primary. Int J Cancer 146(11):3053–3064

    Article  CAS  PubMed  Google Scholar 

  23. Tanizaki J et al (2022) Open-label phase II study of the efficacy of nivolumab for cancer of unknown primary. Ann Oncol 33(2):216–226

    Article  CAS  PubMed  Google Scholar 

  24. Le DT et al (2015) PD‑1 blockade in tumors with mismatch-repair deficiency. N Engl J Med 372(26):2509–2520

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Marcus L et al (2019) FDA approval summary: pembrolizumab for the treatment of microsatellite instability-high solid tumors. Clin Cancer Res 25(13):3753–3758

    Article  CAS  PubMed  Google Scholar 

  26. Diaz LA Jr. et al (2022) Pembrolizumab versus chemotherapy for microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer (KEYNOTE-177): final analysis of a randomised, open-label, phase 3 study. Lancet Oncol 23(5):659–670

    Article  CAS  PubMed  Google Scholar 

  27. Luchini C et al (2019) ESMO recommendations on microsatellite instability testing for immunotherapy in cancer, and its relationship with PD-1/PD-L1 expression and tumour mutational burden: a systematic review-based approach. Ann Oncol 30(8):1232–1243

    Article  CAS  PubMed  Google Scholar 

  28. Quenet F et al (2021) Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy versus cytoreductive surgery alone for colorectal peritoneal metastases (PRODIGE 7): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol 22(2):256–266

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Klinische Kooperationseinheit Molekulare Hämatologie/Onkologie, Deutsches Krebsforschungszentrum (DKFZ) und Medizinische Klinik V, Universitätsklinikum Heidelberg, Heidelberg, Deutschland

    Tilmann Bochtler, Maria Pouyiourou &  Alwin Krämer

  2. Nationales Centrum für Tumorerkrankungen (NCT) Heidelberg, Medizinische Onkologie, Heidelberg, Deutschland

    Tilmann Bochtler

  3. Medizinische Klinik V, Universitätsklinikum Heidelberg, Heidelberg, Deutschland

    Tilmann Bochtler, Maria Pouyiourou &  Alwin Krämer

Authors
  1. Tilmann Bochtler
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  2. Maria Pouyiourou
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  3. Alwin Krämer
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Corresponding author

Correspondence to Alwin Krämer.

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Interessenkonflikt

T. Bochtler berichtet über seine Tätigkeit als Studienonkologe für die CUPISCO Studie. Für diese Tätigkeit wurden von Roche Honorare an seinen Arbeitgeber gezahlt und studienbezogene Reisekosten übernommen. A. Krämer berichtet über persönliche Honorare als eingeladener Redner von Roche; Honorare, die seiner Institution für die Mitgliedschaft im Beirat von Roche gezahlt wurden; institutionelle Förderung von Bristol Myers Squibb (BMS); nichtvergüteter Hauptprüfer für Roche. M. Pouyiourou gibt an, dass kein Interessenkonflikt besteht.

Für diesen Beitrag wurden von den Autor/-innen keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

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Bochtler, T., Pouyiourou, M. & Krämer, A. CUP-Syndrom – die neue ESMO-Leitlinie. Radiologie 63, 329–335 (2023). https://doi.org/10.1007/s00117-023-01126-7

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