The study analyzed 728 mUTUC patients, segregating them into localized (T1-T2) and locally advanced (T3-T4) disease groups. The primary objective was to discern whether NU combined with ST offers a survival advantage compared to ST alone and whether this advantage varies with the tumor stage.
Key Finding
- Localized stage (T1-T2): In this cohort, patients treated with both ST and NU had a median OS of 20 months, compared to 10 months for those receiving ST alone. The multivariable Cox regression analysis, supported by three-month landmark analyses, confirmed that the combination of ST+NU independently predicted lower overall mortality (HR 0.37, p<0.001).
- Locally Advanced stage (T3-T4): For patients with more advanced tumors, the median OS was 12 months with ST+NU versus 10 months with ST alone. The multivariable analyses did not show a significant association between NU and reduced mortality (HR 0.85, p=0.1).
These findings underscore a critical nuance in mUTUC treatment: the stage of the primary tumor significantly impacts the effectiveness of NU. For patients with localized disease (T1-T2), NU combined with ST offers a substantial survival benefit. This could be attributed to the removal of the primary tumor, reducing tumor burden and potentially enhancing the efficacy of systemic treatments.
Conversely, in patients with locally advanced disease (T3-T4), the limited survival benefit suggests that the aggressive nature and extensive spread of the disease may overshadow the potential advantages of surgical intervention. The increased surgical complexity and risk of complications in advanced stages further complicate the decision-making process.
Clinical Implications
The study's findings have profound clinical implications, emphasizing the need for a tailored approach to mUTUC treatment based on tumor stage. For patients with localized disease (T1-T2), incorporating NU into the treatment regimen alongside ST should be strongly considered. This combined approach has the potential to significantly improve survival outcomes, offering a compelling case for aggressive surgical management in this subgroup.
For patients with locally advanced disease (T3-T4), however, the benefits of NU appear limited. In these cases, clinicians must carefully weigh the risks and potential complications of surgery against the modest survival gain. A more conservative approach, focusing on systemic therapy and supportive care, may be more appropriate, and patients should be counseled on the likely outcomes and possible challenges of aggressive surgical intervention.
Conclusion
The study highlights the importance of considering tumor stage in the management of mUTUC. Nephroureterectomy, when combined with systemic therapy, offers a significant survival benefit in patients with localized disease (T1-T2), but not in those with advanced disease (T3-T4). This stage-dependent efficacy underscores the need for personalized treatment strategies in mUTUC, optimizing outcomes based on individual patient profiles and disease characteristics. Future research should aim to further elucidate the underlying mechanisms driving these differential outcomes and explore additional therapeutic options that could enhance survival in patients with advanced mUTUC. Meanwhile, these findings provide a critical foundation for improving clinical decision-making and patient counseling, ultimately aiming to enhance the quality of care and outcomes for mUTUC patients.
Written by: Simone Morra, MD, Urology Resident, University of Naples Federico II, Naples, Italy, Clinical Fellow, Onze Lieve Vrouwziekenhuis Hospital, Aalst, Belgium, Orsi Academy, Ghent, Belgium, Former Research Fellow, Centre Hispitalier de l'Universite' de Montreal (CHUM), Montreal, Canada
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