Management of Small renal tumors Dr. NGAI Ho Yin Division of Urology Department of Surgery United Christian Hospital

Differential Dx of solid renal mass Most common: Renal cell carcinoma Less common: Oncocytoma Renal cortical adenoma AML Rare: Neoplasm: Transitional cell carcinoma Metastatic tumors Infection: Renal abscess Vascular Infarct Vascular malformation

Natural history of small renal tumor Meta-analysis from Uzzo et al. (2006) 234 enhancing renal masses From 9 series Mean follow-up: 34 months Mean initial size: 2.60cm Mean growth rate 0.28cm/yr Uzzo et al. The natural history of observed enhancing renal masses: Meta-analysis and review of the world literature. J Urol 175:425-431. Feb 2006

Analysis of Histology related to Tumor size ( Mayo clinic, from 1970-2000, n=2935 ) % of Tumors that were RCC % of RCC that were G3/G4 <1 cm (n=80) 54% 2% 1-4 cm (n=867) 79% 16% 4-7 cm (n=923) 90% 30% >7 cm (n=1065) 94% 57% Frank I et al. Solid Renal Tumors: an analysis of pathological features related to tumor size.　J Urol 170:2217-2220. Feb 2003

Natural history of small renal tumor For single, small solid renal tumor Almost 50% are benign if <1cm Most will grow slowly, ~0.28cm/yr  size =  chance of RCC & high grade disease Aggressive potential of RCC increase after 3cm

What are the available options in dealing with small renal tumors ? Management strategy What are the available options in dealing with small renal tumors ?

Options Observation Radical Nephrectomy Nephron-Sparing Surgery Tumor Excision Open partial nephrectomy Laparoscopic partial nephrectomy Tumor Ablation Laparoscopic cryoablation Radiofrequency ablation (RFA)

Observation

Radical nephrectomy

Radical nephrectomy Gold Standard curative operation Described by Robson 1963 Surgical Principles Early ligation of the renal artery & vein Removal of the kidney outside Gerota’s fascia +/- Removal of ipslateral adrenal gland +/- Complete lymphadenectomy from the crus of diaphragm to aortic bifurcation

Radical nephrectomy 5 yr survival ( organ-confined ) ~ 95%

Nephron Sparing Surgery

Nephron Sparing Surgery Goal of NSS: Complete oncological excision of tumor with minimal technical complications Optimal functional preservation for renal remnant Indication

Nephron Sparing Surgery 1. Open partial nephrectomy Principles

Nephron Sparing Surgery Open partial nephrectomy Data from 3 major centers including: Cleveland clinic Hafez KS, Novick AC, Butler BP. Management of small solitary unilateral renal cell carcinomas: impact of central versus peripheral tumor location. J Urol 1998;159:1156–60 Mayo clinic Lerner SE, Hawkins CA, Blue ML, et al. Disease outcome in patients with low stage renal cell carcinoma treated with nephron sparing or radical surgery. J Urol 2002;167:884–9. Memorial Sloan-Kettering Cancer Center Lee CT, Katz J, Shi W, Thaler HT, Reuter VE, Russo P. Surgical management of renal tumors 4 cm or less in a contemporary cohort. J Urol 2000;163:730–6. NSS and radical nephrectomy provide equally effective curative treatment for single, small (<=4cm) localized RCC

Nephron Sparing Surgery Open partial nephrectomy Novick AC. Laparoscopic and partial nephrectomy. Clin Cancer Res 2004; 10:6322S-7S Review of 1262 patients with open NSS for RCC since 1990 Mean Cancer-specific survival for all patients undergoing open NSS for localized RCC  88% to 97.5% at Mean Follow-up 4-6 years

Nephron Sparing Surgery Open partial nephrectomy Benefit in decreasing risk of progression to chronic renal insufficiency and ESRF Memorial Sloan-Kettering Cancer Center McKiernan J, Simmons R, Katz J, Russo P. Natural history of chronic renal insufficiency after partial and radical nephrectomy. Urology 2002;59:816–20. Mayo clinic Lau WK, Blute ML, Weaver AL, Torres VE, Zincke H. Matched comparison of radical nephrectomy vs nephron-sparing surgery in patients with unilateral renal cell carcinoma and a normal contralateral kidney. Mayo Clin Proc 2000;75:1236–42. Renal insufficiency (Increase in Serum Cr >2mg/dl) At 10 years time : 12.4% in radical nephrectomy group 2.3% in NSS group

Nephron Sparing Surgery Open partial nephrectomy Gold standard in nephron-sparing surgery Comparable efficacy, morbidity & mortality as radical nephrectomy Additional benefit in renal preservation

Nephron Sparing Surgery 2. Laparoscopic partial nephrectomy Principle

Nephron Sparing Surgery Laparoscopic partial nephrectomy Largest single institutional report of LPN by Gill et al. Comparative analysis of laparoscopic versus open partial nephrectomy for renal tumors in 200 patients. Journal of Urology. 170(1):64-8, 2003 Jul. Patients with solitary renal tumor (<=7cm) in size ( clinical T1 RCC ) LPN (n=100) : Sept 1999 to Jan 2002 OPN (n=100) : Apr 1998 to May 2001

Nephron Sparing Surgery Laparoscopic partial nephrectomy Lap PN Open PN Blood loss 125ml 250ml p<0.001 Morphine equivalent 20.2mg 252.5mg Hospital stay 2 days 5 days Convalescence 4 weeks 6 weeks

Nephron Sparing Surgery Laparoscopic partial nephrectomy Intra-op Complications Lap PN Open PN Renal haemorrhage 3 Ureteral resection 1 Post-op Complications Urine leakage Perirenal haematoma Renal haemorrhage, Embolization Nephrectomy Haematuria Ureteropelvic obstruction Total 11 2 p=0.01

Nephron Sparing Surgery Laparoscopic partial nephrectomy Oncological efficacy of LPN by Allaf et al. ( John Hopkins Medical institution – 3-year follow-up) 48 patients with RCC (Mean tumors size 2.4cm) treated by LPN Intra-op FS margin : all negative Mean FU 37.7 months Final pathology: 42 patients : pT1 6 patients : pT3a Laparoscopic partial nephrectomy: evaluation of long-term oncological outcome. Journal of Urology. 172(3):871-3, 2004 Sep.

Nephron Sparing Surgery Laparoscopic partial nephrectomy Results : No recurrence in 46 patients 1 patient with VHL locally recurred at 18th months 1 patient recurred at new location of same kidney at 4 yrs time

Nephron Sparing Surgery Laparoscopic partial nephrectomy Benefits from LPN: Less blood loss Less analgesic requirement Shorter hospital stay Shorter convalescence Short term data suggesting promising survival outcomes Problems of LPN: Longer warm ischaemic time More major intra-op & post-op urological Cx No long term data concerning the oncological efficacy Laparoscopic NSS is an effective treatment for clinically small localized RCC despite long term result needed.

Nephron Sparing Surgery 3. Laparoscopic Cryoablation

Nephron Sparing Surgery Laparoscopic Cryoablation Method: Usage of a liquid nitrogen-cooled cryoprobe At temperature of –40 ‘C By dual freeze-thaw cycle Direct cellular injury & Indirect damage to microvasculature To ablate normal and cancerous tissues Problems : No histopathology to assume clearance May Need extra biopsy for margin clearance

Nephron Sparing Surgery Laparoscopic Cryoablation Gill et al. Renal cryoablation: outcome at 3 years. Journal of Urology. 173(6):1903-7, 2005 Jun. 3 yrs results 56 patients with small renal tumors 75% reduction in mean cryolesion size at 3 years 38% (17 lesions) completely disappeared Post-op needle biopsy: residual tumor in 2 patients 3 years Cancer-specific survival ( unilateral sporadic renal tumor ) = 98%

Nephron Sparing Surgery Laparoscopic Cryoablation Technically safe and intermediate results are encouraging Longer term follow-up needed for oncological efficacy of cryoablation

Nephron Sparing Surgery 4. Radio Frequency Ablation

Nephron Sparing Surgery Radio Frequency Ablation Using a RFA needle (Percutaneous> open / laparoscopic) Deliver high-frequency alternating current to cancerous tissue Induce ionic agitation  frictional heat  intracellular temperature (60-100 ํC) Desiccation, Cellular protein denaturation and membrane disintegration

Nephron Sparing Surgery Radio Frequency Ablation Rendon et al. 11 renal tumors RFA  Immediate / Delayed nephrectomy Found viable cancer cells in specimen : 4/5 (80%) [immediate group] 3/6 (50%) [delayed group]

Nephron Sparing Surgery Radio Frequency Ablation Michaels et al. 20 renal tumors (mean 2.4cm) in 15 pts RFA  Open Partial Nephrectomy Results: All 20 specimens had evidence of morphologically unchanged tumors

Nephron Sparing Surgery Radio Frequency Ablation Current RFA regimens: Ineffective for total destruction of renal tumor tissue in a significant number of patients. Still experimental in treatment of RCC

Conclusion For small solid renal tumor <= 4cm Most are RCC Evidence suggested NSS is equally effective as radical nephrectomy NSS with better preservation of renal functions in long term OPN is the gold standard among choices of NSS LPN is promising technique with its potential advantages

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