Oza Bhavna, Frangou Eleni, Eisen Tim, Stewart Grant D, Bex Axel, Harrison David, Parmar Mahesh K B, Langley Ruth, Gilbert Duncan, Meade Angela
MRC Clinical Trials Unit at UCL, Institute of Clinical Trials & Methodology, London, UK.
Department of Oncology, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital, Cambridge Biomedical Campus, Cambridge, UK.
Eur Urol Open Sci. 2025 Jul 26;79:19-26. doi: 10.1016/j.euros.2025.07.003. eCollection 2025 Sep.
Outcomes after nephrectomy for intermediate- and high-risk renal cell carcinoma (RCC) according to histological subtype are poorly characterised. This study aims to determine the value of RCC histology in predicting survival and to inform on surveillance strategies in relation to patterns of first recurrence.
We pooled data from phase 3 trials: SORCE ( = 1689) and ASSURE ( = 1853). Of 3542 patients, 2881 had clear-cell RCC (ccRCC), 269 had papillary RCC (pRCC), 201 had chromophobe RCC (chRCC), and 191 had sarcomatoid RCC (sRCC). Relapse rates, median time to relapse (TTR), and first relapse sites were reported. Multivariable Cox regression models evaluated overall survival by histology, adjusting for initial relapse location and other important clinical factors.
Patients with pRCC and ccRCC had similar overall survival (log-rank = 0.1). The median TTR for those with pRCC was 1.34 yr (interquartile range [IQR] 0.76, 2.59) compared with 1.78 yr (IQR 0.96, 3.38) for ccRCC patients ( = 0.012). Patients with chRCC had a median TTR of 2.72 yr (IQR 0.91, 4.11), and those with sRCC had a median TTR of 0.74 yr (IQR 0.50, 1.55). For sRCC patients, relapsing in the chest was associated with a lower risk of death than those relapsing in the abdomen (hazard ratio [HR] 0.5, confidence interval [CI]: 0.3, 0.88; = 0.06). A similar trend was shown for pRCC (HR 0.5, CI: 0.2, 1.3; = 0.1). Recurrence patterns for World Health Organization 2020 molecularly classified RCCs were not included. Despite pooling phase three datasets, small event numbers led to imprecise estimates, particularly for chRCC.
Patients with intermediate and high-risk pRCC relapse earlier than those with ccRCC. Papillary RCC and sRCC first recurring in the abdomen exhibit poor prognosis, warranting consideration of additional abdominal imaging to enhance early relapse detection. ChRCC exhibits favourable prognosis and could avoid image-based surveillance until year 2.
This study evaluates pooled data from large phase 3 trials to precisely delineate relapse patterns for patients with intermediate- and high-risk cell renal cell carcinoma (RCC) according to their histology. The site and timing of first relapse provide useful information to support histology-specific RCC surveillance after nephrectomy. Development of genetic and molecular signatures corresponding to relapses at poor prognosis sites for each histology will individualise follow-up and is the next step.
根据组织学亚型，中高危肾细胞癌（RCC）肾切除术后的预后特征尚不明确。本研究旨在确定RCC组织学在预测生存方面的价值，并为与首次复发模式相关的监测策略提供信息。
我们汇总了3期试验的数据：SORCE（n = 1689）和ASSURE（n = 1853）。在3542例患者中，2881例为透明细胞RCC（ccRCC），269例为乳头状RCC（pRCC），201例为嫌色细胞RCC（chRCC），191例为肉瘤样RCC（sRCC）。报告了复发率、中位复发时间（TTR）和首次复发部位。多变量Cox回归模型按组织学评估总生存情况，并对初始复发部位和其他重要临床因素进行校正。
pRCC和ccRCC患者的总生存情况相似（对数秩检验P = 0.1）。pRCC患者的中位TTR为1.34年（四分位间距[IQR] 0.76，2.59），而ccRCC患者为1.78年（IQR 0.96，3.38）（P = 0.012）。chRCC患者的中位TTR为2.72年（IQR 0.91，4.11），sRCC患者为0.74年（IQR 0.50，1.55）。对于sRCC患者，胸部复发者的死亡风险低于腹部复发者（风险比[HR] 0.5，置信区间[CI]：0.3，0.88；P = 0.06）。pRCC也显示出类似趋势（HR 0.5，CI：0.2，1.3；P = 0.1）。未纳入世界卫生组织2020年分子分类RCC的复发模式。尽管汇总了三期数据集，但事件数量较少导致估计不准确，尤其是对于chRCC。
中高危pRCC患者比ccRCC患者更早复发。首次复发于腹部的乳头状RCC和sRCC预后较差，有必要考虑增加腹部影像学检查以提高早期复发的检测率。chRCC预后良好，在2年之前可避免基于影像的监测。
本研究评估了大型3期试验的汇总数据，以根据组织学精确描绘中高危肾细胞癌（RCC）患者的复发模式。首次复发的部位和时间提供了有用信息，以支持肾切除术后针对特定组织学的RCC监测。针对每种组织学预后不良部位复发的基因和分子特征的开发将使随访个体化，这是下一步的工作。
