In the current era of immune checkpoint inhibitors (ICI), the role and timing of nephrectomy remains unknown, particularly in cases of residual kidney disease after a major response at metastatic sites. In these cases, the rationale for a delayed nephrectomy is that it might achieve a long-term response. This strategy could allow some patients to discontinue treatment and maintain tumor response. Furthermore, this approach might provide a potentially curative option for patients with metastases that are managed with and responding to ICI.
Regarding the results of our first retrospective cohort data (showing that two thirds of patients are free from recurrence without systemic treatment after nephrectomy), we designed a non-comparative randomized phase II trial assessing progression-free survival of patients with complete response or major partial response after ICI-based treatment, operated on delayed nephrectomy with discontinuation of systemic therapy (experimental arm) and in patients managed with continuation of systemic therapy without nephrectomy (control arm).
In a de-escalation approach, this strategy may have sense to allow patients with an excellent response to immunotherapy to stop systemic treatment with a curative objective and a substantial impact from a medico-economic point of view.
Patient aged ≥ 18 years
Diagnosed with synchronous metastatic kidney cancer
With primary tumor still in place (no primary cytoreductive nephrectomy)
Having received systemic ICI immunotherapy-based combination therapy
Women who are or may become pregnant (without effective contraception) or who are breast-feeding.
Person in an emergency situation or unable to give consent.
An adult under legal protection (guardianship, curators or safeguard of justice),
Inability to undergo medical follow-up for geographical, social or psychological reasons.
Parallel
nephrectomy
Procedure/SurgeryNephrectomy scheduled within 3 months of inclusion. Patients may continue their systemic treatment at the usual rate until D-5 prior to surgery. Treatment will not be resumed after surgery. Surgery may consist of partial or enlarged nephrectomy, with or without associated lymph node dissection, depending on technical possibilities and at the surgeon's discretion.
progression-free survival
post-randomization progression-free survival
Overall survival
Overall post-randomization survival
Intraoperative and postoperative complications
Rate of intraoperative and postoperative complications
Immunotherapy-related adverse events
Rate of immunotherapy-related adverse events (including CTCAE grade ≥ 3)
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