EAU 2019: Neoadjuvant Therapy in Localized Renal Cell Carcinoma - Who is Going to Benefit?

Barcelona, Spain (UroToday.com) In this session, Dr. Mir reviewed the role of neoadjuvant therapy in renal cell carcinoma. She reviewed the definition of neoadjuvant therapy, its rationale, how to assess response, the newest data and its future. Neoadjuvant therapy is defined as intervention given prior to primary treatment with the goal of downstaging primary tumors to possibly improve surgical intervention.  In the localized setting, the current role of neoadjuvant therapy has been theorized to facilitate partial nephrectomy, and in the locally advanced setting, to facilitate complete resection. Responses are typically measured via maximum tumor diameter reduction, however, RECIST criteria and RENAL nephrometry or PADUA scoring systems in the past have been utilized as well. Currently, we are not able to utilize biomarkers to predict response, however, multiple studies are actively going.

Two prospective phase II trials support neoadjuvant therapy for locoregional disease and 3 retrospective studies in the tumor thrombi space. Dr. Mir reviewed the Field et al Clinical Genitourinary Cancer 2019 retrospective analysis, a multi-institutional 53 patient analysis. This showed that patients treated with neoadjuvant sunitinib had a median primary tumor size decrease of 1.3 cm and a median IVC thrombus decrease of 1.3cm as well. Most notably, there was a significant improvement in cancer specific survival (OR 3.28).

In the partial nephrectomy space, the potential advantages of neoadjuvant therapy include decrease size or stage to decrease surgical morbidity, facilitate postoperative recovery and surgical resectability, reduce micrometastasis, and lastly, improve sensitivity to treatment. Potential disadvantages include a delay on curative treatment, potential tumor progression or treatment toxicity. The two studies Dr. Mir reviewed (Karam 2014 and Rini 2015) demonstrated a 26-28% median tumor diameter decrease and a partial nephrectomy success rate of 50-75%. Of note, there was a wide variety of absolute tumor diameter change of 3.1-1.5cm. This insinuates the idea of neoadjuvant therapy and its “real world” applicability. A 2015 Cleveland Clinic analysis with presurgical sunitinib of 72 patients demonstrating an 83% downsizing rate and a partial nephrectomy success rate of 63%.

In summary, Dr. Mir stated that phase II studies have demonstrated feasibility in primary tumor shrinkage to facilitate partial nephrectomy and complete resection in locally advanced disease. However, randomized controlled phase III trials are not yet available. Currently, neoadjuvant therapies remain controversial in this space and are not yet a part of accepted guidelines off of a clinical trial. As we move forward with targeted therapies, studying individual or combination PD-1/PD-L1 inhibition with VEGFs in clinical trials, will hopefully allow clinicians to better understand the answers to these questions.

Presented by: Carmen Mir Maresma, MD, Department of Oncology, Instituto Valenciano de Oncología, Valencia, Spain

Written by: David B. Cahn, DO, MBS, @dbcahn Fox Chase Cancer Center at the 34th European Association of Urology (EAU 2019) #EAU19, conference in Barcelona, Spain from March 15-19, 2019.