title: Time trends in survival from cancer of unknown primary: small steps forward.
abstract: BACKGROUND
  Cancer of unknown primary (CUP) is a fatal cancer for which incidence trends have changed but detailed survival trends remain unexplored. These could point out successful diagnostic and therapeutic approaches. We investigate survival trends in CUP according to histology, locations of metastases and site-specific causes of death.
  
  
  METHODS
  A total of 20,523 CUP patients with nodal and extranodal metastases were identified from the Swedish Cancer Registry. Hazard ratios (HRs) were estimated, comparing three different time periods (1987-1993, 1994-2000 and 2001-2008) with respect to histological subtype, CUP location and the cause of death.
  
  
  RESULTS
  Survival for patients with CUP increased over the study period (HR=0.91 [95% confidence interval (CI): 0.78-0.84], p<0.001 for trend). Adenocarcinoma was the only histology associated with increased survival (0.78 [0.74-0.82], p<0.001 for trend). Survival was improved most clearly for CUP of the pelvis (0.55 [0.36-0.83]), peritoneum (0.58 [0.53-0.65]) and nervous system (0.46 [0.29-0.72]). Survival improved substantially in patients with ovarian (0.57 [0.46-0.70]), peritoneal (0.39 [0.24-0.65]) and biliary system cancers (0.67 [0.52-0.87]). Kaplan-Meier curves showed significant survival gains for all CUP and adenocarcinoma patients (p<0.001).
  
  
  CONCLUSIONS
  Over time, survival for patients with CUP increased for adenocarcinoma and for CUP of the pelvis, peritoneum and nervous system. Survival trends in CUP may be related to (1) similar trends in other common metastatic tumours, particularly pancreatic and hepatobiliary cancers, which are common 'hidden' primaries for CUP, (2) earlier detection and (3) advances in the management of metastatic cancers. The improvement in survival at specific locations suggests true therapeutic gains.
authors.affiliation: Division of Molecular Genetic Epidemiology, German Cancer Research Centre (DKFZ), 69120 Heidelberg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Riihimäki
authors.forename: A
authors.initials: A
authors.lastname: Hemminki
authors.forename: K
authors.initials: K
authors.lastname: Sundquist
authors.forename: K
authors.initials: K
authors.lastname: Hemminki
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality* / Q000556:secondary; D000368:Aged; D002423:Cause of Death; D006801:Humans; D053208:Kaplan-Meier Estimate; D009382:Neoplasms, Unknown Primary / Q000175:diagnosis / Q000401:mortality*; D016016:Proportional Hazards Models; D012042:Registries / Q000706:statistics & numerical data*; D015996:Survival Rate / Q000639:trends; D013548:Sweden / Q000453:epidemiology; D013997:Time Factors