Comparative real-world survival outcomes of metastatic papillary and clear cell renal cell carcinoma treated with immunotherapy, targeted therapy, and combination therapy

Riveros, Carlos; Ranganathan, Sanjana; Xu, Jiaqiong; Chang, Courtney R.; Kaushik, Dharam; Morgan, Monica; Miles, Brian J.; Muhammad, Taliah; Anis, Maryam; Aghazadeh, Monty; Zhang, Jun; Efstathiou, Eleni; Klaassen, Zachary; Brooks, Michael; Rini, Brian I.; Wallis, Christopher J.D.; Satkunasivam, Raj

doi:10.1016/j.urolonc.2022.11.022

Cited by 7 publications

(3 citation statements)

References 34 publications

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“…Last, the group of Riveros retrospectively analyzed the outcomes of 594 patients with papillary RCC receiving IO or IO+TKI combinations. Their study showed that patients undergoing CN in addition to systemic therapy experienced longer OS (HR 0.59) [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

Real-World Impact of Upfront Cytoreductive Nephrectomy in Metastatic Non-Clear Cell Renal Cell Carcinoma Treated with First-Line Immunotherapy Combinations or Tyrosine Kinase Inhibitors (A Sub-Analysis from the ARON-1 Retrospective Study)

Fiala,

Buti,

Bamias

et al. 2024

Targ Oncol

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Background About 20% of patients with renal cell carcinoma present with non-clear cell histology (nccRCC), encompassing various histological types. While surgery remains pivotal for localized-stage nccRCC, the role of cytoreductive nephrectomy (CN) in metastatic nccRCC is contentious. Limited data exist on the role of CN in metastatic nccRCC under current standard of care. Objective This retrospective study focused on the impact of upfront CN on metastatic nccRCC outcomes with first-line immune checkpoint inhibitor (IO) combinations or tyrosine kinase inhibitor (TKI) monotherapy. Methods The study included 221 patients with nccRCC and synchronous metastatic disease, treated with IO combinations or TKI monotherapy in the first line. Baseline clinical characteristics, systemic therapy, and treatment outcomes were analyzed. The primary objective was to assess clinical outcomes, including progression-free survival (PFS) and overall survival (OS). Statistical analysis involved the Fisher exact test, Pearson’s correlation coefficient, analysis of variance, Kaplan–Meier method, log-rank test, and univariate/multivariate Cox proportional hazard regression models. Results Median OS for patients undergoing upfront CN was 36.8 (95% confidence interval [CI] 24.9–71.3) versus 20.8 (95% CI 12.6–24.8) months for those without CN ( p = 0.005). Upfront CN was significantly associated with OS in the multivariate Cox regression analysis (hazard ratio 0.47 [95% CI 0.31−0.72], p < 0.001). In patients without CN, the median OS and PFS was 24.5 (95% CI 18.1–40.5) and 13.0 months (95% CI 6.6–23.5) for patients treated with IO+TKI versus 7.5 (95% CI 4.3–22.4) and 4.9 months (95% CI 3.0–8.1) for those receiving the IO+IO combination ( p = 0.059 and p = 0.032, respectively). Conclusions Our study demonstrates the survival benefits of upfront CN compared with systemic therapy without CN. The study suggests that the use of IO+TKI combination or, eventually, TKI monotherapy might be a better choice than IO+IO combination for patients who are not candidates for CN regardless of IO eligibility. Prospective trials are needed to validate these findings and refine the role of CN in current mRCC management. Supplementary Information The online version contains supplementary material available at 10.1007/s11523-024-01065-w.

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Section: Discussionmentioning

confidence: 99%

Real-World Impact of Upfront Cytoreductive Nephrectomy in Metastatic Non-Clear Cell Renal Cell Carcinoma Treated with First-Line Immunotherapy Combinations or Tyrosine Kinase Inhibitors (A Sub-Analysis from the ARON-1 Retrospective Study)

Fiala,

Buti,

Bamias

et al. 2024

Targ Oncol

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“…The systemic therapy of papillary RCC has gone through some progress tracking the development in ccRCC, however, the optimal treatment strategy remains mostly undefined. Discussing the role of CN, Riveros et al reported improved OS in patients with metastatic papillary RCC treated with ICI-based therapy or targeted therapy in combination with CN [60]. While the impact of the histological subtype seems to be critical in the systemic treatment selection, determining the role of CN based on the differences arising from molecular background may not be that plausible [60].…”

Section: Cytoreductive Nephrectomy In Non-clear Cell Subtypesmentioning

confidence: 99%

The Evolving Landscape of Cytoreductive Nephrectomy in Metastatic Renal Cell Carcinoma

Studentova,

Spisarova,

Kopova

et al. 2023

Cancers

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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.

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“…About 60% of cases are detected incidentally and 20% to 30% of patients present with metastatic disease [ 2 ]. In most cases, metastatic renal cancer is incurable [ 2 , 3 ]. Rather than being a single disease, RCC refers to a group of heterogeneous tumors that arise from the renal epithelium [ 4 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

ANO4 Expression Is a Potential Prognostic Biomarker in Non-Metastasized Clear Cell Renal Cell Carcinoma

Sharie

Zu’bi

El‐Elimat

et al. 2023

JPM

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Background: Over the past decade, transcriptome profiling has elucidated many pivotal pathways involved in oncogenesis. However, a detailed comprehensive map of tumorigenesis remains an enigma to solve. Propelled research has been devoted to investigating the molecular drivers of clear cell renal cell carcinoma (ccRCC). To add another piece to the puzzle, we evaluated the role of anoctamin 4 (ANO4) expression as a potential prognostic biomarker in non-metastasized ccRCC. Methods: A total of 422 ccRCC patients with the corresponding ANO4 expression and clinicopathological data were obtained from The Cancer Genome Atlas Program (TCGA). Differential expression across several clinicopathological variables was performed. The Kaplan–Meier method was used to assess the impact of ANO4 expression on the overall survival (OS), progression-free interval (PFI), disease-free interval (DFI), and disease-specific survival (DSS). Univariate and multivariate Cox logistic regression analyses were conducted to identify independent factors modulating the aforementioned outcomes. Gene set enrichment analysis (GSEA) was used to discern a set of molecular mechanisms involved in the prognostic signature. Tumor immune microenvironment was estimated using xCell. Results: ANO4 expression was upregulated in tumor samples compared to normal kidney tissue. Albeit the latter finding, low ANO4 expression is associated with advanced clinicopathological variables such as tumor grade, stage, and pT. In addition, low ANO4 expression is linked to shorter OS, PFI, and DSS. Multivariate Cox logistic regression analysis identified ANO4 expression as an independent prognostic variable in OS (HR: 1.686, 95% CI: 1.120–2.540, p = 0.012), PFI (HR: 1.727, 95% CI: 1.103–2.704, p = 0.017), and DSS (HR: 2.688, 95% CI: 1.465–4.934, p = 0.001). GSEA identified the following pathways to be enriched within the low ANO4 expression group: epithelial–mesenchymal transition, G2-M checkpoint, E2F targets, estrogen response, apical junction, glycolysis, hypoxia, coagulation, KRAS, complement, p53, myogenesis, and TNF-α signaling via NF-κB pathways. ANO4 expression correlates significantly with monocyte (ρ = −0.1429, p = 0.0033) and mast cell (ρ = 0.1598, p = 0.001) infiltration. Conclusions: In the presented work, low ANO4 expression is portrayed as a potential poor prognostic factor in non-metastasized ccRCC. Further experimental studies should be directed to shed new light on the exact molecular mechanisms involved.

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Comparative real-world survival outcomes of metastatic papillary and clear cell renal cell carcinoma treated with immunotherapy, targeted therapy, and combination therapy

Cited by 7 publications

References 34 publications

Real-World Impact of Upfront Cytoreductive Nephrectomy in Metastatic Non-Clear Cell Renal Cell Carcinoma Treated with First-Line Immunotherapy Combinations or Tyrosine Kinase Inhibitors (A Sub-Analysis from the ARON-1 Retrospective Study)

Real-World Impact of Upfront Cytoreductive Nephrectomy in Metastatic Non-Clear Cell Renal Cell Carcinoma Treated with First-Line Immunotherapy Combinations or Tyrosine Kinase Inhibitors (A Sub-Analysis from the ARON-1 Retrospective Study)

The Evolving Landscape of Cytoreductive Nephrectomy in Metastatic Renal Cell Carcinoma

ANO4 Expression Is a Potential Prognostic Biomarker in Non-Metastasized Clear Cell Renal Cell Carcinoma

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