Impact of neoadjuvant immune checkpoint inhibitor therapy on primary tumor size and complexity: Correlation with surgical quality and short term oncological outcomes.

Abstract

390 Background:The concept of primary systemic therapy has gained increasing traction in the management of metastatic and locally advanced Renal Cell Carcinoma (RCC). Most series have evaluated the use of tyrosine-kinase inhibitors, however, with the emergence of immune checkpoint inhibitor therapy as first line agents in advanced RCC, further assessment of efficacy is warranted. We examined the effects of immunotherapy (IO) combinations on the primary tumor and consequent surgical quality and short-term oncological outcomes. Methods: We conducted a multi-center, retrospective analysis of patients with advanced/metastatic RCC having received IO followed by Radical (RN) or partial nephrectomy (PN). Primary outcome was achievement of Bifecta (composite outcome of complete resection and no 30-day post-operative complications). Predictors for achievement of Bifecta were assessed with logistic regression multivariable analysis. Secondary outcomes were change in maximal tumor dimension, RENAL nephrometry score and disease progression. Kaplan-Meier analysis was used to assess progression-free survival (PFS) for Bifecta and non-Bifecta patients. Results: We identified 52 patients with advanced RCC across 9 institutions who were eligible. The median age was 63 years and 60.4% were males. Median tumor size at diagnosis was 9.3 cm. 19.6% had T4 disease and 75% had AJCC Stage IV disease. IO treatment resulted in significant reductions in median tumor size (-25.4%; 9.7 cm vs. 7.3cm p = 0.0129) and RENAL nephrometry score (9 to 8, p = 0.032). 43 (83%) of patients underwent RN and (9) 17% had PN. Median tumor size was smaller for PN (8 vs. 4.1 cm, p < 0.001), and 30 day complication rates were higher (p = 0.024). Bifecta was achieved in 39 patients [33/42 (78.6%) RN and 6/9 (67%) PN, p = 0.264). Predictors for achievement of Bifecta were younger age (OR 1.06, p = 0.01), increasing reduction in tumor size (OR 1.187, p < 0.001), and shorter time between therapy and surgery (OR 1.07, p < 0.001). Kaplan-Meier analysis demonstrated longer median time to progression in the Bifecta-positive group compared to patients who failed to achieve Bifecta (75 vs. 30 months, p = 0.04). Conclusions: Pre-surgical therapy resulted in tumor size and complexity reduction. Tumor size reduction was predictive for achievement of Bifecta, which was associated with improved short term oncological outcomes. To our knowledge, this is the first series evaluating the effect of neoadjuvant systemic therapy on the primary tumor prior to surgical intervention.