Cancer Med. 2018 Jul 17. doi: 10.1002/cam4.1689. [Epub ahead of print]
Cancer of unknown primary-Epidemiological trends and relevance of comprehensive genomic profiling.
Cancer of unknown primary (CUP) is a distinct clinicopathological entity with poor prognosis, frequently resistant to chemotherapy. Comprehensive genomic profiling (CGP) by next-generation sequencing potentially identifies novel treatment options for CUP patients. The objective of this study was to determine incidence and survival trends and to discuss the value of CGP in CUP patients.
Age-standardized incidence rates (ASR) per 100 000 were calculated for 2935 CUP patients from 1981 to 2014 using cancer registry data of the canton of Zurich, Switzerland. Kaplan-Meier survival curves were estimated for sex, age, and histological groups. Cox proportional hazards regression models were used to estimate adjusted hazard ratios (HR). A literature review was conducted to assess the current use of CGP in CUP patients.
ASR of CUP increased from 10.3 to 17.6 between 1981 and 1997 and decreased to 5.8/100 000 in 2014. Mean overall survival remained stable. Mortality was significantly lower for patients with squamous cell carcinoma (HR 0.48 [95% CI, 0.41-0.57]) and neuroendocrine carcinoma (0.75 [0.63-0.88]) and higher for unclassified neoplasms (1.25 [1.13-1.66]) compared to adenocarcinomas. The literature review identified 10 studies using CGP of CUP tissue. Clinically relevant mutations were identified in up to 85% of CUP patients, of which 13%-64% may benefit from currently available drugs.
CUP incidence decreased probably due to improved diagnostics, but mortality did not improve over the last 34 years. CGP testing may help to identify molecular signatures in CUP patients and enable targeted treatment.
© 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
cancer diagnostics; cancer of unknown primary; comprehensive genomic profiling; epidemiology; molecular profiling; next-generation sequencing
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