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The author conveys his response to a feedback about his report on diagnostic methods and therapeutic strategies to patients with carcinoma with unknown primary tumor or CUP syndrome. Topics mentioned include the impact of platinum-based chemotherapies on quality of life, the importance of palliative medical care in disseminated CUP syndrome, and general palliative medical measures in patients with advanced CUP syndrome.

Cancer of unknown primary (CUP) is a heterogeneous entity with a limited prognosis. Novel prognostic markers are needed for patient stratification in prospective clinical trials exploring innovative therapies. Methods: In CUP patients treated at the West German Cancer Center Essen, the prognostic value of 18 F-FDG PET/CT at the initial diagnostic workup was analyzed by comparing overall survival (OS) in patients who underwent 18 F-FDG PET/CT with those who did not. Results: Of 154 patients with a CUP diagnosis, 76 underwent 18 F-FDG PET/CT at the initial diagnostic workup. The median overall survival (OS) of the full analysis set was 20.0 mo. Within the PET/CT subgroup, an SUV max above 20 was associated with significantly superior OS (median OS, not reached vs. 32.0 mo; hazard ratio, 0.261; 95% CI, 0.095-0.713; P = 0.009). Conclusion: Our retrospective work shows that an SUV max above 20 on 18 F-FDG PET/CT at the initial diagnostic workup is a favorable prognostic factor in patients with CUP. This finding deserves further prospective studies for validation., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)

Introduction: Understanding prognosis, especially long-term outcome, in advanced nonsmall cell lung cancer (NSCLC) is crucial to inform patients, guide treatment and plan supportive and palliative care., Methods: Prognostic factors influencing overall survival (OS) and progression-free survival (PFS) in 2082 patients with wild-type (WT)-NSCLC (629 M1a, 249 M1b, 1204 M1c) are reported. Patients were included in the prospective German CRISP registry recruiting in >150 centres. Analysis for pre-therapeutic factors was based on results from Cox proportional hazard models., Results: Current M-descriptors of the Union for International Cancer Control-8 staging system were validated: M1a and M1b patients had significantly longer median time to events compared to M1c (OS/PFS 16.4/7.2 months, 17.8/6.7 months and 10.9/5.4 months, respectively). OS and PFS were influenced by number and location of metastatic organ systems. M1c and four or more metastatic organs involved had shorter OS and PFS than M1c with one to three organs (OS hazard ratio (HR) 1.69, p<0.001; PFS HR 1.81, p<0.001). M1b-liver metastases had shorter OS/PFS than M1b involving other organs (OS HR 2.70, p=0.006; PFS HR 2.48, p=0.007). Based on number of involved organs (orgsys) and liver metastases, two risk groups (low-risk: M1a, M1b-non-liver, M1c-1-3-orgsys-non-liver; high-risk: M1c-liver, M1b-liver, M1c-4+-orgsys) with significantly different prognoses could be amalgamated (median OS/PFS 14.3/6.5 months and 7.7/4.1 months, respectively). Other favourable factors were female gender and Eastern Cooperative Oncology Group stage 0, with age showing no impact. Those with T1- or N0-status were associated with longer OS than T2-4 or N2-3., Conclusion: In this large observational dataset, we further defined factors for outcome in WT-NSCLC, including increased number of involved metastatic organ systems and liver metastases, as those with overall poorer prognosis and reduced survival chance., Competing Interests: M. Metzenmacher has received honoraria for advisory boards from AstraZeneca, BMS, Boehringer Ingelheim, MSD, Novartis, Pfizer, Roche, Sanofi Aventis and Takeda. F. Griesinger has received research funding (paid to institution) from AstraZeneca, Boehringer Ingelheim, BMS, Celgene, Lilly, MSD, Novartis, Pfizer, Roche, Takeda and Siemens, honoraria for educational lectures from AstraZeneca, Boehringer Ingelheim, BMS, Celgene, Lilly, MSD, Novartis, Pfizer, Roche, Takeda, Ariad, Abbvie, Sanofi Genzyme, Siemens, Tesaro/GSK and Amgen, honoraria for advisory boards from Abbvie, AstraZeneca, Boehringer Ingelheim, BMS, Celgene, Lilly, MSD, Novartis, Pfizer, Roche, Sanofi Genzyme, Takeda and Aria, travel support from Roche, MSD, Merck, Takeda, Boehringer Ingelheim, Abbvie, Sanofi Genzyme, BMS and AstraZeneca, and has leadership roles at Ethikkommission, Forschungskommission, Fakultätsrat University of Internal Medicine of Oldenburg. H-D. Hummel has received travel, accommodation, or other expenses from Johnson & Johnson, Boehringer Ingelheim, Bristol-Myers Squibb and Amgen. C. Elender declares that there is no conflict of interest. H. Schäfer has received honoraria for advisory boards from Boehringer Ingelheim, BMS, Pfizer and Roche. M. de Wit reports grants from AstraZeneca, Abbvie and Novartis (paid to institution), has received honoraria for lectures and writing from AstraZeneca, support for meetings and travel from AstraZeneca and Abbvie, and has a leadership position as member of the steering committee in the German Society for Hematology and Oncology (“Deutsche Gesellschaft für Hämatologie und Onkologie”; DGHO). U. Kaiser declares that there is no conflict of interest. J. Kern has received honoraria for scientific meetings from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Lilly, MSD, Novartis, Pfizer, Roche and Takeda, advisory board honoraria from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Lilly, MSD, Novartis, Pfizer, Roche and Takeda, travel support from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Lilly, MSD, Novartis, Pfizer and Roche. M. Jänicke declares that there is no conflict of interest. L. Spring declares that there is no conflict of interest. S. Zacharias declares that there is no conflict of interest. A. Kaiser-Osterhues declares that there is no conflict of interest. A. Groth has received research funding (paid to the employer AIO-Studien-gGmbH) from Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Janssen-Cilag, Lilly, MSD Sharp & Dohme, Novartis, Pfizer, Roche and Takeda. A. Hipper has received research funding (paid to the employer AIO-Studien-gGmbH) from Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Janssen-Cilag, Lilly, MSD Sharp & Dohme, Novartis, Pfizer, Roche and Takeda. G. Zaun declares that there is no conflict of interest. S. Dörfel declares that there is no conflict of interest. B. Güldenzoph has received advisory board honoraria from MSD Oncology, Roche Pharma AG, Amgen and AstraZeneca, and support for travel from Amgen. L. Müller declares that there is no conflict of interest. J. Uhlig has received honoraria for advisory boards and workshops from: Roche, Amgen, Servier, MSD, Bristol-Myers Squibb, Sanofi, Merck, Celgene, Novartis, Janssen-Cilag, Boehringer Ingelheim, Bayer and Biogene. M. Thomas has received honoraria for scientific meetings from AbbVie, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Chugai, Lilly, MSD, Novartis, Pfizer, Roche and Takeda, advisory board honoraria from AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Chugai Pharma, Janssen Oncology, Lilly, MSD, Novartis, Pfizer, Roche and Takeda, travel support from AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Chugai, Janssen Oncology, Lilly, MSD, Novartis, Pfizer, Roche and Takeda, research funding (paid to institution) from AstraZeneca, Bristol-Myers Squibb, Roche and Takeda. M. Sebastian has received research funding (paid to institution) from AstraZeneca, honoraria for advisory boards from AstraZeneca, BMS, MSD/Merck, Roche, Pfizer, Novartis, Boehringer Ingelheim, Takeda, Abbvie, Johnson & Johnson, Amgen, Tesaro and Eli Lilly, honoraria for educational lectures from AstraZeneca, BMS, Novartis, Pfizer, Boehringer Ingelheim, Roche, Lilly, Pfizer, Takeda, Sanofi, GSK, Amgen, MSD, Janssen-Cilag and Eli Lilly, travel support from BMS and Pfizer, patents from CureVax, BioTech, AstraZeneca, Boehringer Ingelheim, Novartis, BMS, Roche, Lilly, Pfizer, Takeda, Sanofi, GSK, Amgen, MSD and Janssen-Cilag. W.E.E. Eberhardt has received honoraria from AstraZeneca, Roche Pharma AG, Bristol Myers Squibb, MSD Oncology, Boehringer Ingelheim, Lilly, Takeda, Pfizer, Amgen, Novartis, Roche, Sanofi Aventis and Abbvie, consulting or advisory role for AstraZeneca, Roche, Bristol Myers Squibb, MSD Oncology, Bayer Health, Lilly, Boehringer Ingelheim, Takeda, Pfizer, MSD/Merck, Novartis, Takeda, Sanofi Aventis, Abbvie, Amgen, Bayer and Janssen-Cilag, research funding from AstraZeneca, Lilly and Bristol Myers Squibb, and is a member of the IASLC Staging Committee, M-track., (Copyright ©The authors 2023.)

Background: 2-4% of newly diagnosed cases of malignant disease involve cancer of unknown primary (CUP). This mixed entity is one of the 6 most common types of malignant disease in Germany. Highly refined treatment strategies can now be offered to patients with CUP., Methods: This review is based on pertinent publications retrieved by a selective search in PubMed with an emphasis on articles from the past decade. The current guidelines and recommendations of specialty societies were also considered in the evaluation., Results: CUP most commonly manifests itself as metastases to the lymph nodes, lungs, liver, or bones. With the aid of imaging studies, including functional hybrid imaging and further medical examination, a primary tumor can be discovered in up to 40% of patients initially diagnosed with CUP. Immunohistochemistry guided by histomorphology often enables precise characterization of the lesion and can be supplemented, in selected cases, by molecular-genetic diagnostic evaluation. The most commonly detected types of primary tumor are cancers of the lung, pancreas, liver, and biliary system. For patients with local metastases, surgical resection or radiotherapy with curative intent is usually indicated, sometimes in the framework of a multimodal treatment concept. The median 2-year survival of patients with disseminated CUP is only 20%. For such patients, specific types of systemic therapy are recommended on the basis of the diagnostic characterization of the disease. Immune-modulatory antibodies can be effective, particularly in the treatment of CUP that has been characterized with biomarkers, but should still be considered experimental at present., Conclusion: A combination of conventional and innovative diagnostic methods enables the provision of highly refined therapeutic strategies to patients with CUP who are undergoing treatment in interdisciplinary cancer centers.