Dataset Information

Balancing cardiovascular (CV) and cancer death among patients with small renal masses: modification by CV risk.

ABSTRACT:

Objective

To assess modification of comparative cancer survival by cardiovascular (CV) risk and treatment strategy among older patients with small renal masses (SRMs).

Patients and methods

Patients with localised T1a renal cell carcinoma were identified in the Surveillance, Epidemiology and End Results-Medicare database (1995-2007). Patients were stratified by CV risk, using major atherosclerotic CV comorbidities identified by the Framingham Heart Study, to compare overall (OS), cancer-specific (CSS), and CV-specific survival (CVSS) for those who deferred therapy (DT) to those undergoing either partial (PN) or radical nephrectomy (RN). Cox proportional hazards and Fine and Gray competing risks regression adjusted for demographics, comorbidities, and tumour size were performed.

Results

In all, 754 (10.5%) patients had DT, 1849 (25.8%) patients underwent PN, and 4574 (63.7%) patients underwent RN. Patients at high CV risk who had DT had the greatest CV-to-cancer mortality rate ratio (2.89), and CV risk was generally associated with worse OS and CVSS. Patients in the high CV risk strata had no difference in CSS between treatment strategies [DT vs PN: hazard ratio (HR) 0.59, 95% confidence interval (CI) 0.25-1.41; DT vs RN: HR 0.81, 95%CI 0.46-1.43)], while there was a 2-4 fold CSS benefit for surgery in the low CV risk strata.

Conclusions

Cancer survival was comparable across treatment strategies for older patients with SRMs with high risk CV disease. Greater attention to CV comorbidity as it relates to competing risks of death and life expectancy may be deserved in selecting patients appropriate for active surveillance because patients at low CV risk might benefit from surgery.

SUBMITTER: Patel HD

PROVIDER: S-EPMC4153794 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature

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Publications

Balancing cardiovascular (CV) and cancer death among patients with small renal masses: modification by CV risk.

Patel Hiten D HD Kates Max M Pierorazio Phillip M PM Allaf Mohamad E ME

BJU international 20140727 1

<h4>Objective</h4>To assess modification of comparative cancer survival by cardiovascular (CV) risk and treatment strategy among older patients with small renal masses (SRMs).<h4>Patients and methods</h4>Patients with localised T1a renal cell carcinoma were identified in the Surveillance, Epidemiology and End Results-Medicare database (1995-2007). Patients were stratified by CV risk, using major atherosclerotic CV comorbidities identified by the Framingham Heart Study, to compare overall (OS), c ...[more]

PMID: 24589376

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Project description:The majority of renal cell carcinoma (RCC) is now incidentally detected and presents as small renal masses (SRMs) defined as ≤ 4 cm in size. SRMs are heterogeneous comprising several histological types of RCC each with different biology and behavior, and benign tumors mainly oncocytoma. The varied prognosis of the different types of renal tumor has implications for management options. A key epigenetic alteration involved in the initiation and progression of cancer is aberrant methylation in the promoter region of a gene. The hypermethylation is associated with transcriptional repression and is an important mechanism of inactivation of tumor suppressor genes in neoplastic cells. We have determined the genome-wide promoter methylation profiles of 47 pT1a and 2 pT1b clear cell, papillary or chromophobe RCC, 25 benign renal oncocytoma ≤ 4 cm and 4 normal renal parenchyma specimens by Infinium HumanMethylation27 beadchip technology. We identify gene promoter hypermethylation signatures that distinguish clear cell and papillary from each other, from chromophobe and oncocytoma, and from normal renal cells. Pairwise comparisons revealed genes aberrantly hypermethylated in a tumor type but unmethylated in normal, and often unmethylated in the other renal tumor types. About 0.4% to 1.7% of genes comprised the promoter methylome in SRMs. The Infinium methylation score for representative genes was verified by gold standard technologies. The genes identified as differentially methylated implicate pathways involved in metabolism, tissue response to injury, epithelial to mesenchymal transition (EMT), signal transduction and G-protein coupled receptors (GPCRs), cancer, and stem cell regulation in the biology of RCC. Our findings contribute towards an improved understanding of the development of RCC, the different biology and behavior of histological types, and discovery of molecular subtypes. The differential methylation signatures may have utility in early detection and particularly differential diagnosis for prognostic stratification as well as identify novel gene and pathway targets for therapeutic intervention.

Project description:PurposeDespite general indolence of small renal masses and no known adversity from treatment delays, broad usage of active surveillance as a means to risk-stratify patients with small renal masses for more selective treatment has not been studied. We describe outcomes for a novel approach in which active surveillance was recommended to all patients with small renal masses lacking predefined progression criteria for intervention.Materials and methodsAll nondialysis dependent patients with nonmetastatic small renal masses seen by 1 urologist at a comprehensive cancer center during January 2013-September 2017 were managed with active surveillance if standardized progression criteria for intervention were absent, with delayed intervention recommended only upon progression criteria for intervention development. Progression criteria for intervention were defined prospectively as small renal mass-related symptoms, unfavorable histology, cT3a stage or either of the following without benign neoplastic biopsy histology: longest tumor diameter >4 cm; growth rate >5 mm/year for longest tumor diameter ≤3 cm or >3 mm/year for longest tumor diameter >3 cm.ResultsIn all, 96% (123/128) of patients with small renal masses lacked progression criteria for intervention at presentation and underwent active surveillance. With median/mean 31/34 months followup, none developed metastasis and 30% (37/123) developed progression criteria for intervention, 78% (29/37) of whom underwent delayed intervention. One (1%) patient crossed over to delayed intervention without progression criteria for intervention. Three-year progression criteria for intervention-free and delayed intervention-free rates were 72% and 75%, respectively. Delayed intervention resections were enriched (62%) for pT3 and/or nuclear grade 3-4 malignant pathology, with no benign resections.ConclusionsActive surveillance using predefined progression criteria for intervention in otherwise unselected patients with small renal masses allows intervention to be focused on at-risk small renal masses with common adverse pathology, avoiding treatment for most patients with small renal masses. Long-term delayed intervention and oncologic safety require study.

Dataset Information

Balancing cardiovascular (CV) and cancer death among patients with small renal masses: modification by CV risk.

Objective

Patients and methods

Results

Conclusions

Publications

Balancing cardiovascular (CV) and cancer death among patients with small renal masses: modification by CV risk.

Similar Datasets

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