1️⃣ Initial Evaluation

 

 

• Imaging: Contrast-enhanced CT abdomen & pelvis (renal protocol) ± CT chest
• MRI: If IVC thrombus suspected or contrast contraindicated
• Biopsy: Consider in small renal masses (SRM), metastatic disease before systemic therapy, or when diagnosis is uncertain
• Risk stratification (metastatic disease):
  • IMDC (Heng) model
  • MSKCC model

 

 

 

 

 

? Localized RCC (cT1–T2, N0, M0)

 

 

 

A) Small Renal Mass (≤4 cm, T1a)

 

 

 

Preferred: Nephron-sparing approach

 

 

• Partial nephrectomy (PN) → Standard of care
• Open / Laparoscopic / Robotic

 

 

 

Alternatives:

 

 

• Active Surveillance (AS)
  • Elderly
  • Significant comorbidity
  • Competing mortality > RCC mortality
• Thermal Ablation (RFA / Cryoablation)
  • Poor surgical candidates

 

 

 

 

 

B) T1b–T2 Tumors (>4 cm, confined to kidney)

 

 

• Partial nephrectomy (if technically feasible)
• Otherwise → Radical nephrectomy (RN)

 

 

 

Radical nephrectomy includes:

 

 

• Kidney
• Perirenal fat
• ± Adrenal (if involved)
• ± Lymph nodes (if clinically enlarged)

 

 

 

 

 

? Locally Advanced RCC (T3–T4)

 

 

 

Venous thrombus (IVC involvement)

 

 

• Surgical removal (RN + thrombectomy)
• May require vascular/cardiac team

 

 

 

Adjuvant therapy

 

 

• High-risk patients after surgery
• Pembrolizumab (based on KEYNOTE-564 trial)

 

 

 

 

 

? Metastatic RCC (mRCC)

 

 

Management depends on:

 

• IMDC risk group
• Performance status
• Tumor burden
• Symptoms

 

 

 

 

 

First-Line Systemic Therapy

 

 

 

1️⃣ Favorable Risk

 

 

• IO + TKI combinations:
  • Pembrolizumab + Axitinib
  • Nivolumab + Cabozantinib
  • Pembrolizumab + Lenvatinib

 

 

 

 

 

2️⃣ Intermediate / Poor Risk

 

 

• Nivolumab + Ipilimumab
  OR
• IO + TKI combinations

 

 

 

 

 

Cytoreductive Nephrectomy (CN)

 

 

• Not routine anymore
• Consider in:
  • Good PS
  • Low metastatic burden
  • After response to systemic therapy

 

 

 

 

 

Second-Line Therapy

 

 

Depends on first-line regimen:

 

• Cabozantinib
• Lenvatinib + Everolimus
• TKI if prior IO
• IO if prior TKI

 

 

 

 

 

? Special Situations

 

 

 

Non-clear cell RCC

 

 

• Less evidence
• Often TKI-based therapy
• Clinical trials preferred

 

 

 

Brain metastasis

 

 

• Surgery or SRS
• Systemic therapy afterward

 

 

 

 

 

? Role of Radiotherapy

 

 

Traditionally radioresistant

Now:

 

• Stereotactic Body Radiotherapy (SBRT)
  • Oligometastatic disease
  • Bone/brain metastasis
  • Palliation

 

 

 

 

 

? Follow-Up After Surgery

 

 

Depends on risk category:

 

• Low risk → Annual imaging
• Intermediate → Every 6 months first 3 years
• High risk → More intensive schedule

 

 

 

 

 

? Changing Paradigm in RCC

 

 

• Shift from TKI monotherapy → Immunotherapy combinations
• Less upfront cytoreductive nephrectomy
• More personalized treatment sequencing
• Adjuvant immunotherapy in high-risk patients