All chapters of the 20221 RCC Guidelines have been updated, based on the 2022 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% treatmentrelated 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-naive 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 |