Pathologic response and surgical outcomes in patients undergoing nephrectomy following receipt of immune checkpoint inhibitors for renal cell carcinoma.

To evaluate the pathologic response, safety, and feasibility of nephrectomy following receipt of immune checkpoint inhibition (ICI) for renal cell carcinoma (RCC). Patients who underwent nephrectomy for RCC after exposure to nivolumab monotherapy or combination ipilimumab/nivolumab were reviewed. Primary surgical outcomes included operative time (OT), estimated blood loss (EBL), length of stay (LOS), readmission rates, and complication rates. Pathologic response in the primary and metastatic sites constituted secondary outcomes. Eleven nephrectomies (10 radical, 1 partial) were performed in 10 patients after ICI with median postoperative follow-up 180 days. Six patients received 1 to 4 cycles of ipilimumab/nivolumab, while 5 received 2 to 12 infusions of nivolumab preoperatively. Five surgeries were performed laparoscopically, and 4 patients underwent concomitant thrombectomy. One patient exhibited complete response (pT0) to ICI, and 3/4 patients who underwent metastasectomy for hepatic, pulmonary, or adrenal lesions exhibited no detectable malignancy in any of the metastases resected. No patients experienced any major intraoperative complications, and all surgical margins were negative. Median OT, EBL, and LOS were 180 minutes, 100 ml, and 4 days, respectively. Four patients experienced a complication, including 3 that were addressed with interventional radiology procedures. One patient died of progressive disease >3 months after surgery, and 1 patient succumbed to pulmonary embolism complicated by sepsis. No complications or readmissions were noted in 6 patients. Nephrectomy following ICI for RCC is safe and technically feasible with favorable surgical outcomes and pathologic response. Timing of the nephrectomy relative to checkpoint dosing did not seem to impact outcome. Biopsies of lesions responding radiographically to ICI may warrant attention prior to surgical excision.

Singla N ，Elias R ，Ghandour RA ，Freifeld Y ，Bowman IA ，Rapoport L ，Enikeev M ，Lohrey J ，Woldu SL ，Gahan JC ，Bagrodia A ，Brugarolas J ，Hammers HJ ，Margulis V ... -  《-》

Perioperative Complications and Oncologic Outcomes of Nephrectomy Following Immune Checkpoint Inhibitor Therapy: A Multicenter Collaborative Study.

Immune checkpoint inhibitors (ICIs) are now a mainstay of metastatic renal cell carcinoma (RCC) management with five current Food and Drug Administration-approved regimens. However, data regarding nephrectomy outcomes following an ICI are limited. To evaluate the safety and outcomes of nephrectomy following an ICI. A retrospective review was performed of patients with primary locally advanced or metastatic RCC undergoing nephrectomy following an ICI in five US academic centers between January 2011 and September 2021. Clinical data, perioperative outcomes, and 90-d complications/readmissions were recorded and evaluated by univariate and logistic regression models. Recurrence-free and overall survival probabilities were estimated by the Kaplan-Meier method. A total of 113 patients with a median (interquartile range) age of 63 (56-69) yr were included. The main ICI regimens were nivolumab ± ipilimumab (n = 85) and pembrolizumab ± axitinib (n = 24). Risk groups included 95% intermediate- and 5% poor-risk patients. Surgical procedures were 109 radical and four partial nephrectomies, including 60 open, 38 robotic, and 14 laparoscopic with five (10%) conversions. Two intraoperative complications were reported (bowel and pancreatic injury). The median operative time, estimated blood loss, and hospital stay were 3 h, 250 ml, and 3 d, respectively. A complete pathologic response (ypT0N0) was noted in six (5%) patients. The 90-d complication rate was 24%, with 12 (11%) patients requiring readmission. On a multivariable analysis, two or more risk factors (odds ratio [OR] 2.91, 95% confidence interval [CI]: 1.09, 7.42) and pathologic T stage ≥T3 (OR 4.21, 95% CI: 1.13-15.8) were independently associated with a higher 90-d complication rate. The 3-yr estimated overall survival and recurrence-free survival rates were 82% and 47%, respectively. Limitations include the retrospective nature and heterogeneous cohort in terms of clinicopathologic characteristics and ICI regimens received. Nephrectomy following ICI therapy is feasible and a potential consolidative therapy option in select patients. Further research in the neoadjuvant setting is also warranted. This study evaluates the outcomes of kidney surgery following immune checkpoint inhibitor therapy (mainly nivolumab and ipilimumab or pembrolizumab and axitinib) for patients with advanced kidney cancer. We utilized data from five academic centers across the USA and found that surgery in this setting did not have more complications or returns to the hospital than similar surgeries, indicating that it is a safe and feasible procedure at this time.

Yip W ，Ghoreifi A ，Gerald T ，Lee R ，Howard J ，Asghar A ，Khanna A ，Cai J ，Aron M ，Gill I ，Thompson RH ，Uzzo R ，Margulis V ，Singla N ，Djaladat H ... -  《European Urology Oncology》

A phase II trial of intermittent nivolumab in patients with metastatic renal cell carcinoma (mRCC) who have received prior anti-angiogenic therapy.

Ornstein MC ，Wood LS ，Hobbs BP ，Allman KD ，Martin A ，Bevan M ，Gilligan TD ，Garcia JA ，Rini BI ... -  《Journal for ImmunoTherapy of Cancer》

The Evolving Landscape of Immunotherapy-Based Combinations for Frontline Treatment of Advanced Renal Cell Carcinoma.

Amin A ，Hammers H 《Frontiers in Immunology》

Oncological Outcomes of Delayed Nephrectomy After Optimal Response to Immune Checkpoint Inhibitors for Metastatic Renal Cell Carcinoma.

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. To assess the oncological outcomes of patients who responded to ICI-based treatments and were subsequently treated with a delayed nephrectomy. 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. Partial or radical nephrectomy after a favorable response to ICI treatment. Disease-free survival (DFS), progression-free survival (PFS), overall survival (OS), and potential discontinuation of systemic treatment were assessed. 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). 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. In this study, we evaluated the clinical outcome in patients who responded well to immunotherapy, and subsequently underwent kidney ablation surgery. Three-quarters of patients experienced no recurrence, and in most cases, medical treatment could be discontinued.

Pignot G ，Thiery-Vuillemin A ，Albigès L ，Walz J ，Lang H ，Balssa L ，Parier B ，Geoffrois L ，Bensalah K ，Schlürmann F ，Ladoire S ，Bigot P ，Borchiellini D ，Cassuto O ，Thibault C ，Ingels A ，Saldana V ，Roubaud G ，Bernhard JC ，Gravis G ，Barthélémy P ... -  《European Urology Oncology》