Assess recurrence risk (KEYNOTE-564–style groups)
Risk groups Intermediate–high risk pT2, Grade 4 or sarcomatoid, NO. MO pT3, any grade, NO, MO High risk pT4, any grade, NO, MO Any pT, any grade, N+, MO M1 NED No evidence of disease after complete resection of metastatic sites (within 1 year from nephrectomy) Lower risk (not eligible for adjuvant pembrolizumab) pT1, any grade, NO, MO pT2, Grade 1-2, NO, MO without other high-risk features
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Lower risk
Active surveillance (see surveillance panel below)
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Active Surveillance Strategy
Imaging: CT chest/abdomen/pelvis (or MRI abdomen/pelvis) q6 months for 3 years, then annually up to 5 years (or as indicated) Labs: CBC, CMP (incl creatinine/eGFR), urinalysis Assess: H&P Symptom review Functional status Educate: Recurrence signs/symptoms Follow-up When to contact care team Re-evaluate: At each visit If recurrence detected → metastatic RCC algorithm
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Intermediate–high risk / High risk / M1 NED
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Postoperative recovery & timing
Aim to start within 12–16 weeks after nephrectomy (EAU recommendation). Checks: Within 12–16 weeks? Adequate wound healing? ECOG 0–1? Renal function stable? No unresolved postoperative complications?
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If not recovered and stable, then delay and reassess
Once recovered: Re-evaluate risk/eligibility Consider within adjuvant window If not feasible → Active surveillance
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Yes, recovered and stable
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Immunotherapy eligibility - Any contraindication/high-risk condition?
Any contraindication/high-risk condition? Active autoimmune disease Prior severe immune-related toxicity Solid organ transplant Chronic immunosuppression Uncontrolled IBD or severe active inflammatory disease Severe prior pneumonitis or immune hepatitis
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Yes, high-risk or contraindication
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Not high risk. Shared decision making
Discuss potential benefits/risks; patient values & preferences. Potential benefits: Improved disease-free survival (OFS) and overall survival (OS) in high-risk clear-cell RCC (KEYNOTE-664) Reduces risk of recurrence Potential risks: Immune-related adverse events (irAEs) Can be serious and may be permanent Requires regular infusions and monitoring Patient values and preferences: Tolerance for irAEs Willingness to receive treatment vs close surveillance Quality of life considerations
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Adjuvant pembrolizumab recommended
Best-fit profile: ccRCC/clear-cell component Intermediate–high risk/high risk/M1 NED Recovered from surgery IO-eligible Acceptable benefit–risk Pembrolizumab 200 mg IV q3w or 400 mg IV q6w for up to 1 year/until recurrence/toxicity/withdrawal.
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Borderline / preference-sensitive (shared decision)
Examples: pT3a without other high-risk features Older/significant comorbidities Mild autoimmune history Strongly values recurrence reduction or avoids toxicity. Choice between adjuvant pembrolizumab vs active surveillance based on informed preference.
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Active surveillance recommended
Best-fit profile: Low-risk localized RCC Pure non–clear cell RCC IO contraindication/poor recovery High competing mortality risk Preference to avoid toxicity (see active surveillance strategy).
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Active Surveillance Strategy
Imaging: CT chest/abdomen/pelvis (or MRI abdomen/pelvis) q6 months for 3 years, then annually up to 5 years (or as indicated) Labs: CBC, CMP (incl creatinine/eGFR), urinalysis Assess: H&P Symptom review Functional status Educate: Recurrence signs/symptoms Follow-up When to contact care team Re-evaluate: At each visit If recurrence detected → metastatic RCC algorithm
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Postoperative recovery & timing
Aim to start within 12–16 weeks after nephrectomy (EAU recommendation). Checks: Within 12–16 weeks? Adequate wound healing? ECOG 0–1? Renal function stable? No unresolved postoperative complications?
-
If not recovered and stable, then delay and reassess
Once recovered: Re-evaluate risk/eligibility Consider within adjuvant window If not feasible → Active surveillance
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Yes, recovered and stable
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Immunotherapy eligibility - Any contraindication/high-risk condition?
Any contraindication/high-risk condition? Active autoimmune disease Prior severe immune-related toxicity Solid organ transplant Chronic immunosuppression Uncontrolled IBD or severe active inflammatory disease Severe prior pneumonitis or immune hepatitis
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Yes, high-risk or contraindication
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Not high risk. Shared decision making
Discuss potential benefits/risks; patient values & preferences. Potential benefits: Improved disease-free survival (OFS) and overall survival (OS) in high-risk clear-cell RCC (KEYNOTE-664) Reduces risk of recurrence Potential risks: Immune-related adverse events (irAEs) Can be serious and may be permanent Requires regular infusions and monitoring Patient values and preferences: Tolerance for irAEs Willingness to receive treatment vs close surveillance Quality of life considerations
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Adjuvant pembrolizumab recommended
Best-fit profile: ccRCC/clear-cell component Intermediate–high risk/high risk/M1 NED Recovered from surgery IO-eligible Acceptable benefit–risk Pembrolizumab 200 mg IV q3w or 400 mg IV q6w for up to 1 year/until recurrence/toxicity/withdrawal.
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Borderline / preference-sensitive (shared decision)
Examples: pT3a without other high-risk features Older/significant comorbidities Mild autoimmune history Strongly values recurrence reduction or avoids toxicity. Choice between adjuvant pembrolizumab vs active surveillance based on informed preference.
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Active surveillance recommended
Best-fit profile: Low-risk localized RCC Pure non–clear cell RCC IO contraindication/poor recovery High competing mortality risk Preference to avoid toxicity (see active surveillance strategy).
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Active Surveillance Strategy
Imaging: CT chest/abdomen/pelvis (or MRI abdomen/pelvis) q6 months for 3 years, then annually up to 5 years (or as indicated) Labs: CBC, CMP (incl creatinine/eGFR), urinalysis Assess: H&P Symptom review Functional status Educate: Recurrence signs/symptoms Follow-up When to contact care team Re-evaluate: At each visit If recurrence detected → metastatic RCC algorithm