Therapeutic role of deferred cytoreductive nephrectomy in patients with metastatic renal cell carcinoma treated with nivolumab plus ipilimumab

Abstract

Objectives To explore the therapeutic role of deferred cytoreductive nephrectomy in patients with metastatic renal cell carcinoma treated with nivolumab plus ipilimumab. Patients and methods Forty-one patients with synchronous metastatic renal cell carcinoma who received nivolumab plus ipilimumab as first-line systemic therapy at our affiliated institutions were retrospectively evaluated. We focused on the prognosis, including tumor responses in primary kidney and metastatic lesions in patients treated with deferred cytoreductive nephrectomy. In addition, the overall survival according to nephrectomy status (i.e. deferred cytoreductive nephrectomy vs. upfront cytoreductive nephrectomy vs. without cytoreductive nephrectomy) was compared. Results During a median follow-up period of 12.0 months, seven (30%) patients received deferred cytoreductive nephrectomy at a median time of 10.4 months after nivolumab plus ipilimumab initiation. All the patients showed tumor shrinkage in their primary kidney lesions, including six (86%) patients with ≥30% of shrinkage. Metastatic lesions were also shrunk by ≥30% in six (86%) patients, including two (29%) obtaining complete response. At the last time of follow-up, three (43%) patients were disease-free. The overall survival rate after nivolumab plus ipilimumab initiation tended to be higher in patients with deferred cytoreductive nephrectomy compared with those with upfront cytoreductive nephrectomy (1-year survival rate: 100% vs. 72.4%, P = 0.0587) and those without cytoreductive nephrectomy (vs. 58.2%, P = 0.0613). Conclusions The present retrospective data showed that deferred cytoreductive nephrectomy had the potential to exert a therapeutic effect in a subset of patients who obtained favorable tumor responses to nivolumab plus ipilimumab for a certain period. Prospective randomized clinical trials are needed to confirm the prognostic impact of deferred cytoreductive nephrectomy after frontline immunotherapy in synchronous metastatic renal cell carcinoma.

The impact of cytoreductive nephrectomy on survival outcomes in patients with metastatic renal cell carcinoma receiving immunotherapy: An evidence-based analysis of comparative outcomes

“…In the sample size > 400 subgroup, the CN group had significantly lower risk of death compared to the No CN group (HR = 0.52, 95% CI 0.32–0.84, p = 0.007, I 2 = 83%) ( 21 – 23 ). Additionally, for the subgroup with a sample size ≤ 400, the CN group was correlated with better OS than for the No CN group (HR = 0.53, 95% CI 0.35–0.80, p = 0.002, I 2 = 87%) ( Figure 5 ) ( 4 , 5 , 24 – 26 ). In the subgroup analysis of the ICIs as first-line therapy, the CN group had significantly lower risk of death compared to the No CN group (HR = 0.50, 95% CI 0.27–0.92, p = 0.03, I 2 = 83%) ( 21 , 22 , 24 ).…”

“…In the studies included, three studies compared the outcomes of deferred versus upfront CN in selected patients. Two studies reported that deferred CN did not lead to a superior OS than upfront CN in patients (21, 26), while one study suggested that OS rate tended to be higher with deferred CN in comparison to upfront CN (24). Ghatalia et al (30) also demonstrated that no statistically significant difference in OS was observed between the upfront and deferred groups.…”

“…A comparative analysis was performed on all the non-RCTs, of which five studies had a moderate risk of bias (22)(23)(24)(25)(26) and one study had a low risk of bias (Table S2). All the non-RCTs were published between 2020 and 2022.…”

“…Additionally, for the subgroup with a sample size ≤ 400, the CN group was correlated with better OS than for the No CN group (HR = 0.53, 95% CI 0.35-0.80, p = 0.002, I 2 = 87%) (Figure 5) (4, 5, 24-26). In the subgroup analysis of the ICIs as first-line therapy, the CN group had significantly lower risk of death compared to the No CN group (HR = 0.50, 95% CI 0.27-0.92, p = 0.03, I 2 = 83%) (21, 22,24). Similarly, the subgroup analysis revealed that both ICIs as second, third line therapy and first, second and third therapy were associated with superior OS compared to the No CN group (HR = 0.61, 95% CI 0.44-0.84, p = 0.002, I 2 = 34%; HR = 0.28, 95% CI 0.20-0.40, p < 0.00001, I 2 = 43%) (Figure 6) (21, 23) (25, 26).…”

Cine magnetic resonance imaging predicts thrombus adhesion in metastatic renal cell carcinoma with an inferior vena cava tumor thrombus: A case of pathological complete response with pembrolizumab plus lenvatinib

“…Reports of pCR in the primary lesion in patients who underwent nephrectomy after first‐line immunotherapy‐based combination regimens are increasing. As shown in Table 2, 11–16 pCR with these novel therapies has been reported in 5.3–30% of patients. However, most of the reports are for ipilimumab plus nivolumab therapy, and the pCR rates for immunotherapy plus TKI are unclear.…”