Understanding the Disease
Renal cell carcinoma (RCC) is the most common form of kidney cancer, accounting for 2–3% of all adult malignancies. Its global incidence continues to increase, largely due to greater use of imaging that detects early kidney masses. Although advances in surgery, targeted therapies, and immunotherapy have improved outcomes, survival rates for many patients remain unsatisfactory.
RCC is biologically diverse: some patients have localized tumors suitable for surgical removal, while others present with advanced disease requiring systemic therapy. Successful management often depends on a patient’s physical fitness and ability to tolerate demanding treatments.
Frailty—a condition characterized by decreased physiological reserve and resilience to stress—has been linked to adverse outcomes in many cancers. As the authors of this study noted, “frailty has been associated with increased postoperative complications, longer hospital stays, and poorer long-term survival across various malignancies.” However, its prognostic role in renal cell carcinoma had not been clearly defined.
Study Purpose and Design
To clarify this, the researchers conducted a systematic review and meta-analysis following PRISMA guidelines to “comprehensively explore the prognostic value of frailty in patients with RCC.”
They searched major databases, including PubMed, Embase, the Cochrane Library, and Web of Science, identifying eight eligible cohort studies that together included 15,989 patients.
Patients were assessed for frailty using validated instruments such as the Modified Frailty Index (mFI), Clinical Frailty Scale (CFS), or Comprehensive Geriatric Assessment (CGA). Study quality, assessed by the Newcastle–Ottawa Scale, ranged from 6 to 9, indicating moderate to high quality.
Major Findings
The authors found that frailty was present in approximately 7% of RCC patients. Across studies, frailty was strongly associated with poorer survival outcomes.
“Frailty was significantly associated with worse overall survival (HR = 1.79, 95% CI 1.45–2.20, I² = 30%),” they reported. Among studies that assessed disease progression, frailty also predicted a higher risk of relapse or progression (HR = 2.17, 95% CI 1.54–3.04, I² = 0%).
These results were consistent across all subgroup analyses—by age, tumor stage, treatment type, frailty measurement, follow-up time, and analytic model. “Sensitivity analyses confirmed the stability of the results,” the authors stated. Publication bias testing using Egger’s test (p = 0.34) suggested that bias was unlikely.
What the Findings Mean
According to the authors, “frailty represents a multidimensional syndrome involving decreased physiological reserve and resistance to stressors.” In patients with RCC, “frailty may reflect not only chronological aging but also the cumulative burden of comorbidities and cancer-related systemic effects.”
They emphasized that frailty assessment provides information beyond chronological age or conventional clinical variables. “Identifying frail patients before surgery or systemic therapy could help clinicians optimize treatment strategies, provide prehabilitation, and improve patient outcomes,” they wrote.
Limitations
The authors acknowledged several limitations. Most included studies were retrospective, introducing possible bias. There was variation in how frailty was defined and measured, and only a few studies reported progression-free survival. In addition, some hazard ratios were unadjusted due to limited data.
Nevertheless, the consistency of results across sensitivity analyses and the moderate heterogeneity (I² = 30% for overall survival) support the reliability of the findings.
Implications and Future Research
The study highlights the importance of incorporating frailty assessment into clinical practice. Frailty screening could improve risk stratification, guide shared decision-making, and inform individualized treatment approaches in RCC.
The authors recommended that “future prospective studies with standardized frailty assessments and longer follow-up are needed to validate these findings.” They also suggested that routine evaluation of frailty could be integrated into prognostic models and preoperative planning.
Conclusion
This meta-analysis of nearly 16,000 patients provides robust evidence that frailty independently predicts poorer overall and progression-free survival in renal cell carcinoma. As the authors concluded, “frailty is independently associated with worse overall and progression-free survival in RCC,” and “routine assessment of frailty may help guide individualized management and improve clinical decision-making.”
The translation of the preceding English text in Chinese:
了解疾病
肾细胞癌（RCC）是最常见的肾癌类型，占所有成人恶性肿瘤的2–3%。其全球发病率仍在上升，主要归因于影像学检查的更广泛应用，使早期肾脏肿块得以发现。尽管手术、靶向治疗和免疫治疗的进步改善了结局，但许多患者的生存率仍不尽如人意。
RCC在生物学上具有异质性：部分患者为适合手术切除的局限性肿瘤，而另一些患者就诊时已为晚期疾病，需要进行全身治疗。成功的管理往往取决于患者的体能状况及其对强度较高治疗的耐受能力。
衰弱（frailty）—一种以生理储备减少和对压力源的复原力下降为特征的状态—已被证明与多种癌症的不良结局相关。正如本研究作者所指出的，“衰弱与术后并发症增加、住院时间延长和不同恶性肿瘤的长期生存较差相关。”然而，其在肾细胞癌中的预后作用尚未得到明确定义。
研究目的与设计
为了澄清这一问题，研究者按照PRISMA指南开展了系统综述与Meta分析，以“全面探索衰弱在肾细胞癌患者中的预后价值。”
他们检索了主要数据库，包括PubMed、Embase、Cochrane Library和Web of Science，最终纳入8项符合条件的队列研究，共计15,989例患者。
研究采用经验证的工具对患者进行衰弱评估，如修订版衰弱指数（mFI）、临床衰弱量表（CFS）或综合老年评估（CGA）。以纽卡斯尔–渥太华量表评估的研究质量范围为6至9分，提示中等到高质量。
主要发现
作者发现，约有7%的RCC患者存在衰弱。跨研究分析显示，衰弱与较差的生存结局密切相关。
“衰弱与较差的总生存显著相关（HR = 1.79, 95% CI 1.45–2.20, I² = 30%），”他们报告称。在评估疾病进展的研究中，衰弱同样提示更高的复发或进展风险（HR = 2.17, 95% CI 1.54–3.04, I² = 0%）。
这些结果在所有亚组分析中均保持一致——按年龄、肿瘤分期、治疗类型、衰弱测量方法、随访时间及统计模型分层。“敏感性分析确认了结果的稳定性，”作者表示。采用Egger检验（p = 0.34）评估发表偏倚，提示偏倚的可能性较低。
这些发现意味着什么
作者指出，“衰弱代表一种多维综合症，涉及生理储备和对压力源的抵抗力下降。”在RCC患者中，“衰弱不仅可能反映了生理年龄的增加，还可能反映了共病负担和癌症相关的全身性影响。”
他们强调，衰弱评估可提供超越生理年龄或传统临床变量的信息。“术前或全身治疗前识别衰弱患者，可帮助临床医生优化治疗策略，提供术前康复，并改善患者结局，”他们写道。
局限性
作者承认本研究存在若干局限性。多数纳入研究为回顾性，可能引入偏倚。对衰弱的定义与测量存在差异，且仅有少数研究报告了无进展生存。此外，由于数据有限，部分危险比未进行调整。
尽管如此，敏感性分析结果的一致性以及中等程度的异质性（总生存I² = 30%）支持研究结论的可靠性。
意义与未来研究
本研究强调将衰弱评估纳入临床实践的重要性。衰弱筛查可改进风险分层，促进医患共同决策，并为RCC的个体化治疗策略提供依据。
作者建议，“未来的前瞻性研究应采用标准化的衰弱评估，并进行更长时间的随访，以验证这些发现。”他们还提出，可将对衰弱的常规评估整合进预后模型与术前规划之中。
结论
这项近16,000名患者的Meta分析提供了有力证据：在肾细胞癌中，衰弱可独立预测较差的总生存与无进展生存。正如作者总结所言，“衰弱与RCC中的较差总生存和无进展生存独立相关，”且“常规评估衰弱可帮助指导个体化管理，并改善临床决策。”
Reference:
Longye Zhang, Weiping Liu, Bo Ning, Bohan Chen
Frailty and survival of patients with renal cell carcinoma: A meta-analysis.
Biomol Biomed [Internet]. 2025 Jul. 18 [cited 2025 Oct. 24];25(12):2620–2631.
Available from: https://www.bjbms.org/ojs/index.php/bjbms/article/view/12687
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