Surgical outcomes after cytoreductive nephrectomy following neoadjuvant immunotherapy for metastatic renal cell carcinoma
Vincent D. D'Andrea, MD1, Steven L. Chang, MD MS1, Matthew Mossanen, MD MPH1, Timothy N. Clinton, MD1, Kendrick Yim, MD1, Graeme S. Steele, MD1, Mark A. Preston, MD MPH1, Grant L. Steele, BA2, Filipe L.F. Carvalho, MD PhD1.
1Brigham & Women's Hospital, Boston, MA, USA, 2Harvard Medical School, Boston, MA, USA.
BACKGROUND: Immunotherapy has caused a paradigm shift in the treatment of metastatic renal cell carcinoma (RCC) with remarkable tumor responses and prolonged patient survival. Much effort has focused on the oncologic outcomes of these patients, but there has yet to be an analysis of surgical outcomes and complication rates in patients treated with neoadjuvant immunotherapy followed by cytoreductive nephrectomy (CN). Case reports have shown conflicting results regarding safety and feasibility of CN following systemic immunotherapy. Our goal is to determine the feasibility of CN following immunotherapy for patients with metastatic RCC. We propose that CN is safe following neoadjuvant immunotherapy and that neoadjuvant treatment decreases the size of the renal mass prior to surgery.
METHODS: We queried an institutional database for all cytoreductive nephrectomies completed between the years of 2019-2021 by 4 urologic surgeons at our single institution. These patients were selected for those who underwent neoadjuvant treatment for metastatic disease. Various demographic, surgical, and follow-up data were collected for the patient cohort. Surgical data collected included operative time, estimated blood loss, tumor size, and final pathology. Follow-up data collected included length of stay, readmission rates, and death rates. Primary outcome was the renal mass size comparison at time of therapy initiation and at time of nephrectomy. Secondary outcomes include estimated blood loss (EBL) and 30-day readmission rate.
RESULTS: 15 patients were found that met the inclusion criteria. Neoadjuvant treatments most-commonly included concurrent treatment with ipilimumab and nivolumab (n=9, 60%) and nivolumab alone (n=3, 27%). Other regimens included cabozantinib/nivolumab, pembrolizumab/axitinib, and lenavatinib/everolimus combination therapy. The most common site of metastasis was lung (n=10, 67%). Other sites included bone and brain. Median age at time of CN was 61 years-old. Mean renal mass size at time of therapy initiation was 11.0cm and mean renal mass size at time of nephrectomy was 8.8cm (p=0.11). Six cases involved IVC thrombectomy, seven nephrectomies were completed open, and eight were completed laparoscopically. The difference between EBL for open vs. laparoscopic approaches was 785cc vs. 207cc, respectively (p=0.06). There were no 30-day readmissions and only one patient died at time of most recent follow-up.
CONCLUSIONS: Neoadjuvant immunotherapy prior to CN is being increasingly used for the treatment of metastatic renal cell carcinoma. Our data shows a decrease in the mean size of the renal mass at time of nephrectomy following immunotherapy, making surgery more feasible and possibly less technically challenging. The fact that the 30-day readmission rate is zero emphasizes the short-term safety of this approach. A further analysis of the data could determine whether there are “responders” and “non-responders” in the patient cohort, as there are some patients whose tumors may respond favorably to neoadjuvant therapy and some whose tumor growth is refractory to treatment. Further subgroup analysis may shed light on the surgical differences between these groups. Additionally, future studies with larger cohorts of patients comparing upfront CN with neoadjuvant immunotherapy followed by CN may further discern the added value of systemic therapy prior to surgery in metastatic RCC.
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