Treatment Outcome and Survival Associated With Metastatic Renal Cell Carcinoma of Non–Clear-Cell Histology

Motzer, Robert J.; Bacik, Jennifer; Mariani, Tania; Russo, Paul; Mazumdar, Madhu; Reuter, Victor E.

doi:10.1200/jco.2002.11.123

Cited by 451 publications

(290 citation statements)

References 32 publications

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“…The low rate of response (5-10%) for some of the trailed chemotherapy like interferon and IL-2 point to the heterogeneous nature of kidney cancers treated. It is clear that, for example, non-clearcell metastatic RCC has a high resistance to systemic therapy and poor survival (Motzer et al, 2002). And even within the subtype such as the clear cell RCC, in the present studies there are at least two major subgroups: one group is characterized by deaths within 5 years and metastasis while the other consist of patients surviving more than 5 years without evidence of metastasis.…”

Section: Discussionmentioning

confidence: 71%

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Molecular subclassification of kidney tumors and the discovery of new diagnostic markers

et al. 2003

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We analysed the expression profiles of 70 kidney tumors of different histological subtypes to determine if these subgroups can be distinguished by their gene expression profiles, and to gain insights into the molecular mechanisms underlying each subtype. In all, 39 clear cell renal cell carcinomas (RCC), seven primary and one metastatic papillary RCC, six granular RCC from old classification, five chromophobe RCC, five sarcomatoid RCC, two oncocytomas, three transitional cell carcinomas (TCC) of the renal pelvis and five Wilms' tumors were compared with noncancerous kidney tissues using microarrays containing 19 968 cDNAs. Based on global gene clustering of 3560 selected cDNAs, we found distinct molecular signatures in clear cell, papillary, chromophobe RCC/ oncocytoma, TCC and Wilms' subtypes. The close clustering in each of these subtypes points to different tumorigenic pathways as reflected by their histological characteristics. In the clear cell RCC clustering, two subgroups emerged that correlated with clinical outcomes, confirming the potential use of gene expression signatures as a predictor of survival. In the so-called granular cell RCC (terminology for a subtype that is no longer preferred), none of the six cases clusters together, supporting the current view that they do not represent a single entity. Blinded histological re-evaluation of four cases of 'granular RCC' led to their reassignment to other existing histological subtypes, each compatible with our molecular classification. Finally, we found gene sets specific to each subtype. In order to establish the use of some of these genes as novel subtype markers, we selected four genes and performed immunohistochemical analysis on 40 cases of primary kidney tumors. The results were consistent with the gene expression microarray data: glutathione S-transferase a was highly expressed in clear cell RCC, a methylacyl racemase in papillary RCC, carbonic anhydrase II in chromophobe RCC and K19 in TCC. In conclusion, we demonstrated that molecular profiles of kidney cancers closely correlated with their histological subtypes. We have also identified in these subtypes differentially expressed genes that could have important diagnostic and therapeutic implications.

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Section: Discussionmentioning

confidence: 71%

“…Frequent loss of sex chromosomes, chromosomes 1 and 14 have been found in renal oncocytoma, a benign tumor composed of large eosinophilic cells arranged in acini (Presti et al, 1996). Accurate subtyping of renal tumors is critical for predicting prognosis and designing appropriate treatment for patients (Motzer et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Molecular subclassification of kidney tumors and the discovery of new diagnostic markers

et al. 2003

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“…8,9 In the metastatic setting, however, papillary RCC is characterized by poor prognosis and a resistance to systemic chemotherapy. [10][11][12] To date, standard treatment with interleukin-2 (IL-2) and interferon-a (IFNa) has demonstrated no efficacy in this disease. 11,13 The majority of clinical trial reports in metastatic RCC do not distinguish between clear and nonclear cell types, making it difficult to access treatment efficacy in this histologic subtype.…”

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confidence: 99%

“…[10][11][12] To date, standard treatment with interleukin-2 (IL-2) and interferon-a (IFNa) has demonstrated no efficacy in this disease. 11,13 The majority of clinical trial reports in metastatic RCC do not distinguish between clear and nonclear cell types, making it difficult to access treatment efficacy in this histologic subtype. 1 We performed a retrospective analysis of clinical features, treatment outcome, and survival for 38 patients who were treated at our center for metastatic papillary RCC.…”

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confidence: 99%

“…Some of these patients have been reported previously and were included here with extended follow-up. 11 A literature review on systemic therapy and outcome in papillary RCC was also performed. The starting point for this analysis was defined as the date of protocol entry for patients treated on a prospective clinical trial and the date of initial evaluation in the setting of clinically evident metastatic disease for the remaining patients.…”

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confidence: 99%

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Treatment outcome for metastatic papillary renal cell carcinoma patients

Ronnen¹,

Kondagunta²,

Ishill³

et al. 2006

Cancer

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BACKGROUND. Most clinical trial reports in metastatic renal cell carcinoma (RCC) do not distinguish between histologic subtypes, making it difficult to assess specific treatment efficacy. The current retrospective study sought to define clinical features and outcome data for metastatic papillary RCC. METHODS. Clinical features, treatment outcome, and survival were evaluated in 38 patients with metastatic papillary RCC who underwent clinical evaluation at Memorial Sloan‐Kettering Cancer Center (MSKCC) between 1985 and 2005. Twenty‐three of 513 individuals were identified from a clinical trial database, 14 of 1895 from a surgery database, and 1 of 357 from a pathology database. A literature review of systemic therapy in metastatic papillary RCC was performed. RESULTS. Among the 38 patients, 30 had been treated at MSKCC with various systemic therapies, including cytokines. Twelve therapies resulted in stable disease, 30 in initial progression of disease, and 1 in an unknown response. One patient had a partial response to sunitinib, a novel multitargeted tyrosine kinase inhibitor. The median overall survival time for the entire study group was 8 months (95% confidence interval, 5–12). A literature review on treatment of metastatic papillary RCC produced 4 reports, confirming a lack of efficacy for systemic therapy. CONCLUSIONS. A resistance to systemic therapy characterizes patients with metastatic papillary RCC. Further understanding of the genetics and molecular biology and subtypes involved may provide the basis for more effective agents. Treatment with targeted therapies or other experimental agents is warranted. Cancer 2006. © 2006 American Cancer Society.

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