What is the role of partial nephrectomy in the context of active surveillance and renal ablation?

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1 What is the role of partial nephrectomy in the context of active surveillance and renal ablation? Dogu Teber Department of Urology University Hospital Heidelberg

2 Coming from Heidelberg obligates to speak about nephronsparing surgery. Vincenz Czerny ( ) First partial nephrectomy for renal tumor in Heidelberg 1887.

3 C.J. Robson, J Urol ; vol.89 pp , 1963 Even in a suspicious lesion radical surgery is mandatory: Including gerota`s fascia, ipsilateral adrenalectomy and extended lymph node dissection. Paradigmal Shift Organprotection

4 NATIONAL CANCER DATABASE ( ) 4.1 cm 3.6 cm (2004) 3.1 cm (2008) Kane et al. Cancer 2008

5 NEJM, 2004

6 The average loss of renal function observed with RN was associated with a 25% increased risk of cardiac death and 17% increased risk of death from any cause. C. J. Weight et al. Nephrectomy Induced Chronic Renal Insufficiency is Associated With Increased Risk of Cardiovascular Death and Death From Any Cause in Patients With Localized ct1b Renal Masses. J Urol, 2010.

7 J. Urology 2009

8 J. Urology 2010

9 Active Surveillance? versus watchfull waiting! Author N Mean Tumor Size (cm) Mean Follow up (mo) Growth rate (cm/yr) No. With Metastasis Mean follow-up: 4 years Cancer specific survival: 93% Overall survival: 65.9 % Neuzillet et al. 2004, Beisland et al. 2009, Abouassaly et al. 2008

10 Kunkle et al. J Urol 2008

11 Imaging Only 17% of all benign tumors were identified accurately preoperatively (CT) 43% of benign lesions were incorrectly defined as suspicious for malignancy unnecessary treatment. Problems of inter- and intraobserver variability +/- 0.3 cm 2.5 mm³ vs 2.07 mm³ tumor volume (exponentially related to diameter) S. Punnen et al. J Urol 2006

12 Mean growth rate of 0.23 cm/year Tumors with zero growth Final specimen 83% RCC. No statistical difference in growth rate between oncocytoma and RCC. No correlation between initial tumor size and growth rate in RCC. Kunkle et al. Cancer 2008.

13 Tumor size benign < 2 cm 24% 2-3 cm 20.4% 3-4 cm 16% In total 30 % benign lesions: At diagnosis pt3a / Fuhrman grade 3-4 <3 cm 10.9 / 5 % 3-4 cm 35.7% / 28.5 % At diagnosis Mets <3 cm 2.4% 3-4 cm 8.4% Analysis of 287 patients.; Remzi et al. J Urol 2006;

14 Biopsy : < 3-4 cm 3-21% biopsy failure under CT < 2 cm 9-37% biopsy failure US/ CT Failed : Normal kidney (sampling error), insufficient amount of tissue, fibrosis (intratumoral, tumor pseudocapsule), necrosis (intratumoral). Improvement possible: > two core (17-20 G needle) : one central and one peripheral (accurancy 96.7%) Remzi et al. 2010

15 Therapy Algorythm Surgical therapy is the only curative therapeutic approach for the treatment of RCC. For T1 tumours, nephron-sparing surgery should be performed whenever possible. EAU Guidelines 2011

16 15145 patients treated for T1-N0M0 RCC Partial Nephrectomy 578 Thermal Ablation Radical Nephrectomy (66%)!!! T1a subgroup ( >50 % Radical Nephrectomy) J.Urology 2011

17 8 clinical cases. For each axial computerized tomographic image were provided. Cases varied by: -tumor size (2 or 4 cm), -location (pole, mid pole or perihilar) -depth ( endophytic or approximately mesophytic). How would you treat this patient? What is important for your decision?

18 Tumor-location and training changes treatment decision! Fellowship trained urologists (OR 0.4; 95% CI 0.2, 0.6; p ) and urologists at academic hospitals are more likely to choose partial nephrectomy than radical nephrectomy or TA. AS was chosen more often if the same tumor (3cm) /in a healthy patient was perihilar compared to mid kidney or polar.

19 Location and size has an impact on treatment * A reliable tool to predict complications! Useful for patient selection? Ficarra et al.2009, * Waldert et al. 2010

20 Laparoscopic vs. Open Partial Nephrectomy Perioperative Data: Significant Differences in 200 matched patients each group. OPN LPN p-value Operative time (min) < Blood loss (cc) < Ischemia time (min) < Urologic complications 5% 9.2% Subsequent procedures 3.5% 7% < Hemorrhage 1.6% 4.2% Technically advanced procedure with potential for complications. Gill et al. J Urol. 2007

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22 Warm ischemia of less than 20 min. or Zero min.? Tumor excision Suturing collecting system and parenchyma B.R. Lane, J Urol. Oct 2010

23 Excision Technique Simple Enucleation vs Traditional Partial Nephrectomy No difference in progression free survival on 10 year follow up* % Standard partial nephrectomy 93.2% Simple enucleation <1 mm normal tissue margin might be sufficient to prevent disease progression.** Pos. margin pats.: secondery surgery showed only 39% residual tumor Close follow-up might be possible.*** *Minervini et al. 2011,** Van Poppel 2011, *** Bensalah et al. 2010

24 Comparison of overall survival in favour of partial nephrectomies even for T1b. C.J. Weight. Elective Partial Nephrectomy in Patients With Clinical T1b Renal Tumors Is Associated With Improved Overall Survival. Urol, 2009.

25 Current Series Complexity of tumors (T1b /% Hilar tumors) Number and grade of Complications Turna et al. 2008

26 Benway et al. J Urol 2009 Robotic- DaVinci System -Decrease in ischemic time? -Decrease in blood loss? -Less complications? -Everybody can do?

27 Heidelberg Hybrid Appoarch Combining laparoscopic and open Surgery for Partial Nephrectomy Current Indications: - Endophytic tumors - Hilar tumors Pahernik et al. 2011

28 Alternative Strategy Patients with small tumours and/or significant co-morbidity who are unfit for surgery should be considered for an ablative approach, e.g. cryotherapy and radiofrequency ablation. EAU Guidelines Thermal ablation in healthy patients is an option to be discussed as a less invasive treatment option but local tumor recurrence is more likely, measures of success are not well defined and surgical salvage may be difficult. AUA Guidelines

29 Consensus Noordwijk 2009 Less invasive + One treatment should be the goal!!

30 Complications - Less Complications compared to surgery - No significant difference in complication rates between RFA and Cryoablation (Bleeding, Urine leakage). Breda et al. 2009

31 Cryotherapy Comparison small vs. large tumors small large N (patients) Tumor size 1-2 cm 3-4 cm Complications 0 Transfusion 38% Others 53% Recurrence 0 4,7% Landman et al. J Endourol. 2008

32 Matched for : Age PADUA Score ( size and location) Preoperative GFR RCC subtypes Fuhrman grade Comorbidity - Similar complication rate (clavien) - 17% higher risk of local recurrence in the Cryo-group.

33 Increased probability for local recurrence with RFA and Cryo compared to Surgery. Excise, Ablate or Observe: The Small Renal Mass Dilemma - A Meta- Analysis and Review, Kunkle, Egleston and Uzzo, J Urol. 2008

34 Cryo RFA Heuer et al., Eur Urol 57: , 2010

35 Rate of tumor progression: 5.2% vs. 12.9% Rate of repeat ablation: 1.3% vs. 8.5% Cryoabplation or Radiofrequence Ablation of renal masses : A Meta-Analysis, Kunkle et al.,cancer 2008

36 - No enhancement in radiography: 24% positive biopsy for RFA - Problem of Tumor-skiping in RFA? Weight et al. Correlation of Radiographic imaging and Histopathology Following Cryoablation and Radiofrequency Ablation for Renal Tumors. J Urol 2008

37 Decision analytic Markov Model (The model simulates the natural history of a hypothetical cohort of patients diagnosed and incorporates : short terms complications,mortality, local/systemic disease recurrence or progression, as well as the development of CRI,risk of death and cardiovascular morbidity) Abouassaly et al., BJUI May 2011

38 Abouassaly et al., BJUI May 2011

39 Abouassaly et al., BJUI May 2011

40 Nephronsparing has an influence on survival. Partial nephrectomy remains the reference standard in the treatment of small renal masses. Cryotherapy and RFA can be less invasive alternatives in selected patients and tumors (<3cm). However the oncological results are poorer than in partial nephrectomy. Biopsy is mandatory Conclusions can change treatment. Active Surveillance in very selected ( elderly and morbid) patients.

41 BUT No prospective randomized data available Meta- Analysis also based on retrospective data Level of evidence remains low Tumor location needs to be comparable (PADUA,R.E.N.A.L. etc. ) Long term data are mandatory for final judgement on RFA and Cryotherapy. We may treat Renal Cell Cancer as a chronic disease??

42 Nephron-sparing surgery

43 Nephron-sparing surgery

44 Nephron-sparing surgery