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(a) Histopathological examination. A metastatic lesion of clear cell carcinoma to the humerus. (b) Histopathological examination. A metastatic lesion of clear cell carcinoma to the humerus in detail.
Source publication
Background and Objectives: Complete pathological response after ipilimumab and nivolumab combination therapy in a patient with intermediate prognosis renal cell carcinoma is an uncommon finding. Case presentation: A 60-year-old man presented with synchronous solitary metastatic bone lesion and renal cell carcinoma and achieved a complete pathologic...
Context in source publication
Context 1
... computed tomography (CT) scan revealed a metastatic lesion of the humerus and a tumor mass size of 5 cm in the left kidney ( Figure 1a). In August 2019, the bone lesion was surgically removed with negative margins, and histology confirmed metastasis of clear cell carcinoma of renal origin (Figure 2a,b). Given the IMDC intermediate-risk classification (<1 year from time of diagnosis to systemic therapy), the combination immunotherapy was initiated in September 2019 with a plan of subsequent surgical therapy of the renal primary. ...
Citations
... However, the diagnosis of objective and complete responses is usually based on imaging, and, without pathological examination of tissue from prospective clinical trials, the rate of pCR is unknown. To our knowledge, only few cases of pCR on specimens from resected RCC after ICI-based combinations are described in the literature [16][17][18][19][20][21][22][23][24][25][26] (Table 1). However, since surgical resection of residual disease is rarely performed, the true rate of pCR to ICI-based treatments may be underestimated. ...
Immune checkpoint inhibitors (ICIs)-based combinations have improved survival outcomes of advanced renal cell carcinoma (RCC) patients and are currently recommended as first-line treatment options. Rheumatoid arthritis (RA) is a systemic autoimmune disease (AD) of unknown etiology characterized by a chronic inflammatory process involving joints and extra-articular organs. Patients with AD are usually excluded from large randomized clinical trials investigating immunotherapeutic drugs. Therefore, little is known about clinical outcomes of patients with a history of RA treated with ICIs in real-world practice. In the present study, we report the clinical outcome of an advanced RCC patient with a history of RA treated with pembrolizumab in combination with axitinib. The patient experienced serious immune-related adverse events (irAEs) and achieved pathological complete response following only one ICI administration. Our case report shows that ICI-based combinations can be administered efficaciously in advanced RCC patients with a history of AD. However, a close monitoring of these patients is required, given the risk of irAEs and clinical exacerbations of symptoms associated with the preexisting AD. Moreover, prospective clinical data are needed to assess the hypothesis of a correlation between the onset of irAEs and AD flares and responses and survival outcomes to ICIs.
... Once a response in the primary as well as the metastatic sites is obtained, CN that has so far been deferred can be offered. Not surprisingly, surgical complete remissions can be achieved including pathologic CRs [126][127][128]. Another important aspect is the discrepancy between the radiological outcome and the pathological findings in the resection specimen as described previously in the literature [129]. ...
Simple Summary
For a significant period of time, the removal of the primary tumor termed cytoreductive nephrectomy has been considered the standard of care in patients with metastatic renal cell carcinoma. The situation is complicated because of a very quickly changing landscape of systemic therapy in metastatic renal cell carcinoma. After the turn of the century, cytokines were substituted by multiple tyrosine kinase inhibitors that dominated the therapy of renal carcinoma for more than a decade. With the expansion of immune-based systemic therapy, the importance of cytoreductive nephrectomy has been widely discussed and often disputed. Due to the absence of prospective data regarding the role of cytoreductive nephrectomy in the immunotherapy era, we can at this moment rely only on retrospective studies with relatively small numbers of patients. Nevertheless, with an individualized approach, we should attempt to identify in the clinical practice patients with favorable prognostic patterns who might benefit from the combination of surgery with systemic treatment.
Abstract
The role of cytoreductive nephrectomy in metastatic renal cell carcinoma (RCC) has been studied intensively over the past few decades. Interestingly, the opinion with regard to the importance of this procedure has switched from a recommendation as a standard of care to an almost complete refutation. However, no definitive agreement on cytoreductive nephrectomy, including the pros and cons of the procedure, has been reached, and the topic remains highly controversial. With the advent of immune checkpoint inhibitors, we have experienced a paradigm shift, with immunotherapy playing a crucial role in the treatment algorithm. Nevertheless, obtaining results from prospective clinical trials on the role of cytoreductive nephrectomy requires time, and once some data have been gathered, the standards of systemic therapy may be different, and we stand again at the beginning. This review summarizes current knowledge on the topic in the light of newly evolving treatment strategies. The crucial point is to recognize who could be an appropriate candidate for immediate cytoreductive surgery that may facilitate the effect of systemic therapy through tumor debulking, or who might benefit from deferred cytoreduction in the setting of an objective response of the tumor. The role of prognostic factors in management decisions as well as the technical details associated with performing the procedure from a urological perspective are discussed. Ongoing clinical trials that may bring new evidence for transforming therapeutic paradigms are listed.
... In the Checkmate-9ER trial 5.6% patients discontinued both agents and nearly 20% patients permanently stopped the combination therapy and continued with single agent therapy due to adverse events (3). Toxicity may develop later during the course of therapy such as the case of a RCC patient who developed hypophysitis 9 months after ICI therapy initiation that manifested during the postoperative course following cytoreductive nephrectomy (25). Adverse events induced by ICIs may be unpredictable and patients whenever received immunotherapy should be carefully followed for potential side effects. ...
Introduction
Neoadjuvant nivolumab and cabozantinib in locally advanced renal cell carcinoma in a horseshoe kidney is a novel therapeutic approach in the preoperative setting.
Methods
We report a case of a 52-year old male who presented with a large inoperable tumor of the horseshoe kidney and achieved major partial radiologic response after neoadjuvant therapy with nivolumab and cabozantinib leading to radical resection of the tumor. The patient remains tumor free on the subsequent follow-up and his renal function is only mildly decreased. The systemic treatment was complicated by hepatotoxicity leading to early nivolumab withdrawal.
Results
Currently, the combination therapy based on immune checkpoint inhibitors and tyrosine kinase inhibitors represents the treatment of choice in treatment-naïve patients with metastatic renal cell carcinoma in any prognostic group. The neoadjuvant treatment approach is being tested in prospective clinical trials and results are eagerly awaited. Renal cell carcinoma in a horseshoe kidney is an uncommon finding that is always challenging. Additionally, management guidance in this patient population is lacking. In some patients neoadjuvant therapy could be the only way to preserve kidney function. The initial treatment strategy should be individualized to patient needs aiming at the radical resection of the primary tumor as the only chance of getting the tumor under control in the long term.
Conclusion
Herein, we highlight the feasibility of neoadjuvant systemic therapy with nivolumab and cabozantinib allowing the subsequent performance of radical tumor resection with negative margins in a patient with advanced renal cell carcinoma in a horseshoe kidney, removing the primary tumor while sparing the patient from lifelong dialysis.
Background/aim:
Surgical treatment of renal cell carcinoma (RCC) with inferior vena cava (IVC) thrombus is associated with high morbidity and mortality rates, therefore presurgical systemic therapies are required in order to improve the safety and feasibility of the surgical procedure by decreasing the thrombus level and burden. The efficacy of presurgical combination therapy of immune checkpoint inhibitors (ICI) and tyrosine kinase inhibitors (TKI) for advanced renal cell carcinoma with IVC thrombus remains unclear.
Case report:
We report a case of a 69-year-old male with cT3bN0M0 locally advanced RCC. We successfully performed a less invasive nephrectomy with thrombectomy, because nivolumab plus cabozantinib administration remarkably reduced the primary tumor and IVC thrombus, resulting in complete pathological response, as assessed with perioperative immunohistochemistry.
Conclusion:
To the best of our knowledge, this is the first report showing that nephrectomy could be safely performed for RCC with IVC thrombus after presurgical nivolumab plus cabozantinib therapy, leading to pathological complete response.
BACKGROUND: Immune checkpoint inhibitors (ICPIs) are widely used in treating metastatic renal cell carcinoma (RCC). Cytoreductive nephrectomy (CN) forms part of multimodality treatment in advanced disease, however there is no prospective evidence for its use in the ICPI era. Trials of neoadjuvant ICPIs in RCC are underway; understanding the anticipated effect of ICPIs on the primary tumour may help clinical decision making in both localised and advanced settings. METHODS: A systematic search (PubMed, Web of Science, clinicaltrials.gov) of English literature from 2012 to 2022 was performed according to PRISMA guidelines. 2,398 records were identified, 54 were included in the analysis. RESULTS: In the metastatic setting, response in the primary tumour (≥30% reduction in size) is seen in 33–56% of patients treated with dual ICPI or ICPI + VEGFR-TKI. Pathological complete response rates were 14% for patients undergoing CN after a period of ICPI therapy. In the neoadjuvant setting there is a single published trial of VEGFR-TKI + ICPI, 30% of patients had a≥30% reduction in size of the primary. This appears superior to single agent ICPI. Grade 3 adverse event rates are comparable to the metastatic setting. CONCLUSIONS: A period of ICPI combination therapy followed by nephrectomy may be considered for selected patients as a strategy to manage metastatic disease. In the neoadjuvant setting, it is not clear whether ICPI + VEGFR-TKI is superior to VEGFR-TKI alone. There is minimal data on whether either CN after ICPI in metastatic patients, or neoadjuvant ICPI therapy for localised disease, improves long term survival.
