THE RATIONALE For PARTIAL NEPHRECTOMY

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1 THE RATIONALE For PARTIAL NEPHRECTOMY Paul Russo MD, FACS Professor of Urology Attending Surgeon Memorial Sloan Kettering Cancer Center Weill School of Medicine Cornell University New York, New York Historical Perspective Surgical Oncology/Kidney Surgery : Radical surgery (Halstead) for all tumors, including kidney : Organ and limb sparing approaches introduced (breast, sarcoma) and accepted : Partial Nephrectomy provides equivalent results to radical nephrectomy for T1a (<4cm) tumors.

2 MSKCC: DFS Partial and Radical Nephrectomy: Tumors 4cm or less across all histologies Lee C et al: J Urol 163: Renal Tumor Surgery Historical Perspective : New information regarding chronic kidney disease (CKD) as a risk factor for cardiovascular disease and worse survival. Kidney tumor patients not the same as kidney donors : Partial nephrectomy prevents or delays CKD and associated cardiovascular events and mortality in T1a tumors : Expanding indications for PN: larger tumors, peri hilar, endophytic, post failed ablation.

3 Renal Tumor Pathology Rationale for Partial Nephrectomy 20% of renal tumors are benign (oncocytoma, AML) 25% are indolent with limited metastatic potential (papillary type 1, cystic RCC, chromophobe). < 7% of patients with tumors < 7 cm will be metastatic at presentation. Patients have approximately 5% life time risk of a contra lateral renal tumor. Kidney donors are not Kidney tumor Patients JAMA 503: , 2010 Type of Nephrectomy Number of Patients Median age (years) Pre Op egfr Donor Nephrectomy ml/min Renal Cancer ml/min

4 Chronic Kidney Disease (CKD) Reduced glomerular filtration (egfr < 60), structural kidney damage, proteinuria 26 million with CKD in USA. 30% of patients undergoing nephrectomy already have CKD. CKD: increased cardiovascular events and worse overall survival. All Cause Mortality in 1,120,295 Outpatients (Age adjusted death rate as per egfr) Go et al. N Engl J Med, 2004.

5 Retrospective review of all patients (N=1479) from 1/1995-6/2005 who had definitive surgery for localized renal cortical tumors at MSKCC Found association between year of surgery and baseline GFR even after controlling for comorbidity, tumor size, and BMI Dose-Dependent survival based upon baseline GFR independent of the tumor stage Findings of this study underscore the importance of preserving renal parenchyma and beg the question of whether treatment of small tumors may be worse than the malignancy itself MSKCC: Mayo Clinic Proceedings. 2008; 83: % of patients undergoing elective PN had egfr <60 c/w CKD

6 RN 1.4x > PN RN 1.38x > PN SEER/Medicare Database J. Urol. 181:55-62, 2009 RCT level 1 evidence : Open PN vs. Open RN, non-inferiority Intention to treat analysis involving 45 centers ( ). Renal mass 5cm suspicious for RCC (83% 4cm) Normal contralateral kidney PN=268; RN=273, closed prematurely (541/1300, 41%) 81 patients randomized to RN and 73 randomized to PN were deleted from the study because of missing data. Median f/u 9.3 yrs

7 55 (14.1%) randomized patients switched treatment, 39 PN patients underwent RN (14.9%) and 16 patients RN patients underwent PN (5.9%). 53 patients (13.5%) lost to follow up were assumed dead of other causes. After 9.3 years, there were only 12/117 (10.3%) renal cancer deaths. 10 year overall survival advantage of 81% for RN versus 75.7% (39 patients analyzed as PN had RN in ITT analysis. No significant difference in survival in renal cancer patients. RN PN Overall survival Underpowered Early 1990 s Intention-to-treat HR 1.50 (95% CI ) Overall survival RCC only Path eligible HR 1.34 RN PN

8 J. Urol: ,2013. Pooled Analysis of Worlds Literature Supports Partial Nephrectomy Kim et al J. Urology 188:51-57, studies involving 31,728 patients comparing partial and radical nephrectomy for localized renal tumors. Partial nephrectomy: 19% reduction in all cause mortality. Partial nephrectomy: 29% reduction in cancer specific mortality. Partial nephrectomy: 61% reduction in CKD.

9 Extending Partial Nephrectomy Technical Feasibility/Selection Factors Patient factors: Age, life expectancy, baseline egfr, medical co morbidities. Tumor factors: Size, location, proximity to hilar vessels, anticipated vascular and collecting system resection and repair. Surgeon factors: Experience with complex kidney surgery, surgical volume, commitment to kidney preservation, reconstructive surgical experience. 7.5 cm exophytic upper pole renal tumor

10 MR PMHx: insomnia, seasonal allergies, GERD 6.5 cm endophytic tumor with renal sinus PSHx: extension R knee Meds: Lunesta, Zegrid, Zyrtec All: IV contrast FHx: NC SocHx: Married, pharma rep, NT, occ EtOH ROS: Negative MSKCC/MAYO CLINIC: PN N=(286) vs RN (N=873) 4-7cm Thompson et al: J. Urol. 182: , 2009

11 Mayo Clinic PN (n=69) v RN (n=207) for T2, T3a, T3b 69 patients with PN (red curve) vs 207 paitents with RN (black curve). J. Urology 183: , 2010 Oncological and Renal Functional Outcomes International Experience: T1b Tumors Japan: PN (N=195 RN vs N=67 PN) CKD prevented by PN with oncological equivalence (Int J. Urol 11:980, 2012) Germany: Lap PN and Open PN provided equivalent renal functional and oncological outcomes in 340 patients. (BJU Int 2012 epub ahead of press) Korea: 70 patients with T1b treated with PN or RN. No difference in oncological outcomes. (Korean J. Urol. 51:596, 2010.)

12 Cleveland Clinic Experience Weight et al (2010): 1004 patients with renal tumors 4-7 cm: RN (N=480) vs. PN (N=524): Radical Nephrectomy associated with 25% increase in cardiac deaths and 17% increase in all cause mortality. (J. Urol. 183: , 2010) Weight et al (2010): 510 patients with renal tumor 4-7 cm with egfr > 60 and normal contra lateral kidney. RN associated with 3.5x greater chance of CKD. PN associated with better overall survival (HR 0.30). (Urology 76:631, 2010) Weight et al (2010): 499/2608 renal tumors (19%) from were benign. RN patients (N=111) had 2.5x greater all cause mortality than the patients treated with PN (N=388). (Eur Urol. 58:293, 2010) MSKCC 2014/PARTIAL NEPHRCTOMY PN planned and attempted for all tumors < 7cm, considered for > 7cm if technically feasible. Technique (lap, robotic & open) less important than safely achieving PN. Active extension of limits of partial nephrectomy to routinely resect hilar and endophytic tumors. Use of intra-operative ultrasound, Gil-Vernet maneuver, kidney split, complex vascular and collecting system repairs, mini-flank surgical incision, iced slush. Routine pre-op calculation of egfr using the MDRD or CKD-epi equation. Judicious use of careful observation in patients that are elderly or have significant pre-existing CVD or CKD.