Impact of prior primary tumor resection on long-term prognosis in patients with metastatic renal cell carcinoma treated with nivolumab plus ipilimumab: a multicenter analysis.

BACKGROUND

Nivolumab plus ipilimumab (NIVO + IPI) is a standard first-line therapy for intermediate-risk and poor-risk metastatic renal cell carcinoma (mRCC), but the long-term prognostic impact of prior primary tumor resection in this setting remains unclear.

METHODS

We retrospectively reviewed patients with mRCC that received NIVO + IPI as first-line therapy at eight Japanese institutions between October 2015 and May 2022. Patients were stratified into groups according to timing of metastasis and prior primary tumor resection (cytoreductive nephrectomy; CN): a metachronous group, a synchronous/CN(+) group, and a synchronous/CN(-) group. Progression-free survival, overall survival, and tumor responses were compared among groups, with a median follow-up of 54 months.

RESULTS

Among 135 eligible patients, 40 were classified into the metachronous group (30%), 37 into the synchronous/CN(+) group (27%), and 58 into the synchronous/CN(-) group (43%). Compared with the synchronous/CN(-) group, both the metachronous and synchronous/CN(+) groups exhibited significantly longer progression-free survival (median: 18 and 19 vs. 6 months, respectively; P < 0.01) and overall survival (median: not reached and 52 vs. 22 months, respectively; P < 0.01). In multivariable analysis, absence of prior primary site resection was independently associated with shorter progression-free survival (P = 0.02) and overall survival (P < 0.01). Objective response and disease control rates were highest in the metachronous group and lowest in the synchronous/CN(-) group.

CONCLUSION

In this multicenter cohort with long-term follow-up, prior primary tumor resection was associated with favorable long-term outcomes in patients with mRCC treated with NIVO + IPI, irrespective of synchronous or metachronous metastasis.