Outcomes for a Multi-institutional Cohort of Patients Treated With Intraoperative Radiation Therapy for Advanced or Recurrent Renal Cell Carcinoma

Abstract

For patients with advanced or recurrent renal cell carcinoma (RCC), the role of intra-operative radiation therapy (IORT) remains controversial. We analyzed outcomes in a multi-institutional cohort of patients with RCC who were treated with IORT. Between 1985 and 2010, 98 patients were treated with IORT for advanced or locally recurrent RCC at 9 institutions. We collected demographic, clinical, pathologic, treatment, and outcomes data for all patients. Overall (OS), disease specific (DSS), and disease-free survival (DFS) were estimated using the Kaplan-Meier method. Chained multiple imputation was performed to account for missing data and a multivariate Cox hazards regression was used for testing significance. IORT was delivered during nephrectomy for advanced disease (28% of patients) or during resection of locally recurrent RCC in the renal fossa (72%). Sixty-nine percent of patients were male and the mean age at RCC diagnosis was 57. At initial nephrectomy, primary T-stage was 17% T1, 12% T2, 55% T3, and 16% T4. Prior to IORT, 87% had a visibly complete surgical resection of tumor. Mean IORT dose delivered was 14.7 Gy (range, 9-20 Gy). Average length of post-op hospitalization was 10.7 days. Pre-operative or post-operative external beam radiation therapy (EBRT) was administered to 27% and 35% of patients, respectively (2% received both pre and post-operative EBRT). Median follow-up after IORT was 1.6 years. OS at 1 and 5 years after IORT was 69% and 37% for advanced patients and 94% and 55% for locally recurrent patients, respectively. DFS at 1 and 5 years was 72% and 39% for advanced patients and 96% and 52% for locally recurrent patients, respectively. DSS at 1 and 5 years was 72% and 41% for advanced patients and 96% and 60% for locally recurrent patients, respectively. For the entire cohort, higher IORT dose (HR 1.3, p < 0.001), positive initial nodal status (HR 2.9-3.6, p < 0.01), and presence of sarcomatoid features (HR 3.7-6.9, p < 0.05) had a statistically significant association with decreased OS, DFS and DSS. Patients who received adjuvant systemic therapy after IORT showed decreased DSS (HR 2.4, p = 0.03). When analyzing locally recurrent tumors alone, positive margin status (HR 2.6, p = 0.01) was associated with decreased OS. We report on the largest known cohort of patients with RCC managed with IORT and we have identified several factors associated with survival. Outcomes in our cohort of patients with locally recurrent RCC treated with local resection and IORT compare favorably to similar groups treated with local resection alone suggesting improved DSS may be possible with IORT.