OnCo

Renal cell carcinoma: lines of therapy

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11 standard-of-care settings across 5 lines and 3 biomarker subgroups. Rows come from the cancer page's standard of care; the grid places each on its line and subgroup.

LineAll comersIMDC riskRisk group
Early / localised3·1
Advanced, first line12·
Second line1··
Special situations1··
Other settings2··

Early / localised

SubgroupSettingApproachProducts and trialsEvidence
All comersLocalisedPartial/radical nephrectomy or ablation; adjuvant pembrolizumab ± belzutifan for high risk.98
All comersSmall renal mass (<4 cm)Active surveillance, partial nephrectomy (usually robotic), or thermal ablation depending on growth, comorbidity, and biopsy; renal mass biopsy increasingly used.40
All comersLocalised T1b-T3Partial or radical nephrectomy; no adjuvant therapy for low/intermediate risk.40
Risk groupHigh-risk after nephrectomy (clear-cell)Adjuvant pembrolizumab for 1 year (KEYNOTE-564, OS benefit); pembrolizumab + belzutifan approved 2026 (LITESPARK-022); sunitinib adjuvant rarely used.98

Advanced, first line

SubgroupSettingApproachProducts and trialsEvidence
All comersMetastaticIO-TKI or IO-IO doublet; belzutifan, cabozantinib, lenvatinib-everolimus later.98
IMDC riskMetastatic, intermediate/poor risk, first lineNivolumab + ipilimumab, or an IO-TKI doublet (pembrolizumab + axitinib, nivolumab + cabozantinib, lenvatinib + pembrolizumab); cytoreductive nephrectomy deferred or omitted (CARMENA) except in selected cases.98
IMDC riskMetastatic, favourable risk, first lineIO-TKI doublet (PFS benefit; OS benefit unproven in this group) or single-agent TKI (sunitinib, pazopanib) with deferred IO; active surveillance for indolent low-volume disease.98

Second line

SubgroupSettingApproachProducts and trialsEvidence
All comersSecond line after IO-based therapySingle-agent TKI (cabozantinib, axitinib, lenvatinib + everolimus, tivozanib); belzutifan after both IO and VEGF-TKI (LITESPARK-005). Do not rechallenge PD-1 (CONTACT-03, TiNivo-2).95

Special situations

SubgroupSettingApproachProducts and trialsEvidence
All comersOligometastatic / oligoprogressive diseaseMetastasectomy or SBRT to limited sites with continuation of systemic therapy or observation.40

Other settings

SubgroupSettingApproachProducts and trialsEvidence
All comersNon-clear-cell RCCCabozantinib (PAPMET), lenvatinib + pembrolizumab (KEYNOTE-B61), or nivolumab + cabozantinib; MET inhibitors for MET-driven papillary; trials preferred.98
All comersVHL diseaseBelzutifan for VHL-associated RCC, CNS haemangioblastoma, and pNET not requiring immediate surgery (LITESPARK-004).87

Sequence and caution pairings

Regimens in the library

Lines and subgroups are parsed from the setting text of each standard-of-care row and can misclassify an unusual phrasing; the row’s own setting is always shown. Guideline chips reflect the NCCN category and ESMO-MCBS grade recorded on the cancer page, checked on its stated date. Not medical advice.