Two11 97B Malignant Renal Tumors - Management

  1. Clinical presentation of RCC?
    • Incidental presentation
    • Symptoms of localized disease:
    • Hematuria
    • Flank pain
    • Abdominal mass
    • Perirenal hematoma (triad - pain, mass, hematuria)

    • Obstruction of the inferior venal cava:
    • Bilateral lower extremity edema
    • Nonreducing or right-sided varicocele

    • Symptoms of systemic disease:
    • Persistent cough
    • Bone pain
    • Cervical lymphadenopathy
    • Constitutional symptoms
    • Weight loss/fever/malaise
    • Paraneoplastic syndromes

    More than 50% of patients with perirenal hematoma of unclear cause have an occult renal tumor, most often AML or RCC
  2. How do RCC cause pain?
    • Stretching of capsule 
    • Invasion of surrounding structures - nerve root or paraspinous muscles 
    • Clot colic
  3. Why RCC a  internist tumor?
    • RCC is diagnosed based on systemic (medical) manifestations rather than urological (surgical) manifestations. 
    • Now, called as radiologists tumor
  4. Paraneoplastic syndromes
    • Raised ESR 
    • Anemia 
    • Polycythemia - 
    • HTN 
    • Hypercalcemia 
    • HTN
    • Stauffer syndrome
  5. Management of Paraneoplastic syndrome?
    Except Hypercalcemia, all other syndrome require surgical excision
  6. Hypercalcemia in RCC?
    • Can be due to either paraneoplastic phenomena or osteolytic metastatic involvement of the bone 
    • Production of parathyroid hormone–like peptides (MC), 1,25-dihydroxycholecalciferol and prostaglandins
    • Signs and symptoms -  nausea, anorexia, fatigue, and decreased deep tendon reflexes.
    • Medical management - vigorous hydration followed by diuresis with furosemide and the selective use of bisphosphonates, corticosteroids, or calcitonin.
    • Bisphosphonate therapy - Zoledronic acid, 4 mg IV every 4 weeks (contraindicated in renal insufficiency)
    • Definitive management - nephrectomy and occasional metastasectomy

    Note - Thiazides increase blood calcium level - used in medical managment of hypercalcuria, furosemide decreases blood calcium level
  7. Causes of HTN in RCC?
    • Secondary to increased production of renin directly by the tumor
    • Compression or encasement of the renal artery or its branches, effectively leading to renal artery stenosis
    • Arteriovenous fistula within the tumor
    • Less common causes - polycythemia, hypercalcemia, ureteral obstruction, and increased intracranial pressure associated with cerebral metastases
  8. Stauffer syndrome?
    • Nonmetastatic hepatic dysfunction
    • Elevated ALP (in 100% cases), PT (67%), hypoalbuminemia, and elevated serum bilirubin or transaminase levels.
    • Fever and weight loss - harbour discrete regions of hepatic necrosis.
    • Hepatic metastases must be excluded.
    • Biopsy when indicated, nonspecific hepatitis associated with a prominent lymphocytic infiltrate.
    • Elevated IL-6 from tumor. IL-6 is a pro-inflammatory cytokine - produce a localised inflammatory response in the liver and subsequent hepatocellular injury and liver derangement.
    • Hepatic function normalizes after nephrectomy in 60% to 70% of cases. Persistence or recurrence of hepatic dysfunction is almost always indicative of the presence of a viable tumor and thus represents a poor prognostic finding.
  9. Screening for RCC?
    Patients with ESRD - only patients with long life expectancy and minimal major comorbidities, beginning during third year on dialysis

    Patientw with VHL - biannual abdominal CT or ultrasound study beginning at the age of 15 to 20 years, Periodic clinical and radiographic screening for nonrenal manifestations

    Relatives with VHL - Obtain genetic analysis.  If positive, follow screening recommendations for patients with known VHL.  If negative, less stringent follow-up is required

    Relatives with other familial forms of RCC - Obtain periodic ultrasound or CT study and consider genetic analysis

    Tuberous sclerosis - Periodic screening with ultrasound examination or CT scan 

    ADPKD - Routine screening not justified
  10. TNM RCC 2017
    • T1
    • - T1a ≤ 4 cm or less
    • - T1b > 4 cm but ≤ 7 cm

    • T2
    • - T2a > 7 cm but ≤ 10 cm
    • - T2b > 10 cm, limited to the kidney

    • T3
    • - T3a Tumour grossly extends into the renal vein or its segmental (muscle-containing) branches, or tumour invades perirenal and/or renal sinus fat (peripelvic fat), but not beyond Gerota fascia (2018 modification - “Muscle containing” changed to “segmental vein”, Invasion of pelvicaliceal system added)
    • - T3b - IVC below diaphragm
    • - T3c - IVC above the diaphragm or invades the wall of the vena cava

    • T4
    • - Tumour invades beyond Gerota fascia (including contiguous extension into the ipsilateral adrenal gland)

    • N1
    • - Metastasis in regional lymph node(s)

    • M1
    • - Distant metastasis

    • Note -
    • - Invasion of the perisinus fat medially has been shown to be a poor prognostic sign. Medial invasion places the tumor in proximity to the venous system and likely increases the risk of metastatic dissemination
    • - Enlarged perirenal lymph nodes noted on CT may be inflammatory, particularly if they are less than 2 cm in diameter. Lymph nodes larger than 2 cm generally contain metastases
  11. Prognostic models in RCC?
    • Localized RCC  (EAU 2020)
    • - UISS - UCLA (University of California Los Angeles) Integrated Staging System (UISS) for Renal Cell Carcinoma (RCC) -  Fuhrman Grading, ECOG Performance status, TNM [@ GPT] . UISS has been modified to include molecular factors like CA-IX, TP53, Ki67 - has been validated  

    - SSIGN (S-SIGN) -  stage, size, grade and necrosis (by Mayo Clinic group)  

    - Post Operative Karakiewicz’s Nomogram - TNM, Fuhrman, S classification (no symptoms, local symptoms, systemic symptoms) 

    Clinical findings that suggest a compromised prognosis in patients with presumed localized RCC include symptomatic presentation, unintended weight loss of more than 10% of body weight, and poor performance status 

    • Metastatic RCC 
    • - MSKCC 
    • - IMDC
  12. Indications of Biopsy in RCC?
    Percutaneous renal tumour biopsies are used:

    • • to obtain histology of radiologically indeterminate renal masses - suspicion of lymphoma, inflammatory mass. Lymphadenopathy outside the primary landing zone raises suspicion of lymphoma/leukemia
    • • to select patients with small renal masses for active surveillance;
    • • to obtain histology before, or simultaneously with, ablative treatments.  In case of recurrances, you must have repeat biopsy, even if the previous HPE reports are available 
    • • to select the most suitable form of medical and surgical strategy in the setting of metastatic disease. Metastatic lesions are small, multiple lesions, usually from lung, breast, and GIT 

    RMB is not indicated for young, healthy patients who are unwilling to accept the limitations of RMB, or for older, frail patients who will be managed conservatively even if RMB suggests a potentially aggressive tumor.
  13. How to do renal biopsy?
    Use coaxial technique through the sheath to minimize bleeding, tumour spillage and the better sample obtained. At least two cores, unfragmented, each core of 1-2cm in length

    In cystic mass, biopsy should be avoided. - EAU strong recommendation 

    In obese patients, when skin to tumor distance is >13 cm, the biopsy yield is poor 

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  14. Limitations of biospy?
    • Synchronous renal tumours 
    • Hybrid renal tumours 
    • A definitive assessment of biopsy accuracy remains difficult 
    • Assessment of Fuhrman grade not optimal

    The main limitation of renal mass biopsy is difficulty differentiating renal oncocytoma, the most common benign renal mass, from eosinophilic variants of conventional, papillary, and chromophobe RCC on biopsy material. While the non-diagnostic rate is between 10% and 15%, the risk of complications is low in the modern era with the use of smaller gauge needles, and needle tract seeding with RCC appears to be a rare event
  15. Indications of genetic counselling?
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    • AUA 2017 -
    • - ≤ 46 years of age with renal malignancy
    • - multifocal or bilateral renal masses
    • - if personal or family history suggests a familial renal neoplastic syndrome
    • - Non-clear cell histology (this criterion is not in AUA 2017)

    • Note
    • -  Bilateral involvement in RCC either synchronously or metachronously occurs in 2% to 4% of patients.
    • - Genetic testing costs around 25000 IC in India
  16. Treatment of locally invasive RCC?
    Important perioperative concerns for patients with locally advanced RCC include a comprehensive preoperative consent, including the potential for increased morbidity and resection of adjacent organs, a full bowel preparation, and consideration for preoperative embolization of the renal arterial blood supply.

    If risk of splenectomy, consider preoperaive vaccination
  17. Adjuvant therapy in locally advanced cancer?
    If negative surgical margin, even in LN involvement or IVC involvement, Adjuvant therapy is not required, irrespective of adverse histopathological reports
  18. What are small renal mass?
    Renal neoplasm 4 cm or less in greatest dimension
  19. Active survillence in RCC?
    • Biopsy before AS - most of the literature have not recorded biopsy before AS, not always required. 
    • Percutaneous biopsy may be considered before active surveillance. AUA 2013

    • AS Indications: 
    • - Old age, not for young, surgically fit pts
    • - Hereditary RCC

    • Contraindications: 
    • - >3 cm
    • - Poorly marginated or nonhomogenous 
    • - HLRCC and SDH syndrome
    • - potentially aggressive RCC 

    • Rate of growth of renal mass - 0.12-0.34 cm/yr
    • Metastastasis in SRM - < 2.0% during 2 to 5 years of
    • follow-up

    Active treatment of SRM in >75 yrs may not confer survival benefit over AS
  20. Follow up protocol for active surviellence?
    If size >4cm, Growth rate > 0.5 or hematuria - undergo CT and plan accordingly either to keep under AS or intervention - AUA ] 

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    E Urology 2015

    patients with AS and RN, Overall survival is the same. RN patients die due to CKD complications.
  21. Management of familial RCC?
    • Pursue nephron-sparing strategies whenever possible, given the multifocal nature of the disease, even for centrally located tumors
    • 3 cm threshold for intervention 
    • HLRCC and SDH-RCC are exceptions in that tumors in these syndromes are typically more aggressive and should be managed accordingly, even when less than 3 cm
    • Genetic counseling and screening for other manifestations of the disease process
    • For patients with VHL, identification of pheochromocytoma or central nervous system hemangioblastoma is particularly important before surgical intervention for RCC
  22. Follow up strategy in RCC?
    • EAU - 
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    • AUA 2013
    • Low risk is T1
    • Moderate to high risk is T2-T4

    • T1 - initial imaging (CT/MRI abdomen) at 3-12 months. If negative 
    • - For radical - not required 
    • - For partial - yearly for 3 years (CT/MRI/USG)

    T2 - Initial imaging (abdominal) at 3-6 months. If negative, repeat imaging every 6 months (USG/CT/MRI) for 3 years, then yearly till 5 years.  

    • Chest
    • low risk -  yearly chest x-ray for 3 years 
    • high risk - chest CT at 3-6 months, with Chest x-ray or CT every 6 months at least for 3 yrs, and annually to 5 yrs

    Other investigations - physical examination (don't forget left supraclavicular LN), CBC, RFT, Urinalysis, LFT, CNS imaging if symptoms, bone scan if raised ALP.

    • Note
    • - Despite significant recurrence rate in RCC, observation remains standard of care. (20-35% distant metastasis, 2-5% local recurrence) None adjuvant therapy is beneficial.
    • -  The risk for developing recurrent malignant disease is greatest in the first 3 years after surgery

    [@ T1 - once per year, T2 and above - Twice per year for 3 years] 
  23. Management of T1 patients AUA?
    • Index 1 - Healthy T1a, Standard - PN, RN, Options - TA, AS 
    • Index 2 - Major comorbiddities, Increased surgical risk - Standard PN, RN, Recommendiation - TA, AS 
    • Index 3 - Healthy T1b, Standard - RN, PN, Options - TA, AS 
    • Index 4 - Major comorbidities, increased surgical risk, Standard RN, Recommendation - PN, AS, Options TA

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  24. What is locally advanced and Locally invasive RCC?
  25. Management of LN positive RCC?
    • In patients with locally advanced disease due to clinically enlarged lymph nodes (LNs), the survival benefit of LN dissection is unproven but LN dissection adds staging information. (EAU 2020) 
    • In patients with clinically enlarged lymph nodes (LNs), perform LN dissection for staging purposes or local control. Weak (EAU 2020)

    • Do not offer adjuvant therapy with sorafenib, pazopanib or axitinib. Strong
    • Do not offer adjuvant sunitinib following surgically resected high-risk clear-cell renal cell carcinoma. Weak

    QQQ - what is high risk RCC? is it only T2-4, does it include N1 or any other parameters?
  26. Features of Sarcoma of kidney/
    • Origin from capsule, perisinous region 
    • Large mass in absence of lymphadenopathy - rapidly growing tumor 
    • Presence of fat/bone 
    • Hypovascular

    Derived from mesenchymal component - free from natural barriers - desseminated tumor. Treatment is enbloc resection of adjacant organs if required along with wide excision of tumor

    Sarcomas typically have a pseudocapsule that cannot be relied on for a plane of dissection because microscopic tumor will be left behind.
  27. Types of sarcoma of kidney?
    • From smooth muscle of capsule - leiomyosarcoma - MC
    • From fat - liposarcoma 
    • From bone - osteogenic sarcoma
    • Malignant hemangiopericytoma - sarcoma are hypovascular except this variant

    • Note
    • - Margin status and tumor grade are the primary prognostic factors for sarcoma.
    • - The most common type of sarcoma in the retroperitoneum is liposarcoma
  28. CT findings of lymphoma?
    • Renal invasion from enlarged retroperitoneal LN 
    • Diffuse renal involvement 
    • Hypovascular pattern on angiography
  29. Features of metastatic tumors in kidney?
    • Multiple small nodules 
    • Clinically silent 
    • Isodense mass that enhance only moderately

    Metastatic tumors to the kidney are common, appearing in 12% of patients who die of other cancers; the most common primary lesions are those of the lung, breast, or gastrointestinal tract, melanoma, or hematologic.
  30. Solitary kidney with huge mass, what are the options?
    • Partial nephrectomy with consent of radical nephrectomy 
    • Radical nephrectomy with RRT

    Some studies are there with Neoadjuvant TKI and downsizing the tumor (reassess at 3 months for response) and partial nephrectomy, if response on TKI after 6  months. Most of these studies have shown benefit just on IVC thrombus and not on main mass.

    If fistula is planned, it is always good idea to make fistula later in LA, rather than trying to make fistula in same setting of radican nephrectomy - chance of thrombosis due to hypotension, patient not keeping the limb separate
  31. How long to wait for renal transplantation after RN?
    2 years

    In recent papers, they recommend only one year for Fuhrman Grade I tumors.
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Two11 97B Malignant Renal Tumors - Management
Management of RCC