Comparative efficacy and safety of ablative therapies in the management of primary localised renal cell carcinoma: a systematic review and meta-analysis

Ryan S Huang, Ronald Chow, Ali Benour, David Chen, Gabriel Boldt, Christopher J D Wallis, Anand Swaminath, Charles B Simone, Michael Lock, Srinivas Raman
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Abstract

Background

Non-invasive and minimally invasive ablative treatments, including stereotactic body radiotherapy (SBRT), radiofrequency ablation, microwave ablation, and cryoablation, have emerged as key treatment options for managing renal cell carcinoma, especially for patients who are unsuitable for surgery. We aimed to compare the clinical efficacy and safety of these emerging treatment methods in patients with localised renal cell carcinoma.

Methods

In this systematic review and meta-analysis, we searched PubMed (MEDLINE), Embase, and the Cochrane Library for publications between Jan 1, 2000, and March 1, 2024. Eligible articles were observational studies and randomised controlled trials including at least five adult patients (age ≥18 years) with primary and localised renal cell carcinoma treated with SBRT, radiofrequency ablation, microwave ablation, or cryoablation and that reported on local control outcomes. Two reviewers independently screened titles and abstracts and then full texts of eligible studies were independently evaluated by the same reviewers, with disagreements resolved via discussion or consultation with a third reviewer. Summary estimates were extracted from published reports manually using a standardised data extraction form. The primary endpoint was local control rate at 1 year, 2 years, and 5 years after start of treatment. A meta-analysis was conducted using a DerSimonian and Laird model to summarise local control rates. Publication bias was evaluated using funnel plots and Egger's test. We also recorded the frequency and severity of adverse events after treatment on the basis of the Common Terminology Criteria for Adverse Events (version 5.0) and Clavien-Dindo complication index. The study protocol was prospectively registered with PROSPERO, CRD42024511840.

Findings

We identified 6668 records, of which 330 were assessed via full-text review, and 133 were included in our systematic review and meta-analysis. The eligible studies included data for 8910 patients (mean age 67·9 years [SD 7·3], 2518 [31·4%] of 8018 patients with available data were female and 5500 [68·6%] were male). Local control rates for SBRT were 99% (95% CI 97–100; I2=6%) at 1 year, 97% (95–99; I2=0%) at 2 years, and 95% (89–98; I2=42%) at 5 years; for radiofrequency ablation were 96% (94–98; I2=73%) at 1 year, 95% (92–98; I2=77%) at 2 years, and 92% (88–96; I2=78%) at 5 years; for microwave ablation were 97% (95–99; I2=74%) at 1 year, 95% (92–98; I2=77%) at 2 years, and 86% (75–94; I2=66%) at 5 years; and for cryoablation were 95% (93–96; I2=61%) at 1 year, 94% (91–96; I2=69%) at 2 years, and 90% (87–93; I2=74%) at 5 years. The proportion of patients who reported grade 3–4 adverse events was 3% (121 of 3726) after cryoablation, 2% (39 of 2503) after radiofrequency ablation, 1% (22 of 2069) after microwave ablation, and 2% (11 of 612) after SBRT. Risk of bias was moderate in most studies (70 [53%] of 133) and no publication bias was observed.

Interpretation

All investigated ablative methods continue to represent effective treatment choices in renal cell carcinoma, and these findings support multi-disciplinary discussions of these treatment methods, along with surgery and surveillance, to individualise treatment decisions in these patients. Future research should aim to conduct randomised controlled trials across larger patient populations to further elucidate the long-term oncological and survival outcomes associated with these treatments.

Funding

None.
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消融治疗原发性局部肾细胞癌的比较疗效和安全性:一项系统回顾和荟萃分析
背景:无创和微创消融治疗,包括立体定向体放疗(SBRT)、射频消融、微波消融和冷冻消融,已成为治疗肾细胞癌的关键治疗选择,特别是对于不适合手术的患者。我们的目的是比较这些新兴的治疗方法在局部肾细胞癌患者中的临床疗效和安全性。方法在这项系统评价和荟萃分析中,我们检索了PubMed (MEDLINE)、Embase和Cochrane图书馆2000年1月1日至2024年3月1日之间的出版物。符合条件的文章是观察性研究和随机对照试验,包括至少5名接受SBRT、射频消融、微波消融或冷冻消融治疗的原发性和局部肾细胞癌成年患者(年龄≥18岁),并报告了局部对照结果。两位审稿人独立筛选标题和摘要,然后由同一位审稿人独立评估符合条件的研究的全文,分歧通过与第三位审稿人讨论或协商解决。使用标准化数据提取表格从已发布的报告中手动提取汇总估计。主要终点是治疗开始后1年、2年和5年的局部控制率。使用DerSimonian和Laird模型进行了荟萃分析,以总结局部控制率。采用漏斗图和Egger检验评价发表偏倚。我们还根据不良事件通用术语标准(5.0版)和Clavien-Dindo并发症指数记录治疗后不良事件的发生频率和严重程度。该研究方案在PROSPERO进行前瞻性注册,编号为CRD42024511840。研究结果:我们确定了6668条记录,其中330条通过全文综述进行了评估,133条纳入了我们的系统综述和荟萃分析。符合条件的研究纳入了8910例患者的数据(平均年龄为67.9岁[SD 7.3], 8018例可获得数据的患者中2518例(31.4%)为女性,5500例(68.6%)为男性)。SBRT的当地控制率为99% (95% CI 97-100;I2=6%), 1年97% (95-99;2年I2=0%), 95% (89-98;I2=42%);射频消融为96% (94-98;I2=73%), 1年95% (92-98;I2=77%), 92% (88-96;I2=78%);微波消融占97% (95 ~ 99;I2=74%), 1年95% (92-98;I2=77%),而86% (75-94;I2=66%);冷冻消融组为95% (93 ~ 96;I2=61%) 1年,94% (91-96;I2=69%)和90% (87-93;I2=74%)。报告3-4级不良事件的患者比例在冷冻消融后为3%(3726例中的121例),射频消融后为2%(2503例中的39例),微波消融后为1%(2069例中的22例),SBRT后为2%(612例中的11例)。大多数研究的偏倚风险中等(133项研究中有70项[53%]),未观察到发表偏倚。所有研究的消融方法仍然是肾细胞癌的有效治疗选择,这些发现支持对这些治疗方法的多学科讨论,以及手术和监测,以使这些患者的治疗决策个体化。未来的研究应致力于在更大的患者群体中进行随机对照试验,以进一步阐明与这些治疗相关的长期肿瘤和生存结果。
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