Sarcomatoid renal cell carcinoma: Biology and treatment advances

Mouallem, Nemer El; Smith, Steven C.; Paul, Asit K.

doi:10.1016/j.urolonc.2017.12.012

Cited by 44 publications

(41 citation statements)

References 56 publications

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“…Adverse histologic features, including necrosis, lymphovascular invasion, high nuclear grade, rhabdoid as well as sarcomatoid histology have a remarkable prognostic value, even in patients with small renal masses [6]. Sarcomatoid histology, which is characterized by the loss of typical epithelial features ("dedifferentiation"), is reported in approximately 5-10% of cases, most frequently in clear-cell RCC [7]. In metastatic RCC patients, sarcomatoid histology was associated with a poor median disease-specific survival of 9 months [6], with chemotherapy and targeted therapy showing disappointing efficacy in these patients [8].…”

Section: Introductionmentioning

confidence: 99%

Outcomes Associated with First-Line anti-PD-1/ PD-L1 agents vs. Sunitinib in Patients with Sarcomatoid Renal Cell Carcinoma: A Systematic Review and Meta-Analysis

Buonerba

Dolce²,

Iaccarino

et al. 2020

Cancers

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: Immunotherapy based on anti PD-1/PD-L1 inhibitors has proven to be more effective than sunitinib in the first-line setting of advanced renal cell carcinoma (RCC). RCC patients with sarcomatoid histology (sRCC) have a poor prognosis and limited therapeutic options. We performed a systematic review and a meta-analysis of randomized-controlled trials (RCTs) of first-line anti PD-1/PDL-1 agents vs. sunitinib, presenting efficacy data in the sub-group of sRCC patients. The systematic research was conducted on Google Scholar, Cochrane Library, PubMed and Embase and updated until 31th January, 2020. Abstracts from ESMO and ASCO (2010–2019) were also reviewed. Full texts and abstracts reporting about RCTs testing first-line anti-PD-1/ PD-L1 agents vs. sunitinib in RCC were included if sRCC sub-group analyses of either PFS (progression-free survival), OS (overall survival) or radiological response rate were available. Pooled data from 3814 RCC patients in the ITT (intention-to-treat) population and from 512 sRCC patients were included in the quantitative synthesis. In the sRCC sub-group vs. the ITT population, pooled estimates of the PFS-HRs were 0.57 (95%: 0.45–0.74) vs. 0.79 (95% CI: 0.70–0.89), respectively, with a statistically meaningful interaction favoring the sRCC sub-group (pooled ratio of the PFS-HRs = 0.64; 95% CI: 0.50–0.82; p < 0.001). Pooled estimates of the difference in CR-R (complete response-rate) achieved with anti-PD-1/PDL-1 agents vs. sunitinib were + 0.10 (95% CI: 0.04–0.16) vs. + 0.04 (95% CI: 0.00–0.07) in the sRCC vs. the non-sRCC sub groups, with a statistically meaningful difference of + 0.06 (95% CI: 0.02–0.10; p = 0.007) favoring the sRCC sub-group. Sarcomatoid histology may be associated with improved efficacy of anti PD-1/PDL-1 agents vs. sunitinib in terms of PFS and CR-R.

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Section: Introductionmentioning

confidence: 99%

Outcomes Associated with First-Line anti-PD-1/ PD-L1 agents vs. Sunitinib in Patients with Sarcomatoid Renal Cell Carcinoma: A Systematic Review and Meta-Analysis

Buonerba

Dolce²,

Iaccarino

et al. 2020

Cancers

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“…Approximately 5% of all RCCs and up to 15% of stage IV cases contain sarcomatoid differentiation [5,6]. Previous studies suggested that sarcomatoid differentiation is associated with aggressive behaviours, poor response to targeted therapy and worse prognosis [6][7][8]. However, the impact of sarcomatoid differentiation on prognosis for RCC with vena caval tumour thrombus treated surgically has not been studied extensively.…”

Section: Introductionmentioning

confidence: 99%

Impact of sarcomatoid differentiation and rhabdoid differentiation on prognosis for renal cell carcinoma with vena caval tumour thrombus treated surgically

Yang

et al. 2020

BMC Urol

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Background: Sarcomatoid differentiation in renal cell carcinoma (RCC) with vena caval tumour thrombus has been shown to be associated with aggressive behaviours and poor prognosis; however, evidence of the impact of rhabdoid differentiation on prognosis is lacking. This study evaluated the impact of sarcomatoid differentiation and rhabdoid differentiation on oncological outcomes for RCC with vena caval tumour thrombus treated surgically. Methods: We retrospectively analysed patients treated surgically for RCC with vena caval tumour thrombus at our institute from Jan 2015 to Nov 2018. Prognostic variables were evaluated for associations with progression-free survival (PFS) and cancer-specific survival (CSS) by Kaplan-Meier survival analysis and log-rank test. Univariate and multivariate analyses were performed to determine independent prognostic variables. Results:We identified 125 patients with RCC and vena caval tumour thrombus, including 17 (13.6%) with sarcomatoid differentiation alone, 8 (6.4%) with rhabdoid differentiation alone and 3 (2.4%) with both sarcomatoid and rhabdoid differentiation. Compared to pure RCC, patients with sarcomatoid differentiation but not rhabdoid differentiation have worse PFS (p = 0.018 and p = 0.095, respectively). The univariate and multivariate analyses both showed sarcomatoid differentiation as a significant predictor of PFS. Compared to pure RCC, patients with sarcomatoid differentiation (p = 0.002) and rhabdoid differentiation (p = 0.001) both had significantly worse CSS. The univariate analysis showed sarcomatoid differentiation, rhabdoid differentiation, metastasis and blood transfusion as significant predictors of CSS (All, p < 0.05). In the multivariate analysis, sarcomatoid differentiation (HR 3.90, p = 0.008), rhabdoid differentiation (HR 3.01, p = 0.042), metastasis (HR 3.87, p = 0.004) and blood transfusion (HR 1.34, p = 0.041) all remained independent predictors of CSS.Conclusions: Sarcomatoid differentiation and rhabdoid differentiation are both independent predictors of poor prognosis in RCC with vena caval tumour thrombus treated surgically.

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“…Since histologic subtypes were unbalanced between arms and unclassified and sarcomatoid histologies have poorer outcomes [20,21], we repeated the analyses excluding these two histologies. This subgroup analysis showed that pazopanib was associated with inferior PFS (median: 8.9 months versus 5.1 months; P = 0.011) and OS (median: 38.7 months versus 14.7 months; P = 0.015) in patients with papillary, chromophobe and MiT family translocation subtypes.…”

Section: Discussionmentioning

confidence: 99%

“…Data evaluating sRCC are scarce; however, some studies suggest poor outcomes with treatment with anti-VEGF TKIs [21,24]. Phase III studies evaluating first-line immune-checkpoint inhibitors for metastatic RCC showed that the subgroup of patients with sRCC has high PD-L1 expression (47%-63%) [25,26].…”

Section: Discussionmentioning

confidence: 99%

Real-world evidence on first-line treatment for metastatic renal cell carcinoma with non-clear cell and sarcomatoid histologies: are sunitinib and pazopanib interchangeable?

Bonadioa

Velho

Marta

et al. 2019

ecancer

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Introduction: Non-clear cell renal cell carcinoma (nccRCC) and sarcomatoid renal cell carcinoma (sRCC) are underrepresented in clinical trials. Treatment approaches are frequently extrapolated from data of clear cell renal cell carcinoma, in which pazopanib is non-inferior to sunitinib. We aim to compare the effectiveness of first-line sunitinib and pazopanib for nccRCC and sRCC. Methods: We evaluated a retrospective cohort of patients with metastatic nccRCC and sRCC treated with first-line sunitinib or pazopanib at an academic cancer centre. Overall survival (OS), progression-free survival (PFS) and response rate were measured. Kaplan-Meier and log-rank analyses were used for time-to-event data. Cox regression was used for prognostic factors. Results: Fifty-three patients were included; 16 (30.1%) treated with sunitinib and 37 (69.9%) with pazopanib. Forty-six (86.8%) patients had nccRCC and 7 (13.2%) had sRCC. The majority had intermediate or poor International Metastatic Renal-Cell Carcinoma Database Consortium risk (93%). Median PFS was 6.6 months with sunitinib and 4.9 months with pazopanib (HR 1.75; P = 0.078). Treatment with pazopanib was associated with inferior OS in comparison with sunitinib (median OS: 30.4 months versus 8.7 months; HR 2.71, 95% CI 1.31-5.58, P = 0.007). These results were confirmed in subgroup analysis of patients with papillary, chromophobe and MiT family translocation histologies (median OS: 38.7 months versus 14.7 months; HR 3.16, 95% CI 1.20-8.29, P = 0.019). Unclassified and sarcomatoid histologies had inferior OS (median: 6.9 and 1.1 months, respectively) regardless of the treatment used. Conclusion: In this patient cohort, pazopanib was associated with inferior OS in comparison with sunitinib for metastatic nccRCC. Larger trials are ideally warranted to confirm these results.

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Sarcomatoid renal cell carcinoma: Biology and treatment advances

Cited by 44 publications

References 56 publications

Outcomes Associated with First-Line anti-PD-1/ PD-L1 agents vs. Sunitinib in Patients with Sarcomatoid Renal Cell Carcinoma: A Systematic Review and Meta-Analysis

Outcomes Associated with First-Line anti-PD-1/ PD-L1 agents vs. Sunitinib in Patients with Sarcomatoid Renal Cell Carcinoma: A Systematic Review and Meta-Analysis

Impact of sarcomatoid differentiation and rhabdoid differentiation on prognosis for renal cell carcinoma with vena caval tumour thrombus treated surgically

Real-world evidence on first-line treatment for metastatic renal cell carcinoma with non-clear cell and sarcomatoid histologies: are sunitinib and pazopanib interchangeable?

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