1. Statistics about unknown primary tumors Riccardo Capocaccia National Centre for Epidemiology, Surveillance and Health Promotion Istituto Superiore di Sanità, Rome

2. Content Source of population-based data Definition of Unknown Primary Tumours Morphological groups Analysis of incidence and survival by morphological group, age, sex, time, population Estimates of cure Conclusions

3. Population-based Cancer Registries Collect data from all cancer patients diagnosed in a defined population Sources: pathology reports, death certificates, hospital admission/discharge, population archives, clinical records, drugs, etc. Exhaustive and representative data Relevant clinical information often missing Follow-up only for vital status Information generally collected at the beginning of the diagnostic workup

4. Aims of population-based Cancer Registries Providing cancer incidence data Etiological studies Providing survival data Providing prevalence data Providing information for Health Care management: impact of prevention, diagnostic delay, adherence to guidelines, costs, etc.

5. Survival studies Clinical RCT: evaluation of the effectiveness of treatment Patients selected by hospital, age, stage, co- morbidity Indicate the highest achievable survival in selected patient groups Ad hoc data collection design Population-based Evaluation of the effectiveness of the heath care systems Include all cancer patients belonging to a demographically defined population (country, region, local area,...) Estimate the average survival actually achieved in the general population Data currently collected by disease (cancer) registries

6. EUROCARE-4 23 countries 93 cancer registries 13.5 millions patients Diagnosed 1978-2002 Follow-up to Dec 31, 2003 ICD-O 3 classification (topo/morpho) malignant tumours only NORTH ICELAND FINLAND FINLAND SWEDEN SWEDEN NORWAY NORWAY DENMARK DENMARK UK & IRELAND ENGLAND ENGLAND WALES WALES SCOTLAND SCOTLAND IRELAND IRELAND N. IRELAND N. IRELAND EAST Poland CENTRE Netherlands Czech Republic CENTRE Netherlands Germany Germany Belgium Belgium AUSTRIA AUSTRIA Switzerland Switzerland France France SOUTH Italy Spain Spain Portugal Portugal MALTA MALTA SLOVAKIA SLOVAKIA

7. EUROCARE-4 GEOGRAPHIC COVERAGE South and West Europe United Kingdom Eastern Europe Nordic countries

8. Data available Demographic: age, sex, place of living Vital status Dates: birth, diagnosis, death Diagnosis: site (IVDO-3), morphology (ICDO-3), microscopic verification sparsely: stage at diagnosis no grading no treatment

9. Unknown Primary Cancers (UPC or CUP) We start analysing all incident cases with topography code C80.9, irrespective of histology. This definition selects a number of 343,425 UPC incident cases from a total of 9,256,282 cancer diagnoses during the period 1978-2002, with an overall proportion of 3.7 %.

10. Morphology distribution of UPC: percent of all cancers

11. Unknown Primary Cancers We finally define UPC as incident cases of solid tumours and topography code C80.9. This definition selects a number of 316,625 UPC incident cases from a total of 9,256,282 cancer diagnoses during the period 1978-2002, with an overall proportion of 3.4 %, that becomes 3.2 % in 1995-2002

12. Comparisons with other studies Randèn et al (Sweden) Acta Oncol 2009: about 2.7% Levi et al (Switzerland) Eur J Cancer 2002: 2% Muir (USA) Cancer, 1995: 2%

13. Cases analyzed

14. Unknown Primary Cancers Incidence rates about 11x100,000, higher for men and slightly decreasing Survival poor: 10% at 1 year, 7% at 5 years Survival not differing by gender Survival highly variable with age and between populations Probable lack of standardization in registration and coding procedures

15. Cancer NOS Account for 1/3 of all UPC Incidence rates about 3x100,000, higher for men and decreasing Survival poor, not differing by gender, but much better for age < 30

16. Carcinoma NOS Accounts for another 1/3 of all UPC Incidence rates about 3x100,000, higher for men and slightly decreasing Survival poor: 9% at 1 year, 4% at 5 years Survival not differing by gender Survival still variable with age, but less that for Cancer NOS

17. Adenocarcinoma Incidence increasing, abour 3x100,000 in 2001 Incidence higher for men Survival not exceeding 10% at 5 years for all age classes Survival not differing by gender

18. Squamous Cell Carcinoma Incidence stable, about 0.3x100,000 M/F ratio = 2 Survival 45% at 1 year, 30% at 5 years Survival better for men Survival decreasing with age

19. Neuroendocrine Cancers Incidence rates sharply increasing up to 0.4 x 100,000 in 2001 Survival at 40% at 1 year, 15% at 5 years, and continues decreasing Survival higher for women and for ages <50

20. Other Specific Morphologies Incidence rates increasing Survival very poor for mesothelioma, intermediate (50% at 1 year) for sarcoma and melanoma Survival not differing by gender Survival better for age <30 for sarcoma, not very dependent on age for melanoma and mesothelioma

21. Conclusions UPC represent in Europe about 3.4% of all cancer diagnoses They report for 2/3 unspecific and for 1/3 specific morphologies Incidence is decreasing for unspecific and increasing or stable for specific ones Survival is generally poor, intermediate for SCC, sarcoma and melanoma In almost all groups, it is better for women and for young age classes No evidence for increasing survival apart from SCC There is suggestion that a limited proportion of cases can be cured Cancer registries may tend to overreport UPC cases when the site of origins is detected late Need for a higher degree of standardization in rporting and coding practices