Renal Cell Cancer Guidelines 2020
Summary of changes
All chapters of the 2020 RCC Guidelines have been updated, based on the 2019 version of the Guidelines.
References have been added throughout the document.
New data have been included in the following sections, resulting in changed recommendations in:
Section 3.4.5 Summary of evidence and recommendations for the management of other renal tumours
| Recommendations | Strength rating |
Treat angiomyolipoma (AML) with selective arterial embolisation or nephron-sparing surgery, in: • large tumours (a recommended threshold of intervention does not exist); • females of childbearing age; • patients in whom follow-up or access to emergency care may be inadequate; • persistent pain or acute or repeated bleeding episodes. | Weak |
| Only offer radical nephrectomy to patients with localised renal medullary carcinoma after a favourable response to systemic therapy. | Weak |
7.1.4.3.7 Summary of evidence and recommendation for therapeutic approaches as alternative to surgery
| Recommendations | Strength rating |
| When radiofrequency ablation, cryoablation and active surveillance are offered, inform patients about the higher risk of local recurrence and/or tumour progression. | Weak |
7.4.2.5 Summary of evidence and recommendations for immunotherapy of metastatic clear-cell RRC
| Summary of evidence | LE |
| The combination of pembrolizumab and axitinib in treatment-naive patients with clear-cell-mRCC across all IMDC risk groups demonstrated overall survival and ORR benefits compared to sunitinib. | 1b |
| Currently, PD-L1 expression is not used for patient selection. | 2b |
Axitinib can be continued if immune-related adverse events results in cessation of axitinib and pembrolizumab. Re-challenge with combination therapy requires expert support. | 4 |
| Patients who do not receive the full four doses of ipilimumab due to toxicity should continue on single-agent nivolumab, where safe and feasible. Re-challenge with combination therapy requires expert support. | 4 |
| Treatment past progression can be justified but requires close scrutiny and the support of an expert multidisciplinary team. | 1b |
| Nivolumab plus ipilimumab and pembrolizumab plus axitinib should be administered in centres with experience of immune combination therapy and appropriate supportive care within the context of a multidisciplinary team. | 4 |
| Recommendations | Strength rating |
| Offer pembrolizumab plus axitinib to treatment-naive patients with any IMDC-risk clear-cell metastatic RCC (cc-mRCC). | Strong |
| Offer ipilimumab plus nivolumab to treatment-naive patients with IMDC intermediate- and poor-risk cc-mRCC. | Strong |
| Patients who do not receive the 4 four doses of ipilimumab due to toxicity should continue on single-agent nivolumab, where safe and feasible. | Weak
|
| Offer axitinib as subsequent treatment to patients who experience treatment-limiting immune-related adverse events after treatment with the combination of axitinib and pembrolizumab. | Weak
|
| Treatment past progression can be justified but requires close scrutiny and the support of an expert multidisciplinary team. | Weak
|
| Offer sunitinib or pazopanib to treatment-naive patients with IMDC favourable-, intermediate-, and poor-risk cc-mRCC who cannot receive or tolerate immune checkpoint inhibition. | Strong |
| Offer cabozantinib to treatment-naive patients with IMDC intermediate- and poorrisk cc-mRCC who cannot receive or tolerate immune checkpoint inhibition. | Strong* |
* While this is based on a randomised phase II trial, cabozantinib (weak) looks at least as good as sunitinib in this population. This justified the same recommendation under exceptional circumstances.
7.4.7 Summary of evidence and recommendations for targeted therapy in metastatic RRC
| Summary of evidence | LE |
| Single-agent VEGF-targeted therapy has been superseded by immune checkpoint-based combination therapy. | 1b |
| Pazopanib is non-inferior to sunitinib in front-line metastatic RCC. | 1b |
| Tivozanib has been EMA approved, but the evidence is still considered inferior over existing choices in the front-line setting. | 3 |
| Single-agent VEGF-targeted therapies are preferentially recommended after front-line PD-L1-based combinations. Re-challenge with treatments already used should be avoided. | 3 |
| Single-agent cabozantinib or nivolumab are superior to everolimus after one or more lines of VEGF-targeted therapy. | 1b |
| Both mTOR inhibitors and VEGF-targeted therapies have limited activity in non-clear cell RCC. There is a non-significant trend for improved oncological outcomes for sunitinib over everolimus. | 2a |
| Lenvatinib in combination with everolimus improved PFS over everolimus alone in VEGF-refractory disease. Its role after immune checkpoint inhibitors is uncertain. There is a lack of robust data on this combination making its recommendation challenging. | 2a |
| Recommendations | Strength rating |
| Offer nivolumab or cabozantinib for immune checkpoint inhibitor-naive vascular endothelial growth factor receptor (VEGFR)-refractory clear-cell metastatic renal cell carcinoma (cc-mRCC). | Strong
|
| Sequencing the agent not used as second-line therapy (nivolumab or cabozantinib) for third-line therapy is recommended. | Weak |
| Offer VEGF-tyrosine kinase inhibitors as second-line therapy to patients refractory to nivolumab plus ipilimumab or axitinib plus pembrolizumab. | Weak |
| Offer cabozantinib after VEGF-targeted therapy in cc-mRCC. | Strong |