H. Van Poppel - Kidney cancer - Surgery (including nephron-sparing surgery)

RCC: Surgery Hein Van Poppel UZ Gasthuisberg Leuven, Belgium Lugano 2011 ECCLU 2011 is held under the auspices of the European School of Urology

Risk factors for RCC Smokin g Obesit y H yp ertension Fruit and ve g etable consumption: linked Occu p ational factors: no definite proof (Lipworth et al., J Urol 176:2353, 2006)

1963 Increasing Incidence of Small RCC Events per 100,000U.S. population HOLLINGSWORTH, JCI 98:1333, 2006 < 2cm 2-4cm 4-7cm > 7cm 1985 1987 1989 1991 2001 1993 1995 1997 1999 n=34.503

Mortality for RCC and all causes Up to 5 y. after surgical therapy Hollingsworth et al. Cancer 2007 Survival non RCC mortality RCC mortality .

Kidney Cancer Treatment through the years Every solid mass….Radical Nephrectomy Imperative Nephron Sparing Surgery Elective Nephron Sparing Surgery Laparoscopic Radical - Partial Nephrectomy Ablative techniques Observation – Watchful Waiting Never a randomized trial has compared any of these treatments

WHAT ABOUT RADICAL NEPHRECTOMY ?

Radical nephrectomy No longer golden standard treatment for SRMs Limited to cases not amenable to NSS Extended lymphnode dissection Patients with detectable LN: no improved survival Can be restricted to staging purposes ? In cN0: a small subgroup could benefit Adrenalectomy Only mandatory in selected cases in which there are risk factors for adrenal involvement (Grade B) 7

Extended LND for RCC R L Crispen et al., Eur.Urol.,2011 8

Dilemma in RCC LND in cN+ pts - Poor prognosis (7-17% 5 yr survival) - Often but not always metastatic - Does LND bring any benefit ? - Nevertheless LND is not debated in these cases LND in cN0 pts - All survivors had only microscopic nodal disease - Can we safely omit LND in cN0 patients? - Risk factors that predict nodal invasion 9

Reassessing the Lymph Node Staging for RCC Terrone C et al. Eur Urol 2006; 49: 324-331 (618 Rad.Nephr.+LND) 10

Reassessing the Lymph Node Staging for RCC Terrone C et al. Eur Urol 2006; 49: 324-331 (618 Rad.Nephr.+LND) p=0.02 11

Reassessing the Lymph Node Staging for RCC Dimashkieh HH et al. J Urol 2006; 176: 1978-1983 ENE =Extranodal extension 12

Tumour, Nodes, Metastases Staging System Nx Regional Lymphnodes Idem cannot be assessed N0 Regional lymphnodes Idem negative N1 Metastasis to a 4 or less positive nodes single node (no extranodal invasion) N2 Metastasis in > > 4 positive nodes 1 Lymph node (extranodal invasion) TNM, 2002 TNM, ?? V.Ficarra 13

What to do in cN+ patients ? Radical Nephrectomy and Robson-LND 14

Lymphnode Dissection? </=4 vs. >4 LNs involved (p=0.02) - Patients without primary LND can develop LN recurrence only C.Terrone et al ,Eur Urol. 2006 There is a rationale for prophylactic LND in cN0 16

Performance of LND 1989 to 2004 Despite stage migration and increasing number of resections : no better OS or PFS P.Russo et al., Cancer, 2008 RCC patients undergoing LND through the years No Yes

Performance of Adrenalectomies 1989 to 2004 P.Russo et al., Cancer, 2008 RCC patients Adrenalectomy No Yes

RCC Incidence RCC Mortality Lipworth et al. J Urol 176:2353, 2006 19

WHAT ABOUT PARTIAL NEPHRECTOMY ?

P.Russo et al., Cancer, 2008 Numbers of Radical or Partial Nephrectomies

Elective Nephron-sparing Surgery for Localized RCC Valdez-Mendoza, 2008 N° pts 5-y DFS (% ) Local recurr. (% ) Median FU (mos) Van Poppel et al . (1998) [44] 51 98 0 75 Herr (1999) [9] 70 97 1.5 120 Hafez et al . (1999) [10] 45 100 0 35 Lee et al . (2000) [4] 37 100 0 40 Lau (2000) [23] 189 98 1 44 Filipas et al . (2000) [49] 180 98 1.6 56.4 McKiernan et al . (2002) [22] 117 100 1.2 25 Kural et al . (2003) [51] 50 100 0 33.1 Patard et al . (2004) [11] 379 97.8 0.8 51

Overall Survival Cure rates of Partial and Radical Nx for small RCC are similar Eur.Urol. 2011 26

Partial vs. Radical Nx Complication rate of partial Nx is higher Length of stay, hospital cost comparable Creatinine failure and dialysis need much lower ° Adkins J.Urol 2003, Huang Lancet Oncol.2006 Quality of life significantly better ° Poulakis Urology 2003, Lesage Eur Urol 2007 Still an underutilized procedure ° Miller J.Urol 2006 27

Partial Nephrectomy for Small Renal Masses D.C. Miller, 2006. SEER Data Part. Nx in 9.6% of cases of RCC (1988-2001) % 4 28

Partial Nephrectomy: An underutilized procedure Urologists fear the higher complication rate Open radical nephrectomy for small lesions is often easy, curative and not-complicated Laparoscopic radical nephrectomy became popular and is now standard for T1 tumors ! There is an obvious need for better training 29

Enucleation Enucleoresection NSS 31

Wedge resection Polar Nephrectomy NSS 34

Intact PseudoCapsule in most RCC’s 39

PseudoCapsular Perforation No PseudoCapsule 41

Multifocality as reason for recurrence 42

SIZE of the MARGIN in NSS Czerny : margin? 1950 Vermooten : margin 1 cm Marberger : no reference margin 1992 Hohenfellner : enucleation + coagulation tumor bed Carini : simple enucleation What is a safe margin? 43

Margin size and local recurrence 232 patients mean tumor size 2,8 cm mean follow-up 76 months (12-225) PURE ENUCLEATION margin size: 0,0 mm 3 local recurrences elsewhere in the kidney No local recurrence at the level of the enucleation Carini et al, Eur.Urol., 2006 44

Enucleation with ablation of the tumour base 97 patients, only 1 local recurrence A.Kutikov et al. BJU Int 2008: 102; 699-691 Experts’ Editorial comment:  pure blunt TE, without the need to coagulate A. Minervini et al. Eur Urol 2008: 54; 1347-1444

Positive Surgical Margins Oncological Outcomes Positive margins ≠ adverse prognosis Vigilant monitoring O. Yossepowitch et al. (from MSKCC), J Urol 2008: 179; 2158-2163 46

OPEN PARTIAL NEPHRECTOMY SURVIVAL vs. TUMOR DIAMETER 0 12 24 36 48 60 72 84 96 108 120 < 4 cm 310 PATS. > 4 cm 175 PATS. Months Ca. specific survival % HAFEZ, J.UROL. 162:1930, 1999 48 0 20 40 60 80 100

T1b Midpole Wedge to Enucleation 49

Larger Tumors : NSS Homburg : 69 elective NSS >4cm Stockle, Eur.Urol. 2006 Florence : 71 simple enucleations 4-7cm Carini, J.Urol. 2006 Mayo and MSKCC : 1159 T1b Thompson, J.Urol. 2009 Mayo Clinic : 69 stage T2 or greater Breau, J.Urol. 2010 50

cT1b Partial Nephrectomy 71 patients mean tumor size 4 - 7 cm mean follow-up 74 months PURE ENUCLEATION margin size: 0,0 mm 3 local recurrences: - 1 kidney recurrence: second partial Nx - 2 local recurrence with M+ 5 and 8 y CSS = 85.1 and 81.6% Carini et al., J.Urol.,2006 51

Conclusions on NSS for T1b - Surgically feasible Local cancer control good Cancer specific survival is OK Prognosis is defined by M+ Note: EAU ‘08, Patard: NSS to be systematically considered regardless of size 53

WHAT ABOUT CENTRAL TUMORS ? 54

Centrally located tumors NSS ? Rad.Nx 55

Hilar (A-V) Clamping Surface Cooling 58

T1a Intrarenal Enucleation 59

WHAT ABOUT MULTIFOCAL TUMORS ? 60

Open Partial Nephrectomy From controversial to well accepted Allows difficult resections with low morbidity Intra-operative ultrasound easily applicable Cooling, clamping, etc. no technical problems Kidney closure mostly easily achieved, if not hemostatic techniques are easily applied Duration of surgery is very short Cost for technical tools very low 62

Partial Nephrectomy (Cleveland Clinic) 0 50 100 150 200 250 1995 1996 1997 1998 2000 2001 2002 2003 2004 Open Laparoscopic I . GILL, AAGUS, 2006 63

Lap. or Open Partial Nx? LPN (at expert centres) compares to OPN - Equal short and long-term outcomes Decreasing complication profile LPN to include most renal tumours hitherto reserved for OPN Larger LPN series needed Longer follow-up Possibly a prospective randomised trial 64

Ischemic renal damage after NSS Warm ischemic time of ≥ 25 min caused irreversible damage Y. Funahaski et al. Eur Urol 2009: 55; 209-216 Is renal warm ischemia over 30 minutes during laparoscopic partial nephrectomy possible? Kidney damage during LPN when warm ischemia is > 30 min F. Porpiglia et al. Eur Urol 2007: 52; 1170-1178 65

Laparoscopic Partial Nephrectomy Expert centers reproduce open surgery Hilar clamping, cooling, intraoperative ultrasound…all have been developed Hemostasis and warm ischemia are the most important issues The complication rate is higher than that of open surgery Open Partial Nx remains the gold standard 68

Management of Renal Tumors (JOHNS HOPKINS) 1998 2000 2001 1999 1997 2005 0 40 60 80 100 20 ORN OPN LRN LPN LRA PRA % PEMPONGKOSOL, BJUInt 98:751, 2006 2002 2003 2004 1996 1995 1994 1993 1992 1991 1621 PATIENTS Open Radical Lap.Radical Open Partial Lap.Partial RFA WW ? 69

WHAT ABOUT ABLATIVE THERAPIES ? 70

“ The best Focal Therapy for RCC … is Surgery” H.Van Poppel, Focal Therapy Meeting Amsterdam, 2009 71

Energy ablative therapies Thermal ablation : cryoablation and RFA Reasonable option for small (< 3 cm) low grade RCC in frail patients, who are not candidates for AS and who accept long-term radiographic surveillance Percutaneous tumour core biopsy prior to ablation Posttreatment biopsies When recurrence or incomplete ablation is suspected Minimal impact on renal function 72

PERCUTANEOUS CRYO J. RICHIE, BRIGHAM, BOSTON 76

HIFU 20-40 W/cm 2 1600-2000 W/cm 2 DEPT. UROLOGY, UNIVERSITY OF VIENNA Still experimental 77

Energy ablative therapies At this time Insufficient data to compare Cryo/RFA Ablation reserved for carefully selected high surgical risk pts with SRMs < 4 cm (Grade C) Other minimally invasive techniques Use of HIFU, radiosurgery, MWT, LITT and PCU should be considered experimental HIFU:High Intensity Focused Ultrasound LITT: Laser Interstitial Thermal Therapy MWT: Microwave Thermotherapy PCU: Pulsed Cavitational Ultrasound 78

RFA and CRYO SAFE AND LOW MORBIDITY IN LOW RISK, PERIPHERAL TU. < 3cm Can be repeated LESS RELIABLE THAN (MORE INVASIVE) PARTIAL NEPHRECTOMY Not experimental, but developmental 79

Renal Cancer Treatment Kim, J Urol ‘03 McDougall, J Urol ‘96 Corman, Br J Urol ‘00 Lotan, Br J Urol ‘05 Kercher, Surg End ‘03 80 Rad Nx Open Part.Nx Lap Part.Nx Ablation Morbidity 15% 16% 20% 2-6% Recovery 35 days 33 days 12 days 1 day Mortality 2% 1.6% <1% <0.5% Hospital Stay 5 days 3 days 1.9 days 0.5-1 day Cost $31,000-35,000 $26,000-32,000 $26,000-32,000 $5,000-10,000

Conclusion Increasing number of small renal masses are diagnosed 1/2 renal tumours are < 4cm at detection If nephrectomy is indicated, laparoscopic radical nephrectomy is standard care in T1 - T2 tumours NSS is an established treatment in tumors < 4cm, in 4-7 cm in expert centers in selected cases Open PN is still standard care – laparoscopic PN should be limited to high volume/experienced centers Radical nephrectomy in T1-T2 tumours will increase the risk of renal insufficiency with time compared to NSS Minimal invasive modalities could be considered in elderly patients not suitable for PN 81

H. Van Poppel - Kidney cancer - Surgery (including nephron-sparing surgery)

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