Reviews
Is radical nephrectomy a legitimate therapeutic option in patients with renal masses amenable to nephron-sparing surgery? Jeffrey J. Tomaszewski, Marc C. Smaldone, Robert G. Uzzo and Alexander Kutikov Division of Urologic Oncology, Fox Chase Cancer Center-Temple University Health System, Philadelphia, PA, USA
The decision to perform a radical nephrectomy (RN) or a partial nephrectomy (PN), not unlike most decisions in clinical practice, ultimately hinges on the balance of risk. Do the higher risks of a more complex surgery (PN) justify the theoretical benefits of kidney tissue preservation? Data suggest that for patients with an anatomically complex renal mass and a normal contralateral kidney, for whom additional surgical intensity may be risky, such as the elderly and comorbid, RN presents a robust treatment option. Nevertheless, PN, especially for small and anatomically simple renal masses in young patients without comorbidities
Introduction Partial nephrectomy (PN) is now the reference standard treatment for the small renal mass. Both the European Association of Urology and the AUA recommend nephron-sparing surgery (NSS) when excision of a mass ≤4 cm is warranted [1–3]. The use of radical nephrectomy (RN) for the management of small renal masses has declined because of concerns that significant loss of renal parenchyma may predispose patients to the sequelae of chronic kidney disease (CKD), including increased cardiovascular risk, increased metabolic risks such as osteoporosis and anaemia, and compromised overall survival [4–7]. While nearly any T1 and the vast majority of T2 lesions can be resected using modern NSS techniques [1,8,9], the intrinsic complexity of NSS carries with it a well-documented elevation of peri-operative risk [8,10,11]. While these risks are largely clinically insignificant in the young and healthy, they can have a substantial impact in elderly people and those with comorbidities [12]. The decision to perform RN or PN, like all decisions in medicine, pivots on a balance of risk. Treatment decisions must be carefully calibrated and weighed against expected efficacy, competing comorbidities and risks of intervention [13,14]. Do the potential higher risks of a more complex surgery (PN) justify the theoretical benefits of renal tissue preservation? For patients with a normal contralateral kidney for whom additional surgical intensity poses higher risk (e.g. © 2014 The Authors BJU International © 2014 BJU International | doi:10.1111/bju.12696 Published by John Wiley & Sons Ltd. www.bjui.org
should remain the surgical reference standard, as preservation of renal tissue can serve as an ‘insurance policy’ not only against future renal functional decline, but also against the possibility of tumour development in the contralateral kidney. In the present review, we outline the ongoing debate between the role of RN and PN in treatment of the enhancing renal mass.
Keywords partial nephrectomy, radical nephrectomy, outcomes
the elderly with complex renal masses), data suggest that RN presents a robust option. Nevertheless, PN, especially for small and anatomically simple renal masses, should probably remain the surgical reference standard for most individuals, as preservation of renal tissue can be conceptualised as an ‘insurance policy’, not only against future renal functional decline, but also against the possibility of developing a tumour in the opposite kidney. Integrated and individualised decision-making based on objective and balanced quantification of risks must replace the ‘partial for all mentality’. In the present article, we review salient data in the RN vs PN debate and explore the challenges of using observational data for comparative effectiveness research.
Comparative Effectiveness of Radical vs Nephron-Sparing Surgery More frequent abdominal imaging has led to a downward stage migration and smaller tumour size at diagnosis for patients presenting with localised RCC. In fact, stage I tumours now account for the vast majority of incidental cases [15]. Given observational studies from institutional and administrative datasets suggesting equivalent oncological outcomes, superior renal function and overall survival in cohorts undergoing PN vs RN [16,17], current guidelines recommend PN for T1 tumours when technically feasible [2,3,18]. Indeed, the increased use of NSS in recent years is
BJU Int 2015; 115: 357–363 wileyonlinelibrary.com
Review
attributable at least in part to the enthusiasm generated by several large retrospective series reporting a correlation between improved renal function, reduced risk of cardiovascular events, and superior survival with renal preservation [7,17,19–21]. Impact of PN and RN on Survival Chronic kidney disease is currently defined as a GFR 90 days. The development of CKD is associated with an increased risk of cardiovascular events and all-cause mortality in large population-based studies, even when controlling for measured and unmeasured confounders [4,22,23]. A systematic review and pooled meta-analysis comparing ∼40 000 patients undergoing RN and PN showed that, in preselected patients, PN is associated with a 19% lower risk of all-cause mortality and a 61% lower risk of severe CKD [24]. Despite the availability of plentiful retrospective observational data suggesting superior outcomes for patients undergoing PN, the quality of these data are less than robust [24]. For instance, the meta-analysis of the available data shows a paradoxical 29% cancer-specific survival advantage to NSS, indicating significant selection bias inherent to these retrospective cohorts [24]. Meanwhile, available level 1 evidence shows that RN is non-inferior to NSS in cohorts with normal contralateral kidneys. In 2011, the European Organisation for the Research and Treatment of Cancer (EORTC) reported data from a phase III trial that prospectively randomised 541 patients with a normal contralateral kidney and a ≤5 cm renal mass to PN or RN [25]. An unanticipated overall survival benefit for RN was observed at a median follow-up of 9.3 years on an intention-to-treat analysis. Given a lack of significant difference in CSS between PN and RN, the observed survival advantage could not be attributed to differences in kidney cancer mortality. Although NSS substantially reduced the incidence of moderate renal dysfunction (estimated GFR 50%) Cardiac and metabolic sequelae
from those with CKD-M. Similarly to patients included in the EORTC 30904 trial, Lane et al. found that patients with CKD-S had stable renal function after an initial immediate decline post-surgery. Meanwhile, patients who had pre-existing CKD-M experienced a continued marked decline in GFR over time. Furthermore, CKD-M, but not CKD-S, was associated with an inferior overall survival when compared with patients who underwent renal surgery but retained normal renal function [38]. In fact, these data hint that renal dysfunction may be an indicator, and not the source, of risk associated with shortened life expectancy. Furthermore, this indicator is only predictive of overall survival reduction in patients who acquire CKD from non-surgical causes. Nevertheless, an important methodological caveat must be highlighted: all patients with CKD-M underwent renal surgery, and so the true natural history of CKD-M is not evaluated in this report. The emerging data regarding a lack of harm resulting from RN in patients with a normal contralateral kidney perfectly dovetail with long-term data from living-related kidney donors. At a mean (± SD) follow-up of 12.2 (± 9.2) years, >3500 patients who underwent RN as part of a kidney donation programme not only had identical overall survival but also the same risk of end-stage renal disease as the general population. Furthermore, these patients largely retained normal albumin excretion and quality of life (QoL) [39]. Although patients undergoing donor nephrectomy tend to be carefully selected and screened for medical comorbidities, and tend to be younger compared with patients with renal tumours, these data are thought-provoking, as they show a lack of long-term harm from RN in patients with a normal contralateral kidney [1].
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© 2014 The Authors BJU International © 2014 BJU International
Balancing the Peri-operative Risks of Radical vs Nephron-Sparing Surgery The controversy regarding the benefits of nephron preservation must be viewed through the lens of the immediate risks associated with PN and RN. Although PN is generally considered a more technically challenging and risky operation than RN [11,23], the clinical landscape of peri-operative outcomes in the localised kidney cancer space is also extremely complex. Radical Nephrectomy While open RN has a relatively low rate of serious complications such as severe haemorrhage (1.2%) and splenic injury (0.4%) [11], the procedure has largely been supplanted by laparoscopic RN. Compared with the open approach, laparoscopic RN is associated with significantly less blood loss, a lower analgesic requirement, a shorter hospital stay and more rapid convalescence [40]. The overall complication rate after laparoscopic RN is low (12.4–37.7%) [40,41], and major complications (1.2–2.2%) are mainly vascular [41]. Partial Nephrectomy Outside of tertiary referral centres, the adoption of PN has remained sluggish [42], largely because of the concurrent development of laparoscopic RN, the technical complexity of performing NSS, and a fear of complications [11,43]. NSS is more technically demanding, time-consuming and associated with a greater risk of surgical complications [10,44,45]. Contemporary series report postoperative complication rates after PN ranging from 19.2 to 24.9% [2,10,45]. The most common peri-operative complications of NSS include haemorrhage (1.2–4.5%), urinary fistula (0–17.4%) and acute renal failure (0–26%) [11]. Interpreting Differences in Complications between RN and PN The inconsistent use of standardised reporting methods has resulted in an existing body of literature on complications that is difficult to interpret and thus renders direct comparison between RN and PN challenging [46]. Using the well-validated Clavien–Dindo classification system, Simhan et al. [10] assessed complication rates after PN in a large cohort from a tertiary referral centre. The study found overall minor and major complication rates of 26.7 and 11.5%, respectively. Furthermore, the investigators documented that increasing tumour anatomic complexity, as quantified using the R.E.N.A.L. nephrometry score, was associated with the development of major complications after PN [10]. Patients with complex renal tumours were 5.4 times more likely to sustain a major complication after PN, while rates of minor complications were similar regardless of tumour complexity
Radical vs partial nephrectomy for enhancing renal masses
[10], suggesting that major complications after PN are affected by a tumour’s anatomical attributes [10]. Comparison of complications in the EORTC 30904 trial, where patients with tumours ≤5 cm were prospectively randomised between NSS and RN, provide perhaps the most meaningful complication comparisons between RN and PN. These data show higher rates of severe haemorrhage (3.1 vs 1.2%) and urinary fistula (4.4 vs 0%) after PN [11].
adjusting for tumour anatomical complexity, risk status, but not surgery type, appears to be the major driver of complication rates for patients with early-stage disease. Importantly, not all PNs carry the same risks, and a subset of patients with low complexity tumours are probably not at an elevated risk of procedure-specific complications relative to RN [10,53].
Indeed urinary fistula is a more common complication of PN that never occurs after RN. While contemporary urinary leak rates after robot-assisted (1.6%) [47] and open (2.3%) [45] PN are relatively low, historical urinary leak rates range from 0.5 to 21%. Recently, a novel risk stratification metric based on intrarenal renal pelvis anatomy was developed to better risk-stratify patients for the likelihood of post-PN urinary leak (the Renal Pelvic Score). Patients with a greater degree of intrarenal renal pelvis anatomy, as quantified by the Renal Pelvic Score, risk a higher rate and duration of urine leak after PN [48]. Increasing renal tumour complexity as measured by the R.E.N.A.L. nephrometry score is also associated with an increased risk of urine leak [49].
Conclusions
The impact of treatment on QoL should also be considered [50]. Among patients treated with open PN or RN, there were no QoL differences 1 year after surgery, but renal functional preservation was noted to have a measurable patient-reported QoL benefit [51]. Comparatively, patients undergoing laparoscopic RN or PN have measurable short-term patient-reported QoL benefits, but the differences disappear after a few months [52]; however, patient fear of cancer and its recurrence, especially among older patients, remains an important factor at 1 year [52]. Treatment options for localised RCC, therefore, have potential QoL implications, which merit consideration during treatment selection. Although upfront comparisons between two procedure types of varying technical complexity is challenging, as experience with PN (open and minimally invasive) grows, expert consensus suggests that PN for anatomically simple lesions can be performed with a similar safety profile to that of RN. In fact, non-genitourinary organ system complication rates are also important to consider and are probably influenced by additional patient factors such as competing medical risks and history of previous surgery [10]. Risk status determined by age and/or comorbidity may contribute more than type of procedure performed to complication risk in patients with low-stage disease. In fact, when the association between high-risk patient status (defined as age >75 years or Charlson comorbidity index >2) and postoperative complications is examined in patients undergoing surgical management for clinically localised renal tumours, the results show that surgery type may be less important than other clinical variables [12]. In fact, the overall burden of 90-day complications in the elderly and infirm is substantial (>22%) when rigorously measured using the Clavien classification system [12]. When
The surgical treatment paradigm for small localised RCC has shifted from radical extirpation to NSS, with the goal of preserving long-term renal function while maintaining oncological efficacy. Data showing an association between CKD, cardiovascular disease and death highlight the increasing importance of nephron preservation. Not unexpectedly, nearly all evidence supporting a survival benefit with NSS has been limited to patients preselected for PN or RN; however, it is likely that no degree of sophisticated ex post facto statistical manipulation can eliminate the unmeasured or unquantifiable biases inherent to observational study designs. As evident from prospective randomised data, the benefits of nephron preservation are not universal across patient groups, and appropriate treatment selection should include an objective and balanced consideration of competing risks. Among elderly and frail patients with complex tumours in whom the higher peri-operative risks of PN for a complex mass are significant and for whom the long-term benefits of PN are uncertain, RN may represent the better option and may not be a therapeutic ‘heresy’. Continued use of insightful clinical judgment in patient management decisions should be coupled with future efforts to refine existing objective tools for better risk stratification to determine which patients are most likely to benefit from nephron preservation.
Conflict of Interest None declared.
References 1
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27 Piaggio G, Elbourne DR, Altman DG, Pocock SJ, Evans SJ, Group C. Reporting of noninferiority and equivalence randomized trials: an extension of the CONSORT statement. JAMA 2006; 295: 1152–60 28 Giordano SH, Kuo YF, Duan Z, Hortobagyi GN, Freeman J, Goodwin JS. Limits of observational data in determining outcomes from cancer therapy. Cancer 2008; 112: 2456–66 29 Smaldone MC, Churukanti G, Simhan J et al. Clinical characteristics associated with treatment type for localized renal tumors: implications for practice pattern assessment. Urology 2013; 81: 269–75 30 Canter D, Kutikov A, Sirohi M et al. Prevalence of baseline chronic kidney disease in patients presenting with solid renal tumors. Urology 2011; 77: 781–5 31 Sun M, Becker A, Tian Z et al. Management of localized kidney cancer: calculating cancer-specific mortality and competing risks of death for surgery and nonsurgical management. Eur Urol 2013; 65: 235–41 32 Korn EL, Freidlin B. Methodology for comparative effectiveness research: potential and limitations. J Clin Oncol 2012; 30: 4185–7 33 Stukel TA, Fisher ES, Wennberg DE, Alter DA, Gottlieb DJ, Vermeulen MJ. Analysis of observational studies in the presence of treatment selection bias: effects of invasive cardiac management on AMI survival using propensity score and instrumental variable methods. JAMA 2007; 297: 278–85 34 Lamont EB, Hayreh D, Pickett KE et al. Is patient travel distance associated with survival on phase II clinical trials in oncology? J Natl Canc Inst. 2003; 95: 1370–5 35 Smaldone MC, Egleston B, Uzzo RG, Kutikov A. Does partial nephrectomy result in a durable overall survival benefit in the Medicare population? J Urol 2012; 188: 2089–94 36 Shuch B, Hanley J, Lai J et al. Overall survival advantage with partial nephrectomy: a bias of observational data? Cancer 2013; 119: 2981–9 37 Weight CJ, Miller DC, Campbell SC, Derweesh IH, Lane BR, Messing EM. The management of a clinical t1b renal tumor in the presence of a normal contralateral kidney. J Urol 2013; 189: 1198–202 38 Lane BR, Campbell SC, Demirjian S, Fergany AF. Surgically induced chronic kidney disease may be associated with a lower risk of progression and mortality than medical chronic kidney disease. J Urol 2013; 189: 1649–55 39 Ibrahim HN, Foley R, Tan L et al. Long-term consequences of kidney donation. N Engl J Med 2009; 360: 459–69 40 Hemal AK, Kumar A, Kumar R, Wadhwa P, Seth A, Gupta NP. Laparoscopic versus open radical nephrectomy for large renal tumors: a long-term prospective comparison. J Urol 2007; 177: 862–6 41 Van Poppel H, Becker F, Cadeddu JA et al. Treatment of localised renal cell carcinoma. Eur Urol 2011; 60: 662–72 42 Smaldone MC, Kutikov A, Egleston B et al. Assessing performance trends in laparoscopic nephrectomy and nephron-sparing surgery for localized renal tumors. Urology 2012; 80: 286–91 43 Miller DC, Hollingsworth JM, Hafez KS, Daignault S, Hollenbeck BK. Partial nephrectomy for small renal masses: an emerging quality of care concern? J Urol 2006; 175: 853–7; discussion 858 44 Pasticier G, Timsit MO, Badet L et al. Nephron-sparing surgery for renal cell carcinoma: detailed analysis of complications over a 15-year period. Eur Urol 2006; 49: 485–90 45 Gill IS, Kavoussi LR, Lane BR et al. Comparison of 1,800 laparoscopic and open partial nephrectomies for single renal tumors. J Urol 2007; 178: 41–6 46 Donat SM. Standards for surgical complication reporting in urologic oncology: time for a change. Urology 2007; 69: 221–5 47 Spana G, Haber GP, Dulabon LM et al. Complications after robotic partial nephrectomy at centers of excellence: multi-institutional analysis of 450 cases. J Urol 2011; 186: 417–21
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48 Tomaszewski JJ, Cung B, Smaldone MC et al. Renal pelvic anatomy is associated with incidence, grade, and need for intervention for urine leak following partial nephrectomy. Eur Urol 2013. doi: 10.1016/j.eururo.2013.10.009 49 Bruner B, Breau RH, Lohse CM, Leibovich BC, Blute ML. Renal nephrometry score is associated with urine leak after partial nephrectomy. BJU Int 2011; 108: 67–72 50 MacLennan S, Imamura M, Lapitan MC et al. Systematic review of perioperative and quality-of-life outcomes following surgical management of localised renal cancer. Eur Urol 2012; 62: 1097–117 51 Clark PE, Schover LR, Uzzo RG, Hafez KS, Rybicki LA, Novick AC. Quality of life and psychological adaptation after surgical treatment for localized renal cell carcinoma: impact of the amount of remaining renal tissue. Urology 2001; 57: 252–6 52 Parker PA, Swartz R, Fellman B et al. Comprehensive assessment of quality of life and psychosocial adjustment in patients with renal tumors undergoing open, laparoscopic and nephron sparing surgery. J Urol 2012; 187: 822–6
53 Hung AJ, Cai J, Simmons MN, Gill IS. ‘Trifecta’ in partial nephrectomy. J Urol 2013; 189: 36–42
Correspondence: Jeffrey J. Tomaszewski, Fox Chase Cancer Center-Temple University Health System, 333 Cottman Avenue, Philadelphia, PA 19111, USA. e-mail: tomaszewski.jeff[email protected] Abbreviations: RN, radical nephrectomy; PN, partial nephrectomy; NSS, nephron-sparing surgery; CKD, chronic kidney disease; EORTC, European Organisation for the Research and Treatment of Cancer; CKD-M, CKD caused by medical aetiologies; CKD-S, CKD that develops after acute surgical nephron reduction; QoL, quality of life.
© 2014 The Authors BJU International © 2014 BJU International
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Is radical nephrectomy a legitimate therapeutic option in patients with renal masses amenable to nephron-sparing surgery? Jeffrey J. Tomaszewski, Marc C. Smaldone, Robert G. Uzzo and Alexander Kutikov Division of Urologic Oncology, Fox Chase Cancer Center-Temple University Health System, Philadelphia, PA, USA
The decision to perform a radical nephrectomy (RN) or a partial nephrectomy (PN), not unlike most decisions in clinical practice, ultimately hinges on the balance of risk. Do the higher risks of a more complex surgery (PN) justify the theoretical benefits of kidney tissue preservation? Data suggest that for patients with an anatomically complex renal mass and a normal contralateral kidney, for whom additional surgical intensity may be risky, such as the elderly and comorbid, RN presents a robust treatment option. Nevertheless, PN, especially for small and anatomically simple renal masses in young patients without comorbidities
Introduction Partial nephrectomy (PN) is now the reference standard treatment for the small renal mass. Both the European Association of Urology and the AUA recommend nephron-sparing surgery (NSS) when excision of a mass ≤4 cm is warranted [1–3]. The use of radical nephrectomy (RN) for the management of small renal masses has declined because of concerns that significant loss of renal parenchyma may predispose patients to the sequelae of chronic kidney disease (CKD), including increased cardiovascular risk, increased metabolic risks such as osteoporosis and anaemia, and compromised overall survival [4–7]. While nearly any T1 and the vast majority of T2 lesions can be resected using modern NSS techniques [1,8,9], the intrinsic complexity of NSS carries with it a well-documented elevation of peri-operative risk [8,10,11]. While these risks are largely clinically insignificant in the young and healthy, they can have a substantial impact in elderly people and those with comorbidities [12]. The decision to perform RN or PN, like all decisions in medicine, pivots on a balance of risk. Treatment decisions must be carefully calibrated and weighed against expected efficacy, competing comorbidities and risks of intervention [13,14]. Do the potential higher risks of a more complex surgery (PN) justify the theoretical benefits of renal tissue preservation? For patients with a normal contralateral kidney for whom additional surgical intensity poses higher risk (e.g. © 2014 The Authors BJU International © 2014 BJU International | doi:10.1111/bju.12696 Published by John Wiley & Sons Ltd. www.bjui.org
should remain the surgical reference standard, as preservation of renal tissue can serve as an ‘insurance policy’ not only against future renal functional decline, but also against the possibility of tumour development in the contralateral kidney. In the present review, we outline the ongoing debate between the role of RN and PN in treatment of the enhancing renal mass.
Keywords partial nephrectomy, radical nephrectomy, outcomes
the elderly with complex renal masses), data suggest that RN presents a robust option. Nevertheless, PN, especially for small and anatomically simple renal masses, should probably remain the surgical reference standard for most individuals, as preservation of renal tissue can be conceptualised as an ‘insurance policy’, not only against future renal functional decline, but also against the possibility of developing a tumour in the opposite kidney. Integrated and individualised decision-making based on objective and balanced quantification of risks must replace the ‘partial for all mentality’. In the present article, we review salient data in the RN vs PN debate and explore the challenges of using observational data for comparative effectiveness research.
Comparative Effectiveness of Radical vs Nephron-Sparing Surgery More frequent abdominal imaging has led to a downward stage migration and smaller tumour size at diagnosis for patients presenting with localised RCC. In fact, stage I tumours now account for the vast majority of incidental cases [15]. Given observational studies from institutional and administrative datasets suggesting equivalent oncological outcomes, superior renal function and overall survival in cohorts undergoing PN vs RN [16,17], current guidelines recommend PN for T1 tumours when technically feasible [2,3,18]. Indeed, the increased use of NSS in recent years is
BJU Int 2015; 115: 357–363 wileyonlinelibrary.com
Review
attributable at least in part to the enthusiasm generated by several large retrospective series reporting a correlation between improved renal function, reduced risk of cardiovascular events, and superior survival with renal preservation [7,17,19–21]. Impact of PN and RN on Survival Chronic kidney disease is currently defined as a GFR 90 days. The development of CKD is associated with an increased risk of cardiovascular events and all-cause mortality in large population-based studies, even when controlling for measured and unmeasured confounders [4,22,23]. A systematic review and pooled meta-analysis comparing ∼40 000 patients undergoing RN and PN showed that, in preselected patients, PN is associated with a 19% lower risk of all-cause mortality and a 61% lower risk of severe CKD [24]. Despite the availability of plentiful retrospective observational data suggesting superior outcomes for patients undergoing PN, the quality of these data are less than robust [24]. For instance, the meta-analysis of the available data shows a paradoxical 29% cancer-specific survival advantage to NSS, indicating significant selection bias inherent to these retrospective cohorts [24]. Meanwhile, available level 1 evidence shows that RN is non-inferior to NSS in cohorts with normal contralateral kidneys. In 2011, the European Organisation for the Research and Treatment of Cancer (EORTC) reported data from a phase III trial that prospectively randomised 541 patients with a normal contralateral kidney and a ≤5 cm renal mass to PN or RN [25]. An unanticipated overall survival benefit for RN was observed at a median follow-up of 9.3 years on an intention-to-treat analysis. Given a lack of significant difference in CSS between PN and RN, the observed survival advantage could not be attributed to differences in kidney cancer mortality. Although NSS substantially reduced the incidence of moderate renal dysfunction (estimated GFR 50%) Cardiac and metabolic sequelae
from those with CKD-M. Similarly to patients included in the EORTC 30904 trial, Lane et al. found that patients with CKD-S had stable renal function after an initial immediate decline post-surgery. Meanwhile, patients who had pre-existing CKD-M experienced a continued marked decline in GFR over time. Furthermore, CKD-M, but not CKD-S, was associated with an inferior overall survival when compared with patients who underwent renal surgery but retained normal renal function [38]. In fact, these data hint that renal dysfunction may be an indicator, and not the source, of risk associated with shortened life expectancy. Furthermore, this indicator is only predictive of overall survival reduction in patients who acquire CKD from non-surgical causes. Nevertheless, an important methodological caveat must be highlighted: all patients with CKD-M underwent renal surgery, and so the true natural history of CKD-M is not evaluated in this report. The emerging data regarding a lack of harm resulting from RN in patients with a normal contralateral kidney perfectly dovetail with long-term data from living-related kidney donors. At a mean (± SD) follow-up of 12.2 (± 9.2) years, >3500 patients who underwent RN as part of a kidney donation programme not only had identical overall survival but also the same risk of end-stage renal disease as the general population. Furthermore, these patients largely retained normal albumin excretion and quality of life (QoL) [39]. Although patients undergoing donor nephrectomy tend to be carefully selected and screened for medical comorbidities, and tend to be younger compared with patients with renal tumours, these data are thought-provoking, as they show a lack of long-term harm from RN in patients with a normal contralateral kidney [1].
360
© 2014 The Authors BJU International © 2014 BJU International
Balancing the Peri-operative Risks of Radical vs Nephron-Sparing Surgery The controversy regarding the benefits of nephron preservation must be viewed through the lens of the immediate risks associated with PN and RN. Although PN is generally considered a more technically challenging and risky operation than RN [11,23], the clinical landscape of peri-operative outcomes in the localised kidney cancer space is also extremely complex. Radical Nephrectomy While open RN has a relatively low rate of serious complications such as severe haemorrhage (1.2%) and splenic injury (0.4%) [11], the procedure has largely been supplanted by laparoscopic RN. Compared with the open approach, laparoscopic RN is associated with significantly less blood loss, a lower analgesic requirement, a shorter hospital stay and more rapid convalescence [40]. The overall complication rate after laparoscopic RN is low (12.4–37.7%) [40,41], and major complications (1.2–2.2%) are mainly vascular [41]. Partial Nephrectomy Outside of tertiary referral centres, the adoption of PN has remained sluggish [42], largely because of the concurrent development of laparoscopic RN, the technical complexity of performing NSS, and a fear of complications [11,43]. NSS is more technically demanding, time-consuming and associated with a greater risk of surgical complications [10,44,45]. Contemporary series report postoperative complication rates after PN ranging from 19.2 to 24.9% [2,10,45]. The most common peri-operative complications of NSS include haemorrhage (1.2–4.5%), urinary fistula (0–17.4%) and acute renal failure (0–26%) [11]. Interpreting Differences in Complications between RN and PN The inconsistent use of standardised reporting methods has resulted in an existing body of literature on complications that is difficult to interpret and thus renders direct comparison between RN and PN challenging [46]. Using the well-validated Clavien–Dindo classification system, Simhan et al. [10] assessed complication rates after PN in a large cohort from a tertiary referral centre. The study found overall minor and major complication rates of 26.7 and 11.5%, respectively. Furthermore, the investigators documented that increasing tumour anatomic complexity, as quantified using the R.E.N.A.L. nephrometry score, was associated with the development of major complications after PN [10]. Patients with complex renal tumours were 5.4 times more likely to sustain a major complication after PN, while rates of minor complications were similar regardless of tumour complexity
Radical vs partial nephrectomy for enhancing renal masses
[10], suggesting that major complications after PN are affected by a tumour’s anatomical attributes [10]. Comparison of complications in the EORTC 30904 trial, where patients with tumours ≤5 cm were prospectively randomised between NSS and RN, provide perhaps the most meaningful complication comparisons between RN and PN. These data show higher rates of severe haemorrhage (3.1 vs 1.2%) and urinary fistula (4.4 vs 0%) after PN [11].
adjusting for tumour anatomical complexity, risk status, but not surgery type, appears to be the major driver of complication rates for patients with early-stage disease. Importantly, not all PNs carry the same risks, and a subset of patients with low complexity tumours are probably not at an elevated risk of procedure-specific complications relative to RN [10,53].
Indeed urinary fistula is a more common complication of PN that never occurs after RN. While contemporary urinary leak rates after robot-assisted (1.6%) [47] and open (2.3%) [45] PN are relatively low, historical urinary leak rates range from 0.5 to 21%. Recently, a novel risk stratification metric based on intrarenal renal pelvis anatomy was developed to better risk-stratify patients for the likelihood of post-PN urinary leak (the Renal Pelvic Score). Patients with a greater degree of intrarenal renal pelvis anatomy, as quantified by the Renal Pelvic Score, risk a higher rate and duration of urine leak after PN [48]. Increasing renal tumour complexity as measured by the R.E.N.A.L. nephrometry score is also associated with an increased risk of urine leak [49].
Conclusions
The impact of treatment on QoL should also be considered [50]. Among patients treated with open PN or RN, there were no QoL differences 1 year after surgery, but renal functional preservation was noted to have a measurable patient-reported QoL benefit [51]. Comparatively, patients undergoing laparoscopic RN or PN have measurable short-term patient-reported QoL benefits, but the differences disappear after a few months [52]; however, patient fear of cancer and its recurrence, especially among older patients, remains an important factor at 1 year [52]. Treatment options for localised RCC, therefore, have potential QoL implications, which merit consideration during treatment selection. Although upfront comparisons between two procedure types of varying technical complexity is challenging, as experience with PN (open and minimally invasive) grows, expert consensus suggests that PN for anatomically simple lesions can be performed with a similar safety profile to that of RN. In fact, non-genitourinary organ system complication rates are also important to consider and are probably influenced by additional patient factors such as competing medical risks and history of previous surgery [10]. Risk status determined by age and/or comorbidity may contribute more than type of procedure performed to complication risk in patients with low-stage disease. In fact, when the association between high-risk patient status (defined as age >75 years or Charlson comorbidity index >2) and postoperative complications is examined in patients undergoing surgical management for clinically localised renal tumours, the results show that surgery type may be less important than other clinical variables [12]. In fact, the overall burden of 90-day complications in the elderly and infirm is substantial (>22%) when rigorously measured using the Clavien classification system [12]. When
The surgical treatment paradigm for small localised RCC has shifted from radical extirpation to NSS, with the goal of preserving long-term renal function while maintaining oncological efficacy. Data showing an association between CKD, cardiovascular disease and death highlight the increasing importance of nephron preservation. Not unexpectedly, nearly all evidence supporting a survival benefit with NSS has been limited to patients preselected for PN or RN; however, it is likely that no degree of sophisticated ex post facto statistical manipulation can eliminate the unmeasured or unquantifiable biases inherent to observational study designs. As evident from prospective randomised data, the benefits of nephron preservation are not universal across patient groups, and appropriate treatment selection should include an objective and balanced consideration of competing risks. Among elderly and frail patients with complex tumours in whom the higher peri-operative risks of PN for a complex mass are significant and for whom the long-term benefits of PN are uncertain, RN may represent the better option and may not be a therapeutic ‘heresy’. Continued use of insightful clinical judgment in patient management decisions should be coupled with future efforts to refine existing objective tools for better risk stratification to determine which patients are most likely to benefit from nephron preservation.
Conflict of Interest None declared.
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Correspondence: Jeffrey J. Tomaszewski, Fox Chase Cancer Center-Temple University Health System, 333 Cottman Avenue, Philadelphia, PA 19111, USA. e-mail: tomaszewski.jeff[email protected] Abbreviations: RN, radical nephrectomy; PN, partial nephrectomy; NSS, nephron-sparing surgery; CKD, chronic kidney disease; EORTC, European Organisation for the Research and Treatment of Cancer; CKD-M, CKD caused by medical aetiologies; CKD-S, CKD that develops after acute surgical nephron reduction; QoL, quality of life.
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