ASCO GU 2018: Timing and Patient Selection for Cytoreductive Nephrectomy

San Francisco, CA ( Dr. Bex reviewed the data surrounding cytoreductive nephrectomy during his presentation and he began by asking the audience while factors are important in selecting patients for cytoreductive surgery?  We consider performance status, local or paraneoplastic symptoms, information on prognostic risk scores, ratio between volume of primary tumor and metastasis, location of metastatic sites, information on histology and subtype. 

Prognostic models have been externally validated, but not developed to decide whether or not the patient should undergo cytoreductive nephrectomy.  Median overall survival is a categorical value per risk group, not an individual predictive value after cytoreduction.  Additionally, preoperative variables have been utilized to identify patients who are unlikely to benefit (albumin, LDH, liver metastases, symptoms, higher stage, etc).  Treatment options include immediate cytoreduction and then observation, immediate cytoreduction and first line therapy, or pre-surgical therapy with VEGF/TKI followed by cytoreduction. 

A 2016 Lancet Oncology study demonstrated that 48 patients with a majority of clear cell histology underwent active surveillance for metastatic RCC on a phase 2 trial had a 14.9-month median time to targeted therapy and 9.4 months median progression free survival. 

EORTC 30073 SURTIME was a trial randomizing patients to immediate or deferred surgery with a clear cell RCC resectable primary and good performance status without prior systemic therapy.  The progression free survival rate at week 28 was reported as the primary endpoint due to poor accrual.  Secondary endpoints included overall survival, adverse events, and post-operative progression.  No statistically significant differences were seen between the treatment arms in progression free response (immediate 42.0% versus deferred 42.9%).  Overall survival of the intention to treat cohort demonstrated a survival advanced for deferred therapy (HR 0.57 95% CI 0.34-0.95; p =0.032) with a median OS of 32.4 months vs 15.1 months.  In terms of adverse surgical complications, fewer were seen in the deferred arm (27.5%) compared to 43.5% of patients treated with immediate cytoreduction.  Dr. Bex stated that the presurgical strategy exposes more patients to systemic therapy, which is safe and identifies resistance patterns prior to cytoreduction.

In summary, the landscape of cytoreductive nephrectomy has changed with the advent of newer systemic agents that have better efficacy and tolerability profiles.  Individualized patient decision making in a multidisciplinary setting is best for these complex situations.  We look forward to the release of future data to guide recommendations in this space.

Presented by: Axel Bex, MD, PhD The Netherlands Cancer Institute

Written by: David B. Cahn, DO, MBS @dbcahn, Fox Chase Cancer Center, Philadelphia, PA at the 2018 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, February 8-10, 2018 - San Francisco, CA