Outcomes for Patients with Metastatic Renal Cell Carcinoma Achieving a Complete Response on Targeted Therapy: A Registry-based Analysis

Büchler, Tomáš; Bortlíček, Zbyněk; Poprach, Alexandr; Pavlík, Tomáš; Veškrňová, Veronika; Honzírková, Michaela; Zemanová, Milada; Fiala, Ondřej; Kubáčková, Kateřina; Slabý, Ondřej; Svoboda, Marek; Vyzula, Rostislav; Dušek, Ladislav; Melichar, Bohuslav

doi:10.1016/j.eururo.2015.12.031

Cited by 41 publications

(28 citation statements)

References 21 publications

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“…The chance of CR seems to be influenced more by the site of metastasis than by the number of metastatic sites. In addition, our data showed that TKI interruption at CR was not a predictor of DFS at univariate and multivariate analysis, in accordance with the recent results from the registry-based analysis led by Buchler et al [11]. Taken together, these data support a personalized follow-up for mRCC patients based on the metastatic sites in CR.…”

Section: Discussionsupporting

confidence: 92%

Risk of recurrence and conditional survival in complete responders treated with TKIs plus or less locoregional therapies for metastatic renal cell carcinoma

Santini

Santoni

Conti³

et al. 2016

Oncotarget

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PURPOSEWe retrospectively analyzed the risk of recurrence and conditional Disease-Free Survival (cDFS) in 63 patients with complete remission during treatment with tirosin kinase inhibitor (TKI), alone or with local treatment in metastatic renal cell carcinoma.RESULTS37% patients achieve CR with TKI alone, while 63% with additional loco-regional treatments. 49% patients recurred after CR, with a median Disease free survival of 28.2 months. Patients treated with multimodal approaches present lower rate of recurrence (40% vs 61%) and longer Disease free survival compared to patient treated with TKI alone (16.5 vs 41.9 months, p=0.039).Furthermore the rate of recurrence was higher in patients with brain (88%), pancreatic (71%) and bone metastasis (50%). Patients who continued TKI therapy after complete response had a longer disease free survival than patients who stopped therapy, although the difference was not significant (42.1 vs 25.1 months, p=0.254). 2y-cDFS was better in patients treated with multimodal treatment and who continued TKIs than the other patient arms.CONCLUSIONSThe prognostic value of CR depends on the site where was obtained and how was obtained (with or without locoregional treatment). Cessation of TKI should be carefully considered in complete responder patients.

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Section: Discussionsupporting

confidence: 92%

Risk of recurrence and conditional survival in complete responders treated with TKIs plus or less locoregional therapies for metastatic renal cell carcinoma

Santini

Santoni

Conti³

et al. 2016

Oncotarget

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“…From a clinical point of view, discontinuation of first-line anti-VEGF therapy might also be associated with reduced resistance towards antiangiogenetic drugs. Although Buchler et al (1) did not report data about second-line treatments, they reported that patients who discontinued anti-VEGF treatment after CR seemed to have better PFS rates after initiation of second-line therapy. Clearly, the potential advantage of treatment discontinuation after CR for better cancer control at second-line treatment still needs to be properly addressed, since several treatments with proven efficacy in second-line setting exist (6,22,23).…”

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confidence: 99%

“…However, it is important to note that these studies involved a relative small numbers of patients. In this regard, the report from Buchler et al (1) contains the largest series of patients who achieved CR after medical treatment for mRCC reported to date (n=100) allowing sub analyses in specific subgroup of individuals.…”

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confidence: 99%

“…In a recent issue of European Urology, Buchler et al (1) reported population-based results from a cohort of patients who achieved complete response (CR) after treatment with first-line targeted anti-vascular endothelial growth factor (VEGF) therapy. From the initial cohort of 2,803 patients, 100 individuals achieving CR were identified (3.6%).…”

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confidence: 99%

“…Interestingly, the majority of patients enrolled by Buchler et al (1) were treated with sunitinib, a generally recognized standard first-line treatment (19). The second most represented treatment group was of individuals treated with sorafenib, which (7,19) is no longer used as first-line therapy.…”

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confidence: 99%

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Complete response after treatment with first-line targeted anti-vascular endothelial growth factor therapy in metastatic renal cancer: what next?

2016

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Preservation of truncal genomic alterations in clear cell and papillary renal cell carcinomas with sarcomatoid features: An intra‐ and intertumoral, multifocal fluorescence in situ hybridization analysis reveals limited genetic heterogeneity

Sanfrancesco

Eble

Grignon

et al. 2017

Molecular Carcinogenesis

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Understanding tumor genomic heterogeneity may offer vital information in an age of targeted therapy for renal cell carcinoma. We sought to investigate hallmark truncal chromosomal alterations between conventional, sarcomatoid, and matched metastatic tumor foci in clear cell and papillary renal cell carcinomas. A retrospective review identified 58 cases including clear cell (CCRCC) and papillary renal cell carcinomas (PRCC). All cases contained sarcomatoid transformation. Additionally, 10 of 58 patients had matched metastatic disease available for analysis. Three separate foci of conventional and sarcomatoid morphologies were analyzed in each tumor using dual color interphase fluorescence in situ hybridization. In the CCRCC cohort, hallmark chromosome 3p deletion was identified in 71% of cases (37/52). Complete concordance of chromosomal status between intratumoral foci in sarcomatoid and conventional foci was 89% and 86%, respectively. Overall chromosome 3p status between matched conventional and sarcomatoid morphologies was identified in 98% of cases (51/52). Hallmark 3p deletion was present in 91% of CCRCC metastatic samples (10/11) and was concordant with the matched primary CCRCC tumor in 91% (10/11). In the PRCC cohort, trisomy 7 and 17 was identified in all six cases (6/6). Complete concordance between intratumoral foci of trisomy 7 and 17 was 83% (5/6). Trisomy 7 and 17 were identified in all metastatic PRCC samples with 100% concordance with the matched primary tumor. These data show the relative preservation of truncal chromosomal abnormalities between conventional and sarcomatoid morphologic as well as matched metastatic settings.

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Outcomes for Patients with Metastatic Renal Cell Carcinoma Achieving a Complete Response on Targeted Therapy: A Registry-based Analysis

Cited by 41 publications

References 21 publications

Risk of recurrence and conditional survival in complete responders treated with TKIs plus or less locoregional therapies for metastatic renal cell carcinoma

Risk of recurrence and conditional survival in complete responders treated with TKIs plus or less locoregional therapies for metastatic renal cell carcinoma

Complete response after treatment with first-line targeted anti-vascular endothelial growth factor therapy in metastatic renal cancer: what next?

Preservation of truncal genomic alterations in clear cell and papillary renal cell carcinomas with sarcomatoid features: An intra‐ and intertumoral, multifocal fluorescence in situ hybridization analysis reveals limited genetic heterogeneity

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