junio 2019

Predictive value of single-nucleotide polymorphism signature for recurrence in localised renal cell carcinoma: a retrospective analysis and multicentre validation study

Wei J, Feng Z, Cao Y, et al.
Lancet Oncol. April 2019
DOI: 10.1016/S1470-2045(18)30932-X

Summary

BACKGROUND:

Identification of high-risk localised renal cell carcinoma is key for the selection of patients for adjuvant treatment who are at truly higher risk of reccurrence. We developed a classifier based on single-nucleotide polymorphisms (SNPs) to improve the predictive accuracy for renal cell carcinoma recurrence and investigated whether intratumour heterogeneity affected the precision of the classifier.

METHODS:

In this retrospective analysis and multicentre validation study, we used paraffin-embedded specimens from the training set of 227 patients from Sun Yat-sen University (Guangzhou, Guangdong, China) with localised clear cell renal cell carcinoma to examine 44 potential recurrence-associated SNPs, which were identified by exploratory bioinformatics analyses of a genome-wide association study from The Cancer Genome Atlas (TCGA) Kidney Renal Clear Cell Carcinoma (KIRC) dataset (n=114, 906 600 SNPs). We developed a six-SNP-based classifier by use of LASSO Cox regression, based on the association between SNP status and patients’ recurrence-free survival. Intratumour heterogeneity was investigated from two other regions within the same tumours in the training set. The six-SNP-based classifier was validated in the internal testing set (n=226), the independent validation set (Chinese multicentre study; 428 patients treated between Jan 1, 2004 and Dec 31, 2012, at three hospitals in China), and TCGA set (441 retrospectively identified patients who underwent resection between 1998 and 2010 for localised clear cell renal cell carcinoma in the USA). The main outcome was recurrence-free survival; the secondary outcome was overall survival.

FINDINGS:

Although intratumour heterogeneity was found in 48 (23%) of 206 cases in the internal testing set with complete SNP information, the predictive accuracy of the six-SNP-based classifier was similar in the three different regions of the training set (areas under the curve [AUC] at 5 years: 0,749 [95% CI 0,660–0,826] in region 1, 0,734 [0,651–0,814] in region 2, and 0,736 [0,649–0,824] in region 3). The six-SNP-based classifier precisely predicted recurrence-free survival of patients in three validation sets (hazard ratio [HR] 5,32 [95% CI 2,81–10,07] in the internal testing set, 5,39 [3,38–8,59] in the independent validation set, and 4,62 [2,48–8,61] in the TCGA set; all p<0·0001), independently of patient age or sex and tumour stage, grade, or necrosis. The classifier and the clinicopathological risk factors (tumour stage, grade, and necrosis) were combined to construct a nomogram, which had a predictive accuracy significantly higher than that of each variable alone (AUC at 5 years 0,811 [95% CI 0,756–0,861]).

INTERPRETATION:

Our six-SNP-based classifier could be a practical and reliable predictor that can complement the existing staging system for prediction of localised renal cell carcinoma recurrence after surgery, which might enable physicians to make more informed treatment decisions about adjuvant therapy. Intratumour heterogeneity does not seem to hamper the accuracy of the six-SNP-based classifier as a reliable predictor of recurrence. The classifier has the potential to guide treatment decisions for patients at differing risks of recurrence.

FUNDING:

National Key Research and Development Program of China, National Natural Science Foundation of China, Guangdong Provincial Science and Technology Foundation of China, and Guangzhou Science and Technology Foundation of China.

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Frequency and Predictors of Renal Transplantation Among Patients Rendered Surgically Anephric for Sporadic Renal Cancer

Boswell T, Sharma V, Westerman M, et al.
Urology. April 2019.
DOI: 10.1016/j.urology.2018.12.037

Abstract

OBJECTIVE:

To assess the frequency of renal transplantation in patients rendered surgically anephric during treatment of renal cancers as well as the clinicopathologic factors associated with receipt of transplantation.

METHODS:

A retrospective review was conducted to identify patients rendered surgically anephric between 2001 and 2016 due to cancer in both renal units or cancer in an anatomically or functionally solitary kidney. Patient demographics, comorbidities, and cancer features were compared between patients who subsequently received a renal transplantation and those who did not. Time-to-event analysis was used to compare time to transplantation across varied identified parameters.

RESULTS:

Among 27 patients rendered anephric, 4 (15%) received a renal transplantation over a median follow-up of 21.6 months (interquartile range 7.2, 53.3). All transplanted patients were less than 70 years of age and had cT1a renal parenchymal mass at the time of nephrectomy. No patient undergoing completion nephrectomy for upper tract urothelial carcinoma received transplantation. Patients who were evaluated by the transplant service prior to nephrectomy were more likely to eventually undergo transplantation (60% vs 5%; P < .01). On time-to-event analyses, a cT1a renal parenchymal mass (P < .01) and a pre-nephrectomy transplant evaluation (P < .01) were associated with receipt of a transplant.

CONCLUSION:

Patients rendered anephric via nephrectomy for cancer are more likely to receive renal transplantation if they are less than 70 years old, have a cT1a renal parenchymal mass, and receive transplant consultation before nephrectomy. These data may inform future patient counseling.

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Selecting Patients with Small Renal Masses for Active Surveillance: A Domain Based Score from a Prospective Cohort Study

Sotimehin A, Patel H, Alam R, et al.
J Urol. May 2019
DOI: 10.1097/JU.0000000000000033

Abstract

PURPOSE:

We sought to identify predictors of active surveillance in a prospective cohort study of patients with a small renal mass demonstrating favorable outcomes. We generated a summary score to discriminate patients selected for active surveillance or primary intervention.

MATERIALS AND METHODS:

We analyzed the records of 751 patients from 2009 to 2018 who were enrolled in the DISSRM (Delayed Intervention and Surveillance for Small Renal Masses) Registry to compare active surveillance and primary intervention in the domains of demographics, tumor characteristics, comorbidity and patient reported quality of life. Regression models were created to assess univariable and multivariable model discrimination by the AUC and quality by the AIC (Akaike information criterion). The DISSRM score was based on the most predictive combination of variables and validated for its association with overall survival by Kaplan-Meier survival curves and a Cox proportional hazards regression model.

DESIGN, SETTING, AND PARTICIPANTS:

Multicenter retrospective analysis of 653 patients aged >75 yr who underwent PN (REnal SURGery in Elderly [RESURGE] Group).

RESULTS:

Of the patients 410 (55%) elected active surveillance and 341 (45%) elected primary intervention. Of the domains patient age, the Charlson comorbidity index, tumor diameter and the SF-12® Physical Component Score had the greatest discrimination for clinical selection into active surveillance. These domains made up the DISSRM score (AUC 0.801). The maximum DISSRM score was 7. The average score for active surveillance was 4.19 (median 4, IQR 2–6) and 72% of scores were 4 or greater. The average score for primary intervention was 3.03 (median 3, IQR 1–5) and 63% of scores were 3 or less. A higher DISSRM score was associated with worse overall survival, for example a score of 6-7 had a HR of 10.45 (95% CI 1.25–87.49, p = 0.03).

CONCLUSIONS:

The DISSRM score represents a measure of oncologic and competing risks of death in various important domains in patients with a small renal mass. It could be used to guide the management selection. Patients with intermediate scores that express illness uncertainty may require additional workup, such as confirmatory biopsy, to reach a treatment decision.

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Trifecta Outcomes of Partial Nephrectomy in Patients Over 75 Years Old: Analysis of the REnal SURGery in Elderly (RESURGE) Group

Bindayi A, Autorino Rb, Capitanio U, et al.
Eur Urol Focus Feb 2019.
DOI: 10.1016/j.euf.2019.02.010

Abstract

BACKGROUND:

Partial nephrectomy (PN) in elderly patients is underutilized with concerns regarding risk of complications and potential for poor outcomes.

OBJECTIVES:

To evaluate quality and functional outcomes of PN in patients >75 yr using trifecta as a composite outcome of surgical quality.

DESIGN, SETTING, AND PARTICIPANTS:

Multicenter retrospective analysis of 653 patients aged >75 yr who underwent PN (REnal SURGery in Elderly [RESURGE] Group).

INTERVENTION:

PN.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:

Primary outcome was achievement of trifecta (negative margin, no major [Clavien ≥3] urological complications, and ≥90% estimated glomerular filtration rate [eGFR] recovery). Secondary outcomes included chronic kidney disease (CKD) stage III and CKD upstaging. Multivariable analysis (MVA) was used to assess variables for achieving trifecta and functional outcomes. Kaplan-Meier survival analysis (KMA) was used to calculate renal functional outcomes.

RESULTS AND LIMITATIONS:

We analyzed 653 patients (mean age 78.4 yr, median follow-up 33 mo; 382 open, 157 laparoscopic, and 114 robotic). Trifecta rate was 40.4% (n = 264). Trifecta patients had less transfusion (p < 0.001), lower intraoperative (5.3% vs 27%, p < 0.001) and postoperative (25.4% vs 37.8%, p = 0.001) complications, shorter hospital stay (p = 0.045), and lower ΔeGFR (p < 0.001). MVA for predictive factors for trifecta revealed decreasing RENAL nephrometry score (odds ratio [OR] 1.26, 95% confidence interval 1.07–1.51, p = 0.007) as being associated with increased likelihood to achieve trifecta. Achievement of trifecta was associated with decreased risk of CKD upstaging (OR 0.47, 95% confidence interval 0.32–0.62, p < 0.001). KMA showed that trifecta patients had improved 5-yr freedom from CKD stage 3 (93.5% vs 57.7%, p < 0.001) and CKD upstaging (84.3% vs 8.2%, p < 0.001). Limitations include retrospective design.

CONCLUSIONS:

PN in elderly patients can be performed with acceptable quality outcomes. Trifecta was associated with decreased tumor complexity and improved functional preservation.

PATIENT SUMMARY:

We looked at quality outcomes after partial nephrectomy in elderly patients. Acceptable quality outcomes were achieved, measured by a composite outcome called trifecta, whose achievement was associated with improved kidney functional preservation.

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