# Propensity Score-Matched Analysis of Neoadjuvant vs. Adjuvant Therapy in Renal Cell Carcinoma

## TL;DR

This study suggests that treating high-risk kidney cancer before surgery may lead to better survival and lower recurrence compared to treatment after surgery.

## Contribution

The study provides new evidence that neoadjuvant therapy may be more effective than adjuvant therapy in high-risk localized kidney cancer.

## Key findings

- Neoadjuvant therapy was associated with reduced all-cause and cancer-specific mortality.
- Adjuvant immunotherapy was linked to lower all-cause mortality.
- Both targeted therapy and immunotherapy as neoadjuvant treatments showed similar positive outcomes.

## Abstract

Patients with high-risk localized kidney cancer often receive systemic therapies either before or after surgery, but it is unclear which approach leads to better outcomes. In this study, we compared survival and recurrence rates in patients treated with neoadjuvant therapy versus adjuvant therapy. We used a propensity score matching model to fairly compare the two groups. Our results suggest that receiving treatment before surgery may reduce the risk of death and cancer recurrence, especially when using targeted therapy or immunotherapy. These findings highlight the need for future clinical trials to determine the best timing for systemic treatment in patients with aggressive kidney cancer.

Objective: The aim was to compare outcomes in high-risk localized RCC (HRL-RCC) patients treated with adjuvant (AT) and neoadjuvant therapy (NT) utilizing a propensity score-matched model (PSM). Methods: We conducted a multicenter analysis (USA and Japan) for patients who underwent AT or NT. AT was defined as systemic therapy given postoperatively in the absence of metastases; NT was presurgical therapy in the setting of localized disease. AT and NT utilized included target molecular therapy (TMT) or immunotherapy (IO). The PSM model was generated using a nearest neighbor matching algorithm in a 1:2 ratio. The primary outcome was All-Cause Mortality (ACM); the secondary outcomes were Cancer-Specific Mortality (CSM) and recurrence. Cox regression multivariable analysis (MVA) was utilized to elucidate predictors of outcomes. Results: After PSM modeling, 311 patients were analyzed [adjuvant n = 221, 127 TMT vs. 94 IO; neoadjuvant n = 90, 61 TMT vs. 29 IO]; the median follow-up was 44 (IQR 20–74) months. MVA revealed AT as associated with increased ACM (HR = 1.97, p = 0.007), CSM (HR = 2.37, p = 0.007) and recurrence (HR 1.64, p = 0.02). Sub-analysis of the AT cohort revealed IO to be associated with decreased ACM (HR 0.59, p = 0.015). In the neoadjuvant cohort, TMT and IO were associated with decreased ACM (HR 0.49; p = 0.016; HR 0.32, p = 0.016, respectively) and CSM risk (HR 0.47, p = 0.036; HR 0.18, p = 0.017). Conclusions: Our findings suggest a potential advantage of NT in HRL-RCC. Adjuvant immunotherapy was associated with decreased risk of ACM, while in the neoadjuvant group, TMT and IO therapy had similar outcomes. Our findings call for the consideration of a clinical trial to compare the outcomes of AT vs. NT.