Introduction:

Neoadjuvant chemotherapy (NAC) has grown in popularity in the management of upper tract urothelial carcinoma (UTUC). Retrospective data on NAC has shown promise in pathological downstaging rates, a surrogate endpoint of improved cancer-specific survival. However, most NAC series are limited to single centers and no randomized trials have been published. The aim of our study is to provide a multinational matched comparison of pathological complete response (pCR) and nodal downstaging (NDS) rates between patients who receive NAC + RNU vs. RNU alone. 

Methods:

Patients were abstracted from an international cohort of 13 high-volume centers across the United States, Europe, and Asia (Robotic surgery for Upper Tract Urothelial Cancer Study, ROBUUST 2.0) undergoing treatment for UTUC from 2011-2022. We then focused on cM0, histologically confirmed UTUC. Clinical and pathologic data was collected. Endpoints consisted of PCR (defined as ≤pT0N0) and NDS (cN > pN). Subgroup analyses for >cN0 was completed for NDS.  Inverse probability of treatment weighting (IPTW) adjusted Cox regression analyses were used to assess odds of pCR and NDS. To minimize baseline differences among groups, IPTW weighted by age, sex, multifocality, tumor site, presence of hydroureteronephrosis, and clinical tumor stage (cT). Patients with missing data on age, tumor site, pT, pN, etc. were excluded.

Results:

72 (6.5%) and 1,035 (93.5%) patients were treated with NAC + RNU vs. RNU alone, respectively. Follow-up length was 26.0 (22.7) and 31 (25.9) months for the NAC+RNU and RNU alone. The most common NAC regimen consisted of Gemcitabine/Cisplatin (61%), followed by ddMVAC (24%) (Figure 1), with a median (IQR) number of cycles of 4 (3-4). IPTW-adjusted Cox regression analysis demonstrated pCR to be significantly higher in the NAC+RNU group with an OR of 2.49 (95% CI: 1.75 – 3.54, P<0.001). Additionally, those who received NAC were significantly more likely to experience NDS, OR: 9.56 (95% CI: 4.11-22.26, P<0.001). Standardized differences between the two treatment groups were < 0.1 for all variables, indicating strong matching.

Conclusion:

Real world data from high volume centers suggests that neoadjuvant chemotherapy confers patients 2.49 times greater odds of experiencing a pathological complete response, compared to a matched UTUC cohort on multivariable analysis. This is one of the largest multinational experiences of neoadjuvant chemotherapy in UTUC to date. Ultimately, these results should be interpreted within the framework of a retrospective design, and randomized trials evaluating the efficacy of NAC are necessary.

Funding: N/A