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International audience; PURPOSE:A substantial proportion of cancer survivors experience fatigue after diagnosis. Physical activity (PA) can impact fatigue after cancer. In this study, we evaluated the prevalence and association of fatigue and the practice of PA in a population with early cancer.METHODS:Using the national population-based French cross-sectional study Vie après le cancer 2, we included 1984 patients with early breast (61.1%), prostate (21.5%), and colorectal (17.4%) cancer. Severe fatigue at 2 years postdiagnosis was defined by a score ≥40 in the European Organization for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ C30) fatigue subscale. PA was defined as (a) self-reported PA before diagnosis (active/inactive) and (b) change in PA since diagnosis (increased/maintained exposure vs decreased exposure/remaining inactive). Multivariate regression examined associations of severe fatigue with PA, adjusting for baseline clinical and treatment variables.RESULTS:Median age was 52 years. 51.5% of patients experienced severe fatigue 2 years post-diagnosis. 87.7% reported to be physically active before cancer diagnosis; 53.3% of patients either decreased PA or remained inactive at 2 years postdiagnosis. At 2 years postdiagnosis, severe fatigue was associated with a change in PA since diagnosis: patients with decreasing PA/remaining inactive from pre- to postdiagnosis had a higher risk of severe fatigue vs those with increasing/maintaining PA (adjusted odds ratio [95% confidence interval] 2.32 [1.85-2.90]).CONCLUSION:Fatigue continues to be a substantial problem for cancer survivors 2 years after cancer diagnosis and is associated with PA decreasing/remaining inactive since diagnosis. Interventions to maintain or increase PA for cancer survivors should be tested to mitigate long-term fatigue after cancer.

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., Effective therapeutic regimens are lacking for patients with cancers of unknown primary (CUP). This article reports the clinic‐pathological challenges associated with diagnosis of unfavorable CUP in the CUPSICO trial and suggests refinements for diagnostic algorithms.