Table 1.
Summary of Asian recommendations
| Recommendations | Acceptability consensus (%) |
|---|---|
| Recommendation 1: diagnosis and pathology/molecular biology | |
| 1a. Laboratory examinations of serum creatinine, haemoglobin, differential leukocyte and platelet counts, and serum-corrected calcium tests should be carried out to confirm a suspicion of RCC (full blood counts, and renal profile tests are essential, the remainder of the tests may be carried out to facilitate the diagnosis/prognosis of RCC) [V, B]. | 100 |
| 1b. For accurate staging, US and contrast-enhanced chest, abdominal and pelvic CT scans are recommended [III, A]. | 100 |
| 1c. A renal tumour core biopsy is recommended before treatment with ablative therapies and in patients with metastatic disease before starting systemic treatment [III, B]. | 100 |
| 1d. Pathology should be assessed using the 2016 WHO histological classification of renal tumours and International Society of Urological Pathology grading. | 100 |
| Recommendation 2: staging and risk assessment | |
| 2. The UICC TNM 8 staging system should be used. | 100 |
| Recommendation 3: management of local/locoregional disease | |
| 3a. For organ confined T1 tumours <7 cm, partial nephrectomy is recommended [I, A]. Laparoscopic radical nephrectomy is recommended if partial nephrectomy is not feasible [I, A]. | 100 |
| 3b. In patients with compromised renal function, solitary or bilateral tumours, partial nephrectomy is also recommended with no tumour size limitation. | 100 |
| 3c. Radiofrequency ablation, microwave ablation or cryoablation are options in patients with small cortical tumours (≤3 cm), frail patients, high surgical risk, solitary kidney, compromised renal function and hereditary RCC or bilateral tumours [III, B]. | 100 |
| 3d. When nephrectomy is not contemplated or possible, a renal biopsy is recommended to confirm malignancy and histopathological subtype [V, C]. | 100 |
| 3e. Active surveillance may be selected for elderly patients with significant comorbidities or those with a short life expectancy and solid renal tumours <40 mm [II, B]; renal biopsy is recommended to select these patients. | 100 |
| 3f. For T2 tumours >7 cm, laparoscopic radical nephrectomy is the preferred option. | 100 |
| 3g. For T3 and T4 tumours (locally advanced), open radical nephrectomy is the standard of care, although a laparoscopic approach can be considered. | 100 |
| Recommendation 4: management of advanced/metastatic disease | |
| Ablative therapy | |
| 4a. Cytoreductive nephrectomy is recommended in patients with good PS, low metastatic burden and/or symptomatic primary tumours either as up-front surgery or delayed nephrectomy [III, B]. | 100 |
| 4b. Image-guided RT techniques such as volumetric-modulated arc therapy or stereotactic body radiotherapy are needed to enable the delivery of a high dose [IV, B]. | 100 |
| 4c. Radiotherapy is an effective treatment for palliation of local and symptomatic mRCC disease or to prevent the progression of metastatic disease in critical sites such as bones or brain [III, A]. | 100 |
| 4d. For mRCC patients with brain metastases, the use of corticosteroids can provide temporary relief of cerebral symptoms. Whole-brain radiotherapy between 20 and 30 Gy in 4-10 fractions is recommended for effective symptom control [II, B]. | 100 |
| 4e. For mRCC patients with a limited number of brain metastases, surgery and/or stereotactic radiosurgery with or without whole-brain radiotherapy should be considered [II, A]. | 100 |
| Systemic therapy | |
| First-line systemic treatment | |
| 4f. The combination of axitinib and pembrolizumab is recommended as a first-line therapeutic option for patients with advanced disease, irrespective of IMDC prognostic subgroups and PD-L1 biomarker status [I, A; ESMO-MCBS v1.1 score: 4]. | 100 |
| 4g. The combination of cabozantinib and nivolumab is recommended as a first-line therapeutic option for advanced disease irrespective of IMDC prognostic subgroup and PD-L1 biomarker status [I, A; ESMO-MCBS v1.1 score: 4]. | 100 |
| 4h. Lenvatinib and pembrolizumab join the other VEGFR/PD-1-targeting combinations (axitinib and pembrolizumab or nivolumab and cabozantinib) to be recommended as a first-line treatment option for patients with advanced ccRCC, irrespective of the IMDC subgroup and PD-L1 biomarker status [I, A; ESMO-MCBS v1.1 score: 4]. The combination of ipilimumab and nivolumab should be considered as a first-line option in patients with IMDC intermediate- and poor-risk disease [I, A; ESMO-MCBS v1.1 score: 4]. | 100 |
| 4i. Sunitinib [I, A], pazopanib [I, A], and tivozanib [II, B] are alternatives to immune checkpoint inhibitor-based first-line combinations when immune therapy is contraindicated or not available. Cabozantinib is also an alternative for the treatment of IMDC intermediate-risk [II, A, ESMO-MCBS v1.1 score: 3], and poor-risk disease in those patients who cannot receive first-line immune checkpoint inhibitor-based therapy [II, B; ESMO-MCBS v1.1 score: 3].]. | 100 |
| 4j. Sunitinib or pazopanib are potential alternatives to immune checkpoint inhibitor-based combination therapy in patients with IMDC favourable-risk disease due to a lack of clear superiority for immune checkpoint inhibitor-based combinations over sunitinib in this subgroup of patients in RCTs. Pazopanib was found to be non-inferior to sunitinib in the COMPARZ study [III, C; ESMO-MCBS v1.1 score: 4]. | 100 |
| 4k. Active surveillance is an alternative approach in a small subset of patients. This requires careful consideration in patients with good prognostic features [III, B]. | 100 |
| 4l. Axitinib and avelumab, and bevacizumab and atezolizumab, are not yet associated with an overall survival advantage and are therefore not recommended [I, C]. | 100 |
| 4m. Cessation of immune checkpoint inhibitors can be considered after 2 years of therapy in selected patients with good disease control [IV, B]. | 100 |
| Second-line systemic treatment | |
| 4n. For second-line treatment, following TKIs, nivolumab [l, A; ESMO-MCBS v1.1 score: 5] or cabozantinib is recommended [l, A; ESMO-MCBS v1.1 score: 3]. | 100 |
| 4o. The combination of lenvatinib and everolimus is FDA- and EMA-approved after TKI failure [II, B; ESMO-MCBS v1.1 score: 4] and could be considered following progression after first-line TKI monotherapy or a TKI in combination with an immune checkpoint inhibitor [IV, C]. | 100 |
| 4p. In patients already treated with two lines of TKI therapy, and whose disease has progressed, either nivolumab [I, A; ESMO-MCBS v1.1 score: 5] or cabozantinib [I, A; ESMO-MCBS v1.1 score: 3] may be considered. | 100 |
| 4q. Sequencing VEGFR TKI therapy after PD-1-based first-line therapy is associated with modest response rates. Thus, patients should receive a VEGFR-targeted agent that they have not received previously [III, A] | 100 |
| 4r. RCT data to support continued immune checkpoint inhibition after established progression is lacking and hence it is not recommended. | 100 |
| Non-ccRCC | 100 |
| 4s. Cabozantinib is the preferred first-line agent in patients with advanced papillary RCC who have not undergone additional molecular testing [II, B]. | 100 |
| 4t. Alternative options include sunitinib [II, B] and pembrolizumab [III, B], while in MET-driven tumours, savolitinib can be considered (where available) [III, C]. | 100 |
| 4u. Immune checkpoint inhibitor-based therapy is particularly active in sarcomatoid renal tumours and should be recommended ahead of single-agent VEGFR-targeted therapy [II, A]. | 100 |
| 4v. Second-line therapy should focus on those first-line agents that have not been used previously [IV, C]. | 100 |
| Recommendation 5: follow-up, long-term implications and survivorship | |
| 5a. Follow-up for high-risk patients includes CT scans of thorax and abdomen every 3-6 months for the first 2 years although the risk of late or even very late relapses should be taken into account; an annual CT scan is recommended for low-risk patients | 100 |
| 5b. For mRCC patients receiving systemic therapy, 2- to 4-month follow-up with a CT scan is advised | 100 |
| 5c. RECIST is the most frequently used method to assess drug efficacy | 100 |
ccRCC, clear cell renal cell carcinoma; CT, computed tomography; EMA, European Medicines Agency; ESMO-MCBS, European Society for Medical Oncology-Magnitude of Clinical Benefit Scale; FDA, Food and Drug Administration; Gy, gray; IMDC, International Metastatic RCC Database Consortium; MET, mesenchymal-epithelial transition; mRCC, metastatic renal cell carcinoma; PD-1, programmed cell death protein 1; PD-L1, programmed death-ligand 1; PS, performance status; RCC, renal cell carcinoma; RCT, randomised controlled trial; RT, radiotherapy; TKIs, tyrosine kinase inhibitors; TNM, tumour–node–metastasis; UICC, Union for International Cancer Control; US, ultrasound; VEGFR, vascular endothelial growth factor receptor; WHO, World Health Organization.