Cancer of unknown primary: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up

Krämer, Alwin; Bochtler, Tilmann; Pauli, Chantal; Baciarello, Giulia; Delorme, Stefan; Hemminki, Kari; Mileshkin, Linda; Moch, Holger; Oien, Karin A.; Thibault, Olivier; Patrikidou, Anna; Wasan, Harpreet; Zarkavelis, George; Pentheroudakis, George; Fizazi, Karim

doi:10.1016/j.annonc.2022.11.013

Cited by 84 publications

(108 citation statements)

References 110 publications

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“…Comparisons of survival-based outcomes were conducted using log-rank tests and Cox regression analyses that were described as Second analysis was defined as an unsuccessful first attempt of CGP, with a successful second attempt. Favorable CUP was defined by obvious analogies to certain cancers with a known primary (Krämer et al 2023) hazard ratios with 95% confidence intervals (95% CI). p values < 0.05 were considered statistically significant.…”

Section: Discussionmentioning

confidence: 99%

“…This is a retrospective observational study, analyzing 61 patients with CUP diagnosis presented to the molecular tumor board at a tertiary care center (University Hospital Munich) between June 2016 and February 2022. CUP diagnosis was defined as a carcinoma or undifferentiated neoplasm for which a standardized diagnostic work-up failed to identify the primary tumor responsible for metastatic seeding (Krämer et al 2023). Minimal standard diagnostic work-up for initial diagnosis included blood analysis, radiologic imaging, and detailed medical history.…”

Section: Methodsmentioning

confidence: 99%

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Cancer of unknown primary (CUP) through the lens of precision oncology: a single institution perspective

Weiss

Heinrich

Zhang

et al. 2023

J Cancer Res Clin Oncol

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Purpose For patients with cancer of unknown primary (CUP), treatment options are limited. Precision oncology, the interplay of comprehensive genomic profiling (CGP) and targeted therapies, aims to offer additional treatment options to patients with advanced and hard-to-treat cancers. We aimed to highlight the use of a molecular tumor board (MTB) in the therapeutic management of CUP patients. Methods In this single-center observational study, CUP patients, presented to the MTB of the Comprehensive Cancer Center Munich LMU, a tertiary care center, were analyzed retrospectively. Descriptive statistics were applied to describe relevant findings. Results Between June 2016 and February 2022, 61 patients with unfavorable CUP were presented to the MTB, detected clinically relevant variants in 74% (45/61) of patients, of which 64% (29/45) led to therapeutic recommendation. In four out of 29 patients (14%), the treatment recommendations were implemented, unfortunately without resulting in clinical benefit. Reasons for not following the therapeutic recommendation were mainly caused by the physicians’ choice of another therapy (9/25, 36%), especially in the context of worsening of general condition, lost to follow-up (7/25, 28%) and death (6/25, 24%). Conclusion CGP and subsequent presentation to a molecular tumor board led to a high rate of therapeutic recommendations in patients with CUP. Recommendations were only implemented at a low rate; however, late GCP diagnostic and, respectively, MTB referral were found more frequent for the patients with implemented treatment. This contrast underscores the need for early implementation of CGP into the management of CUP patients.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Cancer of unknown primary (CUP) through the lens of precision oncology: a single institution perspective

Weiss

Heinrich

Zhang

et al. 2023

J Cancer Res Clin Oncol

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“…Eine strenge Organspezifität liegt jedoch nur sehr selten vor. Zusammen mit den ESMO-Guidelines werden in der Literatur unterschiedliche Algorithmen zur immunhistochemischen Tumorklassifikation vorgeschlagen [ 9 , 18 ]. Damit kann im Idealfall eine Bestimmung des Primärtumors erreicht werden.…”

Section: Linienspezifischere Aufarbeitungunclassified

“…Immunhistochemisch kann ein Verlust von BRCA1-assoziiertem Protein 1 (BAP1) oder des AT-reichen interaktiven Domäne enthaltenden Proteins 1A (ARID1A) die Diagnose eines intrahepatischen Cholangiokarzinoms unterstützen. Die endgültige Diagnose kann jedoch nur nach Korrelation mit der klinischen und insbesondere radiologischen Präsentation gemacht werden [ 18 ]. Gleiches gilt für Pankreaskarzinome, bei denen SMAD4 (DPC4, MADH4) hinzugezogen werden kann.…”

Section: Linienspezifischere Aufarbeitungunclassified

“…Eine Liste von genomischen Aberrationen, welche die Diagnose spezifischer Neoplasien unterstützen, findet sich in Tab. 3 [ 18 ]. In mehreren retrospektiven Studien konnte gezeigt werden, dass bei auf Gewebe- oder Flüssigbiopsie basierten zellfreien zirkulierenden Tumor-DNA(cfDNA)-Analysen in 65–90 % der Patienten mit CUP ≥ 1 onkogene Treibermutation identifiziert werden kann [ 26 ].…”

Section: Molekulare Diagnostikunclassified

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CUP-Syndrom – Diagnostik aus Sicht der Pathologie

Pauli

2023

Radiologie

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Zusammenfassung Problemstellung Die histologische und immunhistochemische Aufarbeitung von Tumormaterial aus Metastasen eines bis dahin unbekannten Primärtumors („cancer of unknow primary“, CUP) ist ein wichtiges Werkzeug zur Identifizierung ihrer Herkunft, reicht aber hierfür ohne klinisch-onkologische und radiologische Beurteilung oft nicht aus. Vorgehen Bei der initialen CUP-Situation tragen die histologische und immunhistochemische Aufarbeitung sowie die klinisch-radiologische Korrelation wesentlich zur Identifikation des Primärtumors bei. Mittlerweile gibt es akzeptierte Richtlinien, denen man während der CUP-Diagnostik folgen kann. Mittels molekularer Diagnostik werden Veränderungen auf der Ebene von Nukleinsäuren untersucht, was u. a. auch Hinweise für den Primärtumor geben kann. Gelingt es trotz breiter und interdisziplinärer Diagnostik nicht, den Primärtumor zu identifizieren, handelt es sich um ein CUP-Syndrom. Liegt eine echte CUP-Situation vor, gilt es, den Tumor so gut wie möglich einer Tumorklasse oder einer bestimmten therapiesensitiven Untergruppe zuzuordnen, so dass die bestmögliche Therapie erfolgen kann. Für eine endgültige Zuordnung zu einem Primärtumor oder eine Einstufung als CUP ist jedoch ein Abgleich mit medizinisch-onkologischen und bildgebenden Befunden unentbehrlich. Schlussfolgerung Beim Verdacht auf ein CUP-Syndrom ist eine enge interdisziplinäre Abstimmung zwischen Pathologie, medizinischer Onkologie und Bildgebung unerlässlich, um eine tragfähige Einstufung als CUP oder eine Identifizierung eines anzunehmenden Primärtumors zu erreichen, im Interesse einer möglichst spezifischen und wirksamen Therapie für die betroffenen Personen.

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Exploring the molecular landscape of cancer of unknown primary: A comparative analysis with other metastatic cancers

Andersen,

Christensen,

Kjær

et al. 2024

Molecular Oncology

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Cancer of unknown primary (CUP) tumors are biologically very heterogeneous, which complicates stratification of patients for treatment. Consequently, these patients face limited treatment options and a poor prognosis. With this study, we aim to expand on the current knowledge of CUP biology by analyzing two cohorts: a well‐characterized cohort of 44 CUP patients, and 213 metastatic patients with known primary. These cohorts were treated at the same institution and characterized by identical molecular assessments. Through comparative analysis of genomic and transcriptomic data, we found that CUP tumors were characterized by high expression of immune‐related genes and pathways compared to other metastatic tumors. Moreover, CUP tumors uniformly demonstrated high levels of tumor‐infiltrating leukocytes and circulating T cells, indicating a strong immune response. Finally, the genetic landscape of CUP tumors resembled that of other metastatic cancers and demonstrated mutations in established cancer genes. In conclusion, CUP tumors possess a distinct immunophenotype that distinguishes them from other metastatic cancers. These results may suggest an immune response in CUP that facilitates metastatic tumor growth while limiting growth of the primary tumor.

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Cancer of unknown primary: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up

Cited by 84 publications

References 110 publications

Cancer of unknown primary (CUP) through the lens of precision oncology: a single institution perspective

Cancer of unknown primary (CUP) through the lens of precision oncology: a single institution perspective

CUP-Syndrom – Diagnostik aus Sicht der Pathologie

Exploring the molecular landscape of cancer of unknown primary: A comparative analysis with other metastatic cancers

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