1. Improved diagnosis, therapy and outcomes for patients with CUP
F. Anthony Greco 2016

2. Introduction Primary may only be found at autopsy
Series of 884 autopsies on CUP patient; 75% had small (clinically occult) primaries
1980s: favourable subsets identified (15% of CUP pts).
Treated like corresponding primary.
1990s: empirical chemo explored.
Limited clinical benefit; median OS 9 months
2000s: Improved IHC & molecular cancer-classifier assays

3. Molecular Cancer-Classifier Assays
Benefit is established
Only 30% of CUP pts receive an accurate single-cancer type diagnosis on IHC
MCCA complement IHC + clinical features = establish tissue-of-origin diagnosis in 90% of pts.

4. Molecular Cancer-Classifier Assays
Moran et al- multicentre retrospective study, 216 CUP pts, EPICUP test:
-Single tissue-of-origin predicted for 187/216 (87%)
-33/38 (87%) pts who had latent primary identified matched that of MCCA.
-31 pts received chemo considered SOC based on MCCA prediction; median OS 13.6 months
-61 pts who received empirically selected chemo, not considered SOC based on MCCA; median OS 6 months (p=0.0051)

5. Molecular Cancer-Classifier Assays
Hainsworth et al- multicentre, prospective study, CancerTYPE ID:
Single tissue of origin (one of 26 types) predicted for 98% of pts
Site-specific therapies selected according MCCA; median OS 13.4 months
Historical control group receiving empirical chemo; median OS 9.1 months
‘Responsive’ cancer types on MCCA; median OS 13.4 months
‘Less responsive’ cancer types on MACC; median OS 7.4 months (p=0.04).

6. Molecular Cancer-Classifier Assays
Other small number, mostly retrospective studies, showing OS benefit if MCCA guides site-specific treatment.
Paper suggests CUP biopsy samples should be tested with IHC panel and MCCA, if necessary.
Patients who have a likely single site identified, should then be treated as for that site.
Empirical chemo should be for CUP NOS only.

7. Thoughts
NICE ‘Do not use gene-expression-based profiling to identify primary tumours in patients with provisional CUP.’
If site suggested by MCCA, do we organise onward molecular testing to guide treatment even further? Funding for this?
Access to drugs/funding? Immunotherapy?
Who treats patients- CUP specialist or site oncologist?