Nephrectomy after response to immune checkpoint inhibitors for metastatic renal cell carcinoma (mRCC): A surgical challenge allowing favorable oncological outcomes.
Authors: Pignot Geraldine , Thiery-Vuillemin Antoine , Walz Jochen , Gaillard Victor , Lang Herve , Balssa Loic , Geoffrois Lionnel , Albiges Laurence , Bensalah Karim , Schlurmann Friederike , Ladoire Sylvain , Bigot Pierre , Ingels Alexandre , Roubaud Guilhem , Cassuto Ophelie , Parier Bastien , Bernhard Jean-Christophe , Borchiellini Delphine , Gravis Gwenaelle , Barthelemy Philippe 
Published: June 2021

e16557

Background: In the current era of Immune checkpoint inhibitors (ICI), the role and timing of nephrectomy is still unknown. We aimed to evaluate the oncological outcomes of patients with metastatic renal cell carcinoma (mRCC) managed with nephrectomy for residual disease after complete response (CR) or major partial response (mPR defined as > 80%) on metastatic sites following ICI. Methods: Patients who underwent nephrectomy after prior ICI between 2015 and 2020 were retrospectively included and clinicopathological data were reviewed. Perioperative data, postoperative complications, toxicities related to ICI, continuation or discontinuation of systemic treatment following surgery, and 1-year oncological outcomes were recorded. Results: Twenty-five patients without initial cytoreductive nephrectomy at diagnosis underwent delayed nephrectomy after long ICI administration because of CR (or mPR) on metastatic sites. Median age was 62 years [38-79]. 88% of patients had clear cell RCC on the initial biopsy. IMDC prognostic group was intermediate (80%) or poor (20%). ICI was administered as first-line therapy in 56.0% of cases and as second-line option after TKI in 44.0% of cases. Treatments regimens were: nivolumab + ipilimumab (n = 12), nivolumab + tivozanib (n = 2) or nivolumab alone (n = 11). The mean duration of ICI treatment was 11.8 months (range: 3-38 months) and the mean number of cycles was 19 (range: 6-75). Twelve patients had a CR on metastatic sites while 13 patients had a mPR ( > 80%). Overall, 64% of patients experienced toxicities related to ICI treatment. Median operative time was 210 minutes [90-345] and mean blood loss was 558 cc [40-4000]. In 80.0% of cases, surgeons experienced difficulties in finding dissection plans due to adhesions and/or inflammatory infiltration. The 30-day Clavien-Dindo postoperative complication rate was 36.0%, including 1 surgery-related death. Pathological report showed lymphocyte and/or macrophage infiltration in 60% of cases and complete pathological response (pT0) in 3 cases (12%). After a mean follow-up of 19.4 months, 79.2% of the patients were free from progression and 70.8% free from systemic treatment. The recurrence-free survival (RFS) and overall survival (OS) at 1 year were 79.5% and 89.8% respectively. CR on metastatic sites was significantly associated with good RFS compared to mPR (1-year RFS = 100% vs. 56.8%, median RFS = 21.6 vs. 4.25 months, p = 0.006) while the duration of IO treatment exposure was not. Conclusions: Nephrectomy following ICI for mRCC can be a difficult procedure. However, it may provide good long-term RFS, with systemic treatment discontinuation following surgery in most cases. This strategy may be offered in well-selected patients, especially in case of CR on metastatic sites before surgery.