9Kidney / Renal Cell
Snapshot. Most kidney cancers are RCC (renal cell carcinoma); ~75% clear-cell (remainder papillary, chromophobe, and rare aggressive sarcomatoid/rhabdoid). Usually found incidentally on imaging — the classic triad (flank pain + haematuria + mass) is late and uncommon. Clear-cell is driven by the VHL (von Hippel-Lindau) → HIF (hypoxia-inducible factor) → VEGF (vascular endothelial growth factor) axis → intensely angiogenic (why anti-VEGF drugs work) and immune-responsive (why checkpoint inhibitors work). No useful tumour marker.
Workup
Multiphase contrast CT or MRI abdomen (characterises the mass) · CT chest for staging · biopsy not always needed before nephrectomy (imaging is often diagnostic) — reserved for metastatic disease, before ablation, or diagnostic uncertainty · baseline renal function (drives systemic options) · stage by TNM (tumour-node-metastasis) · IMDC (International Metastatic RCC Database Consortium) risk — 6 factors: performance status, time to systemic therapy <1 yr, anaemia, high calcium, high neutrophils, high platelets · GERMLINE / hereditary-RCC referral if age <46, bilateral or multifocal tumours, a first-degree relative with RCC, or syndromic features — VHL (von Hippel-Lindau; also the belzutifan setting) · HLRCC (fumarate hydratase — aggressive; cutaneous/uterine leiomyomas) · Birt-Hogg-Dubé (FLCN — fibrofolliculomas, lung cysts/pneumothorax) · SDH-deficient · hereditary papillary (MET). It changes surveillance, nephron-sparing intent, and family cascade testing.
Treatment by setting
| Setting | Treatment |
|---|
| Small renal mass / localised | Partial (nephron-sparing) nephrectomy where feasible
otherwise radical nephrectomy Elderly / comorbid with a small mass → active surveillance or ablation
cryo / radiofrequency |
Resected, high-risk clear-cell
intermediate-high/high-risk after nephrectomy (pT2 grade 4/sarcomatoid, pT3, pT4, or N+), or M1-NED after metastasectomy | Adjuvant pembrolizumab ×1 yr (KEYNOTE-564)
improves disease-free and overall survival (48-mo OS 91% vs 86%) · now an NCCN category 1 recommendation |
Metastatic clear-cell — 1st line
by IMDC risk | Cytoreductive nephrectomy — NOT routine (CARMENA)
sunitinib alone was non-inferior in intermediate / poor-risk disease; an exception may exist for low-burden, single-risk-factor patients Metastasectomy for oligometastatic disease · SBRT / palliative RT for bone or brain mets |
| Metastatic clear-cell — later lines | VEGFR-TKI — cabozantinib, lenvatinib + everolimus, tivozanib
VEGF-receptor tyrosine kinase inhibitors Belzutifan after a PD-1/PD-L1 inhibitor + a VEGFR-TKI (LITESPARK-005)
a HIF-2α inhibitor — especially VHL-associated disease |
| Non-clear-cell | Lenvatinib + pembrolizumab (KEYNOTE-B61)
or nivolumab + cabozantinib, or cabozantinib alone · enrol in a trial where possible |
Watch
VEGFR-TKIs → hypertension, hand-foot skin reaction, proteinuria, bleeding, fatigue, hypothyroidism. Ipilimumab + nivolumab → high rate of irAEs (immune-related adverse events) — any organ (endocrine/hepatitis/colitis, rare myocarditis). Belzutifan → anaemia + hypoxia (on-target, class effect — check O2 sat before dosing).