June 2020

Construction of a novel gene-based model for prognosis prediction of clear cell renal cell carcinoma

Zhang, Z., Lin, E., Zhuang, H. et al.
Cancer Cell Int 20, 27 (2020).
DOI: 10.1186/s12935-020-1113-6

Abstract

Background

Clear cell renal cell carcinoma (ccRCC) comprises the majority of kidney cancer death worldwide, whose incidence and mortality are not promising. Identifying ideal biomarkers to construct a more accurate prognostic model than conventional clinical parameters is crucial.

Methods

Raw count of RNA-sequencing data and clinicopathological data were acquired from The Cancer Genome Atlas (TCGA). Tumor samples were divided into two sets. Differentially expressed genes (DEGs) were screened in the whole set and prognosis-related genes were identified from the training set. Their common genes were used in LASSO and best subset regression which were performed to identify the best prognostic 5 genes. The gene-based risk score was developed based on the Cox coefficient of the individual gene. Time-dependent receiver operating characteristic (ROC) and Kaplan–Meier (KM) survival analysis were used to assess its prognostic power. GSE29609 dataset from GEO (Gene Expression Omnibus) database was used to validate the signature. Univariate and multivariate Cox regression were performed to screen independent prognostic parameters to construct a nomogram. The predictive power of the nomogram was revealed by time-dependent ROC curves and the calibration plot and verified in the validation set. Finally, Functional enrichment analysis of DEGs and 5 novel genes were performed to suggest the potential biological pathways.

Results

PADI1, ATP6V0D2, DPP6, C9orf135 and PLG were screened to be significantly related to the prognosis of ccRCC patients. The risk score effectively stratified the patients into high-risk group with poor overall survival (OS) based on survival analysis. AJCC-stage, age, recurrence and risk score were regarded as independent prognostic parameters by Cox regression analysis and were used to construct a nomogram. Time-dependent ROC curves showed the nomogram performed best in 1-, 3- and 5-year survival predictions compared with AJCC-stage and risk score in validation sets. The calibration plot showed good agreement of the nomogram between predicted and observed outcomes. Functional enrichment analysis suggested several enriched biological pathways related to cancer.

Conclusions

In our study, we constructed a gene-based model integrating clinical prognostic parameters to predict prognosis of ccRCC well, which might provide a reliable prognosis assessment tool for clinician and aid treatment decision-making in the clinic.

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Female Gender Predicts Favorable Prognosis in Patients With Non-metastatic Clear Cell Renal Cell Carcinoma Undergoing Curative Surgery: Results From the International Marker Consortium for Renal Cancer (INMARC)

Fukushima H, Saito K, Yasuda Y, et al
Clinical Genitourinary Cancer, Vol 18, Issue 2, P111-116.E1, April 2020
DOI: 10.1016/j.clgc.2019.10.027

Abstract

Background

There is no clear consensus regarding gender differences in the prognosis of patients with clear-cell renal cell carcinoma (ccRCC). In the present study, we investigated the prognostic value of gender in patients with non-metastatic ccRCC undergoing curative surgery using the inverse probability of treatment weighting (IPTW) method to balance the difference in baseline factors between females and males.

Patients and Methods

We retrospectively reviewed the International Marker Consortium for Renal Cancer (INMARC) dataset and included 2055 patients with cT1-4N0M0 ccRCC who underwent partial or radical nephrectomy. The IPTW method was used to adjust for baseline characteristics between females and males (age, race, surgery type, and pT stage), and the association of gender with recurrence-free survival (RFS) was evaluated.

Results

During the follow-up (median, 30 months), 162 (8%) patients had disease recurrence (5-year RFS rate, 88%). Female gender (n = 712; 35%) was significantly associated with a lower Fuhrman grade (unweighted, P = .022; IPTW-weighted, P < .001). Females had significantly better RFS compared with males (unweighted, 5-year RFS rate, 92% vs. 87%; P = .005; IPTW-weighted, 5-year RFS rate, 92% vs. 86%; P = .002). IPTW-weighted multivariate analysis showed that female gender was an independent predictor for better RFS (hazard ratio, 0.59; P = .005) along with lower pT stage and lower Fuhrman grade. The prognostic significance of female gender was also observed in the unweighted multivariate analysis.

Conclusions

Female gender was significantly associated with a lower Fuhrman grade and better prognosis for patients with non-metastatic ccRCC undergoing curative surgery.

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Deferred Cytoreductive Nephrectomy Following Presurgical Vascular Endothelial Growth Factor Receptor–targeted Therapy in Patients with Primary Metastatic Clear Cell Renal Cell Carcinoma: A Pooled Analysis of Prospective Trial Data

de Bruijn, Roderick et al.
European Urology Oncology, Volume 3, Issue 2, 168 – 173
DOI: 10.1016/j.euo.2019.12.004

Abstract

Background

Cancer du Rein Métastatique Nephrectomie et Antiangiogéniques (CARMENA) concluded that sunitinib alone is not inferior to cytoreductive nephrectomy (CN) followed by vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) in patients with metastatic renal cell carcinoma. It remains uncertain whether deferred CN is beneficial in this setting.

Objective

The aim of this study was to compare outcome in patients treated with presurgical VEGFR-TKI followed by CN (deferred CN) with that in patients receiving CN followed by VEGFR-TKI (upfront CN).

Design, setting, and participants

Pooled data from prospective trials in which a strategy of deferred CN in the absence of disease progression was investigated were compared with a retrospective dataset of upfront CN.

Outcome measurements and statistical analysis

Overall survival (OS) in the Memorial Sloan-Kettering Cancer Center (MSKCC) intermediate-risk group.

Results and limitations

Patients were treated between 2006 and 2016. In the MSKCC intermediate-risk group, 144 patients with a strategy of deferred CN after systemic therapy were compared with 131 patients treated with upfront CN. OS in the deferred cohort was 33.0 mo (95% confidence interval [CI] 25.0–51.0) compared with 22.8 mo (95% CI 17.9–30.6) after upfront CN (hazard ratio 0.72 [95% CI 0.52–0.996], p = 0.047). This study is limited by retrospective comparison of data, subgroup analysis, and a lack of intention-to-treat data for the upfront CN cohort.

Conclusions

In MSKCC intermediate-risk patients, a strategy of deferred CN in the absence of progression yields OS, which compares favourably with upfront CN and published trial data from CARMENA. This warrants a formal individual patient data analysis of CARMENA, SURTIME, and single-arm prospective studies to define the role and timing of deferred CN in intermediate-risk patients.

Patient summary

In this study, we report outcomes in patients with metastatic renal cell cancer treated with targeted therapy followed by nephrectomy, which compared favourably with nephrectomy followed by targeted therapy and results from published studies.

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Immunotherapy-based combinations versus standard first-line treatment for metastatic clear cell renal cell carcinoma: a systematic review and meta-analysis

Buti, S., Petrelli, F., Ghidini, A. et al.
Clin Transl Oncol (2020).
DOI: 10.1007/s12094-020-02292-z

Abstract

Purpose

Considering the recent publication of the results of several clinical trials for metastatic clear cell renal cell carcinoma (mRCC), we performed a systematic review and meta-analysis of randomized studies comparing standard first-line VEGFR-targeted therapy to immune checkpoint inhibitors-based combinations for mRCC patients.

Methods

3960 patients from 5 randomized clinical trials where available for evaluation.

Results

In the all-comers population, immunotherapy-based combinations were able to decrease the risk of death over the standard of care by 26% (HR 0.74; 95% CI 0.60–0.92; p = 0.006), to decrease the risk of progression by 21% (HR 0.79; 95% CI 0.72–0.86; p < 0.00001), and to increase the relative risk of response by 40% (HR 1.40; 95% CI 1.11–1.77; p = 0.006). For poor/intermediate-risk patients, the risk of death is decreased by 41% and the risk of progression by 27%.

Conclusion

The benefit of immunotherapy-based combinations in mRCC patients is independent from the IMDC risk group, but it is stronger for poor/intermediate-risk patients.

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Impact of Resection Technique on Perioperative Outcomes and Surgical Margins after Partial Nephrectomy for Localized Renal Masses: A Prospective Multicenter Study

Minervini A, Campi R, Lane B, et al.
Journal of Urology Vol. 203, 496-504, March 2020
DOI: 10.1097/JU.0000000000000591

Abstract

Purpose

The impact of resection technique on partial nephrectomy outcomes is controversial. The aim of this study was to evaluate the pattern of resection techniques during partial nephrectomy and the impact on perioperative outcomes, acute kidney injury, positive surgical margins and the achievement of the Trifecta (negative surgical margins, no perioperative Clavien-Dindo grade 2 or greater surgical complications and no postoperative acute kidney injury).

Materials and Methods

We prospectively collected data on consecutive patients with cT1-2N0M0 renal masses treated with partial nephrectomy at a total of 16 referral centers from September 2014 to March 2015. After partial nephrectomy the resection technique was classified by the surgeon as enucleation, enucleoresection or resection according to the SIB (Surface-Intermediate-Base) margin scores 0 to 2, 3 or 4 and 5, respectively. Multivariable logistic regression analysis was done to evaluate the potential impact of the resection technique on postoperative surgical complications, positive surgical margins, acute kidney injury and Trifecta achievement.

Results

Overall 507 patients were included in analysis. The resection technique was classified as enucleation in 266 patients (52%), enucleoresection in 150 (30%) and resection in 91 (18%). The resection technique (enucleoresection vs enucleation and resection) was the only significant predictor of positive surgical margins. Tumor complexity, surgical approach (open and laparoscopic vs robotic) and resection technique (enucleoresection vs enucleation) were significant predictors of Clavien-Dindo grade 2 or greater surgical complications. The surgical approach (open and laparoscopic vs robotic), the resection technique (enucleoresection vs enucleation) and warm ischemia time were significantly associated with postoperative acute kidney injury and Trifecta achievement.

Conclusion

Resection techniques significantly impact surgical complications, early functional outcomes and positive surgical margins after partial nephrectomy of localized renal masses.

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