【原】2022EAU指南肾细胞癌(1):内容变化部分

1.5. 发布历史和更改摘要

1.5.1. 出版历史

EAU RCC指南于2000年首次发布。这份2022年RCC指南文件是对2021年出版物的重大更新。

1.5.2. 更改摘要

《2022年RCC指南》的所有章节均已根据2021年版《指南》进行了更新。在整个文档中添加了引用。

以下各节中包含了新数据，导致证据摘要和建议发生变化：

5.4 RCC诊断评估的证据和建议摘要

建议	强度等级
在考虑全身治疗或细胞减灭性肾切除术时，为转移患者提供脑部 CT/MRI。	弱
不要对囊性肾肿块进行肾肿瘤活检，除非在影像学检查中可见明显的固体成分。	强

5.5 RCC遗传评估的证据和建议摘要

证据摘要	L
遗传性肾癌被认为占所有肾癌病例的5-8%，尽管这个数字可能被低估了。	3
在肾癌的情况下，如果患者的年龄为46岁或更年轻，和/或伴有双侧或多灶性肿瘤和/或具有RCC的一级或二级亲属和/或具有已知致病变异和/或具有特定组织学特征的近亲（见文本），则风险或遗传性癌症显着更高。	3
遗传性RCC检测对决策和随访具有独特的意义。	3

建议	强度等级
对 46 岁<、双侧或多灶性肿瘤和/或 RCC 一级或二级亲属和/或具有已知致病变异和/或特定组织学特征的近亲进行遗传评估，提示存在遗传性 RCC。	强
如果疑似遗传性肾癌，将患者转诊至癌症遗传学家或综合临床护理中心。	强

7.1.2.2.4 局部RCC治疗的证据和建议摘要

建议	强度等级
不要为器官受限疾病患者提供扩展淋巴结清扫术。	弱

7.1.3.4 根治性和部分性肾切除术的证据和建议摘要

证据摘要	L
经腹膜和腹膜后腹腔镜 PN 在术后手术和躯体并发症、手术切缘阳性和肾功能方面没有差异。	2a

建议	强度等级
加强手术切缘阳性患者的随访，尤其是上期 pT3a 患者。	弱

7.2.4.3 静脉肿瘤血栓RCC治疗的证据和建议摘要

建议	强度等级
在肾切除术期间，切除临床上肿大的淋巴结以进行分期，预后和随访意义。	弱

7.2.5.1 新辅助和辅助治疗的证据和建议摘要

证据摘要	L
辅助 TKI 治疗不能改善肾切除术后的 OS。	1b
在高危 RCC 患者肾切除术后辅助使用派姆单抗可提高无进展生存期。	1b
在一项随机对照试验中，在选定的中/高危或高危患者或无疾病证据的 M1 患者中，辅助 pembrolizumab 可提高无病生存率。	1b

建议	强度等级
对于手术后具有治愈意图且存在试验中定义的复发风险的透明细胞 （cc） RCC 患者，提供 pembrolizumab 辅助治疗。	弱

*pT2 G4 或 pT3 任何 G;pT4 任何 G;pN+ 任何 G。

7.3.2.6 转移性RCC转移灶局部治疗的证据和建议摘要

证据摘要	乐
一项单臂前瞻性和回顾性研究支持，在由于进展而需要全身治疗之前，寡异构酶可观察到长达 16 个月。	2a

建议	强度等级
在转移灶切除术前对疾病状态进行确认性轴向扫描，以排除需要全身治疗的快速进行性转移性疾病。	弱
在开始对无法切除的寡变异酶进行全身治疗之前，请与您的患者讨论观察期，直到确认进展。	弱

7.4.2.4 透明细胞转移性RCC靶向治疗的证据和建议摘要

建议	强度等级
为具有肉瘤样特征的晚期 cc-mRCC 提供免疫检查点抑制剂联合治疗。	弱

7.4.4.1.2 透明细胞转移性RCC免疫治疗的证据和建议摘要

证据摘要	乐
测序全身治疗
Nivolumab加ipilimumab与15%的3-5级毒性和1.5%的治疗相关死亡相关。基于酪氨酸激酶抑制剂的IO联合疗法与3-5级毒性相关，在治疗相关死亡中，61-72%至1%。。	1b

建议	强度等级
未接受治疗的患者
在一两线治疗后，为免疫检查点抑制剂 -初见血管内皮生长因子受体 （VEGFR）-难治性透明细胞转移性肾细胞癌 （cc-mRCC） 提供 nivolumab 或 cabozantinib。	强

7.4.4.1.3.1 具有肉瘤样特征的RCC靶向治疗的证据和建议摘要

证据摘要	L
在具有肉瘤样特征的cc-RCC的试验亚组分析中，免疫检查点抑制剂联合治疗在PFS和OS方面优于舒尼替尼。	2a

建议	强度等级
为具有肉瘤样特征的晚期 cc-mRCC 提供免疫检查点抑制剂联合治疗。	弱

7.4.4.2.1 非透明细胞转移性RCC靶向治疗的证据和建议摘要

证据摘要	乐
mTOR抑制剂和VEGF靶向治疗在非cc-mRCC中的活性均有限。舒尼替尼优于依维莫司的肿瘤学结局没有显著趋势。	2a
在非cc-mRCC中，在II期试验和患者亚组的系统评价中，舒尼替尼比依维莫司改善了PFS。	2a

建议	强度等级
向乳头状 RCC 以外的其他非 ccRCC 亚型患者提供舒尼替尼。	弱

7 . 4 . 4 . 3 . 1 状转移性 RCC 靶向治疗的证据和建议摘要

证据摘要	乐
Cabozantinib在晚期pRCC患者中改善了PFS优于舒尼替尼，无需额外的分子检测。	2a
与舒尼替尼相比，萨沃利替尼在 MET 驱动的晚期 pRCC 患者中改善了 PFS。	2a
Pembrolizumab在pRCC亚组的单组研究中导致长期中位OS。	2a

建议	强度等级
向晚期乳头状 RCC （ pRCC ）患者提供卡博替尼，无需进行分子检测。	弱
向 MET 驱动的晚期 pRCC 患者提供沃利替尼。	弱
向晚期 pRCC 患者提供 pembrolizumab，无需进行分子检测。	弱

7.5.1 局部疾病治疗后局部复发性RCC的证据和建议摘要

证据摘要	乐
在没有全身进展的情况下，应考虑手术或经皮治疗局部复发，特别是在没有不良预后参数和良好体力状态的情况下。	3
未确定保留肾单位或肾切除术后局部复发性 RCC 的最佳局部治疗方式。	3

建议	强度等级
在技术上可行的情况下，在平衡不良预后特征、合并症和预期寿命后，对局部复发性疾病进行局部治疗。

1.5. Publication history and summary of changes

1.5.1. Publication history

The EAU RCC Guidelines were first published in 2000. This 2022 RCC Guidelines document presents a substantial update of the 2021 publication.

1.5.2. Summary of changes

All chapters of the 2022 RCC Guidelines have been updated, based on the 2021 version of the Guidelines. References have been added throughout the document.

New data have been included in the following sections, resulting in changed evidence summaries and recommendations in:

5.4 Summary of evidence and recommendations for the diagnostic assessment of RCC

Recommendations	Strength rating
Offer brain CT/MRI in metastatic patients when systemic therapy or cytoreductive nephrectomy is considered.	Weak
Do not perform a renal tumour biopsy of cystic renal masses unless a significant solid component is visible at imaging.	Strong

5.5 Summary of evidence and recommendations for genetic assessment of RCC

Summary of evidence	LE
Hereditary kidney cancer is thought to account for 5–8% of all kidney cancer cases, though that number is likely an underestimate.	3
In case of renal cancer, if patient’s age is 46 years or younger, and/or with bilateral or multifocal tumours and/or with a first or second-degree relative with RCC and/or with close blood relative with a known pathogenic variant and/or with specific histologic characteristics (see text), the risk or hereditary cancer is significantly higher.	3
Hereditary RCC detection has unique implications for decision-making and follow-up.	3

Recommendations	Strength rating
Perform a genetic evaluation in patients aged < 46 years, with bilateral or multifocal tumours and/or a first or second-degree relative with RCC and/or a close blood relative with a known pathogenic variant and/or specific histologic characteristics which suggest the presence of a hereditary form of RCC.	Strong
Refer patients to a cancer geneticist or to a comprehensive clinical care centre in case of suspected hereditary kidney cancer.	Strong

7.1.2.2.4 Summary of evidence and recommendations for the treatment of localised RCC

Recommendation	Strength rating
Do not offer an extended lymph node dissection to patients with organ-confined disease.	Weak

7.1.3.4 Summary of evidence and recommendations for radical and partial nephrectomy techniques

Summary of evidence	LE
Transperitoneal and retroperitoneal laparoscopic PN do not differ in in post-operative surgical and medical complications, positive surgical margins and kidney function.	2a

Recommendation	Strength rating
Intensify follow-up in patients with a positive surgical margin, especially in upstaged pT3a patients.	Weak

7.2.4.3 Summary of evidence and recommendations for the management of RCC with venous tumour thrombus

Recommendation	Strength rating
During nephrectomy, remove clinically enlarged lymph nodes for staging, prognosis and follow-up implications.	Weak

7.2.5.1 Summary of evidence and recommendations for neoadjuvant and adjuvant therapy

Summary of evidence	LE
Adjuvant TKI therapy does not improve OS after nephrectomy.	1b
Adjuvant pembrolizumab after nephrectomy in patients with high-risk RCC improves progression-free survival.	1b
In one RCT, in selected intermediate/high- or high-risk patients or M1 patients without evidence of disease, adjuvant pembrolizumab improved disease-free survival.	1b

Recommendation	Strength rating
Offer adjuvant pembrolizumab to patients with clear-cell (cc) RCC following surgery with curative intent with a risk of recurrence as defined in the trial.*	Weak

*pT2 G4 or pT3 any G; pT4 any G; pN+ Any G.

7.3.2.6 Summary of evidence and recommendations for local therapy of metastases in metastatic RCC

Summary of evidence	LE
A single-arm prospective and retrospective study support that oligometastases can be observed for up to 16 months before systemic therapy is required due to progression.	2a

Recommendations	Strength rating
Perform a confirmatory axial scan of disease status prior to metastasectomy to rule out rapid progressive metastatic disease which requires systemic treatment.	Weak
Before initiating systemic therapy for oligometastases that cannot be resected, discuss with your patient a period of observation until progression is confirmed.	Weak

7.4.2.4 Summary of evidence and recommendations for targeted therapy in clear-cell metastatic RCC

Recommendation	Strength rating
Offer immune checkpoint inhibitor combination therapy for advanced cc-mRCC with sarcomatoid features.	Weak

7.4.4.1.2 Summary of evidence and recommendations for immunotherapy in clear-cell metastatic RCC

Summary of evidence	LE
Sequencing systemic therapy
Nivolumab plus ipilimumab was associated with 15% grade 3-5 toxicity and 1.5% treatment-related deaths. Tyrosine kinase inhibitor-based IO combination therapies were associated with grade 3-5 toxicity ranging between 61-72% and 1% of treatment-related deaths.	1b

Recommendation	Strength rating
Treatment-naïve patients
Offer nivolumab or cabozantinib for immune checkpoint inhibitor-naïve vascular endothelial growth factor receptor (VEGFR)-refractory clear-cell metastatic renal cell carcinoma (cc-mRCC) after one or two lines of therapy.	Strong

7.4.4.1.3.1 Summary of evidence and recommendation for targeted therapy in RCC with sarcomatoid features

Summary of evidence	LE
Immune checkpoint inhibitor combination therapy was superior to sunitinib in terms of PFS and OS in trial subset analysis of cc-RCC with sarcomatoid features.	2a

Recommendation	Strength rating
Offer immune checkpoint inhibitor combination therapy for advanced cc-mRCC with sarcomatoid features.	Weak

7.4.4.2.1 Summary of evidence and recommendation for targeted therapy in non-clear-cell metastatic RCC

Summary of evidence	LE
Both mTOR inhibitors and VEGF-targeted therapies have limited activity in non-cc-mRCC. There is a non-significant trend for improved oncological outcomes for sunitinib over everolimus.	2a
In non-cc-mRCC, sunitinib improved PFS over everolimus in a systematic review of phase II trials and subgroups of patients.	2a

Recommendation	Strength rating
Offer sunitinib to patients with other non-ccRCC subtypes than papillary RCC.	Weak

7.4.4.3.1 Summary of evidence and recommendations for targeted therapy in papillary metastatic RCC

Summary of evidence	LE
Cabozantinib improved PFS over sunitinib in patients with advanced pRCC without additional molecular testing.	2a
Savolitinib improved PFS over sunitinib in patients with MET-driven advanced pRCC.	2a
Pembrolizumab resulted in long-term median OS in a single arm study in the pRCC subgroup.	2a

Recommendations	Strength rating
Offer cabozantinib to patients with advanced papillary RCC (pRCC) without molecular testing.	Weak
Offer savolitinib to patients with MET-driven advanced pRCC.	Weak
Offer pembrolizumab to patients with advanced pRCC without molecular testing.	Weak

7.5.1 Summary of evidence and recommendation on locally recurrent RCC after treatment of localised disease

Summary of evidence	LE
Surgical or percutaneous treatment of local recurrences in absence of systemic progression should be considered, especially in absence of adverse prognostic parameters and favourable performance status.	3
The most optimal modality of local treatment for locally recurrent RCC after nephron-sparing procedures or nephrectomy is not defined.	3

Recommendation	Strength rating
Offer local treatment of locally recurrent disease when technically possible and after balancing adverse prognostic features, comorbidities and life expectancy.	Weak