Stomach cancer, here is the proposal for complete molecular profiling

Gastric carcinoma is an aggressive neoplasm with a particularly poor prognosis both due to its frequent presentation in an advanced stage and the high rate of recurrence, even after radical surgery: 14,000 new cases per year (2024) with 9,900 deaths (2022) and a 5-year survival rate of 32%, as reported by Aiom-Airtum in “The numbers of cancer in Italy, 2024”.

Chemotherapy has been the only treatment for this tumor for years: the addition of targeted drugs and immunotherapy, more recently introduced, has expanded the availability of effective therapies. Therefore, it is currently possible to modulate the treatment of advanced gastric tumors according to the expression of 5 biomarkers: HER2, PD-L1, MMR (or MSI molecular analysis), claudin 18.2; furthermore, targeting FGFR2b could enter the diagnostic/therapeutic armamentarium at the conclusion of the ongoing phase III studies.

Molecular profiling of gastric cancer is currently and in the coming years based on the 5 biomarkers listed above, which can be analyzed with 8 immunohistochemical methods: 1 IHC for HER2; 1 IHC for PD-L1; 4 IHC for MMR; 1 IHC for claudin 18.2 and 1 IHC for FGFR2b, if the ongoing phase III studies are positive. Immunohistochemistry is a method present in all pathology laboratories, relatively simple and rapid, with limited costs. Obviously, as with all methods, there are limitations that can affect the result of the analysis, mainly related to the pre-analytical phase of sample preparation and the diagnostic sensitivity determined by the adequacy and representativeness of the sampling of the lesion.

The aim of the analysis by the Multidisciplinary Innovation Group (Gmi) - composed of oncologists, pathologists and health economists, coordinated by Economia Sanitaria - was to verify the congruence of the costs of immunohistochemical profiling/characterization tests for gastric cancer with the rates of the Lea nomenclature (in force since 30.12.2024). In particular, the analysis was carried out with a view to a comprehensive approach that considers all the biomarkers indicated above. The economic evaluation estimated a total cost of 447.00 euros to perform the 8 IHCs mentioned above, with a SSN reimbursement of 252.60 euros: thus underlining the need to update the specific Lea rate for predictive immunohistochemistry, currently underestimated, compared to the real absorption of resources.

In April 2025, a Prime Ministerial Decree was proposed to update the Lea (under evaluation by the Conference of Regions), in which it would be relevant to include a "package" for the immunohistochemical characterization of advanced gastric cancer, which includes the 5 biomarkers reported, essential for choosing the most appropriate and effective therapy. The fee could be assimilated to that of 450 euros, indicated in the Prime Ministerial Decree for the profiling of a single alteration (biomarker) with any genomic analysis method.