Indications For Partial Nephrectomy Christopher G. Wood, M. D., FACS Professor and Deputy Chairman Douglas E. Johnson, M. D. Endowed Professorship in Urology Department of Urology The University of Texas MD Anderson Cancer Center
Indications For Partial Nephrectomy Indications for Partial Nephrectomy Expanding Our Horizons Should we be conserving nephrons at all costs? Isradical nephrectomy for T1b/T2 disease a surgical defeat? Should we/can we treat central and hilar tumors with nephron sparing surgery? Are We Overtreating The Small Renal Mass?
Renal Cell Carcinoma 64,770 patients were diagnosed with renal tumors in 2012 (~90% RCC) 13,570 died of disease RCC rate increased d2% per year Siegel CA. Cancer J Clin 2012
Incidence of RCC In The US
Mortality From RCC In The US
Overdiagnosis of RCC Welch HG and Black WC JNCI 2010
Imaging Epidemic: Defensive Medicine Welch HG and Black WC JNCI 2010
Will RCC be the cause of death? Welch HG and Black WC JNCI 2010
Incidental Renal Mass Increase Incidence RCC Increased Prevalence RCC Increased Detection RCC
68 y/o WM with 3 cm renal mass Active Surveillance Energy Ablation Partial Nephrectomy Open Robotic Assisted/Laparoscopic
Why Surgery? It is definitive!!! Offending lesion is removed Pathologicexamination provides complete assessment of margins, histology, grade» Can accurately and definitively assess risk of recurrence Can be performed minimally invasively (when appropriate)» Laparoscopic» Robotic Assisted
Why Surgery? It is effective!!! Equivalent cancer control to radical nephrectomy for appropriately selected patients» Location more important than size or stage» Can be more universally applied than AS or Ablation It is nephron sparing It is cost effective» Can tailor follow up to accurate assessment of risk of recurrence
Why not surgery? It is morbid So is the management of metastatic renal cell carcinoma in inadequately treated patients Up to 30% of lesions are benign Not all benign lesions act benignly» Pain, Bleeding, Compromise Renal Function Biopsy can be non diagnostic in up to 20 25% of cases Risk of non cancer related death is greater Can t be predicted in an individual patient Appropriate patient selection is key!! There are equally effective minimally i invasive i or noninvasive therapies Not supported in the literature Controversy exists regarding appropriate endpoints for treatment success
NCCN Guidelines v2.2012 2012 Partial Nephrectomy (Preferred) Stage IA Radical Nephrectomy (If partial not feasible or central location) Active Surveillance (Selected patients) Ablation (Nonsurgical candidates) Category 2A: Based upon lower level evidence, there is uniform NCCN consensus that the intervention is appropriate. www.nccn.org
AUA Guidelines 2009 Partial Nephrectomy (Standard) ct1a Radical Nephrectomy (Standard) Active Surveillance or Ablation If healthy (Option) If not healthy(recommendation) Campbell S. J Urol 2009
Indications For Nephron Sparing Surgery Tumor in a solitary kidney Bilateral renal tumors Multifocal tumors Threat of bilateral recurrence Severely compromised renal function Threat of future loss of renal function Comorbidities: HTN, DM, PVD Small amenable renal tumor (< 4 cm) with normal contralateral kidney Location more than tumor size is the critical factor
Lower Risk of Death With Partial Nephrectomy vs RN Retrospective review of outcomes in 648 patients undergoing PN (55%) or RN (45%) All tumors 4 cm 77% of patients alive at median of 7 years post surgery In patients <65 years old, RN associated with 2 fold risk of death from any cause vs PN RR, 2.16; P =.02 10 year OS rate with ihpn vs RN, 93% vs 82% OS = overall survival RR = relative risk Thompson RH et al. J Urol. 2008;179:468.
Lower Risk of Death With PN vs RN in Younger Patients Survival advantage of PN over RN significant ifi after adjusting for Year of surgery (RR, 2.34; P =.016) Preoperative creatinine level (RR, 2.15; P =.027) Charlson Romano index (RR, 2.14; P =.037) Sex (RR, 2.16; P =.025) Symptoms at presentation (RR, 2.17; P =.023) Diabetes at presentation (RR, 2.23; 23; P =.028) Histology (RR, 2.32; P =.015) Thompson RH et al. J Urol. 2008;179:468.
Increase Risk of Non Cancer Related Mortality with Radical Nephrectomy N= 4449 Controlled for: Age Tumor Size Year of Surgery Fuhrman Grade Zini L et al., Cancer 2009
So the push was on.save nephron mass at all costs!!!!
Central/Hilar Tumors: Laparoscopic Outcomes No differences when compared to non hilar tumors OR Time Blood Loss PSM Rate WIT Transfusions Postoperative Complications Changes in Cr or GFR CONCLUSION In the hands of an experienced laparoscopist, LPN can safely be p p p, y performed for hilar tumors, with preservation of perioperative outcomes and durable renal functional and oncologic outcomes. UROLOGY 83: 111e115, 2014. George AK et al.
PN vs RN in Larger T1 Tumors Retrospective analysis of patients with T1N0M0 tumors undergoing resection 1454 patients had PN (26%) or RN (74%) Mean follow up, 52 5.2 years No differences with PN vs RN in T1a or T1b tumors according to Local or distant recurrence rates Cancer specific deaths Patard JJ et al. J Urol. 2004;171(6 Pt 1):2181.
PN, RN Outcomes in Selected Patients with 4 7 cm Tumors Review of 932 patients with 4 7 cm tumors undergoing PN (10%) or RN (90%) No significant survival differences in adjusted analysis 5-Year Outcome PN (N = 91) RN (N = 841) Cancer-specific survival 98% 86% Distant metastases-free survival 94% 83% Recurrence-free survival 94% 98% Leibovich BC et al. J Urol. 2004;171:1066.
NSS Equivalent to RN in Selected Patients with T2 T3bN0M0 RCC Patients with T2 T3b RCC underwent NSS (N=34) or RN (N=567) In adjusted analysis, procedure type not predictive of recurrence or cancer related death 5 year recurrence free survival higher with NSS vs RN (82% vs 62%; P <.012) 5 year cancer free survival similar with NSS vs RN (78% vs 74%; P =.113) Margulis V et al. BJU Int. 2007;100:1235.
PN Appropriate in Selected Patients With Larger Tumors Review of 474 patients receiving PN at single institution Tumors 4 cm, 78.5%; tumors >4 cm, 21.5% Outcomes similar betweentwogroupstwo Outcome Small tumors Large tumors (N = 372) (N = 102) 5-year cancer-specific survival 97.9% 95.8% 10-year cancer-specific survival 94.9% 95.8% 5-year recurrence-free survival 98.5% 98.3% 10-year recurrence-free survival 93.9% 98.3% Pahernik S et al. J Urol. 2008;179:71.
Disease Stage More Prognostic Than Tumor Size In adjusted danalysis, risk of tumor related ddeath higher in stage III vs lower stage disease RR, 6.63 (95% CI, 1.2 35.8; P =.03) Caveat: small cohort (N = 21 with stage III disease) Factors not predicting cancer specific survival Tumor grade 3 vs lower grade Clear cell pathology Tumor size >4 cm Pahernik S et al. J Urol. 2008;179:71.
Mortality after Radical Nephrectomy Huang et al, J Urol 2009 2,991 patients SEER database 65 years or older Partial or radical nephrectomy Tumors < 4 cm (1995 2002)
Renal insufficiency after 1 year (< 60 cc/hour) 100 80 65% 60 40 20 20% 0 Radical nephrectomy Partial nephrectomy
75% Partial Nx 68% Radical
All available evidence suggests that t PN is as effective as RN in the management of T1 disease, regardless of tumor size maybe we should do a RCT to confirm?
EORTC Phase 3 Trial Van Poppel et al, Eur Urol 2007 1992 and 2003 541 pts, renal mass 5 cm, normal contralateral kidney Prospective, randomized to PN vs. RN Inclusion if creat 1.25
EORTC 30904 Median follow up: 9.3 years Survival better for RN than NSS HR: 1.50, p < 0.03
EORTC 30904 Risk of Dialysis the Same Lowest GFR (ml/min/1.73 m2) RN NSS 95% CI <60 85.7% 64.7% 13.8 to 28.3 < 45 49% 27.1% 13.8 to 20.2 < 30 10% 6.3% NS < 15 15% 1.5% 16% 1.6% NS Scosyrev et al, Eur Urol 2014
Survival after RN vs. PN SEER Database Matched cohort study (NCI) SEER Medicare data set Study group: 5,770 pts; mass 4 treated with PN or RN Compared overall survivalwith controls Non cancer NMIBC Shuch et al, Cancer 2013
SEER Observational Data Radical Nephrectomy vs. Partial Nephrectomy Shuch et al, Cancer 2013
SEER Observational Data Radical Nephrectomy vs. Controls RN vs. Non Cancer Controls RN vs. Bladder Cancer Controls Shuch et al, Cancer 2013
SEER Observational Data Partial Nephrectomy vs. Non cancer Controls Partial nephrectomy survival BETTER than noncancer controls VERY IMPROBABLE! MAKES NO SENSE!! Shuch et al, Cancer 2013
Survival after RN vs. NSS for T1b Badalato et al BJU Int 2012 (Columbia) SEER database 11,256 pts, RCC between 4 7 cm Overall and Cancer Specific survival compared No difference in survival Then why subject patient to complications?
Renal disease and Cardiovascular Events Go et al, NEJM 2009 Community based study; 120,295 adults GFR < 60 ml/min/1.73 m2 Independent d risk kfactor for CAD, CHF, stroke, death Go et al. NEJM 2009; 360: 459 69
Maximal Preservation of Renal Function We Lose Kidney Function As We Age -HTN, DM Accelerate That Loss- CKD Definition Dfiii If egfr by K/DOQI MDRD <60 ml/min/1.73 m 2 or; If egfr by K/DOQI MDRD 60 ml/min/1.73 m 2 abnormal albumin/creatinine i ratio ( CR 30 mg/g) KEEP N = 45,311. NHANES N = 9,718. KEEP Annual Data Report, 2006
Surgically Induced vs. Medical Chronic Kidney Disease Lane, Campbell et al J Urol 2013 CCF 4,180 underwent renal surgery for a mass 28% hd had a GFR < 60 preoperatively 22% developed GFR < 60 after surgery
Survival Stratified by Chronic Kidney Disease Annual renal function decline: 4.7 vs. 0.7%
Survival Stratified by Postop GFR Patients with Preoperative Chronic Kidney Disease Patients without Preoperative Chronic Kidney Disease Postop GFR predicted death only with medical CKD
Nephron Loss Perhaps renal function much more complex than creatinine i clearance alone Diabetes Hypertension Other factors Not just about losing nephrons but the quality of the ones you retain
Campbell SC et al. J Urol, 2013
Are We Overtreating Our Patients? YES!!!!
The Role of Competing Risks in Patients Treated for a Small Renal Mass: SEER Study, N=30,801 Kutikov A JCO 2010
Survival in Patients >75 Years Old Overall Survival in patients undergoing AS, NSS, or radical nephrectomy Cumulative incidence of cancerspecific or cardiovascular mortality Lane BR Cancer 2010
What do our patients want? Cure Free of local disease Free of metastatic disease Alive Minimal long term complications Minimal morbidity Kidney function preservation
Treatment Options i S ill Active Surveillance Energy Ablation Radiofrequency ablation (RFA) Cryoablation Partial nephrectomy Open Robotic Assisted Radical nephrectomy Open Laparoscopic
Factors to consider Pti Patient tfactors: Age Performance status Renal function Comorbidities Other cancers Wishes and expectations Tumor factors: Size Location Growth rate Biopsy pyresult
Doctor, is this a cancer? Kutikov A et al., Eur Urol, 2011
Is This A Lethal Cancer? Kutikov A et al., JCO 2009
If all you have is a hammer, everything starts looking like a nail!! We need to be Urologic Oncologists that can utilize whatever technology or treatment We need to be Urologic Oncologists that can utilize whatever technology or treatment approach is necessary to best suit the needs of our patients, not technicians that try to fit our technology into whatever situation presents itself.
Thank You