Discussion

This retrospective study describes the real-world survival determinants of patients with hemispheric GB treated at a specialized center in Uruguay. The cohort’s median OS of 17 months aligns with the classical international benchmark established by Stupp et al. (14.6 months) [1] and with historical regional data (18 months) reported by a local cohort [3]. This survival estimate represents a substantial improvement over the historical baseline at our institution during the pre-TMZ era (1980-2000), when median OS was approximately 11 months [3], and highlights the impact of equitable public health policy, specifically universal public coverage of oral TMZ under the FNR since 2009 [2].

Nonetheless, translating these controlled-trial protocols into real-world practice reveals a persistent biological ceiling. Although complete adherence to the frontline Stupp regimen significantly extended median survival to 24 months, long-term outcomes remained limited, with only 3.1% of patients reaching five-year survival.

Study limitations and molecular profiling constraints

A primary limitation of this retrospective analysis is the absence of advanced molecular characterization, including MGMT promoter methylation status and IDH1/2 mutation status [4]. During the study period (2009-2017), these biomarkers were not systematically integrated into local public health diagnostic pathways because of structural resource limitations; MGMT status was known for only one patient in our sample. The absence of these markers precludes advanced prognostic stratification and limits our ability to evaluate inherent resistance to alkylating agents. In addition, the small sample size (N = 32) limits the statistical power of the multivariate model, and the hazard ratios should be interpreted with caution. Future regional studies should systematically incorporate molecular profiling in accordance with current World Health Organization classifications [4].

Health policy implications for the immunotherapy era

The international GB treatment landscape is shifting from conventional cytotoxic regimens toward advanced, personalized biological therapies, such as dual immune checkpoint inhibition (e.g., nivolumab plus relatlimab) [5] and chimeric antigen receptor (CAR) T-cell platforms [6,7]. While these approaches offer unprecedented therapeutic potential, they also introduce a substantial socioeconomic challenge for public health systems in middle-income countries.

The FNR has successfully guaranteed universal funding for generic TMZ, underpinning the 17-month survival baseline observed in this study [2]. As an oral, bioavailable medication, TMZ is a highly sustainable intervention. In contrast, advanced immunotherapies and autologous cellular platforms carry a substantial financial burden, often exceeding US$300,000-500,000 per patient globally.

Our findings show that the Uruguayan public health system can successfully deliver complex, standardized oncological protocols when universal funding is guaranteed. However, extending similar universal coverage to experimental biological therapies could threaten systemic financial stability; when advanced biotechnologies remain excluded from public formularies because of unfavorable cost-effectiveness ratios, health equity may be compromised. We therefore believe that a shift from fragmented, individual administrative decision-making toward regional, evidence-based health policy frameworks - supported by collaborative international pricing mechanisms and structured risk-sharing agreements - is warranted. Middle-income countries should use historical baselines, such as the one presented here, to inform participation in global clinical trial networks and to negotiate equitable access so that economic constraints do not determine patient survival in the immunotherapy era.