Kidney Cancer
Clear cell, papillary, chromophobe RCC and variant histologies
DefinitionClick to collapse
Renal cell carcinoma (RCC) is a cancer that originates from the renal tubular epithelium of the kidney. It is a heterogeneous group of malignancies arising from the renal parenchyma, distinct from urothelial carcinoma of the renal pelvis. The embryological origin is from the metanephric mesenchyme. The anatomical boundaries are defined by the kidney and its surrounding structures, with staging determined by the extent of the primary tumor (T), involvement of regional lymph nodes (N), and presence of distant metastases (M). The most common presentation is as a solid renal mass, often discovered incidentally on imaging [MS-4].
EpidemiologyClick to collapse
SubtypesClick to collapse
Clear Cell Renal Cell Carcinoma (ccRCC)
The most common histologic subtype, characterized by cells with clear cytoplasm due to lipid and glycogen accumulation.
Papillary Renal Cell Carcinoma
The second most common subtype, with tumor cells arranged in papillary or tubulopapillary structures.
Chromophobe Renal Cell Carcinoma
Cells with prominent cell membranes and pale cytoplasm.
Collecting Duct Carcinoma
An aggressive, rare subtype originating from the collecting ducts of the renal medulla.
Renal Medullary Carcinoma (RMC)
A rare and aggressive variant associated with sickle-cell trait or disease.
Translocation RCC (TFE3/TFEB-altered)
Molecularly defined subtypes characterized by gene rearrangements involving TFE3 or TFEB.
Succinate Dehydrogenase (SDH)-Deficient RCC
A molecularly defined subtype associated with SDH gene mutations.
FH-Deficient RCC (including HLRCC-associated RCC)
A molecularly defined subtype associated with fumarate hydratase (FH) mutations.
BAP1-Tumor Predisposition Syndrome (TPDS)-associated RCC
A molecularly defined subtype associated with BAP1 gene mutations.
Molecular PathogenesisClick to collapse
The molecular pathogenesis of RCC is complex and varies by subtype. For clear cell RCC (ccRCC), the key genomic event is inactivation of the von Hippel-Lindau (VHL) tumor suppressor gene on chromosome 3p, leading to activation of the hypoxia-inducible factor (HIF) pathway and overexpression of vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) [MS-4]. Other important alterations include mutations in PBRM1, SETD2, and BAP1 genes. For papillary RCC, mutations in the MET proto-oncogene are common in hereditary forms. TFE3 and TFEB gene rearrangements define translocation RCC subtypes. SDH-deficient RCC is characterized by germline mutations in SDH genes (SDHA, SDHB, SDHC, SDHD). FH-deficient RCC is caused by germline mutations in the FH gene. BAP1-TPDS-associated RCC involves mutations in the BAP1 gene [MS-32, MS-34].
Risk FactorsClick to collapse
Smoking
Tobacco smoking is an established risk factor for RCC development [MS-4].
Obesity
Obesity is an established risk factor for RCC development [MS-4].
Hypertension
Hypertension is an established risk factor for RCC development [MS-4].
Family history of RCC
A family history of RCC may indicate an inherited predisposition, such as a hereditary RCC syndrome [MS-5].
Hereditary RCC syndromes
Several hereditary syndromes predispose to RCC, including von Hippel-Lindau (VHL) disease, hereditary leiomyomatosis and renal cell cancer (HLRCC), Birt-Hogg-Dubé syndrome, and others [MS-4, MS-32].
Sickle-cell trait or disease
Almost exclusively associated with renal medullary carcinoma [MS-30].
Clinical FeaturesClick to collapse
Typical Presentation
Patients with renal cell carcinoma (RCC) typically present with a suspicious renal mass identified incidentally on imaging, as increased use of imaging methods including abdomen CT with or without pelvis CT and MRI has led to more frequent incidental detection of RCC [MS-4]. The classic triad of hematuria, flank mass, and flank pain is now less commonly seen at diagnosis compared to historical presentations [MS-4]. Among the approximately 80,450 Americans estimated to be diagnosed with cancers of the kidney and renal pelvis in 2026, approximately 66% are diagnosed as localized disease, and the 5-year survival rate between 2015 and 2021 is 79% [1, MS-4]. The median age at diagnosis is 65 years [2, MS-4]. RCC comprises approximately 85% of kidney tumors, with approximately 80% to 90% having clear cell histology (ccRCC) [17-20, MS-4]. Less common histologies include papillary, oncocytic and chromophobe, TFE3-rearranged and TFEB-altered (translocation) RCC, collecting duct carcinoma, and SMARCB1-deficient medullary renal carcinoma [21-23, MS-4]. Hereditary RCC syndromes account for approximately 3% of all RCC cases and should be suspected in younger patients (≤46 years), those with bilateral or multifocal tumors, or those with a family history [242, MS-32].
Symptoms
Hematuria
Classically described as part of the triad of hematuria, flank mass, and flank pain, though now less common at presentation due to incidental detection [MS-4].
Flank pain
Classically described as part of the triad of hematuria, flank mass, and flank pain, though now less common at presentation due to incidental detection [MS-4].
Flank mass
Classically described as part of the triad of hematuria, flank mass, and flank pain, though now less common at presentation due to incidental detection [MS-4].
Bone pain
May indicate bone metastases; bone metastasis occurs in approximately 30% to 40% of patients with advanced RCC [14, 233, 235]. Most bone and brain metastases are symptomatic at diagnosis [34, MS-4].
Constitutional symptoms
Fever, weight loss, and anemia may occur as presenting features of RCC [MS-4].
Pulmonary symptoms
Pulmonary symptoms attributable to lung parenchyma or mediastinal metastases may be the presenting feature; lung metastases occur in 50% to 60% of patients with relapse [MS-4, 103].
Adenopathy
Lymphadenopathy may be the presenting feature of metastatic RCC [MS-4].
Varicocele
A varicocele may be an unusual presenting sign of RCC [MS-4].
Signs
Incidental renal mass on imaging
As the use of imaging methods (eg, abdomen CT with or without pelvis CT, MRI) has become more widespread, the frequency of incidental detection of RCC has increased [MS-4].
Suspicious mass on CT or MRI
The initial workup includes abdomen ± pelvis CT or MRI performed with and without contrast, such as a renal protocol for the abdomen [KID-1, MS-5].
Palpable abdominal/flank mass
A palpable mass may be detected on physical examination, though less common with contemporary incidental detection [MS-4].
Red FlagsClick to collapse
Hematuria (visible or microscopic) — warrants complete evaluation including imaging and potentially urological assessment [KID-1, MS-4]
Flank mass detected on physical examination — suspicious for renal malignancy [MS-4]
Flank pain with or without hematuria — requires imaging evaluation [MS-4]
Bone pain with or without elevated serum alkaline phosphatase (ALP) — suggests possible bone metastases; bone scan may be indicated [34, MS-4]
Pulmonary symptoms (cough, dyspnea) — may indicate lung metastases; most common site of distant recurrence in 50% to 60% of relapsed patients [103, MS-4]
Lymphadenopathy on examination or imaging — requires further evaluation for regional or distant metastatic disease [MS-4]
Fever, weight loss, anemia — constitutional symptoms that may indicate advanced or metastatic disease [MS-4]
Neurologic symptoms — may indicate brain metastases; brain MRI should be performed [MS-4, MS-31]
Bilateral or multifocal renal masses in a young patient (≤46 years) or patient with family history — raises suspicion for hereditary RCC syndrome and warrants genetic evaluation [HERED-RCC-1, MS-33]
Suspected or confirmed VHL or PGL/PCC syndrome — patients are at increased risk for pheochromocytomas and should have blood and/or urine screening prior to any surgical procedure [HERED-RCC-C]
RMC or collecting duct histology — extremely aggressive variants requiring platinum-based chemotherapy as preferred first-line therapy; immune checkpoint therapies should be avoided outside clinical trials due to limited efficacy and potential for rapid progression [KID-D 3 of 3, MS-30]
InvestigationsClick to collapse
Diagnostic
History and physical examination (H&P)
To evaluate symptoms including hematuria, flank mass, flank pain, bone pain, constitutional symptoms, and to assess performance status; to obtain family history suggesting hereditary RCC syndromes [KID-1, MS-4].
Complete blood count (CBC) with differential
To evaluate for anemia, polycythemia (paraneoplastic erythropoietin production), or leukocytosis; part of the standard initial workup [KID-1, MS-5].
Comprehensive metabolic panel
To assess renal function (serum creatinine), liver function (LFTs), serum corrected calcium (which may be elevated as a paraneoplastic manifestation or bone metastases marker), and electrolytes; part of standard initial workup [KID-1, MS-5].
Urinalysis
To evaluate for microscopic or gross hematuria; part of the standard initial workup [KID-1, MS-5].
Abdomen ± pelvis CT or MRI with and without IV contrast (renal protocol)
Essential initial imaging to detect, characterize, and stage the renal mass; CT with and without contrast (renal protocol) is strongly preferred; MRI can evaluate the inferior vena cava if tumor involvement is suspected and can be used instead of CT when contrast cannot be administered due to allergy or moderate renal insufficiency [KID-1, MS-5].
CT chest (preferred) or chest x-ray
Essential for staging to evaluate for pulmonary metastases, the most common site of distant recurrence [KID-1, MS-5].
Bone scan or bone survey
Performed when clinically indicated — elevated serum alkaline phosphatase (ALP) or bone pain — to evaluate for osseous metastases [KID-1, MS-4].
Brain MRI
Performed when clinically indicated if neurologic signs, presentation, or symptoms suggest brain metastases [KID-1, MS-4].
Staging
Abdomen/pelvis CT or MRI with and without contrast
Primary imaging modality for staging local extent of disease, regional lymph nodes, venous involvement (renal vein, IVC), and adrenal glands [KID-1, MS-5].
CT chest (preferred) or chest x-ray
Essential staging study to evaluate for pulmonary metastases [KID-1, MS-5].
MRI (preferred for IVC evaluation)
Preferred for evaluation of inferior vena cava (IVC) when tumor involvement is suspected; can be used instead of CT for detecting renal masses and staging when contrast cannot be administered [MS-5].
Bone scan
To evaluate for osseous metastases; not routinely performed unless elevated serum ALP or bone pain [34, MS-4].
Brain MRI
To evaluate for brain metastases; brain metastases occur in 2%-8% of advanced RCC patients [233, MS-31].
FDG-PET/CT
Not a routine imaging tool to diagnose kidney cancer or follow for relapse after nephrectomy [36, MS-5]. However, FDG-PET is useful in certain circumstances including: bone-predominant disease; assessment prior to metastasectomy; FH-deficient RCC; and SDHB-deficient RCC [37, 38, MS-13, MS-31].
Core needle biopsy
Biopsy of small lesions may be considered to obtain or confirm a diagnosis of malignancy and guide decisions on surveillance, percutaneous ablation, SBRT, and/or surgery [35, KID-1]. Biopsy should also be considered if a central lesion or homogeneous infiltration of renal parenchyma is observed to rule out urothelial carcinoma or lymphoma [MS-5].
Biomarkers
Tumor histology and grade (ISUP/WHO grading system)
Essential for determining histologic subtype (clear cell, papillary, chromophobe, etc.) and nuclear grade (G1-G4); grade is a critical prognostic factor; grade 4 includes tumors with marked nuclear pleomorphism, multinucleate giant cells, rhabdoid, and/or sarcomatoid differentiation [ST-1, MS-4].
Genetic evaluation for hereditary RCC syndromes
Criteria for further genetic risk evaluation include: personal or family history with known P/LP variant; RCC diagnosed at age ≤46 years; bilateral or multifocal tumors; ≥1 first- or second-degree relative with RCC; personal or family history of mesothelioma, uveal melanoma, GIST, pheochromocytoma, paraganglioma, cutaneous/uterine leiomyoma; histologic features associated with specific hereditary syndromes [HERED-RCC-1].
StagingClick to collapse
AJCC Cancer Staging Manual, 8th Edition (2017) [ST-1]
T Categories
| Stage | Description |
|---|---|
| TX | Primary tumor cannot be assessed |
| T0 | No evidence of primary tumor |
| T1 | Tumor ≤7 cm in greatest dimension, limited to the kidney |
| T1a | Tumor ≤4 cm in greatest dimension, limited to the kidney |
| T1b | Tumor >4 cm but ≤7 cm in greatest dimension, limited to the kidney |
| T2 | Tumor >7 cm in greatest dimension, limited to the kidney |
| T2a | Tumor >7 cm but ≤10 cm in greatest dimension, limited to the kidney |
| T2b | Tumor >10 cm, limited to the kidney |
| T3 | Tumor extends into major veins or perinephric tissues, but not into the ipsilateral adrenal gland and not beyond Gerota's fascia |
| T3a | Tumor extends into the renal vein or its segmental branches, or invades the pelvicalyceal system, or invades perirenal and/or renal sinus fat but not beyond Gerota's fascia |
| T3b | Tumor extends into the vena cava below the diaphragm |
| T3c | Tumor extends into the vena cava above the diaphragm or invades the wall of the vena cava |
| T4 | Tumor invades beyond Gerota's fascia (including contiguous extension into the ipsilateral adrenal gland) |
N Categories
| Stage | Description |
|---|---|
| NX | Regional lymph nodes cannot be assessed |
| N0 | No regional lymph node metastasis |
| N1 | Metastasis in regional lymph node(s) |
M Categories
| Stage | Description |
|---|---|
| M0 | No distant metastasis |
| M1 | Distant metastasis |
Stage Groupings
| Group | Criteria | Clinical Meaning | Five Yr Survival | Treatment Intent |
|---|---|---|---|---|
| Stage I | T1, N0, M0 | Tumor ≤7 cm confined to the kidney without regional lymph node or distant metastasis; 5-year survival for localized disease is 79% (2015-2021 data) [1, MS-4]. Treatment is curative with surgery as primary approach; options include partial nephrectomy (preferred), percutaneous ablation, SBRT, active surveillance, or radical nephrectomy in select patients [KID-1]. | 79% for localized disease (2015-2021) [1, MS-4] | Curative [KID-1] |
| Stage II | T2, N0, M0 | Tumor >7 cm confined to the kidney without regional lymph node or distant metastasis; higher risk of recurrence than Stage I; radical nephrectomy is curative therapy [MS-9]; for clear cell histology, adjuvant pembrolizumab (category 1) or adjuvant belzutifan + pembrolizumab (category 2A) is an option for Grade 4 tumors with clear cell histology ± sarcomatoid features [KID-2]. | None | Curative [KID-2] |
| Stage III | T1-T2 with N1, M0; OR T3 with any N (NX, N0, or N1), M0 | Tumor with regional lymph node involvement or tumor extending into major veins or perinephric tissues; curative therapy is radical nephrectomy [MS-9]; adjuvant pembrolizumab (category 1) or adjuvant belzutifan + pembrolizumab (category 2A) is recommended for clear cell histology [KID-2]; larger tumors have substantially higher risk of both local and metastatic recurrence [MS-13]. | None | Curative [KID-2] |
| Stage IV (Resectable T4, M0) | T4, any N, M0 | Tumor invades beyond Gerota's fascia without distant metastasis; nephrectomy is recommended for resectable disease; adjuvant pembrolizumab or adjuvant belzutifan + pembrolizumab is an option for clear cell histology after resection [KID-3]. | None | Potentially curative with aggressive multimodal approach [KID-3] |
| Stage IV (M1, potentially surgically resectable primary) | Any T, any N, M1 | Metastatic disease with potentially surgically resectable primary; systemic therapy (category 1) is now the preferred approach, with consideration of cytoreductive nephrectomy in select patients; individualized treatment based on symptoms and extent of metastatic disease [KID-3, MS-15]. | None | Palliative/systemic control [KID-3] |
| Stage IV (M1, surgically unresectable) | Any T, any N, M1 | Metastatic disease with surgically unresectable primary; tissue sampling to confirm diagnosis and guide management; systemic therapy is recommended [KID-3]. | None | Palliative/systemic control [KID-3] |
Staging Pearls
- The most important prognostic determinants of 5-year survival are the tumor stage, grade, local extent of the tumor, presence of regional nodal metastases, and evidence of metastatic disease at presentation [4-13, MS-4].
- Approximately 66% of kidney cancer cases are diagnosed as localized disease, and the 5-year survival rate between 2015 and 2021 is 79% [1, MS-4].
- RCC primarily metastasizes to the lung, bone, liver, lymph nodes, adrenal gland, and brain [14-16, MS-4].
- For metastatic disease, the Memorial Sloan Kettering Cancer Center (MSKCC) and International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic models are used to stratify risk and guide treatment [KID-E, MS-14].
- IMDC risk groups: favorable-risk (no adverse factors) — median OS not reached; intermediate-risk (1-2 factors) — median OS 27 months, 2-year OS 53%; poor-risk (3-6 factors) — median OS 8.8 months, 2-year OS 7% [113, MS-14].
- MSKCC prognostic factors include: interval from diagnosis to treatment of <1 year, KPS <80%, serum LDH >1.5× ULN, corrected serum calcium > ULN, and serum hemoglobin < LLN [112, KID-E].
- IMDC prognostic factors include: <1 year from diagnosis to systemic therapy, PS <80% (Karnofsky), hemoglobin < LLN, calcium > ULN, neutrophil > ULN, and platelets > ULN [113, KID-E].
- Grade 4 histology (marked nuclear pleomorphism and/or multinucleate giant cells and/or rhabdoid and/or sarcomatoid differentiation) is an important prognostic factor that determines eligibility for adjuvant pembrolizumab in Stage II clear cell RCC [ST-1, KID-2].
- After surgical excision of localized tumors, 20% to 30% of patients experience relapse, with a median time to relapse of 1 to 2 years and most relapses occurring within 3 years [103, 104, MS-11].
- Lung metastasis is the most common site of distant recurrence, occurring in 50% to 60% of patients [103, MS-11].
Management PrinciplesClick to collapse
The management of renal cell carcinoma (RCC) requires a multidisciplinary approach, emphasizing nephron-sparing surgery when feasible and risk stratification for adjuvant and systemic therapy decisions. Treatment intent varies from curative for localized disease to palliative for advanced stages. Active surveillance is a viable option for select patients with small renal masses and significant comorbidities. For metastatic disease, the choice of systemic therapy is guided by histology, risk stratification (MSKCC/IMDC), and prior therapy history. Supportive care and management of treatment-related toxicities are integral throughout the disease trajectory. [KID-A, KID-D]
Curative
Localized RCC (Stages I-III, resectable T4, M0)
Primary treatment involves surgical resection (partial or radical nephrectomy) or ablative techniques (percutaneous ablation, SBRT) for medically inoperable patients. Adjuvant pembrolizumab is recommended for clear cell histology with high-risk features (stage II grade 4 ± sarcomatoid, stage III). Neoadjuvant systemic therapy may be considered for select patients with large or locally advanced tumors to achieve cytoreduction. [KID-1, KID-2, KID-3]
Palliative/Control
Stage IV (M1, unresectable T4, M0) or relapsed disease
Treatment aims to prolong survival and maintain quality of life. Options include systemic therapy (first-line and subsequent lines), cytoreductive nephrectomy in selected patients, and metastasectomy or SBRT for oligometastatic disease. Best supportive care is recommended for all patients. [KID-3, KID-4]
Management should involve a multidisciplinary team including urologic oncologists, medical oncologists, radiation oncologists, pathologists, radiologists, and palliative care specialists. Genetic counseling should be offered to patients with suspected hereditary RCC syndromes. For complex cases (e.g., inferior vena cava tumor thrombus, hereditary syndromes), referral to high-volume centers is recommended. [KID-A, HERED-RCC-1]
Performance status (PS) influences treatment eligibility. For localized disease, patients with ECOG PS 0-1 are candidates for surgery. For cytoreductive nephrectomy, candidates generally have excellent PS (ECOG PS <2) and no brain metastasis. For systemic therapy, PS is a key factor in treatment selection and tolerability. Patients with poor PS may be better candidates for best supportive care or less intensive regimens. [KID-A, KID-3]
Management PathwaysClick to collapse
Branching: Tumor size (≤4 cm), Patient fitness and comorbidities, Tumor location and complexity, Patient preference
Branching: Tumor size (4-7 cm), Patient fitness and comorbidities, Tumor location and complexity, Patient preference
Branching: Histology (clear cell vs. non-clear cell), Grade (Grade 4 ± sarcomatoid features), Patient fitness for surgery
Branching: Histology (clear cell vs. non-clear cell), Resectability, Patient fitness for surgery
Branching: Histology, Resectability, Patient fitness
Branching: Risk category (MSKCC/IMDC: favorable, intermediate, poor), Patient comorbidities and preferences, Histology confirmation
Branching: Prior immuno-oncology (IO) therapy status, Patient comorbidities and preferences, Risk category
Branching: Histology subtype (papillary, chromophobe, unclassified, etc.), Risk category, Patient comorbidities, Clinical trial availability
Branching: Number and location of metastases, Disease control with systemic therapy, Patient fitness and preferences
Branching: Complete resection of all disease, Histology, Time from nephrectomy
Branching: Tumor size (3 cm rule), Patient fitness, Presence of other VHL manifestations
Branching: Tumor size and grade, Metastatic vs. localized, Patient fitness
Pretreatment EvaluationClick to collapse
Clinical Assessment
Laboratory Studies
Imaging Studies
Pathologic Evaluation
Risk Assessment and Prognostic Modeling
Multidisciplinary Consultation
SurgeryClick to collapse
Surgical resection remains the primary curative treatment for localized RCC and a palliative option for select patients with metastatic disease. The goal is complete tumor removal while maximizing preservation of renal function when feasible.
Nephron-sparing surgery (partial nephrectomy) is preferred for stage I tumors and whenever technically feasible to preserve renal function and reduce chronic kidney disease risk. [KID-A]
Radical nephrectomy is indicated for larger or locally advanced tumors (stage II, III, resectable T4) or when partial nephrectomy is not feasible. [KID-A, KID-2, KID-3]
Open, laparoscopic, or robotic techniques are acceptable; outcomes are equivalent in experienced hands. [KID-A]
Regional lymph node dissection is optional but should be considered for patients with adenopathy on imaging or palpable nodes at surgery. Extended dissection templates are provided for right- and left-sided tumors. [KID-A]
Ipsilateral adrenalectomy may be omitted if the adrenal gland is uninvolved and not high-risk. [KID-A]
Percutaneous ablation (cryosurgery, radiofrequency, microwave) is an option for clinical stage T1 lesions, particularly for non-surgical candidates. Biopsy prior to or at ablation is recommended. [KID-A, KID-1]
Stereotactic body radiation therapy (SBRT) is an option for non-optimal surgical candidates with T1 and T2a tumors. Referral to a high-volume center is recommended. [KID-A, KID-B]
Procedures
Partial Nephrectomy (Nephron-Sparing Surgery)
Stage I–III tumors when technically feasible; imperative indications (solitary kidney, chronic kidney disease, bilateral tumors); hereditary RCC syndromes. [KID-A]
Radical Nephrectomy
Stage II, III, resectable stage IV (T4, M0) disease; tumor extends into inferior vena cava or involves >50% of kidney; partial nephrectomy would result in poorly functioning kidney. [KID-A, KID-2, KID-3]
Cytoreductive Nephrectomy
Stage IV, M1 disease with surgically resectable primary tumor in select patients (excellent PS, no brain metastasis). [KID-3]
Metastasectomy
Oligometastatic disease with controlled primary tumor and good performance status. [KID-4]
Percutaneous Ablation
Clinical stage T1 renal lesions, particularly for non-surgical candidates. Suitable for masses ≤3 cm. [KID-A, KID-1]
Radiation TherapyClick to collapse
Radiation therapy (RT) is primarily used for palliation of symptomatic metastases and as a definitive or adjuvant treatment for select patients with localized disease who are not surgical candidates. SBRT is the preferred modality for most indications due to superior local control. [KID-B]
Principles
- SBRT should be considered as the primary radiation modality in all situations unless precluded by anatomic site, proximity to organs at risk (OAR), or past treatments. [KID-B]
- A biopsy should be obtained whenever possible prior to SBRT. [KID-B]
- All patients should have a urologic evaluation. [KID-B]
- Strict adherence to normal tissue constraints is mandatory to minimize toxicity. [KID-B]
- For primary disease, SBRT is an option for non-optimal surgical candidates with T1 and T2a tumors (≤10 cm). When tumors abut bowel, a 5-fraction schedule with strict adherence to bowel constraints is recommended. Volumetric image guidance with motion management is required. On-table adaptive technology should be considered when available. [KID-B]
- For distant metastatic disease, SBRT is preferred for oligometastases unless metastasectomy is planned or SBRT cannot be delivered. SBRT may offer more durable local control. [KID-B]
Dose Frameworks
| Name | Total Dose | Dose Per Fraction | Fractions | Schedule | Indication |
|---|---|---|---|---|---|
| Primary Disease - Single Fraction | 25-26 Gy | 25-26 Gy | 1 | Single fraction | Small tumors (≤4 cm). [KID-B] |
| Primary Disease - 3 Fractions | 39-48 Gy | 13-16 Gy | 3 | Consecutive or non-consecutive days | Tumors 4-10 cm. [KID-B] |
| Primary Disease - 4 Fractions | 48 Gy | 12 Gy | 4 | Consecutive or non-consecutive days | Alternative fractionation. [KID-B] |
| Primary Disease - 5 Fractions | 40-50 Gy | 8-10 Gy | 5 | Consecutive or non-consecutive days | Larger tumors or when dose-volume criteria for OAR cannot be met with higher BED regimens. Every-other-day schedule may be considered to mitigate GI toxicity. [KID-B] |
Approaches
| Name | Dose Fractionation | Concurrent Chemotherapy | Indication | Key Trial | Toxicities |
|---|---|---|---|---|---|
| SBRT for Primary Disease | See dose_frameworks above. | Not applicable. | Non-optimal surgical candidates with clinical stage T1a (category 2A), T1b (category 2A), stage II (category 2B), or stage III (category 3) RCC. [KID-1, KID-2, KID-B] | TROG 15.03 FASTRACK II trial (100% local control at 12 months for T1 tumors). [KID-B] | Mostly grade 1-2; grade 3 events (e.g., nausea, vomiting, pain) in 10% of patients. [KID-B] |
| SBRT for Distant Metastatic Disease | Spine: 16-24 Gy in 1 fraction, 24-28 Gy in 2 fractions, 24-30 Gy in 3 fractions, 30-40 Gy in 5 fractions. Other sites: 16-24 Gy in 1 fraction, 48-60 Gy in 3 fractions, 40-60 Gy in 4-5 fractions. [KID-B] | Not routinely recommended. | Oligometastatic disease. SBRT should be considered unless metastasectomy is planned or SBRT cannot be delivered. [KID-4, KID-B] | SABR-COMET trial (improved PFS for oligometastatic cancers treated with SBRT). [KID-B] | Site-specific; strict adherence to OAR constraints is required to minimize toxicity. [KID-B] |
| Palliative Radiation Therapy | 8 Gy in 1 fraction, 20 Gy in 5 fractions, 30 Gy in 10 fractions. [KID-B] | Not applicable. | Symptomatic extracranial metastases. Higher doses or hypofractionated regimens may provide more durable palliation. [KID-B] | Not specified. | Depends on site; generally well-tolerated. |
| Stereotactic Radiosurgery (SRS) for Brain Metastases | Based on tumor size: ≤20 mm: up to 24 Gy; 21-30 mm: up to 18 Gy; 31-40 mm: up to 15 Gy. Larger tumors may be treated with fractionated SRT (e.g., 24-27 Gy in 3 fractions, 25-35 Gy in 5 fractions). [KID-B] | Not applicable. | Brain metastases. Primary treatment or adjuvant after resection. [KID-B] | RTOG 90-05 dose escalation study. [KID-B] | Risk of radionecrosis, headache, seizures. |
Systemic TherapyClick to collapse
Systemic therapy for advanced RCC includes immune checkpoint inhibitor (ICI) combinations with tyrosine kinase inhibitors (TKIs), ICI monotherapy, and TKI monotherapy. Treatment selection is guided by histology (clear cell vs. non-clear cell), risk stratification (MSKCC/IMDC for clear cell), and prior therapy history. For non-clear cell RCC, clinical trials are preferred, and tumor genomic testing is recommended. [KID-D]
Key Regimens
Treatment Response AssessmentClick to collapse
Title
Assessment of Treatment Response and Disease Surveillance
Timing
Response assessment is performed periodically during systemic therapy, typically every 6-16 weeks based on treatment schedule and clinical status. For localized disease, surveillance follows stage-specific guidelines. [KID-C, KID-4]
Response Logic
-
For patients on systemic therapy, imaging (CT or MRI with and without contrast) is performed at baseline and every 6-16 weeks to assess response per RECIST criteria. Interval may be adjusted based on rate of disease change and sites of active disease. [KID-C, KID-4]
-
For localized disease post-treatment, surveillance imaging is based on stage and treatment type (e.g., active surveillance, ablation, nephrectomy, SBRT). [KID-C]
-
Clinical assessment includes history, physical examination, and laboratory evaluation as per treatment requirements. [KID-C, KID-4]
Imaging Recommendations
-
Abdominal imaging (CT or MRI with and without contrast) is the primary modality for assessing renal and local recurrence. [KID-C]
-
Chest CT is used to evaluate for pulmonary metastases. [KID-C]
-
Brain MRI is considered if neurological symptoms or risk of brain metastases. [KID-C, KID-4]
-
Bone scan or bone survey as clinically indicated for bone pain or elevated alkaline phosphatase. [KID-C, KID-4]
-
FDG-PET is useful in certain circumstances (e.g., bone-predominant disease, prior to metastasectomy, FH-deficient RCC, SDHB-deficient RCC). [KID-C, KID-4]
Biopsy Or Salvage Logic
-
If imaging suggests residual or recurrent disease after local therapy (e.g., ablation), biopsy or further treatment may be indicated. [KID-C]
-
For progression on systemic therapy, subsequent therapy options are considered based on prior treatments and histology. [KID-D]
-
Tissue biopsy should be obtained at recurrence when feasible to confirm histology and guide therapy, especially for non-clear cell subtypes or clinical trial eligibility. [KID-4, KID-D]
SurveillanceClick to collapse
Clinical Follow Up Schedule
| Stage | Schedule |
|---|---|
| Stage I (after nephrectomy) | H&P and laboratory tests annually. Abdominal CT/MRI within 3-12 months, then annually for up to 5 years or longer. Chest CT annually for at least 5 years. |
| Stage II | H&P and laboratory tests annually. Abdominal/pelvic CT/MRI every 6 months for 2 years, then annually for up to 5 years. Chest CT annually for at least 5 years. |
| Stage III or T4,NXM0 | H&P and comprehensive metabolic panel every 3-6 months for 3 years, then annually for up to 5 years. Abdominal/pelvic CT/MRI every 3-6 months for at least 3 years, then annually for up to 5 years. Chest CT every 3-6 months for at least 3 years, then annually for up to 5 years. Additional imaging (bone scan, brain MRI) as symptoms warrant. |
| Stage IV or relapsed disease | H&P every 6-16 weeks during systemic therapy. Imaging (CT/MRI of chest, abdomen, pelvis) every 6-16 weeks, adjusted based on disease status and treatment schedule. MRI of head at baseline and as clinically indicated. Bone scan/survey as clinically indicated. |
Imaging Strategy
Imaging with and without IV contrast (e.g., renal protocol CT) is strongly preferred for abdomen evaluation. Chest CT is preferred over chest x-ray for higher sensitivity. MRI is an alternative if contrast is contraindicated. FDG-PET may be useful in specific circumstances (e.g., bone-predominant disease, pre-metastasectomy assessment, FH-deficient or SDHB-deficient RCC).
Laboratory Monitoring
- Complete blood count (CBC) with differential
- Comprehensive metabolic panel (including serum creatinine, calcium, liver function tests)
- Urinalysis (if clinically indicated)
- Monitoring specific to systemic therapy (e.g., thyroid function for lenvatinib/pembrolizumab, liver function for pazopanib)
Supportive Follow Up
- Assessment of performance status and quality of life
- Management of treatment-related toxicities (e.g., hypertension, diarrhea, hand-foot syndrome)
- Monitoring for immune-mediated adverse events during immunotherapy
- Renal function monitoring, especially after nephrectomy or with nephrotoxic therapies
- Psychosocial support and distress screening
ComplicationsClick to collapse
Disease-Related
| Complication | Management |
|---|---|
| Metastatic disease (lung, bone, liver, lymph nodes, adrenal gland, brain) | Systemic therapy, surgery (metastasectomy), radiation therapy (SBRT), or active surveillance depending on volume, location, and symptoms. |
| Skeletal-related events (SREs) from bone metastases | Bone-modifying agents (denosumab or bisphosphonates like zoledronic acid), palliative radiation therapy (SBRT preferred), and pain management. |
| Brain metastases (occurs in ~2-8% of advanced RCC) | Stereotactic radiosurgery (SRS) or fractionated stereotactic radiation therapy (SRT) for limited metastases; whole-brain radiation therapy (WBRT) only for palliative purposes when SRS/SRT is not feasible. |
Supportive CareClick to collapse
Supportive care is a mainstay of therapy for all patients with metastatic RCC and should be integrated throughout the disease course. The goal is to manage symptoms, treatment-related toxicities, and improve quality of life. The NCCN Guidelines for Palliative Care should be consulted.
Nutritional assessment and support are recommended as needed to manage weight loss, anorexia, or treatment-related gastrointestinal side effects (e.g., diarrhea, stomatitis).
Anti-emetic prophylaxis and treatment should be based on the emetogenic potential of the systemic therapy regimen used, following anti-emetic guidelines.
Granulocyte colony-stimulating factor (G-CSF) support should be considered for regimens with a high risk of febrile neutropenia or in patients with risk factors.
Venous thromboembolism (VTE) prophylaxis is recommended for high-risk patients, including those with active cancer, immobilization, or prior VTE history. Treatment with VEGFR-TKIs may increase hypertension and bleeding risk, requiring careful assessment.
Pain should be assessed and managed according to the NCCN Guidelines for Adult Cancer Pain. This includes pharmacologic (analgesics, adjuvants) and non-pharmacologic approaches. Radiation therapy, particularly SBRT, is recommended for painful bone metastases.
Psychosocial assessment and support should be offered to address distress, anxiety, depression, and quality of life concerns. Referral to social work, psychology, or palliative care teams is recommended.
Dental evaluation prior to starting bone-modifying agents (bisphosphonates, denosumab) is recommended to prevent osteonecrosis of the jaw. Good oral hygiene and avoidance of invasive dental procedures during treatment are advised.
PrognosisClick to collapse
Kidney cancer prognosis varies significantly by stage and histology. Approximately 66% of cases are diagnosed as localized disease, with an overall 5-year survival rate of 79% (2015-2021 data). The most important prognostic determinants of 5-year survival are tumor stage, grade, local extent of the tumor, presence of regional nodal metastases, and evidence of metastatic disease at presentation. RCC primarily metastasizes to the lung, bone, liver, lymph nodes, adrenal gland, and brain.
By Stage
| Stage | Five Yr Survival | Context |
|---|---|---|
| Localized (Stages I-II) | Not explicitly stated; overall localized disease 5-year survival is 79%. | Patients with localized tumors have a good prognosis. After surgical excision, 20% to 30% of patients with localized tumors experience relapse. Lung metastasis is the most common site of distant recurrence, occurring in 50% to 60% of patients. The median time to relapse after surgery is 1 to 2 years, with most relapses occurring within 3 years. |
| Locally Advanced (Stage III or T4,NXM0) | Not explicitly stated. | These patients have a substantially higher risk of both local and metastatic recurrence, which warrants an increased follow-up frequency. The most important prognostic determinants of 5-year survival are the tumor stage, grade, local extent of the tumor, presence of regional nodal metastases, and evidence of metastatic disease at presentation. |
| Metastatic (Stage IV) | Not explicitly stated; median overall survival varies by risk group. | The International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model stratifies patients into risk groups with different median OS: Favorable-risk (no adverse factors): median OS not reached, 2-year OS 75%; Intermediate-risk (1-2 factors): median OS 27 months, 2-year OS 53%; Poor-risk (3-6 factors): median OS 8.8 months, 2-year OS 7%. |
Prognostic Factors
- Tumor stage (AJCC TNM staging)
- Histologic grade (Fuhrman grade, nuclear grade)
- Local extent of the tumor
- Presence of regional nodal metastases
- Evidence of metastatic disease at presentation
- Performance status (ECOG, Karnofsky)
- Laboratory markers (LDH, hemoglobin, calcium, neutrophil count, platelet count)
- Time from diagnosis to treatment
- Histologic subtype (clear cell vs. non-clear cell)
- Presence of sarcomatoid or rhabdoid features
Follow UpClick to collapse
Post Curative Treatment
Follow-up after curative treatment for localized RCC (e.g., nephrectomy, ablation, SBRT) is individualized based on stage, histology, and risk of recurrence. It includes history and physical (H&P), laboratory tests, and imaging (abdominal and chest CT). The frequency and duration of follow-up may be extended beyond 5 years at the clinician's discretion, as late recurrences can occur.
Surveillance Rationale
The rationale for surveillance is to detect recurrence or metastatic disease early, when it may still be amenable to curative or life-prolonging interventions (e.g., metastasectomy, SBRT). It also allows monitoring of renal function and treatment-related side effects. The frequency is risk-stratified, with higher-risk patients (e.g., stage III, high-grade) requiring more intensive follow-up.
Late Effects Screening
- Chronic kidney disease: Monitor renal function (serum creatinine, eGFR) regularly, especially after nephrectomy.
- Cardiovascular disease: Monitor blood pressure and manage cardiovascular risk factors, as both RCC and some treatments (VEGFR-TKIs) can increase cardiovascular risk.
- Recurrence or metachronous tumors: Continued abdominal and chest imaging to detect local recurrence, contralateral kidney tumors, or pulmonary metastases.
Recurrence Patterns
Most recurrences occur within the first 3-5 years after surgery, but late recurrences (>5 years) are possible. Lung metastases are the most common site of distant recurrence (50-60%), followed by bone, lymph nodes, liver, and brain. Local recurrence rates are lower for smaller tumors after partial nephrectomy (1.4-2%) versus larger tumors (10%).
Key TrialsClick to collapse
| Acronym | Full Name | Year | N | Intervention | Comparator | Population | Primary Endpoint | Key Result | Secondary Outcomes | Practice Change | Journal |
|---|---|---|---|---|---|---|---|---|---|---|---|
| KEYNOTE-426 | Pembrolizumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma | 2019 | 861 | Axitinib + Pembrolizumab | Sunitinib | Treatment-naïve advanced clear cell RCC, favorable-, intermediate-, or poor-risk, Karnofsky PS ≥70%. | Overall survival and progression-free survival in PD-L1 positive and overall population. | Axitinib + Pembrolizumab significantly improved OS (HR 0.68, 95% CI 0.57-0.81) and PFS (HR 0.69, 95% CI 0.59-0.81) vs. sunitinib. ORR: 60.6% vs. 39.6%. | Consistent benefit across risk groups. Updated 67-month follow-up showed continued OS benefit (median OS 47.2 vs. 40.8 months). | Established axitinib+pembrolizumab as a category 1 preferred first-line therapy for advanced RCC. | New England Journal of Medicine |
| CheckMate 9ER | Nivolumab plus Cabozantinib versus Sunitinib for Advanced Renal-Cell Carcinoma | 2021 | 651 | Cabozantinib + Nivolumab | Sunitinib | Treatment-naïve advanced clear cell RCC, favorable-, intermediate-, or poor-risk, Karnofsky PS ≥70%. | Progression-free survival. | Cabozantinib + Nivolumab significantly improved PFS (HR 0.58, 95% CI 0.49-0.70) and OS (HR 0.70, 95% CI 0.55-0.90) vs. sunitinib. ORR: 55.7% vs. 27.1%. | Benefit observed across all risk groups, including patients with sarcomatoid features. | Established cabozantinib+nivolumab as a category 1 preferred first-line therapy for advanced RCC. | New England Journal of Medicine |
| CLEAR | Lenvatinib plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma | 2021 | 1069 | Lenvatinib + Pembrolizumab | Sunitinib | Treatment-naïve advanced clear cell RCC, favorable-, intermediate-, or poor-risk, Karnofsky PS ≥70%. | Progression-free survival. | Lenvatinib + Pembrolizumab significantly improved PFS (HR 0.39, 95% CI 0.32-0.49) and OS (HR 0.66, 95% CI 0.50-0.87) vs. sunitinib. ORR: 71.0% vs. 36.1%. | Final OS analysis at 49 months median follow-up showed significant OS benefit (median OS 53.7 vs. 54.3 months, HR 0.79, P=0.0424). | Established lenvatinib+pembrolizumab as a category 1 preferred first-line therapy for advanced RCC. | New England Journal of Medicine |
| CheckMate 214 | Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma | 2018 | 1096 | Ipilimumab + Nivolumab | Sunitinib | Treatment-naïve advanced clear cell RCC; intermediate- or poor-risk (co-primary endpoint), favorable-risk (exploratory). | Overall survival, objective response rate, and progression-free survival in intermediate/poor-risk patients. | Ipilimumab + Nivolumab significantly improved OS (HR 0.69, 95% CI 0.59-0.81) and ORR (42.4% vs. 27.5%) in intermediate/poor-risk patients. No significant OS benefit in favorable-risk patients initially. | 8-year follow-up showed trend towards improved OS in favorable-risk patients (HR 0.82, 95% CI 0.60-1.13). | Established ipilimumab+nivolumab as a category 1 preferred first-line therapy for intermediate/poor-risk RCC. | New England Journal of Medicine |
| KEYNOTE-564 | Adjuvant Pembrolizumab after Nephrectomy in Renal-Cell Carcinoma | 2021 | 994 | Pembrolizumab | Placebo | Localized RCC with intermediate or high risk of recurrence (stage II grade 4, stage III, or M1 NED) after nephrectomy. | Disease-free survival. | Pembrolizumab significantly improved DFS (HR 0.68, 95% CI 0.53-0.87, P=0.002) and OS (HR 0.62, 95% CI 0.44-0.87, P=0.005) vs. placebo. | Benefit observed across risk subgroups. 57-month follow-up confirmed DFS and OS benefit. | Established adjuvant pembrolizumab as a category 1 recommendation for intermediate/high-risk clear cell RCC after nephrectomy. | New England Journal of Medicine |
| CABOSUN | Cabozantinib versus Sunitinib as Initial Targeted Therapy for Patients with Metastatic Renal Cell Carcinoma of Poor or Intermediate Risk | 2017 | 157 | Cabozantinib | Sunitinib | Intermediate- or poor-risk metastatic clear cell RCC, ECOG PS 0-2. | Progression-free survival. | Cabozantinib significantly improved PFS (HR 0.66, 95% CI 0.50-0.87) and ORR (33% vs. 12%) vs. sunitinib. | OS favored cabozantinib but not statistically significant (HR 0.80, 95% CI 0.50-1.26). | Established cabozantinib as a category 2A preferred first-line option for poor/intermediate-risk RCC. | Journal of Clinical Oncology |
| METEOR | Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma | 2015 | 658 | Cabozantinib | Everolimus | Advanced clear cell RCC with progression after prior VEGFR-TKI. | Progression-free survival. | Cabozantinib significantly improved PFS (HR 0.51, 95% CI 0.41-0.62) and OS (HR 0.70, 95% CI 0.58-0.85) vs. everolimus. | ORR: 17% vs. 3%. | Established cabozantinib as a subsequent therapy option after prior VEGFR-TKI. | New England Journal of Medicine |
| LITESPARK-005 | Belzutifan versus Everolimus for Advanced Renal-Cell Carcinoma | 2024 | 746 | Belzutifan | Everolimus | Advanced clear cell RCC progressed after 1-3 prior therapies including PD-1/L1 and VEGF-TKI. | Progression-free survival. | Belzutifan significantly improved PFS (HR 0.75, 95% CI 0.63-0.90, P<0.001) and ORR (21.9% vs. 3.5%). | OS not significantly different (HR 0.88, 95% CI 0.73-1.07, P=0.20). | Established belzutifan as a category 2A subsequent therapy option after prior IO and VEGF-TKI. | New England Journal of Medicine |
Clinical PearlsClick to collapse
- Pearl 1: Partial nephrectomy (nephron-sparing surgery) is preferred for stage I tumors when feasible, as it provides comparable oncologic outcomes to radical nephrectomy while preserving renal function and reducing cardiovascular risk.
- Pearl 2: Adjuvant pembrolizumab is a category 1 recommendation for patients with intermediate- or high-risk clear cell RCC after nephrectomy, based on the KEYNOTE-564 trial showing improved DFS and OS.
- Pearl 3: For metastatic clear cell RCC, first-line combination regimens (axitinib+pembrolizumab, cabozantinib+nivolumab, ipilimumab+nivolumab, lenvatinib+pembrolizumab) are category 1 preferred options across all risk groups.
- Pearl 4: Risk stratification using MSKCC or IMDC criteria is essential for guiding treatment selection and predicting prognosis in metastatic RCC.
- Pearl 5: Active surveillance may be an option for select patients with small renal masses (<2 cm), T1a tumors, or those with significant comorbidities. For metastatic RCC, active surveillance can be considered in select asymptomatic patients with favorable-risk disease.
- Pearl 6: SBRT is a viable alternative for non-optimal surgical candidates with stage I (T1a, T1b) or stage II RCC, and for palliation of oligometastatic disease.
- Pearl 7: Genetic evaluation is recommended for patients with RCC diagnosed at ≤46 years, bilateral/multifocal tumors, or a family history of RCC, as ~3% of RCC cases are hereditary.
- Pearl 8: For non-clear cell RCC, cabozantinib is a preferred first-line option, and clinical trial enrollment is strongly encouraged due to limited data compared to clear cell histology.
Special SituationsClick to collapse
Hereditary RCC Syndromes (e.g., VHL, HLRCC, BHDS, TSC, HPRC, PGL/PCC, BAP1-TPDS)
Non-Clear Cell RCC (nccRCC)
Oligometastatic Disease
Cytoreductive Nephrectomy in Metastatic RCC
Renal Medullary Carcinoma (RMC)
Guidelines ResourcesClick to collapse
NCCN Clinical Practice Guidelines in Oncology: Kidney Cancer
AJCC Cancer Staging Manual, 8th Edition
IMDC Criteria for Prognostic Risk Stratification
MSKCC Prognostic Model for Advanced RCC
Protective FactorsClick to collapse
- None explicitly mentioned in the source text.
Initial WorkupClick to collapse
The initial workup for a patient with a suspicious kidney mass includes a history and physical (H&P), complete blood count (CBC) with differential, comprehensive metabolic panel, urinalysis, abdomen/pelvis CT or MRI, and chest CT (preferred) or chest x-ray [KID-1]. If clinically indicated, a bone scan or brain MRI may be performed. A core needle biopsy may be considered for small lesions to confirm malignancy and guide treatment decisions [KID-1, footnote c]. If urothelial carcinoma is suspected, urine cytology, ureteroscopy, or percutaneous biopsy should be considered. For patients with multiple renal masses, age ≤46 years, or family history, genetic evaluation for hereditary RCC syndromes should be considered [KID-1].
Stage I T1AClick to collapse
Follow Up: Follow-up is individualized. For active surveillance: H&P annually, laboratory tests annually as clinically indicated, abdomen imaging (CT, MRI, or US) within 6 months and then annually, and repeat chest imaging if intervention is considered [KID-C]. For post-ablation: H&P annually, lab tests annually, abdomen imaging with contrast at 1-3 months, 6 months, 12 months, then annually; chest CT annually for 5 years [KID-C]. For post-SBRT: abdomen/chest CT every 3 months for year 1, every 6 months for year 2, every 9 months for years 3-4, and annually for year 5; renal function evaluation on same schedule [KID-C]. For post-nephrectomy: H&P annually, lab tests annually, baseline abdomen CT or MRI within 3-12 months, then annually for up to 5 years; chest CT annually for at least 5 years [KID-C].
Stage I T1BClick to collapse
Follow Up: Same follow-up recommendations as for Stage I (T1a) disease [KID-C].
Stage IiClick to collapse
Adjuvant Treatment: For clear cell histology: surveillance, adjuvant pembrolizumab (category 1), or adjuvant belzutifan + pembrolizumab for Grade 4 tumors with clear cell histology ± sarcomatoid features [KID-2]. For non-clear cell histology: surveillance [KID-2].
Follow Up: H&P annually, laboratory tests annually, abdomen/pelvis CT or MRI every 6 months for 2 years, then annually for up to 5 years; chest CT annually for at least 5 years [KID-C].
Stage IiiClick to collapse
Adjuvant Treatment: For clear cell histology: adjuvant pembrolizumab (category 1) or adjuvant belzutifan + pembrolizumab. For non-clear cell histology: surveillance or clinical trial [KID-2].
Follow Up: H&P every 3-6 months for 3 years, then annually for up to 5 years. Comprehensive metabolic panel and other tests every 3-6 months for 3 years, then annually for up to 5 years. Abdomen/pelvis CT or MRI within 3-6 months, then every 3-6 months for at least 3 years, then annually for up to 5 years. Chest CT within 3-6 months, then every 3-6 months for at least 3 years, then annually for up to 5 years. Additional imaging (bone scan, brain imaging) as symptoms warrant. FDG-PET useful in certain circumstances (e.g., FH-deficient or SDHB-deficient RCC) [KID-C].
Stage Iv Resectable T4 M0Click to collapse
Follow Up: Same as for Stage III disease [KID-C].
Stage Iv M1 Or RelapsedClick to collapse
Follow Up
H&P every 6-16 weeks for patients receiving systemic therapy. Laboratory evaluation as per requirements for therapeutic agent. Chest, abdomen, pelvis CT or MRI every 6-16 weeks as per physician discretion. Consider head MRI at baseline and as clinically indicated. Bone scan/bone survey as clinically indicated. FDG-PET useful in certain circumstances (e.g., bone-predominant disease, prior to metastasectomy, FH-deficient or SDHB-deficient RCC) [KID-C].
First Line Therapy Clear CellClick to collapse
Other Recommended: Axitinib + avelumab, pazopanib, sunitinib [KID-D].
Useful In Certain Circumstances: Active surveillance, axitinib [KID-D].
Subsequent Therapy Clear CellClick to collapse
Systemic Therapy Non Clear CellClick to collapse
Other Recommended: Erlotinib + bevacizumab (for selected patients with papillary RCC including HLRCC), everolimus/lenvatinib, ipilimumab + nivolumab, nivolumab, pembrolizumab, sunitinib [KID-D].
Useful In Certain Circumstances: Axitinib, everolimus, everolimus + bevacizumab [KID-D].
Special Considerations: For collecting duct or renal medullary carcinoma (RMC), platinum-based chemotherapy regimens (e.g., gemcitabine/carboplatin, paclitaxel/carboplatin, gemcitabine/cisplatin) are preferred first-line. Immune checkpoint therapies should be avoided in RMC outside of a clinical trial [KID-D, footnote i].
Hereditary Rcc SyndromesClick to collapse
Genetic Testing And Surveillance: Individuals with a personal or family history of an RCC syndrome should undergo genetic risk evaluation. Screening recommendations vary by syndrome (e.g., abdomen MRI or CT starting at different ages and intervals) [HERED-RCC-1, HERED-RCC-B].
Surgical Recommendations: Nephron-sparing surgery is preferred for syndromes with multifocal/bilateral tumors (e.g., BHDS, HPRC, TSC). Radical nephrectomy is recommended for aggressive syndromes like HLRCC [HERED-RCC-C].
Systemic Therapy: Syndrome-specific recommendations include belzutifan for VHL-associated RCC, everolimus for TSC-associated angiomyolipoma, and erlotinib + bevacizumab for HLRCC-associated RCC [HERED-RCC-D].