In this issue of the BJUI, two papers from the Tran group, based at the Royal Free London NHS Foundation Trust, provide evidence to support initial active surveillance (AS) of renal oncocytomas [1] while demonstrating that this approach is not universally accepted across the urological community [2]. Their paper, ‘Renal oncocytoma: landscape of diagnosis and management’, presents the results from a survey of 68, predominately high-volume, renal surgeons from across the globe. It showed that clinicians were more likely to offer conservative management for biopsy-proven renal oncocytomas when the masses were small, or the patients were older or had comorbidities [2]. Such an approach is accepted by many, even for malignant renal tumours, faced with these tumour and patient characteristics, given the likely low risk of adverse outcome. However, the agreement on AS was not universal and there was less consensus when the tumours were larger, or the patients were younger. Although not assessed in the study, this divergent practice may be greater still if a larger cohort of surgeons were surveyed across more countries or healthcare systems, or there was greater representation from lower-volume surgeons.

The lack of universal acceptance of AS as the optimal treatment for renal oncocytomas may stem from the diagnostic uncertainty of the renal biopsy and, indeed, only 29% of respondents in the survey routinely perform renal biopsy in small renal masses. Concordance between renal biopsy results demonstrating oncocytoma with final resection pathology was only 64.5% in a systematic review and meta-analysis, although the numbers included are small and there was a lack of clarity on the full biopsy assessment process [3]. This diagnostic discordance is likely to be attributable to the overlapping features of oncocytoma with malignant chromophobe RCC (ChRCC), particularly the eosinophilic variant, and hybrid oncocytoma-chromophobe tumours. However, even with the risk of mis-labelling a potentially malignant ChRCC as oncocytoma, the risk of metastasis of a small T1a ChRCC is extremely low [4] and may still warrant an AS approach.

While renal biopsies are safe [5] and can identify rare aggressive malignant small renal tumours, alternative diagnostic methods may be more acceptable to both patients and clinicians. Imaging techniques offer promise, with 99mTc-sestamibi single-photon emission CT/CT able to reliably differentiate benign and low-grade renal tumours from malignant renal cancers [6], and the Tran group plan to evaluate this in the NHS in a prospective study [2]. Diffusion-weighted MRI has also been shown to be able to differentiate subtypes of small renal masses, including oncocytomas and ChRCCs, although prospective validation is also required [7]. For those who do undergo biopsy, use of artificial intelligence techniques and automated analysis of histology slides to reduce inter-reporter variability [8] or additional molecular markers may improve confidence in the diagnosis of oncocytoma. There are promising results from transcriptomic, genomic and, potentially most interestingly, methylation studies to differentiate oncocytoma from ChRCC. A recent study has shown that a 30-marker methylation profile can distinguish oncocytoma from ChRCC with an area under the curve between 0.87 and 0.96, as well as differentiating oncocytoma from other RCC subtypes [9]. If diagnostic certainty could be improved, perhaps through use of a combination of imaging and biopsy, it might encourage clinicians to recommend AS for patients with oncocytoma, potentially with less rigorous follow-up, or even allow them to be discharged.

Nevertheless, even if there is certainty in the diagnosis of oncocytoma, clinicians must be confident that they understand the natural history of the disease and that their patients are not going to come to harm without treatment. In this issue, Neves et al. [1] demonstrate that AS of oncocytoma up to 7 cm is safe, with no disease-related deaths and with preservation of renal function during surveillance even with tumour growth. Furthermore, no patients developed symptoms, adding to the growing evidence in support of AS particularly for smaller oncocytomas. This is in contrast to the small but significant risk of death (0.1%) or significant morbidity (Clavien–Dindo grade ≥3a complications 5%) associated with partial nephrectomy reported in the literature [10]. However, the median follow-up of the patients with oncocytomas reported in this paper is a modest 29 months and longer-term outcomes would be welcome. Caution should also be taken with regard to the surveillance of larger oncocytomas, given the relatively small number in this cohort, which was likely to be subject to selection bias. This is highlighted by the number of patients who proceeded directly to treatment without AS and the significant proportion of patients with a high Charlson comorbidity index (CCI) who may be appropriate for AS or watchful waiting even in the presence of RCC given their likely short life expectancy (median CCI=3 with 10-year overall survival of 77%, but Q3 CCI= 5 with a 10-year overall survival of 22% and any patients with a CCI have a 10-year overall survival of 0%). This potential selection bias also raises the question of who should proceed directly to treatment and which parameters should prompt treatment during AS. Larger tumours, faster-growing tumours, tumours where there remains diagnostic uncertainty; particularly in younger and fitter patients, seems intuitive but these issues have not been addressed in a scientific manner. Furthermore, we still do not know the optimal imaging technique, frequency, and duration for follow-up. Nor do we know the quality-of-life impact of surveillance compared to definitive treatment for patients with oncocytomas. In addition, while there have been studies suggesting improved cost-effectiveness for surveillance compared with treatment in small renal cancers, the applicability of this for patients with oncocytomas, who may require less follow-up after definitive treatment, needs to be confirmed.

The work presented in this issue will be enough to support the AS approach taken by many for managing oncocytomas already, and will encourage others to consider this option for their patients. It also highlights the many uncertainties and areas for further research and development. The Tran group should be commended for bringing these issues to the forefront and attempting to answer some of these key questions.

在本期BJUI 中，来自皇家自由伦敦 NHS 基金会信托基金会的 Tran 小组的两篇论文提供了支持肾嗜酸细胞瘤的初始主动监测 (AS) [ 1 ] 的证据，同时证明这种方法并未得到普遍接受泌尿外科界 [ 2 ]。他们的论文“肾嗜酸细胞瘤：诊断和管理的前景”展示了对来自全球 68 名主要是大容量肾外科医生的调查结果。结果表明，当肿块较小、患者年龄较大或有合并症时，临床医生更有可能为活检证实的肾嗜酸细胞瘤提供保守治疗 [ 2]。]。鉴于不良结果的风险可能较低，这种方法被许多人接受，即使对于恶性肾肿瘤，也面临这些肿瘤和患者特征。然而，对于 AS 的共识并不普遍，当肿瘤较大或患者较年轻时，共识较少。尽管在研究中未进行评估，但如果在更多国家或医疗保健系统中对更多外科医生进行调查，或者有更多来自小规模外科医生的代表，则这种不同的做法可能会更大。

缺乏普遍接受 AS 作为肾嗜酸细胞瘤的最佳治疗方法可能源于肾活检的诊断不确定性，事实上，调查中只有 29% 的受访者定期对小肾肿块进行肾活检。在一项系统评价和荟萃分析中，证明嗜酸细胞瘤与最终切除病理的肾活检结果之间的一致性仅为 64.5%，尽管所包括的数字很小，并且完整的活检评估过程缺乏明确性 [ 3]]。这种诊断不一致可能归因于嗜酸细胞瘤与恶性嫌色细胞 RCC (ChRCC) 的重叠特征，特别是嗜酸性变体，以及嗜酸细胞瘤-嫌色细胞瘤的混合特征。然而，即使存在将潜在恶性 ChRCC 错误标记为嗜酸细胞瘤的风险，小型 T1a ChRCC 的转移风险也极低 [ 4 ]，并且仍可能需要采用 AS 方法。

虽然肾活检是安全的 [ 5 ] 并且可以识别罕见的侵袭性恶性小肾肿瘤，但患者和临床医生可能更容易接受替代诊断方法。成像技术提供了希望，99mTc-sestamibi 单光子发射 CT/CT 能够可靠地区分良性和低级别肾肿瘤与恶性肾癌 [ 6 ]，Tran 小组计划在一项前瞻性研究中在 NHS 中对此进行评估[ 2 ]。弥散加权 MRI 也已被证明能够区分小肾肿块的亚型，包括嗜酸细胞瘤和 ChRCC，尽管还需要前瞻性验证 [ 7]]。对于那些确实接受活检的人，使用人工智能技术和组织学载玻片的自动分析来减少报告者间的变异性 [ 8 ] 或其他分子标记可能会提高对嗜酸细胞瘤诊断的信心。转录组学、基因组学和可能最有趣的甲基化研究都取得了有希望的结果，以区分嗜酸细胞瘤和 ChRCC。最近的一项研究表明，30 个标记的甲基化谱可以区分嗜酸细胞瘤和 ChRCC，曲线下面积在 0.87 和 0.96 之间，以及区分嗜酸细胞瘤和其他 RCC 亚型 [ 9]]。如果可以提高诊断的确定性，也许通过结合使用影像学和活检，它可能会鼓励临床医生为嗜酸细胞瘤患者推荐 AS，可能不需要严格的随访，甚至允许他们出院。

尽管如此，即使嗜酸细胞瘤的诊断是肯定的，临床医生也必须确信他们了解疾病的自然病程，并且他们的患者在不接受治疗的情况下不会受到伤害。在这个问题上，Neves 等人。[ 1 ] 证明嗜酸细胞瘤的 AS 高达 7 cm 是安全的，没有与疾病相关的死亡，并且在监测期间即使肿瘤生长也能保持肾功能。此外，没有患者出现症状，这增加了支持 AS 的越来越多的证据，特别是对于较小的嗜酸细胞瘤。这与文献中报道的与肾部分切除术相关的小而显着的死亡风险 (0.1%) 或显着发病率 (Clavien-Dindo 等级≥3a 并发症 5%) 形成对比 [ 10]]。然而，本文报道的嗜酸细胞瘤患者的中位随访时间为 29 个月，长期结果将受到欢迎。考虑到该队列中较大的嗜酸细胞瘤的数量相对较少，因此在监测较大的嗜酸细胞瘤时也应谨慎，这可能会受到选择偏倚的影响。突出显示的是，在没有 AS 的情况下直接接受治疗的患者数量以及具有高 Charlson 合并症指数 (CCI) 的患者的显着比例可能适合 AS 或即使在存在 RCC 的情况下观察等待，因为他们可能寿命很短预期（中位 CCI=3，10 年总生存率为 77%，但 Q3 CCI=5，10 年总生存率为 22%，任何患有 CCI 的患者10 年总生存率为 0%）。这种潜在的选择偏差还提出了谁应该直接进行治疗以及哪些参数应该在 AS 期间促进治疗的问题。较大的肿瘤、生长速度较快的肿瘤、仍存在诊断不确定性的肿瘤；尤其是在更年轻和更健康的患者中，似乎很直观，但这些问题尚未以科学的方式解决。此外，我们仍然不知道随访的最佳成像技术、频率和持续时间。我们也不知道与嗜酸细胞瘤患者的最终治疗相比，监测对生活质量的影响。此外，虽然有研究表明，与治疗小肾癌相比，监测的成本效益有所提高，但这种方法对嗜酸细胞瘤患者的适用性，

本期中介绍的工作将足以支持许多人已经为管理嗜酸细胞瘤采取的 AS 方法，并将鼓励其他人为他们的患者考虑这种选择。它还强调了许多不确定性和进一步研究和开发的领域。Tran 小组将这些问题带到了最前沿并试图回答其中一些关键问题，因此应该受到赞扬。