Is active surveillance an option for metachronous metastatic renal cell carcinoma?
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ABSTRACT:
SUBMITTER: Ficarra V
PROVIDER: S-EPMC6462645 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundSystemic therapy (ST) can be deferred in patients who have metastatic renal cell carcinoma (mRCC) and slow-growing metastases. Currently, this subset of patients managed with active surveillance (AS) is not well described in the literature.MethodsThis was a prospective observational study of patients with mRCC across 46 US community and academic centers. The objective was to describe baseline characteristics and demographics of patients with mRCC initially managed by AS, reasons for AS, and patient outcomes. Descriptive statistics were used to characterize demographics, baseline characteristics, and patient-related outcomes. Wilcoxon 2-sample rank-sum tests and χ2 tests were used to assess differences between ST and AS cohorts in continuous and categorical variables, respectively. Kaplan-Meier survival curves were used to assess survival.ResultsOf 504 patients, mRCC was initially managed by AS (n = 143) or ST (n = 305); 56 patients were excluded from the analysis. Disease was present in 69% of patients who received AS, whereas the remaining 31% had no evidence of disease. At data cutoff, 72 of 143 patients (50%) in the AS cohort had not received ST. The median overall survival was not reached (95% CI, 122 months to not estimable) in patients who received AS versus 30 months (95% CI, 25-44 months) in those who received ST. Quality of life at baseline was significantly better in patients who were managed with AS versus ST.ConclusionsAS occurs frequently (32%) in real-world clinical practice and appears to be a safe and appropriate alternative to immediate ST in selected patients.
| S-EPMC8251950 | biostudies-literature
Project description:To assess the prognostic and predictive factors of time to treatment failure (TTF) and overall survival (OS), respectively, in patients with metachronous metastatic renal cell carcinoma (mRCC) who were treated with targeted agents.We retrospectively reviewed metachronous mRCC patients, defined as individuals diagnosed with metastatic disease >3 months after initial nephrectomy, treated at an institute since 2005. Cox proportional hazard regression analysis was performed to discover the most determinant variables associated with TTF and OS.Sarcomatoid features, absence of metastasectomy, multiple site metastasis, time to metastasis <1.5 year, and increased corrected calcium were independent prognostic factors of OS. The low risk group (0-1 risk factors) did not reach the median OS, whereas the OS for the intermediate (2 risk factors) and high risk groups (3-5 risk factors) were 58.6 and 23.6 months, respectively (p<0.001). When a death event was considered the dependent factor, the area under the receiver operating characteristic curve was significantly higher than in the existing International mRCC Database Consortium (IMDC; p=0.010) and Memorial Sloan Kettering Cancer Center (MSKCC; p=0.010) risk criteria models.Initial tumor size or T stage did not affect TTF or OS. Patients who could not undergo metastasectomy and rapidly developed multiple metastases with higher corrected calcium and initial tumors with sarcomatoid features were less likely to benefit from targeted therapy; thus, the new agents under development or clinical trials could be more helpful than the use of standard targeted agents.
| S-EPMC5668001 | biostudies-literature
Project description:BackgroundThe differences in progression-free survival (PFS) and cancer-specific survival (CSS) of metastatic renal cell carcinoma (mRCC) patients according to treatment, type of metastasis, and Heng criteria risk are unclear. In this study, we compared survival according to various such parameters.MethodsBetween 2000 to 2014, 214 mRCC patients, of whom 171 (79.9%) were intermediate-risk and 43 (20.1%) were poor-risk, were retrospectively selected; 126 (58.9%) patients were treated with immunotherapy (IT) and 88 (41.1%) with targeted therapy (TT). Moreover, 144 patients had synchronous mRCCs (67.3%, SM) and 70 had metachronous mRCCs (32.7%, MM). The Kaplan-Meier method and log-rank test were used to compare progression-free survival (PFS) and CSS.ResultsDuring a median 4.2 (1.0-70.4) months of systemic treatment and 98.3 (4.8-147.6) months of follow-up, the median PFS and CSS were 4.7 (95% confidence interval [CI]: 3.8-5.5) and 13.8 (95% CI, 9.8-18.3) months, respectively. The PFS and CSS were significantly better in the MM (5.9 and 21.3?months) and intermediate-risk groups (5.2 and 18.3?months) than those in the SM (4.4 and 9.6?months) and poor-risk groups (2.7 and 5.8?months), respectively (p <?0.05). Further stratification showed that TT produced significantly better PFS than IT in intermediate-risk patients with SM and a treatment-free interval (TFI) <?1?year, and in those with MM with a TFI ?1?year (p <?0.05). There were no differences in survival outcomes according to various other subgroup stratifications (p >?0.05).ConclusionDividing patients into specific subcategories helps to better predict therapeutic outcomes.
| S-EPMC6631605 | biostudies-literature
Project description:Targeted agents have revolutionized the management of metastatic renal cell carcinoma (RCC). Axitinib, an inhibitor of vascular endothelial growth factor receptor (VEGFR), has been an important addition to currently available therapies for advanced RCC. Its ability to inhibit VEGFRs at nanomolar concentrations distinguishes it as a potent tyrosine kinase inhibitor, with increased selectivity for VEGFR-1, 2, and 3 at clinically applicable concentrations. The phase 3 AXIS trial has established its superiority in prolonging progression-free survival (PFS) in previously treated RCC patients (median PFS 6.7 months for axitinib vs. 4.7 months for sorafenib). Common toxicities of axitinib include hypertension, diarrhea, nausea, hand-foot syndrome, fatigue, and hypothyroidism. Axitinib-induced diastolic blood pressure elevation may be associated with improved clinical outcome, likely reflecting the "on-target" effect of axitinib. Dose escalation to achieve therapeutic plasma drug levels is of considerable clinical interest. Although axitinib has established efficacy in patients treated with one previous agent, its use in the frontline setting is currently the subject of ongoing research.
| S-EPMC3873008 | biostudies-other
Project description:Sunitinib represents a widely used therapy for metastatic renal cell carcinoma patients. Even so, there is a group of patients who show toxicity without clinical benefit. In this work, we have analysed pivotal molecular targets involved in angiogenesis (vascular endothelial growth factor (VEGF)-A, VEGF receptor 2 (KDR), phosphorylated (p)KDR and microvascular density (MVD)) to test their potential value as predictive biomarkers of clinical benefit in sunitinib-treated renal cell carcinoma patients.Vascular endothelial growth factor-A, KDR and pKDR-Y1775 expression as well as CD31, for MVD visualisation, were determined by immunohistochemistry in 48 renal cell carcinoma patients, including 23 metastatic cases treated with sunitinib. Threshold was defined for each biomarker, and univariate and multivariate analyses for progression-free survival (PFS) and overall survival (OS) were carried out.The HistoScore mean value obtained for VEGF-A was 121.6 (range, 10-300); for KDR 258.5 (range, 150-300); for pKDR-Y1775 10.8 (range, 0-65) and the mean value of CD31-positive structures for MVD visualisation was 49 (range, 10-126). Statistical differences for PFS (P=0.01) and OS (P=0.007) were observed for pKDR-Y1775 in sunitinib-treated patients. Importantly, pKDR-Y1775 expression remained significant after multivariate Cox analysis for PFS (P=0.01; HR: 5.35, 95% CI, 1.49-19.13) and for OS (P=0.02; HR: 5.13, 95% CI, 1.25-21.05).Our results suggest that the expression of phosphorylated (i.e., activated) KDR in tumour stroma might be used as predictive biomarker for the clinical outcome in renal cell carcinoma first-line sunitinib-treated patients.
| S-EPMC4037833 | biostudies-other
Project description:BackgroundEffective systemic treatment of non-clear cell renal carcinoma (nccRCC) is still an unmet clinical need, with few studies to support an evidence-based approach. To date, the only recommended standard first-line treatment is sunitinib. Pazopanib may also be used in nccRCC but its place in therapy is not clearly established. It has comparable efficacy and better tolerability than sunitinib in clear cell renal carcinoma. Our objective was to review the use of pazopanib in metastatic nccRCC.MethodsWe conducted a systematic review according to PRISMA guidelines. Any type of study reporting the use of pazopanib in metastatic renal cell carcinoma including cases with non-clear cell histology was eligible.ResultsIn all, 15 studies were included in our analysis, including a total of 318 nccRCC patients treated with pazopanib. Most studies were retrospective (n = 12); three were prospective trials. The specific outcomes of nccRCC patients were reported by four studies. Pazopanib alone as first-line treatment gave overall response rates ranging from 27% to 33%, disease control rates of 81-89%, median progression free survival of 8.1-16.5 months and median overall survival of 17.3-31.0 months. Grade 3-4 adverse events rates were 21-55%.ConclusionThe present review provides for the first time a systematic summary of evidence about the possible use of pazopanib as first-line treatment for nccRCC, with a favorable outcome despite the low strength of evidence. Pazopanib could be considered as a possible therapeutic option in this setting.
| S-EPMC7278098 | biostudies-literature
Project description:The treatment of metastatic renal cell carcinoma (mRCC) has changed dramatically in the past decade. As the number of available agents, and related volume of research, has grown, it is increasingly complex to know how to optimally treat patients. The authors are practicing medical oncologists at the US Oncology Network, the largest community-based network of oncology providers in the country, and represent the leadership of the Network's Genitourinary Research Committee. We outline our thought process in approaching sequential therapy of mRCC and the use of real-world data to inform our approach. We also highlight the evolving literature that will impact practicing oncologists in the near future.
| S-EPMC5345527 | biostudies-other
Project description:Renal cell carcinoma (RCC) is a malignant tumor that can metastasize easily. Hence, many patients have already developed metastasis when they are diagnosed. It is also one of the most common tumors that metastasize to the head and neck through extranodal disease. Herein, we reported a case of a 53-year-old man with cervical metastasis from bilateral RCC. Interestingly, whole exome sequencing (WES) and clonal evolution analysis revealed that bilateral renal tumor lesions and neck metastases (squamous cell carcinoma) share the same subclones and a large number of gene variants, while the pathological morphology is different (left nephrotic foci, a mixed pattern of mucinous tubular and spindle cell carcinoma (MTSCC) with papillary adenoma; right renal foci, papillary renal cell carcinoma (PRCC)). This was first reported in RCCs to the best of our knowledge. This case suggests that genotype analysis can be a powerful supplementary examination for clinical histopathological diagnosis. Gene detection has great significance for the accurate diagnosis and treatment of RCC metastasis or multiple lesions.
| S-EPMC8354027 | biostudies-literature
Project description:The introduction of targeted therapy has revolutionized the treatment of patients with metastatic renal cell carcinoma (mRCC). The current standard of care focuses on the inhibition of angiogenesis through the targeting of the vascular endothelial growth factor receptor (VEGFR) and the mammalian target of rapamycin (mTOR). Over the past few years, research exploring novel targeted agents has blossomed, leading to the approval of various targeted therapies. Furthermore, results from the CheckMate025 and the METEOR trials have brought about two additional novel options: the programmed cell death 1 (PD-1) checkpoint inhibitor nivolumab and the MET/VEGFR/AXL inhibitor cabozantinib, respectively. With the variety of therapeutic agents available for treatment of mRCC, research examining appropriate sequencing and combinations of the drugs is ongoing. This review discusses the role of prognostic criteria, such as those from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) criteria. It also covers the current standard of treatment for mRCC with targeted therapy in first-, second-, and third-line setting. Additionally, the novel mechanism of action of nivolumab and cabozantinib, therapeutic sequencing and ongoing clinical trials are discussed.
| S-EPMC4943094 | biostudies-literature
Project description:Despite the rapid development of therapeutic modalities for metastatic renal cell carcinoma (mRCC) over the past decade to include a number of targeted antiangiogenic therapies and traditional immunotherapy, such as high-dose interleukin-2 and interferon-?, mRCC continues to be associated with poor prognosis. Currently, several novel immunotherapy agents, such as cancer vaccines, adoptive cell therapy, and checkpoint inhibitors, such as programmed cell death-1 (PD-1 present on T cells), one of its ligands (PD-L1 present on antigen-presenting cells and tumor cells), and cytotoxic T-lymphocyte-associated protein-4 pathways, are being studied in mRCC and are showing promise as important steps in the management of this disease. This review summarizes the current landscape of standard and emerging immune therapeutics and other modalities for mRCC.
| S-EPMC5494344 | biostudies-literature