In the current era of immune checkpoint inhibitors (ICIs), the role and optimal timing of a nephrectomy in patients with metastatic renal cell carcinoma (mRCC) remain unknown.
Objective
To assess the oncological outcomes of patients who responded to ICI-based treatments and were subsequently treated with a delayed nephrectomy.
Design, setting, and participants
This national retrospective evaluation included 30 patients with mRCC who underwent a nephrectomy after a complete response (CR) or a major partial response (>80%) to ICI treatment at metastatic sites.
Intervention
Partial or radical nephrectomy after a favorable response to ICI treatment.
Outcome measurements and statistical analysis
Disease-free survival (DFS), progression-free survival (PFS), overall survival (OS), and potential discontinuation of systemic treatment were assessed.
Results and limitations
ICI-based treatments included ipilimumab-nivolumab (40%), ICI + tyrosine kinase inhibitor (10%), and nivolumab (50%). A delayed nephrectomy was performed after a median ICI treatment duration of 10 mo. In 19 cases (63.3%), surgeons faced difficulties due to adhesions or inflammatory changes. A complete pathological response was observed in 16.7% of patients. After a median follow-up of 19.5 mo after nephrectomy, 76.7% of patients achieved DFS. At 1 yr, 66.7% of patients were free from systemic treatment. The PFS and OS rates were, respectively, 96.7% and 100% at 1 yr, and 78.3% and 86.1% at 2 yr. Patients with a CR at metastatic sites had a better prognosis than those with a major partial response, in terms of DFS (p = 0.022) and PFS (p = 0.014).
Conclusions
Despite potentially challenging surgery, a delayed nephrectomy for patients who responded to ICI treatment provided promising oncological outcomes, and the majority of patients could discontinue systemic treatment.
Oncological outcomes and surgical morbidity with dCN after immune checkpoint inhibitors
Commentary by Dr. Teele Kuusk
This retrospective evaluation assessed 30 patients with synchronous mRCC who underwent a nephrectomy after a complete response (CR) or a major partial response (>80%) to ICI treatment at metastatic sites. Eighty % were IMDC intermediate risk. ICI-based first line treatments included ipilimumab-nivolumab (40%), ICI + tyrosine kinase inhibitor (10%), and nivolumab (50%). A delayed nephrectomy was performed after a median ICI treatment duration of 10 mo. After a median follow-up of 19.5 mo after nephrectomy, 76.7% of patients achieved DFS. At 1 yr, 66.7% of patients were free from systemic treatment. The PFS and OS rates were, respectively, 96.7% and 100% at 1 yr, and 78.3% and 86.1% at 2 yr. Patients with a CR at metastatic sites had a better prognosis than those with a major partial response, in terms of DFS (p = 0.022) and PFS (p = 0.014). A complete pathological response was observed in 16.7% of patients.
Regarding surgical safety in 73.3% of cases (n = 22/30), surgeons described inflammatory changes at the surgery site during surgery. In 63.3% of cases (n = 19/30), they experienced difficulties in finding dissection planes, due to fibrosis in the kidney and surrounding tissues. The median hospital stay was 6.3 days (range: 1–27 days). The 30-day postoperative complication rate was 33.3% (n = 10/30). Of these, three (10%) were major complications: one postoperative haematoma with percutaneous drainage (Clavien IIIa), one postoperative haemorrhage that required surgical management due to acute tubular necrosis and temporary dialysis (Clavien IV), and one surgery-related death due to haemorrhagic shock and hypovolemia with multiorgan failure (Clavien V).
This cohort is the largest to date to assess dCN after ICI therapy demonstrating that patients with complete response at metastatic sites are good candidates for deferred surgery regarding progression free survival, nevertheless overall survival was similar with the patients who had PR at metastasis. CR was more common in patients receiving Nivolumab and Ipilimumab combination. Unfortunately, the cohort lacked a comparative group without CN which could give further insights about dCN efficacy. Also indications for dCN were not reported. However, oncological outcomes after dCN were favourable and two third of the patients could discontinue systemic treatment and were still treatment free after 1 year. dCN could reduce treatment toxicity, resistance, lower costs and possibly improve patients quality of life. Yet, surgical morbidity in dCN even in expert hands is remarkable and would require a detailed discussion and counselling about its possible risks as stated above.
In conclusion, delayed initiation of systemic therapy in exchange for tumour volume reduction, and delaying the emergence of treatment resistance by reducing tumour heterogeneity using CN, remain relevant in the immunotherapy era. But careful consideration of not only disease-specific risk scores but also surgical risk, resectability, morbidity, surgical expertise and the patient’s personal preference must be taken into account in the decision-making process.