Articles

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.

Read article

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.

Read article

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.

Read article

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.

Read article

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.

Read article

Chronic Kidney Disease and Kidney Cancer Surgery: New Perspectives

Huang W, Donin N, Levey A and Campbell S
Journal of Urology Vol. 203, 475-485, March 2020
DOI: 10.1097/JU.0000000000000326

Abstract

Purpose

We sought to provide a contemporary understanding of chronic kidney disease and its relevance to kidney cancer surgery. Another purpose was to resolve points of discrepancy regarding the survival benefits of partial vs radical nephrectomy by critically evaluating the results of prospective and retrospective studies in the urological literature.

Materials and Methods

We performed a comprehensive literature search for relevant articles listed in MEDLINE® from 2002 to 2018 using the key words radical nephrectomy, partial nephrectomy, glomerular filtration rate, kidney function and chronic kidney disease. We also assessed select review articles and society guidelines about chronic kidney disease pertinent to urology and nephrology.

Results

Complete evaluation of the potential consequences of chronic kidney disease involves assessment of the cause, the glomerular filtration rate level and the degree of albuminuria. Chronic kidney disease is commonly defined in the urological literature solely as a glomerular filtration rate less than 60 ml/minute/1.73 m 2. This ignores the significance of the cause of chronic kidney disease, and the presence and degree of albuminuria. Although this glomerular filtration rate is relevant for preoperative assessment of patients who undergo surgery of kidney tumors, recent studies suggest that a glomerular filtration rate less than 45 ml/minute/1.73 m 2 represents a more discerning postoperative prognostic threshold. Reported survival benefits of partial over radical nephrectomy in retrospective studies were likely influenced by selection bias. The lack of survival benefit in the partial nephrectomy cohort in the only randomized trial of partial vs radical nephrectomy was consistent with data demonstrating that patients in each study arm were at relatively low risk for mortality due to chronic kidney disease when accounting for the chronic kidney disease etiology and the postoperative glomerular filtration rate.

Conclusion

The prognostic risk of chronic kidney disease in patients with kidney cancer is increased when the preoperative glomerular filtration rate is less than 60 ml/minute/1.73 m 2 or the postoperative rate is less than 45 ml/minute/1.73 m 2. Additional factors, including nonsurgical causes of chronic kidney disease and the degree of albuminuria, can also dramatically alter the consequences of chronic kidney disease after kidney cancer surgery. Urologists must have a comprehensive knowledge of chronic kidney disease to assess the risks and benefits of partial vs radical nephrectomy when managing tumors with increased complexity and/or oncologic aggressiveness.

Read article

Long-term Risk of Recurrence in Surgically Treated Renal Cell Carcinoma: A Post Hoc Analysis of the Eastern Cooperative Oncology Group—American College of Radiology Imaging Network E2805 Trial Cohort

Jamil, Marcus L. et al.
European Urology, Volume 77, Issue 2, 277 – 281
DOI: 10.1016/j.eururo.2019.10.028

Abstract

Currently, surveillance guidelines following surgical resection of clinically localized renal cell carcinoma (RCC) are clear within the first 5 yr; however, these lack the same degree of objectivity following this cutoff. We sought to investigate the long-term risk of recurrence in surgically treated RCC in order to determine the utility of long-term surveillance. A post hoc analysis of patients within the Eastern Cooperative Oncology Group—American College of Radiology Imaging Network (ECOG-ACRIN) E2805 trial cohort was performed. The 36-mo cumulative incidence of recurrence was assessed at set intervals following surgery, in order to dynamically assess recurrence through the use of a conditional survival model. Of the 1943 patients included in the original cohort, 730 developed recurrence. The 36-mo cumulative incidences of recurrence were found to be 31%, 26%, 19%, 16%, 19%, and 20% for patients at 0, 12, 24, 36, 48, and 60 mo from surgery, respectively. At 0 mo from surgery, age, pathological T3/4 stage (hazard ratio [HR] = 1.56), pathological N1/2 stage (HR = 2.38), and Fuhrman grades 3 and 4 (HR = 1.36 and HR = 2.41, respectively) were independent predictors of recurrence; however, this was not seen at 60 mo following surgery. These findings support that surveillance imaging should be performed beyond 5 yr following surgical resection of intermediate- to high-risk RCC.

Patient summary

Follow-up for surgically resected localized renal cell carcinoma should be performed beyond 5 yr, for the rates of recurrence remain significant beyond this 5 yr endpoint.

Read article

Comparable efficacy and safety between second-line and later-line nivolumab therapy for metastatic renal cell carcinoma

Ishihara, H., Takagi, T., Kondo, T. et al.
Int J Clin Oncol 25, 705–712 (2020).
DOI: 10.1007/s10147-019-01605-9

Abstract

Background

The aim of this study was to compare the efficacy and safety of nivolumab as second-line and later-line (third-line or thereafter) therapy in metastatic renal cell carcinoma (mRCC).

Methods

Sixty-seven patients who received nivolumab after the failure of at least one molecular-targeted therapy were evaluated. The patients were divided into two groups based on the line of nivolumab: second-line and later-line groups. Efficacy was assessed using progression-free survival and overall survival (OS) after nivolumab initiation, and objective response rate. Safety was assessed using the incidence of immune-related adverse events. These outcomes were compared between the second-line and later-line groups.

Results

Forty-two patients (62.7%) received nivolumab as second-line therapy. There was no significant difference in the progression-free survival (median: 5.06 vs. 6.28 months, p = 0.691) or objective response rate (35.7% vs. 32.0%, p = 0.757) between the second-line and later-line groups. The OS tended to be longer in the second-line group (not reached vs. 26.0 months, p = 0.118), and the rate of patients who received subsequent therapy after nivolumab failure was significantly higher in the second-line group (90.9% vs. 55.0%, p = 0.0025). There was no difference in the incidences of immune-related adverse events between the second-line and later-line groups (any grade: 54.8% vs. 48.0%, p = 0.592; grade ≥ 3: 19.1% vs. 20.0%, p = 0.924).

Conclusion

The efficacy of nivolumab did not deteriorate and the tolerability was also maintained even in later-line therapy. However, a tendency of longer OS and a higher chance of subsequent therapy after nivolumab failure were observed with nivolumab as second-line therapy.

Read article

Long-Term Survival after Percutaneous Radiofrequency Ablation of Pathologically Proven Renal Cell Carcinoma in 100 Patients

Marshall, Harry R. et al.
Journal of Vascular and Interventional Radiology, Volume 31, Issue 1, 15 – 24
DOI: 10.1016/j.jvir.2019.09.011

Abstract

Purpose

To determine the long-term survival of patients treated with percutaneous radiofrequency (RF) ablation for pathologically proven renal cell carcinoma (RCC).

Materials and Methods

In this single-center retrospective study, 100 patients with 125 RCCs (100 clear-cell, 19 papillary, and 6 chromophobe) 0.8–8 cm in size treated with RF ablation were evaluated at a single large tertiary-care center between 2004 and 2015. Technical success, primary and secondary technique efficacy, and pre- and postprocedural estimated glomerular filtration rate (eGFR) at 3–6 months and 2–3 years were recorded. Overall survival, cancer-specific survival, and local tumor progression–free survival were calculated by Kaplan–Meier survival curves. Complications were classified per the Clavien–Dindo system. Statistical testing was done via χ2tests for proportions and paired t test for changes in eGFR. Statistical significance was set at α = 0.05.

Results

Overall technical success rate was 100%, and primary and secondary technique efficacy rates were 90% and 100%, respectively. Median follow-up was 62.8 months, ranging from 1 to 120 months. The 10-year overall, cancer-specific, and local progression–free survival rates were 32%, 86%, and 92%, respectively. The number of ablation probes used was predictive of residual unablated tumor (P < .001). There were no significant changes in preprocedure vs 2–3-years postprocedure eGFR (65.2 vs 62.1 mL/min/1.73 m2; P = .443). There was a 9% overall incidence of complications, the majority of which were grade I.

Conclusion

Image-guided percutaneous RF ablation of RCCs is effective at achieving local control and preventing cancer-specific death within 10 years from initial treatment.

Read article
You don't have permission to register