Presentation, risk factors and subtypes
Presentation
- Incidental imaging finding (>60% in UK)
- Visible (macroscopic) haematuria
- Flank or back pain
- Palpable abdominal mass
- Constitutional: weight loss, fevers, night sweats
- Paraneoplastic: hypercalcaemia, polycythaemia (EPO production), Stauffer's syndrome (deranged LFTs), anaemia
- Varicocele (especially left-sided new-onset) — venous invasion
- Bone pain or fracture from metastases
Risk Factors
- Smoking
- Obesity
- Hypertension
- Chronic kidney disease and acquired cystic disease in dialysis patients
- Family history / inherited syndromes (VHL, BHD, HLRCC, tuberous sclerosis)
- Sickle cell trait (renal medullary carcinoma)
- Workplace: trichloroethylene, asbestos
Subtypes
- Clear cell RCC (~75%) — VHL pathway, vascular, characteristic enhancement on CT
- Papillary RCC type 1 (~10%) — usually indolent, lower enhancement
- Papillary RCC type 2 (~5%) — more aggressive
- Chromophobe RCC (~5%) — usually slow-growing
- Collecting duct carcinoma (rare, aggressive)
- Renal medullary carcinoma (sickle trait, aggressive)
- Oncocytoma — benign mimic; sometimes diagnosed on biopsy
- Angiomyolipoma — benign, fat-containing; often associated with tuberous sclerosis
HEREDITARY SYNDROMES — suspect if multifocal, bilateral, young age, family history:
- Von Hippel-Lindau (VHL gene)
- Birt-Hogg-Dubé (FLCN)
- Hereditary leiomyomatosis and RCC (FH)
- Tuberous sclerosis (TSC1/2)
- Hereditary papillary RCC (MET)
Refer to clinical genetics for testing.
Diagnosis and staging
Imaging
- Contrast-enhanced CT abdomen/pelvis: the standard for characterising a renal mass; assess venous extension, lymph nodes, contralateral kidney
- MRI: alternative if iodinated contrast contraindicated; better characterisation of renal vein / IVC thrombus
- Chest CT for staging
- Bone scan or MRI if symptoms of metastases
- PET-CT not routinely used
Renal Mass Assessment
- Bosniak classification for cystic renal masses (I-IV: I/II benign, IIF surveillance, III/IV usually surgical)
- RENAL nephrometry score and PADUA score quantify surgical complexity (size, polar location, exophytic/endophytic, nearness to collecting system)
Biopsy
- Increasingly used for small renal masses (especially before ablation or active surveillance) and to subtype before systemic therapy
- Image-guided core biopsy is safe; bleeding and tract seeding are rare
Staging (Tnm 8)
- T1a ≤4 cm, T1b 4-7 cm, T2 >7 cm, T3 invasion of vein/perinephric fat, T4 beyond Gerota's fascia
- N1: regional lymph nodes
- M1: distant metastases
PROGNOSTIC SCORES (metastatic disease):
- International Metastatic RCC Database Consortium (IMDC) — favourable, intermediate, poor risk
- Six factors: time from diagnosis to treatment <1 year, Karnofsky <80%, low Hb, high calcium, high neutrophils, high platelets
Baseline Kidney Function
- eGFR, urine ACR
- Important for surgical planning (loss of nephrons is dose-dependent)
- Consider split renal function (DMSA / MAG3) if pre-operative eGFR is low
Kidney Vitality is a daily multivitamin developed by a UK Consultant Nephrologist using renal nutrition principles. It contains no added potassium, magnesium, phosphorus or iron, and no herbal blends. See the formulation.
Treatment by stage
Localised Disease (T1-t2)
- Partial nephrectomy: preferred for T1 tumours where anatomically feasible — preserves nephrons, reduces long-term CKD risk
- Radical nephrectomy: for larger tumours or unfavourable anatomy; laparoscopic / robotic now standard
- Thermal ablation (cryoablation or radiofrequency ablation): for T1a tumours in patients with comorbidity, single kidney, or hereditary syndromes
- Active surveillance: for small renal masses (<2 cm) particularly in older or unfit patients; grow at 2-3 mm/year on average; intervene if rapid growth, change in features, or patient preference
- Adjuvant therapy: pembrolizumab post-nephrectomy for high-risk RCC (KEYNOTE-564) — NICE TA871
Locally Advanced (T3-t4)
- Surgical excision when feasible (sometimes with IVC thrombectomy)
- Lymph node dissection selective
- Consider clinical trial; adjuvant pembrolizumab if eligible
METASTATIC CLEAR CELL RCC (first-line):
- Favourable risk IMDC: pembrolizumab + axitinib OR pembrolizumab + lenvatinib OR nivolumab + cabozantinib
- Intermediate / poor risk IMDC: nivolumab + ipilimumab (CheckMate 214) — preferred for poor-risk; also IO + TKI combinations
- Sunitinib or pazopanib monotherapy when IO contraindicated
- Cytoreductive nephrectomy: not routine (CARMENA trial); consider for oligometastatic, good-prognosis, or symptomatic primary
- Stereotactic radiotherapy for oligometastases
Later Lines
- Cabozantinib, lenvatinib + everolimus, tivozanib, axitinib monotherapy, belzutifan (HIF-2α inhibitor — VHL disease and some sporadic RCC; UK access expanding)
- Clinical trials encouraged
Non-clear Cell Rcc
- Less consensus; cabozantinib, IO ± TKI; clinical trials important
- Renal medullary and collecting duct: platinum-based chemotherapy combinations
Surveillance, CKD risk and patient support
Post-nephrectomy Surveillance
- Follows European Association of Urology and UK ROC pathways
- Typically: CT chest-abdomen at 3, 6, 12 months, then annually for 5 years (or longer for high-risk)
- Lower-frequency for small T1a partial nephrectomy
CKD After Nephrectomy
- Radical nephrectomy halves nephron mass — long-term CKD risk significant, particularly with pre-existing CKD, age >60, diabetes, hypertension
- Partial nephrectomy preserves more function but does not eliminate CKD risk
- Post-operative care: monitor eGFR and ACR at 6 weeks, 3 months, then annually
- BP target <130/80; ACE inhibitor or ARB if proteinuric
- Statin per cardiovascular risk
- Avoid NSAIDs and iodinated contrast where possible
- Lifestyle: smoking cessation, weight, exercise
Managing Immunotherapy Toxicity
- Immune-related adverse events affect any organ (colitis, pneumonitis, hepatitis, endocrinopathies, dermatitis, nephritis)
- Acute interstitial nephritis from checkpoint inhibitors — discuss with nephrology, withhold drug, consider steroids; can usually rechallenge after recovery
Screening
- Not recommended for general population
- Surveillance imaging for hereditary syndromes per specialist genetics protocols (e.g. annual MRI from age 16 in VHL)
- Dialysis patients with acquired cystic disease — periodic ultrasound
KEY MESSAGE: in the era of incidental small renal masses, the decision is no longer 'cut or not cut' but a tailored choice between partial nephrectomy, ablation and surveillance — taken in an MDT, with the long-term kidney function and patient preference at the centre.
