current trends in renal cell carcinoma

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  2. 2. Renal Cell Carcinoma Commonest malignant lesion of kidney most lethal of the urologic cancers accounts for 2% to 3% of all adult malignant neoplasms male: female= 3;2 Majority are sporadic and 4% familial sixth and seventh decades of life ~ 1/2 discovered incidentally 5 fold increase in small (< 3 cm) tumors in last 20 years Slow growing
  3. 3. Classification Mode of presentation Sporadic Familial VHL- von Hippel Lindau symdrome Hereditary papillary RCC Others Histological Conventional (70-80%) Clear cell Granular Mixed Chromophillic (10-15%) Chromophobic Collecting duct
  4. 4. Clinical features Majority asymptomatic 50% incidentally detected Dull flank pain hematuria Abdominal mass anorexia Hypertension Anaemia Triad- flank pain, gross hematuria, palpable abdominal mass now rare Features of paraneoplastic syndrome
  5. 5. Investigations Ultrasonography CT- Scan (plain & contrast enhanced) IVU MRI Angiography, venocavography FNAB
  6. 6. Robsons staging
  7. 7. Staging and Prognosis Cohen HT, McGovern FJ. NEJM. 2005;353:2477.
  8. 8. Treatment options Surgery Rad. Nephrectomy Partial nephrectomy Nephron sparing surgery Minimal invasive methods (thermal ablative therapy) Immunotherapy Chemotherapy radiotherapy Vaccines & cytokines Targated agents Hormone therapy
  9. 9. Surgical modalities Rad.Neph Open Lap N.S.S Open Lap Minimally invasive approach Cryoablation open P.C LapR.F.A open P.C LAP Noninvasive HIFU ablation
  10. 10. No Prospective & randomized trials have been performed to compare elective partial nephrectomies with Rad. Neph. or to compare evolving techniques of minimally invasive surgery with Std. Open Surgical tech.
  11. 11. Localized RCC Treatment Surgery is the only curative therapy for stage I-III Radical nephrectomy is gold standard Partial nephrectomy in selected patients No role for adjuvant therapy except under investigational protocol 20-30% of patients relapse within 2-3 years - Metastases to the lung most common 50% - Local recurrence is rare 2-3%
  12. 12. Management of localised RCC
  13. 13. Rad. Nephrectomy ORN was the gold std. for localized RCC Surgical approach for R.N is determined by size/location of tumor & pt related factors. Disadvantage ofTransperitoneal approach is longer post op. ileus & intra abd. Adhesions. R. Nephrectomy consists of early control of vasculature and removing kidney outside G.F with removal of ipsilat Adr. Gland . Adrenalectomy should be part of R.N for RCC of > 5 cm. as risk of unexpected microscopic invasion of Adr. has been shown to be as high as 7.5%. Therapeutic value of lymph adenectomy remains controversial.
  14. 14. Lap.Rad.Nephrectomy L.R.N :- (a)Transperitoneal (b) R.Peritoneal becoming std.T/t for localizedT1-2 tumors that are not amenable to NSS. Benefits of LRN :- (1) Decreased P.O pain (2) Shortened hospital stay. (3) Quick convalescence & improved cosmesis. 5Yrs ds free rates for Lap R.N & ORN are comparable.. C/I :- Rad. Neph. shdnt be done for small < 4 cm size tumor that is amenable to PN.
  15. 15. Lap R.N shdnt be done in large vol. tumor i.e. of > 8 cm / locally advanced RCC/RCC with R.V or I.V.C involvement. R.Neph. Shdnt be done if at all possible in a functionally or anatomically solitary kidney thus forcing the pt into Chr. Dialysis. Complications include vascular injury ,splenic injury, bowel perforation; pneumothorax, port site metastasis & rupture / morcellation of bagged kidney that could obliterate tumor margin.
  16. 16. NephronSparingSurgery(NSS) OPEN N.S.S- (a) simple enucleation (b) wedge resection (c) polar segmentalnephrectomy (d) transverse resection (e) Ext.corp.neph.with auto transplantation
  17. 17. Results of open P.N in term of long term cancer free survival with unilat, unifocal ds of < 4 cm is equivalent to open R.N. 3 D volume rendered CT is must before P.N. Indication (1) Absolute (2) Relative or Elective Absolute B/L synchr. tumor ; tumor in solitary kidney or significant renal failure. N.S.S
  18. 18. Relative Contralat kidney has preexisting renal ds. Elective tumor of < 4cm in presence of N-Contralat kidney. Intra op. tumor free status is assessed by USG/Frozen- section analysis for surgical margin. C/I Large tumor, where ve tumor free margin cant be achieved and large tumor with R.V / IVC involv. Complications --- Haemorrhage Urinary fistula Renal insufficiency R.I is common b/c ofARF seen in pt undergoing N.S.S with tumor > 7 cm or when >50% of parenchyma is excised or b/c of > 60 min. of Ischemia time. Major disadvantage is LTR (10%).
  19. 19. Cryotherapy Kidney is favoured site b/c it can readily be dissected from adjacent organs & usually gives rise to unifocal malig. Can be used in P.C / Open/ Lap approach Temp. of -20 degree C induces cell necrosis. Rapid freezing causes crystal form in microvasculature & E.C spaces and within cells , this results in failure of oxid.phosph. and failure of microvasculature. Adequate cryodestruction requires Intraop. monitoring of resultant ice ball with U.S.G. COMPLICATIONS --- Ur. Fistula formation --- PostT/t haemorrhage --- Injury to adjacent structure Criticism ---- Histological documentation of complete tumor destruction is not currently available.
  20. 20. RFA & HIFU Pr. Mech of tissue destruction by both is thermonecrosis. R.F energy can be used PC/Lap/ in open surgery . R.F energy of 10-90W are applied to raise the temp.>60 degree C to induce coagulative necrosis. Probe carries an A.C of high freq. radiowaves that causes the local ions to vibrate ,resistance in the tissue creates heat thus causing thermal caugalation. U.S.G, Fluroscopy, CT & MRT is used for P.C placement of probe; but none of these is reliable for monitoring R.F lesions & completness of cancer call death.
  21. 21. HIFU aims to completely ablate renal tumor in a non invasive manner. Indications :- -- small exophytic tumor most suitable ; success rate decrease with increase in size of tumor & as the location becomes central. -- patient withVHL ds & patient with multiple renal tumor. Complications risk of ureteral / calyceal injury in cases of centrally located lesions. ---- Perinephric haemotoma ---- Skin metastasis
  22. 22. Conclusions Lap. RN is rapidly replacing the ORN withT1-2 tumor. ORN is mainly reserved forT3 tumor/tumor of >8 cm / tumor with R.V or IVC involv. NSS will play a major role in small < 4 cm peripheral tumor. Open PN is still the std. form of NSS but with refined tech. Lap PN may be soon coming.
  23. 23. OBSERVATION Bosniaks data suggests observation policy for small; solid enhancing; well marginated homogenous renal lesions (i.e RCC of < 3 cm) in elderly poor risk cases & follow up with serial renal imaging at 6mth/1 yr. Tumor growth rate in these subset of pt. is 1.3 cm/yr & incidence of metastasis is quite low i.e. 1-3%.
  24. 24. Advanced RCC Treatment Primary treatments are systemic therapy with molecularly targeted therapy or immunotherapy Surgery is palliative therapy Solitary recurrence following nephrectomy - Symptoms related to bulkiness of disease including pain, nausea, or GI obstruction
  25. 25. Laparoscopic ablation Percutaneous ablation Open partial Laparoscopic nephrectomy Laparoscopic partial Changing trends in surgical management Trend towards less invasive options Radical nephrectomyRadical nephrectomy Open partial
  26. 26. Thermal ablative therapy a. cryotherapy b. radiofrequency ablation Cryotherapy Advanced age Co morbidity not fit for surgery Local recurrence after NSS Hereditary renal cancer Tumour size- 60 degree C to induce coagulative necrosis. Probe carries an A.C of high freq. radio waves that causes the local ions to vibrate ,resistance in the tissue creates heat thus causing thermal coagulation. U.S.G, Fluroscopy, CT & MRT is used for P.C placement of probe; but none of these is reliable for monitoring R.F lesions & completness of cancer call death.
  27. 35. New technology- (HIFU) high intensity focusedUSG, image guided radio surgical treatment Under development May be used as extracorporeal approach HIFU aims to completely ablate renal tumor in a non invasive manner
  28. 36. Targeted Therapy Based on advances in the understanding of the molecular biology of RCC - Highly vascularlized tumor with increased VEGF and EGFR expression - Tumor growth mediated viaVEGF pathway and mammalian target of rapamycin (mTOR) pathway
  29. 37. VEGF Pathway Inhibition Tyrosine kinase (TK) inhibitors block the intracellular domain of theVEGF receptor - Sunitinib (Sutent) - Sorafenib (Nexavar) Monoclonal antibody that binds circulating VEGF preventing the activation of theVEGF receptor - Bevacizumab (Avastin)
  30. 38. Sunitinib Two phase II trials evaluating activity and safety in previously treated advanced RCC - 25-36% of patients had an objective response - Progression free survival (PFS) 8.3-8.7 months - Median survival 16.4 months Side effects include fatigue, HTN, nausea, diarrhea, mucositis, and hypothyroidism
  31. 39. Sunitinib Phase III trial 750 pts with untreated stage IV RCC Sunitinib vs. INFa Sunitinib showed prolonged median PFS 11 vs. 5m and higher response rate of 31% vs. 6% Motzer RJ, et al. NEJM. 2007;356:115-124
  32. 40. Sorafenib Phase II and phase III trials in advanced RCC Phase IIITARGET study of 903 previously tx pts w/ stage IV RCC randomized to Sorafenib vs. placebo - Sorafenib improved median PFS