Adjuvant Radiation Therapy After Radical Nephrectomy in Patients with Localized Renal Cell Carcinoma: A Systematic Review and Meta-analysis

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Abstract

Context

Adjuvant radiation therapy has been recommended for patients at higher risk of relapse from renal cell carcinoma (RCC) to improve disease-free survival (DFS) and overall survival (OS) after radical nephrectomy.

Objective

To quantify the benefit of adjuvant radiation therapy.

Evidence acquisition

A systematic review of electronic databases identified publications exploring the association between adjuvant radiation therapy and locoregional recurrence (LRR), DFS, and OS among patients after radical nephrectomy for early-stage RCC. Hazard ratios for DFS were weighted and pooled using the generic inverse variance and random effects model. Odds ratios for LRR, DFS, and OS at 5 yr were weighted and pooled in a meta-analysis using Mantel-Haenszel random-effects modeling.

Evidence synthesis

Twelve studies comprising 1624 patients were included in the analysis. Ten studies were retrospective and two were randomized controlled trials. Adjuvant radiation therapy was delivered to 37% of patients. The median follow-up was 49 mo. Adjuvant radiation therapy was not associated with better DFS or OS at 5 yr, but was associated with less LRR.

Conclusions

With the caveat that confounding by indication may result from pooling data from predominantly nonrandomized studies, adjuvant radiation after radical nephrectomy was not associated with improved DFS or OS but was associated with less LRR.

Patient summary

Radiation therapy after resection of renal cell carcinoma with a high risk of relapse may reduce the risk of local recurrence but not the risk of disease recurrence or death after 5 yr.

Introduction

Surgical resection is the standard therapy for nonmetastatic renal cell carcinoma (RCC) and is often curative [1]. However, in 20–40% of patients with localized disease RCC will recur, and recurrence is associated with risk factors such as pathologic evidence of invasion of the renal capsule, perinephric fat, or renal vein, or lymph node involvement [2].

There is no generally accepted adjuvant treatment for RCC [3], and results for the role of postoperative radiotherapy and more recently adjuvant sunitinib have been controversial [4]. For adjuvant radiotherapy, some of the studies were performed using outdated treatment planning and delivery techniques, with one study closing prematurely owing to a high rate of complications [5]. The most common side effects during treatment were nausea and vomiting, but late toxicity including small bowel stenosis and bleeding has been reported and is associated with morbidity and mortality [6].

Clinical data supporting the efficacy of adjuvant radiation are limited and based mostly on retrospective analyses or small randomized control trials. The optimal treatment remains uncertain as there is insufficient information to make evidence-based decisions on the use of adjuvant radiotherapy. In addition, evaluation of the efficacy of modern radiotherapy techniques is needed for RCC.

Here we report a systematic review and meta-analysis evaluating the efficacy of adjuvant radiation therapy in patients with nonmetastatic RCC.

Section snippets

Search strategy

This analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines [7]. We performed a systematic literature search of Cancerlit (host: Ovid), Medline (host: PubMed), Scopus, and Cochrane databases from database inception to January 2017. The searches used the keywords: kidney, cancer, carcinoma, hypernephroma, radiotherapy, adjuvant, and postoperative or related terms in different combinations, such as (renal OR kidney) AND Cancer AND

Evidence synthesis

Of the 5052 abstracts initially identified, 4993 were excluded and 59 full-text articles were retrieved for detailed evaluation. Forty-seven articles were excluded because they did not meet the inclusion criteria, including 37 review articles and ten articles on non-adjuvant radiotherapy. From the remaining 12 publications, two duplicate articles were excluded [9], [10]. In the remaining ten articles, two additional studies were identified from the reference lists. As a result, 12 studies were

Discussion

The present study suggests that adjuvant radiation therapy for patients with nonmetastatic RCC after nephrectomy is not associated with an improvement in OS or DFS, although the results suggest an improvement in LRR.

The risk of relapse after radical nephrectomy for local or locoregional RCC can be as high as 40%. Given such a high risk of relapse and the subsequent risk of cancer-related mortality, identification of effective adjuvant treatment is desirable. Predictors of relapse include RCC

Conclusions

The studies reviewed do not suggest that adjuvant radiation for patients with nonmetastatic RCC improves either OS or DFS. However, improvement in LRR was observed. Contemporary prospective studies with newer radiation planning techniques may be able to demonstrate better efficacy and lower toxicity and should be considered. At present, adjuvant radiation therapy cannot be recommended outside of a clinical trial.

This study was presented at the 2015 ESMO-ECCO meeting as a poster highlight.

Author

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