A Challenging Task: Identifying Patients with Cancer of Unknown Primary (CUP) According to ESMO Guidelines: The CUPISCO Trial Experience.
Cancer of unknown primary
Comprehensive genomic profiling
Diagnosis
Histology
Molecularly guided therapy
Next-generation sequencing
Journal
The oncologist
ISSN: 1549-490X
Titre abrégé: Oncologist
Pays: England
ID NLM: 9607837
Informations de publication
Date de publication:
05 2021
05 2021
Historique:
received:
23
10
2020
accepted:
19
02
2021
pubmed:
10
3
2021
medline:
6
7
2021
entrez:
9
3
2021
Statut:
ppublish
Résumé
CUPISCO is an ongoing randomized phase II trial (NCT03498521) comparing molecularly guided therapy versus platinum-based chemotherapy in patients newly diagnosed with "unfavorable" cancer of unknown primary (CUP). Patients with an unfavorable CUP diagnosis, as defined by the European Society of Medical Oncology (ESMO), and available cancer tissue for molecular sequencing are generally eligible. Potential patients with CUP entering screening undergo a review involving reference histopathology and clinical work-up by a central eligibility review team (ERT). Patients with "favorable" CUP, a strongly suspected primary site of origin, lack of tissue, or unmet inclusion criteria are excluded. As of April 30, 2020, 628 patients had entered screening and 346 (55.1%) were screen failed. Screen fails were due to technical reasons (n = 89), failure to meet inclusion and exclusion criteria not directly related to CUP diagnosis (n = 89), and other reasons (n = 33). A total of 124 (35.8%) patients were excluded because unfavorable adeno- or poorly differentiated CUP could not be confirmed by the ERT. These cases were classified into three groups ineligible because of (a) histologic subtype, such as squamous and neuroendocrine, or favorable CUP; (b) evidence of a possible primary tumor; or (c) noncarcinoma histology. Experience with CUPISCO has highlighted challenges with standardized screening in an international clinical trial and the difficulties in diagnosing unfavorable CUP. Reconfirmation of unfavorable CUP by an ERT in a clinical trial can result in many reasons for screen failures. By sharing this experience, we aim to foster understanding of diagnostic challenges and improve diagnostic pathology and clinical CUP algorithms. A high unmet need exists for improved treatment of cancer of unknown primary (CUP); however, study in a trial setting is faced with the significant challenge of definitively distinguishing CUP from other cancer types. This article reports the authors' experience of this challenge so far in the ongoing CUPISCO trial, which compares treatments guided by patients' unique genetic signatures versus standard chemotherapy. The data presented will aid future decision-making regarding diagnosing true CUP cases; this will have far-reaching implications in the design, execution, and interpretation of not only CUPISCO but also future clinical studies aiming to find much-needed treatment strategies.
Sections du résumé
BACKGROUND
CUPISCO is an ongoing randomized phase II trial (NCT03498521) comparing molecularly guided therapy versus platinum-based chemotherapy in patients newly diagnosed with "unfavorable" cancer of unknown primary (CUP).
MATERIALS AND METHODS
Patients with an unfavorable CUP diagnosis, as defined by the European Society of Medical Oncology (ESMO), and available cancer tissue for molecular sequencing are generally eligible. Potential patients with CUP entering screening undergo a review involving reference histopathology and clinical work-up by a central eligibility review team (ERT). Patients with "favorable" CUP, a strongly suspected primary site of origin, lack of tissue, or unmet inclusion criteria are excluded.
RESULTS
As of April 30, 2020, 628 patients had entered screening and 346 (55.1%) were screen failed. Screen fails were due to technical reasons (n = 89), failure to meet inclusion and exclusion criteria not directly related to CUP diagnosis (n = 89), and other reasons (n = 33). A total of 124 (35.8%) patients were excluded because unfavorable adeno- or poorly differentiated CUP could not be confirmed by the ERT. These cases were classified into three groups ineligible because of (a) histologic subtype, such as squamous and neuroendocrine, or favorable CUP; (b) evidence of a possible primary tumor; or (c) noncarcinoma histology.
CONCLUSION
Experience with CUPISCO has highlighted challenges with standardized screening in an international clinical trial and the difficulties in diagnosing unfavorable CUP. Reconfirmation of unfavorable CUP by an ERT in a clinical trial can result in many reasons for screen failures. By sharing this experience, we aim to foster understanding of diagnostic challenges and improve diagnostic pathology and clinical CUP algorithms.
IMPLICATIONS FOR PRACTICE
A high unmet need exists for improved treatment of cancer of unknown primary (CUP); however, study in a trial setting is faced with the significant challenge of definitively distinguishing CUP from other cancer types. This article reports the authors' experience of this challenge so far in the ongoing CUPISCO trial, which compares treatments guided by patients' unique genetic signatures versus standard chemotherapy. The data presented will aid future decision-making regarding diagnosing true CUP cases; this will have far-reaching implications in the design, execution, and interpretation of not only CUPISCO but also future clinical studies aiming to find much-needed treatment strategies.
Identifiants
pubmed: 33687747
doi: 10.1002/onco.13744
pmc: PMC8100559
doi:
Types de publication
Clinical Trial, Phase II
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e769-e779Informations de copyright
© 2021 The Authors. The Oncologist published by Wiley Periodicals LLC on behalf of AlphaMed Press.
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