# Neuroblastoma by Stage at Diagnosis and Other Prognostic Factors: The Results of the BENCHISTA Italian Project—A Population-Based Study

## TL;DR

This study finds that neuroblastoma survival in Italy is high and consistent across regions, thanks to centralized treatment and standardized care.

## Contribution

The study demonstrates nationwide equity in neuroblastoma care and survival outcomes in Italy using population-based data.

## Key findings

- Three-year survival exceeds 95% for localized and MS stages but drops to 78% for metastatic stage IV.
- No regional disparities in stage distribution or survival were observed, indicating equitable care.
- Centralized treatment in high-volume centers in central and northern Italy was common.

## Abstract

This population-based study aims to interpret possible survival differences for neuroblastoma in Italy. We investigate the impact of stage at diagnosis using the Toronto guidelines to standardise the classification of stage. This study, covering the 80% of the childhood population, reports high survival rates for children with neuroblastoma in Italy, with survival exceeding 95% in localized and MS stages and decreasing to about 78% in metastatic stage IV disease. No significant differences were observed across Italian regions in terms of stage at diagnosis or survival outcomes, indicating a high level of equity in care nationwide. Surgical and radiotherapy treatments were mainly centralized in high-volume centers located in the Centre and North of Italy. Patient migration from Southern regions was limited and appeared appropriate, reflecting referral to specialized centers. Overall, the findings highlight the effectiveness of the national clinical network in providing high-quality, standardized care for neuroblastoma across the country. Compared with earlier studies, regional variability completely reduced. The study also emphasizes the continued importance of maintaining a population-based childhood cancer registry, possibly increasing the population coverage versus a national childhood cancer registry, to ensure comprehensive monitoring of outcomes and to support ongoing improvements in paediatric oncology care.

Background: Neuroblastoma is the most common embryonal cancer. Since several population-based studies in Europe have revealed differences in 5-year survival across countries and regions. Objectives: We principally investigated the impact of stage at diagnosis on survival in Italy. Methods: Data were obtained from 26 population-based cancer registries (PBCRs), covering 319 cases (ages 0–14) diagnosed between 2013 and 2017, representing about 80% of the national population. Stage was classified according to the Toronto guidelines. Information on treatment and treating hospitals was also collected. Stage at diagnosis was further refined using probabilistic linkage with the Italian Neuroblastoma Registry (RINB). Results: Overall survival (OS), defined as all-cause mortality, was estimated using the Kaplan–Meier method. Most patients presented with stage M disease (37%), while a small proportion remained unclassified (2%). Three-year survival analysis showed significant differences between stages, ranging from >95% in localised (stage I) and MS stages to 78% in stage M (stage IV). No significant disparity across the Italian regions was observed in stage distribution or survival. Surgery and radiotherapy treatments of neuroblastoma were mostly centralized in the Centre and North of Italy. However, the cross-regional health migration from the South was limited to, and interpreted as appropriate for, high-volume centres. Conclusions: This population-based study highlights the high quality of care provided to children with neuroblastoma by an effective national clinical network. Compared with previous studies, we observed very limited variation across regions. A national childhood cancer registry remains essential to obtain a comprehensive picture of the country.