Dataset Information

Prognostic analysis of postoperative clinically nonmetastatic renal cell carcinoma.

ABSTRACT:

Objectives

To investigate the survival characteristics of postoperative nonmetastatic renal cell carcinoma (RCC) patients, and the predictive value of a prognostic model.

Materials and methods

We retrospectively evaluated data from 1202 postoperative nonmetastatic RCC patients who were treated between 1999 and 2012 at West China Hospital, Sichuan University (Chengdu, China). In addition, we also evaluated data relating to 53 205 cases acquired from the Surveillance, Epidemiology, and End Results (SEER) program. Survival analysis was performed on the cases, and subgroups, using the Kaplan-Meier and Cox regression methods. The concordance index of the Stage Size Grade Necrosis (SSIGN), Leibovich, and the UCLA integrated staging system, scores was determined to evaluate the accuracy of these outcome prediction models.

Results

The 5-year overall survival rate for RCC cases in West China Hospital was 87.6%; this was higher than that observed for SEER cases. Survival analysis identified several factors that exerted significant influence over prognosis, including the time of surgery, Eastern Cooperative Oncology Group performance status, tumor stage, size, nuclear differentiation, pathological subtypes, along with necrotic and sarcomatoid differentiation. Moreover tumor stage, size, and nuclear grade were all identified as independent predictors for both our cases and those from the SEER program. Patient groups with advanced RCC, and poorly differentiated RCC subgroups, were both determined to have a poor prognosis. The SSIGN model yielded the best predictive value as a prognostic model, followed by the Leibovich, and UCLA integrated staging system; this was the case for our patients, and for sub-groups with a poor prognosis.

Conclusion

The prognosis of RCC was mostly influenced by tumor stage, size, and nuclear differentiation. SSIGN may represent the most suitable prognostic model for the Chinese population.

SUBMITTER: Shao Y

PROVIDER: S-EPMC6997064 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Publications

Prognostic analysis of postoperative clinically nonmetastatic renal cell carcinoma.

Shao Yanxiang Y Xiong Sanchao S Sun Guangxi G Dou Weichao W Hu Xu X Yang Weixiao W Lia Thongher T Deng Shi S Wei Qiang Q Zeng Hao H Li Xiang X

Cancer medicine 20191216 3

<h4>Objectives</h4>To investigate the survival characteristics of postoperative nonmetastatic renal cell carcinoma (RCC) patients, and the predictive value of a prognostic model.<h4>Materials and methods</h4>We retrospectively evaluated data from 1202 postoperative nonmetastatic RCC patients who were treated between 1999 and 2012 at West China Hospital, Sichuan University (Chengdu, China). In addition, we also evaluated data relating to 53 205 cases acquired from the Surveillance, Epidemiology, ...[more]

PMID: 31840431

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Project description:BACKGROUND:Greater than 40% of renal cell carcinoma (RCC) cases in the United States are attributed to excessive body weight. Moreover, obesity also may be linked to RCC prognosis. However, the molecular mechanisms underlying these associations are unclear. In the current study, the authors evaluated the role of promoter methylation in obesity-related genes in RCC tumorigenesis and disease recurrence. METHODS:Paired tumors (TU) and normal adjacent (N-Adj) tissues from 240 newly diagnosed and previously untreated white patients with RCC were examined. For the discovery phase, 63 RCC pairs were analyzed. An additional 177 RCC pairs were evaluated for validation. Pyrosequencing was used to determine CpG methylation in 20 candidate obesity-related genes. An independent data set from The Cancer Genome Atlas also was analyzed for functional validation. The association between methylation and disease recurrence was analyzed using multivariate Cox proportional hazards models and Kaplan-Meier survival analysis. RESULTS:Methylation in neuropeptide Y (NPY), leptin (LEP), and leptin receptor (LEPR) was significantly higher in TU compared with N-Adj tissues (P<.0001) in both the discovery and validation groups. High methylation in LEPR was associated with an increased risk of disease recurrence (hazard ratio, 3.15; 95% confidence interval, 1.23-8.07 [P = .02]). Patients with high methylation in LEPR had a shorter recurrence-free survival compared with patients in the low-methylation group (log-rank P = 2.25 × 10-3 ). In addition, high LEPR methylation in TU was associated with more advanced features (P≤.05). Consistent with the findings of the current study, lower LEPR expression in TU compared with N-Adj tissues (P = 1.00 × 10-3 ) was found in data from The Cancer Genome Atlas. CONCLUSIONS:Somatic alterations of promoter methylation in the NPY, LEP, and LEPR genes are involved in RCC tumorigenesis. Furthermore, LEPR methylation appears to be associated with RCC recurrence. Future research to elucidate the biology underlying this association is warranted. Cancer 2017;123:3617-27. © 2017 American Cancer Society.

Project description:Previous studies have shown a modest impact of tyrosine kinase inhibitors on primary renal tumors. Those studies were mostly retrospective or heterogeneous in their eligibility criteria with regard to histology, disease stage, duration of therapy, and time off therapy prior to surgery.To prospectively investigate the safety and efficacy of axitinib in downsizing tumors in patients with nonmetastatic biopsy-proven clear cell renal cell carcinoma (ccRCC).This was a single-institution, single-arm phase 2 clinical trial. Patients with locally advanced nonmetastatic biopsy-proven ccRCC were eligible.Patients received axitinib 5mg for up to 12 wk. Axitinib was continued until 36h prior to surgery. Patients underwent partial or radical nephrectomy after axitinib therapy.The primary outcome was objective response rate prior to surgery. Secondary outcomes included safety, tolerability, and quality of life. A dedicated radiologist independently reviewed all computed tomography scans to evaluate for response using Response Evaluation Criteria in Solid Tumors (RECIST).A total of 24 patients were treated. Twenty-two patients continued axitinib for 12 wk; 1 patient continued axitinib for 11 wk and underwent surgery as planned. One patient stopped treatment at 7 wk due to adverse events (AEs). Median reduction of primary renal tumor diameter was 28.3%. Eleven patients experienced a partial response per RECIST; 13 had stable disease. There was no progression of disease while on axitinib. The most common AEs were hypertension, fatigue, oral mucositis, hypothyroidism, and hand-foot syndrome. Postoperatively, 2 grade 3 and 13 grade 2 complications were noted. No grade 4 or 5 complications occurred. Functional Assessment of Cancer Therapy-Kidney Specific Index-15 changed over time, with quality of life worsening while on therapy, but by week 19, it was not statistically different from screening. Limitations include single-arm design and small patient numbers.Axitinib was clinically active and reasonably well tolerated in the neoadjuvant setting in patients with locally advanced nonmetastatic ccRCC.In this prospective clinical trial, we found that axitinib, when given prior to surgery, results in significant shrinking of kidney cancers. Larger studies are needed prior to further clinical use.This clinical trial was registered with clinicaltrials.gov (NCT01263769).

Dataset Information

Prognostic analysis of postoperative clinically nonmetastatic renal cell carcinoma.

Objectives

Materials and methods

Results

Conclusion

Publications

Prognostic analysis of postoperative clinically nonmetastatic renal cell carcinoma.

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