1. Renal cell carcinoma : alternative treatment LUKMAN HAKIM DEPARTMENT OF UROLOGY, AIRLANGGA UNIVERSITY/DR. SOETOMO GENERAL HOSPITAL

2. Epidemiology & etiology  2-3% of all cancers  Increased 2% worlwide  1 : 5,1 male predominance  RCC in ESKD : 4% of patients  Definite risk factors : obesity, hypertension, smoking  Moderate alcohol consumption : protective effect

3. Histological types  WHO 2004 and ISUP Vancouver classification (85-95%) :  Clear cell (ccRCC)  Papillary (pRCC)  Chromophob (chrRCC) Nuclear grade, sarcomatoid features, ascular invasion, tumor necrosis, invasion of he collecting system and perirenal fat. Fuhrman vs novel ISUP nuclear grading system. Sarcomatoid variants, multilocular ccRCC, bellini type, renal medullary type, translocation RCC, ACKD-associated, tubulocystic, metanephric, hybrid oncocytic chromophob, oncocytome, unclassified

4. Histological types  Except for AML, most other tumours cannot be differentiated from RCC by radiology and should be treated in the same way as RCC  In advanced uncommon renal tumours, a standardized oncological tx approach does not exist

5. Staging The sub-classification of T1 < 4 cm for NSS might not be optimal The value of T2 stratification has been questioned Sub T-stages (pT2b, pT3a, pT3c, and pT4) may overlap

6. Diagnostic evaluation  Symptoms  > 50% incidentally detected; triad-symptoms are rare  Paraneoplastic syndrome in 30%  Physical examinations  Palpable mass, palpable cervical lymphadenopathy, non-reducing varicocele, bilateral lymphedema  Laboratory findings  GFR, CBC, LFT, AFP, LDH, urinalysis  Urine cytology ?  Imaging  US, contrast-enhanced CT/MRI for staging and diagnosis  Chest-CT for metastases; bone imaging as indication

7. Bosniak classification Bosniak cysts > type III should be regarded as RCC and treated accordingly

8. Renal biopsy  Percutaneous renal biopsy (US or CT guided)  Small renal tumor for active surveillance  Obtain histology prior to ablative treatment  Optimizing treatment strategy in metastases disease  Needle-core biopsy have better accuracy compared with FNA

9. Prognostic factors  Anatomical  Tumor size, venous invasion, renal capsular invasion, adrenal involvement, LN and distant metastases  Histological  Fuhrman grade, RCC subtype, sarcomatoid features, microvascular invasion, tumor necrosis and invasion of the PCS Based on TNM staging and Grading for RCC)Based on histological type

10. Prognostic factors  Clinical  Molecular  CaIX, VEGF, Ki67, p53, PTEN, E-cadherin, CRP, osteopontin, CD44  Prognostic systems and nomograms  Not routinely recommended

11. Treatment – localized disease  Surgery is curative Tx for localized RCC  PN for T1a  PN should be favoured over RN in T1b, if possible  LND is not recommend unless clinical evidence exist  Lap RN is recommended for T2, localized but not treatable with PN  If PN in T1 is possible, RN is not recommended  In elderly and or comorbid px with small renal masses and limited expectancy : active surveillance  No recommendation for RFA and cryoablation

12. Treatments – locally advanced disease  In clinically enlarged LNs, LND can be performed for staging or local control  Excision of the kidney tumor and caval thrombus in non-metastatic RCC  No indication for adjuvant therapy following surgery

13. Treatments – advanced/metastatic disease  Cytoreductive nephrectomy is recommended in appropriately selected patients with mRCC. No general recommendation, should be individualized  Good KS, large primary tumours and low metastatic volume  For most patients with mRCC, CN is palliative and require systemic treatments  In clear-cell mRCC, chemotherapy is not effective  Monotherapy with IFN-α or HD bolus IL-2 is not routinely recommended as first-line therapy  Surgical resection of local recurrent disease may result in durable local control and improved survival

14. Treatments – advanced/metastatic disease  Local therapy for metastases in mRCC :  Metastasectomy or not ; complete or incomplete  Bone metasatses : stereotactic bone radiotherapy, image-guided radiotherapy and conventional radiotherapy  Brain metastases : stereotactic radiosurgery; whole brain radiotherapy  No general recommendation can be made, should be individualised

15. Targeted therapies for mRCC Sequencing of targeted agents is recommended

16. Survival following targeted therapies

17. Follow up following RN, PN and AT  Based on risk factors and type of tx  In low-risk disease : CT/MRI can be used infrequently  In intermediate-risk disease : intensified follow-up should be performed : CT/MRI at regular interval  In high-risk disease : CT/MRI should be included  Tumors > 7cm treated with NSS or positive margin : intensified follow-up

18. Thank You