enero 2020

Complete Surgical Metastasectomy for Renal Cell Carcinoma in the Post-cytokine Era

Lyon TD, Thompson RH, Shah PH, et al.
Journal of Urology, August 2019
DOI: https://doi.org/10.1097/JU.0000000000000488

Abstract

Purpose

Data supporting complete metastasectomy (CM) for metastatic renal cell carcinoma (RCC) is derived primarily from the era of cytokine therapy, and whether CM remains beneficial among patients receiving more recently approved systemic therapies has not been well studied. The objective of this study was to examine survival outcomes among patients treated with CM in the era of targeted therapy and checkpoint blockade availability.

Methods

We queried our institutional nephrectomy registry to identify 586 patients who underwent partial or radical nephrectomy for unilateral, sporadic RCC with a first occurrence of metastases between 2006 and 2017, including 158 treated with CM. Associations of CM with cancer-specific and overall survival were assessed using Cox proportional hazards models.

Results

Median follow-up after diagnosis of metastases was 3.9 years, during which time 403 patients died, including 345 from RCC. Of the CM patients, 147 (93%) did not receive any systemic treatment for their index metastatic lesion(s). Two-year CSS was significantly greater for patients with CM than for those without (84% vs. 54%, p<0.001). After adjusting for age, sex, and the timing, number, and location of metastases, CM was associated with a significantly reduced likelihood of death from RCC (HR 0.47, 95% CI 0.34-0.65, p<0.001).

Conclusions

Complete surgical resection of metastases from RCC is associated with improved CSS in the post-cytokine era and may be considered for appropriate patients following a process of shared decision-making.

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

Singla N, Elias R, Ghandour RA, et al.
Urologic Oncology, September 2019
DOI: https://doi.org/10.1016/j.urolonc.2019.08.012

Abstract

Objective

To evaluate the pathologic response, safety, and feasibility of nephrectomy following receipt of immune checkpoint inhibition (ICI) for renal cell carcinoma (RCC).

Methods

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.

Results

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.

Conclusions

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.

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The Evaluation of Response to Immunotherapy in Metastatic Renal Cell Carcinoma: Open Challenges in the Clinical Practice

Raimondi A, Randon G, Sepe P, et al.
Int. J. Mol. Sci, 20(17), 4263; August 2019
DOI: https://doi.org/10.3390/ijms20174263

Abstract

Immunotherapy has changed the therapeutic scenario of metastatic renal cell carcinoma (mRCC), however the evaluation of disease response to immune-checkpoint inhibitors is still an open challenge. Response evaluation criteria in solid tumors (RECIST) 1.1 criteria are the cornerstone of response assessment to anti-neoplastic treatments, but the use of anti-programmed death receptor 1 (PD1) and other immunotherapeutic agents has shown atypical patterns of response such as pseudoprogression. Therefore, immune-modified criteria have been developed in order to more accurately categorize the disease response, even though their use in the everyday clinical practice is still limited. In this review we summarize the available evidence on this topic, with particular focus on the application of immune-modified criteria in the setting of mRCC.

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