Partial, Radical Nephrectomy After ICIs for Complex Locally Advanced RCC

Surgery for locally advanced renal cell carcinoma (RCC) may be safe for patients after neoadjuvant durvalumab +/- tremelimumab, according to the results of a phase 1b study presented at the 24^th Annual Meeting of the Society of Urologic Oncology.

Prior research has demonstrated the effectiveness of immune checkpoint inhibitors (ICIs) for metastatic RCC, and new studies are beginning to investigate the utility of ICIs in the neoadjuvant and adjuvant settings. Currently, the changes resulting from immune checkpoint inhibition on the renal and perinephric tissue remain unclear, and the surgical safety and efficacy for partial and radical therapy for patients with complex locally advanced renal tumors is not well understood.

Jason M. Scovell, MD, PhD, and colleagues designed a study to evaluate surgical outcomes after neoadjuvant ICI therapy to better understand the safety of this treatment approach after partial and radical nephrectomy for complex locally advanced RCC. Twenty-five patients were given neoadjuvant durvalumab +/- tremelimumab at either the Cleveland Clinic or the University of Minnesota between 2016 and 2020. Patients had RCC clinical stage T2b-4 and/or N1, M0 disease, Eastern Cooperative Oncology Group performance status 0-1, and adequate organ function.

Researchers evaluated 4 cohorts. In the neoadjuvant setting, cohort 1 received durvalumab (1 dose), and cohorts 2, 2a, and 3 received durvalumab plus tremelimumab (1 dose). In the adjuvant setting, cohorts 1 and 2 received one dose of durvalumab, cohort 2a received durvalumab for 1 year, and cohort 3 received durvalumab plus tremelimumab (1 dose) followed by durvalumab for 1 year.

Among the total patient population, 23 underwent neoadjuvant and adjuvant therapy, whereas the remaining 2 received neoadjuvant therapy alone.

Dr. Scovell and colleagues noted that tumors were surgically complex, and the most common RENAL score was 11xh. Renal vein involvement was present in 6 tumors (Level 1=2 patients; Level 2=1 patient; Level 3=2 patients; Level 4=1 patient). Tumors were managed with minimally invasive (n=8) or open (n=17) approaches. The majority of patients underwent radical nephrectomy (n=23).

The median estimated blood loss was 375cc (interquartile range [IQR], 188–775). Three patients were transfused postoperatively for a total of 4 units, and no intraoperative complications were noted. Margins were positive for 5 patients, all located at the renal vein wall.

Researchers found that the median length of stay was 4 days (IQR, 3-5), and 3 patients required readmission for diabetic ketoacidosis, thrombocytopenia, or pulmonary embolism. Notably, there were 5 30-day and 90-day Clavien complications.

These results led study authors to conclude that “surgery for locally advanced RCC is safe for patients after neoadjuvant durvalumab +/- tremelimumab.”