Introduction

Laparoscopic Radical Nephrectomy (RN) is the current standard of care for large organ confined renal tumors while Partial Nephrectomy (PN) is recommanded for tumor sizes up to 7 cm. PN preserves long term renal function with possible effect on overall survival. Axitinib, a potent VEGFR TKI can reduce the size of primary tumor in metastatic setting. Our primary objective was to test the ability of axitinib to reduce the size of large tumors for shifting from a RN to a PN indication.

Methods

Patients with localized (cT2N0M0) RCCs were enrolled in a prospective phase II trial assessing the effect of neoadjuvant axitinib prior to surgery (PN or RN). Main inclusion criteria were: age ≥ 18, histologically proven clear cell RCC, MDRD creatinin clearance ≥ 60 ml/min, cT2a N0NxM0 tumors (&[null]> 7cm; ≤ 10 cm). Medical treatment consisted in axitinib 5 mg up to 10 mg tw/d during 2 to 6 months prior surgery according to radiological response.

Results

A total of 18 patients including 11 men (61%) and 7 women (39%) with a median age of 60 yrs were enrolled. Median baseline tumor size, RENAL score, serum creatinine and MDRD estimated GFR were: 7.6 cm, 11, 0.8 mg/dl and 96.5 ml/min respectively. Duration of treatment was 2, 4 and 6 months in 12 (66%), 3 (17%) and 3 cases (17%), respectively. Median interval from treatment stop to surgery was 6 days. After neoadjuvant treatment median tumor size and RENAL score decreased to 6.2 cm and 10. 89% of patients presented a decrease in maximum tumor diameter, with median size reduction of 19%. Out of the 17 patients who were operated, 16 (94%) underwent a PN (9 robotic & 7 open), including 67% of the cases which were performed for tumors ≤ 7cm. At 1 month from surgery, median serum creatinin and MDRD estimated GFR were 0.9 mg/dl and 87 ml/min, respectively. Medical and surgical complications included 1 embolization for severe bleeding and 1 Clavien V complication at 1 month after surgery due to massive myocardial infarction.

Conclusions

Neoadjuvant axitinib in cT2 renal tumors allowed cT1 downstaging and nephron sparing surgery in almost 70% of the cases. However, PN procedures remained high complexity cases requiring adequate surgeon expertise and information of the patients for possible morbidity of these procedures.

Funding

none