- Email: [email protected]
Morbidity and Clinical Outcome of Nephron-Sparing Surgery in Relation to Tumour Size and Indication
european urology 52 (2007) 148–154
available at www.sciencedirect.com journal homepage: www.europeanurology.com
Kidney Cancer
Morbidity and Clinical Outcome of Nephron-Sparing Surgery in Relation to Tumour Size and Indication Jean-Jacques Patard a,*, Allan J. Pantuck b, Maxime Crepel a, John S. Lam b, Laurent Bellec c, Baptiste Albouy d, David Lopes e, Jean-Christophe Bernhard f, Franc¸ois Guille´ a, Bertrand Lacroix g, Alexandre De La Taille e, Laurent Salomon e, Christian Pfister d, Michel Soulie´ c, Jacques Tostain g, Jean-Marie Ferriere f, Claude C. Abbou e, Marc Colombel h, Arie S. Belldegrun b a
Department of Urology, Rennes University Hospital, Rennes, France Department of Urology, University of California Los Angeles, Los Angeles, CA c Department of Urology, University of Toulouse, Toulouse, France d Department of Urology, University of Rouen, Rouen, France e Department of Urology, CHU Henri Mondor, Creteil, Creteil, France f Department of Urology, University of Bordeaux, Bordeaux, France g Department of Urology, University of Saint Etienne, Saint Etienne, France h Departement of Urology, University of Lyon, Lyon, France b
Article info
Abstract
Article history: Accepted January 9, 2007 Published online ahead of print on January 16, 2007
Objective: To analyse through a large multicentre series, morbidity of nephron-sparing surgery (NSS) in relation to tumour size and surgical indication. Methods: The study included patients from eight international academic centres. Age, sex, TNM stage, tumour size, Fuhrman grade, Eastern Cooperative Oncology Group performance status (ECOG-PS), surgical margins, local and distant recurrences, and overall and cancerspecific survival rates were collected and analysed. Indication for elective or mandatory NSS, medical and surgical complication rates, mean blood loss, blood transfusion, and length of hospital stay were specifically recorded for the purpose of this study. Groups were compared for qualitative and quantitative variables by using x2 (Fischer exact test) and Student t tests, respectively. Results: A total of 1048 NSS procedures were included in this study. Mean tumour size was 3.4 2.1 cm. In 730 elective procedures mean operative time ( p = 0.002), mean blood loss ( p = 0.01), the need for blood transfusion ( p = 0.001), and urinary fistula rate ( p = 0.01) were significantly increased for tumours >4 cm. However, these differences did not result in significantly increased medical ( p = 0.4), surgical complication rates ( p = 0.6), or length of hospital stay ( p = 0.9). Finally, in elective procedures for malignant tumours, positive surgical margins, local or distant recurrence rates, and cancer-specific survival were not significantly different in tumours 4 cm and >4 cm. Conclusion: Excellent cancer control and outcomes can be achieved with NSS in carefully selected patients with tumours >4 cm. Expanding the size indication of elective NSS results in an increased but acceptable morbidity.
Keywords: Carcinoma Morbidity Nephrectomy Renal cell
Please visit www.eu-acme.org/ europeanurology to read and answer questions on-line. The EU-ACME credits will then be attributed automatically.
# 2007 European Association of Urology. Published by Elsevier B.V. All rights reserved. * Corresponding author. Rennes University Hospital, Rennes, France. Tel. +33 2 99 28 42 70; Fax: +33 2 99 28 41 13. E-mail address: [email protected] (J.-J. Patard).
0302-2838/$ – see back matter # 2007 European Association of Urology. Published by Elsevier B.V. All rights reserved.
doi:10.1016/j.eururo.2007.01.039
european urology 52 (2007) 148–154
1.
Introduction
The use of partial nephrectomy has historically been limited to patients who would be rendered anephric following radical nephrectomy. Such patients include those with a solitary functioning kidney, bilateral renal cell carcinoma (RCC), or unilateral RCC with some compromise of the contralateral kidney [1]. Due to the increased use of routine body imaging, a greater number of small renal lesions are now being discovered, and elective partial nephrectomy has been adopted more frequently for the treatment of such tumours [2]. It has been extensively demonstrated that for tumours <4 cm in size, partial nephrectomy provides excellent survival and recurrence rates comparable to those achieved with radical nephrectomy [3–5]. However, other studies have demonstrated significantly better survival in patients undergoing partial nephrectomy for tumours 4 cm compared to those with tumours >4 cm in size [4,5]. As a result, 4 cm has served as a commonly accepted cut-off size for renal neoplasms that can be treated by elective partial nephrectomy. Recently, two studies have shown equivalent cancer control when comparing radical nephrectomy and partial nephrectomy in T1b tumours, thus suggesting that it may be safe to increase the indications of nephron-sparing surgery (NSS) from 4 to 7 cm [6,7]. Even though NSS has an acceptable morbidity in experienced hands even in patients with solitary kidneys [8], partial procedures are technically more challenging in large tumours and it may be a concern that broadening the indications may result in increased morbidity. Therefore, the primary objective of our study was to analyse through a large multicentre series the morbidity of NSS in relation to both tumour size and surgical indication. 2.
Methods
2.1.
Data collection
The study included patients from eight academic centres: Rennes, Saint Etienne, Cre´teil, Bordeaux, Lyon, Toulouse, and Rouen in France, and the University of California at Los Angeles (UCLA) in the United States. Partial nephrectomy accounted for at least 30% of the surgical management for renal tumours at each institution. Patient records were extracted from each institutional database to obtain data regarding age, sex, TNM stage, tumour size, Fuhrman grade, Eastern Cooperative Oncology Group performance status (ECOG-PS), symptoms at diagnosis, tumour histology, and overall and cancer-specific survival. Specific data collected for the purpose of this study included American Society of Anesthesiologists (ASA) score, medical and surgical complication rates, mean blood loss, the need for renal vessel clamping,
149
collecting system repair, blood transfusion, and length of hospital stay. Additionally, preoperative and postoperative serum creatinine levels as well as information regarding surgical margins and local and distant recurrence rates were also noted when available. Years of treatment ranged from 1984 to 2005. NSS was defined as elective when the contralateral kidney was anatomically normal with overall normal renal function. NSS was considered imperative in cases of solitary kidney, atrophic contralateral kidney, bilateral tumour, or compromised renal function with risk of end-stage renal disease in case of total nephrectomy. Tumour stage was determined according to the 2002 Union Internationale Contre le Cancer (UICC) revised TNM classification [9]. Tumour histology for malignant tumours was classified according to the Heidelberg classification and tumours were graded according to the Fuhrman grading scheme by pathologists at each of the eight institutions [10,11]. ECOG-PS was determined according to the original criteria set forth by Oken et al [12]. ASA score was determined according to the ASA risk score [13].
2.2.
Statistical analysis
Qualitative and quantitative variables were compared by using x2 (Fischer exact test) and Student t tests, respectively. All p values were two sided and a p < 0.05 was considered significant. All data analysis was processed through the SPSS 12.0 statistical software (Chicago, IL).
3.
Results
3.1.
Patients and tumours
A total of 1048 NSS procedures performed at eight academic institutions were included in this retrospective study. Patients included 694 men (66.2%) and 354 women (33.8%). Mean age at diagnosis was 59.1 12.9 yr and mean tumour size was 3.4 2.1 cm. Most tumours were discovered incidentally (76%) and were malignant at histology (80.1%). Poor ECOG-PS (1) was noted in only 16.8% of the cases. NSS was performed for a mandatory indication in 318 cases (30.3%) including 145 solitary kidneys cases (13.8%). The number of procedures from each institution was 104(9.9%), 79 (7.5%), 195 (18.6%), 53(5.1%), 59 (5.6%), 74 (7.1%), 127 (12.1%), and 357 (34.1%) from Rennes, Cre´teil, Bordeaux, Saint Etienne, Toulouse, Rouen, Lyon (France), and UCLA (United States), respectively. Main tumour characteristics regarding TNM stage, nuclear grade, and histology are described in Table 1. 3.2.
Procedures and morbidity
Mean operative time for the entire cohort was 155 59 min. Renal vessels were clamped in 61.8%
150
european urology 52 (2007) 148–154
Table 1 – Patient and tumour characteristics in 1048 partial nephrectomies including 839 procedures for malignant tumours Mean age, yr (SD) Sex, male (%) Mean tumour size, cm (SD) Tumour size 4 cm Incidental tumours (n = 724) ASA score 3 (n = 698) ECOG 1 (n = 567) Benign tumours Elective procedures Solitary kidney History of bilateral tumours No. of tumours >1 (n = 1007)
59.1 12.9 694 (66.2%) 3.4 2.1 801 (76.4%) 550 (76%) 212 (30.4%) 95 (16.8%) 209 (19.9%) 730 (69.7%) 145 (13.8%) 214 (20.4%) 140 (13.9%)
Histologic subtype in malignant tumours (n = 807) Clear cell carcinomas Papillary carcinomas Chromophobe carcinomas
590 (73.1%) 168 (20.8%) 49 (6.1%)
T stage in malignant tumours T1 T2 T3
743 (88.6%) 28 (3.3%) 68 (8.1%)
N stage 1 M stage: 1 Fuhrman grade in malignant tumours (n = 817) G1 G2 G3 G4
12 (1.4%) 31 (3.7%)
190 458 161 8
(23.3%) (56.1%) (19.6%) (1%)
ASA = American Society of Anesthesiologists; ECOG = Eastern Cooperative Oncology Group.
of the cases for a mean duration of 20.1 10.9 min. Overall, medical and surgical complications occurred in 131(12.5%) and 133(12.7%) cases, respectively. Urinary fistula was noted in 32 cases (3.1%). Blood transfusion rate was 15.3% and median blood loss was 350 ml (range: 0–4000 ml). Mean hospital stay was 8.3 6.2 d.
Table 2 shows that NSS performed for tumours 4 cm or >4 cm were significantly different for age ( p = 0.03), symptoms at presentation ( p = 0.0001), Fuhrman grade ( p = 0.002), and preoperative serum creatinine ( p = 0.01) reflecting a higher proportion of absolute indications (57.4%) and solitary kidneys (21.1%) in the group with larger tumours. Then, we focused on morbidity in elective indications. A total of 730 elective NSS procedures were analyzed, including 130 for tumours >4 cm. Detailed results are described in Table 3. Mean operative time ( p = 0.002), mean blood loss ( p = 0.01), the need for collecting system repair, blood transfusion ( p = 0.001), and urinary fistula rate ( p = 0.01) were significantly increased in patients with tumours >4 cm. However, these differences did not result in significantly increased medical ( p = 0.4) or surgical complication rates ( p = 0.6) or length of hospital stay ( p = 0.9). As expected, differences in term of morbidity were even more pronounced when comparing elective and mandatory procedures. Table 4 describes the details of this comparison. The two groups exhibited significantly different comorbidities and performance status as measured by ASA score ( p = 0.0001) and ECOG-PS ( p = 0.008). Additionally, mean operative time, mean blood loss, the need for blood transfusion, medical complication rate, and length of hospital stay were dramatically increased in the mandatory group ( p = 0.0001). Similarly, the risk for surgical complications ( p = 0.02), including urinary fistulas ( p = 0.03), was significantly increased in the mandatory group. 3.3.
Oncologic results
Finally, we compared in elective procedures oncologic results according to tumour size. Of the 730 elective procedures, 550 were performed for
Table 2 – Comparison of 1048 nephron-sparing surgical procedures for patient and tumour characteristics according to tumour size Variables No. of patients Mean age, yr SD Sex, male ASA 3 (n = 698) ECOG 1 (n = 567) Benign tumours Symptoms (n = 724) Fuhrman grade, G 3 (n = 817) Elective surgery Solitary kidney Mean preoperative serum creatinine, mM/l (n = 794)
Tumours 4 cm
Tumours >4 cm
801 59.5 12.7 538 (67.2%) 159 (29.2%) 63 (15%) 151 (18.9%) 110 (19.4%) 117 (18.4%) 600 (74.9%) 93 (11.6%) 100.2 46.2
247 57.6 13.5 156 (63.2%) 53 (34.6%) 32 (21.6%) 58 (23.5%) 64 (41%) 52 (28.7%) 130 (52.6%) 52 (21.1%) 110.1 49.8
ASA = American Society of Anesthesiologists; ECOG = Eastern Cooperative Oncology Group.
p 0.03 0.2 0.2 0.06 0.11 0.0001 0.002 0.0001 0.0001 0.01
151
european urology 52 (2007) 148–154
Table 3 – Comparison of operative characteristics and morbidity in 730 elective nephron-sparing surgical procedures Tumours 4 cm
Tumours >4 cm
600 146.8 49.4 205 (60.3%) 19.3 10.9 133 (39.2%) 386.0 369.0 65 (10.8%) 52 (8.7%) 36 (6.3%) 10 (1.7%) 7.7 6.0 103.0 52.1
130 165.4 61.4 40 (63.5%) 17.4 6.4 39 (62.9%) 510.5 502.7 16 (12.3%) 14 (10.8%) 19 (14.8%) 7 (5.4%) 7.6 6.3 109.8 71.4
No. of patients Mean operative time, min SD (n = 572) Clamping of renal vessels (n = 403) Mean warm ischaemic time, min (n = 240) Collecting system repair (n = 401) Mean blood loss, ml SD (n = 411) Surgical complications Medical complications Blood transfusion (n = 704) Urinary fistula Mean hospital stay, d SD, (n = 706) Mean postoperative serum creatinine, mM/l (n = 538)
p 0.002 0.6 0.2 0.001 0.01 0.6 0.4 0.001 0.01 0.9 0.3
Table 4 – Comparison of 1048 nephron-sparing surgical procedures for patient and tumour characteristics and morbidity according to the indication Elective indication
Nonelective indication
730 58.3 12.9 3.2 1.8 54 (13.9%) 121 (24.4%) 149.7 51.8 413.3 404.7 55 (7.8%) 81 (11.1%) 17 (2.3%) 66 (9.4%) 7.6 6.0 104.1 55.6
318 60.8 12.9 4.0 2.6 41 (22.9%) 91 (44.8%) 172.9 59.9 703.0 622.3 100 (32.7%) 52 (16.4%) 15 (4.7%) 65 (20.4%) 9.8 6.3 156.6 87.9
No. of patients Mean age, yr SD Mean tumour size, cm SD ECOG 1 (n = 567) ASA score 3 (n = 698) Mean operative time, min SD (n = 821) Mean blood loss, ml SD (n = 587) Blood transfusion (n = 1010) Surgical complications Urinary fistula Medical complications Mean hospital stay, d SD (n = 1009) Mean postoperative serum creatinine, mM/l, SD (n = 788)
p 0.004 0.0001 0.008 0.0001 0.0001 0.0001 0.0001 0.02 0.03 0.0001 0.0001 0.0001
ASA = American Society of Anesthesiologists; ECOG = Eastern Cooperative Oncology Group.
malignant tumours. Median follow-up for this group was 36 mo (range: 1–120 mo). In this subset, positive surgical margins, local or distant recurrences, overall or cancer-specific deaths as well as depth of surgical margins were not significantly different in tumours 4 cm and >4 cm. Detailed results are given in Table 5. Finally, when comparing cancerspecific survival curves in the elective subset no significant difference was found according to the 4-cm tumour size cut-off (log rank test, p = 0.8; Fig. 1).
4.
Discussion
Open NSS is considered to be the standard of care for small renal tumours. Currently, 4 cm is considered as a commonly accepted cut-off size for delineating the indications between NSS and radical nephrectomy. The 4 cm cut-off level was determined based on the knowledge that there was an increased risk for recurrence and progression beyond this arbitrary limit [4,5]. However, it has been shown recently from several independent
Table 5 – Comparison of 550 elective nephron-sparing surgical procedures for oncologic results according to tumour size
Positive margins (n = 542) Margin size, mm SD (n = 148) Local recurrence (n = 520) Distant recurrence (n = 506) Deaths (n = 500) Cancer-related deaths (n = 498)
Tumours 4 cm
Tumours >4 cm
7 (1.5%) 4.2 3.7 4 (0.9%) 7 (1.6%) 20 (4.7%) 9 (2.1%)
1 (1.3%) 5.3 4.9 1 (1.3%) 3 (3.9%) 7 (9.3%) 2 (2.7%)
p 0.9 0.2 0.7 0.2 0.1 0.8
152
european urology 52 (2007) 148–154
Fig. 1 – Cancer-specific survival according to tumor size in 550 elective nephron-sparing surgical procedures.
large series that the risk for dying from cancer beyond a 4 cm tumour size cut-off was increased both for radical and NSS. Subsequently, it was suggested that it was the inherent tumor biology rather than the surgical approach that dictated outcomes and that the tumour size limit of NSS could be expanded from 4 to 7 cm [6,7]. More recently, additional studies have challenged the validity of the 4-cm cut-off, confirming that it is safe for cancer control to expand the indications of NSS [14–17]. Although we previously reported that NSS and radical nephrectomy achieved comparable results for all T1 tumours [7], it is obvious that absolute indication represents an heterogeneous and nonselected group potentially containing poor prognostic tumours. Therefore, the additional strength of the present study was the ability to separate elective from absolute indications. Our data clearly suggest that in the highly selected population of elective NSS, surgical margins, local recurrences, and cancerrelated death rates are not affected by tumour size. Another important finding of the present study was that NSS for absolute indications carries significantly increased morbidity. Indeed, ‘‘imperative’’ tumours are different from the electives, being greater in size and occurring in patients with poorer performance status along with increased comorbidities. In this subset, intraoperative bleeding as well as urinary fistula rates were almost doubled. The need for blood transfusion was four times more frequent for absolute than it was for elective indications. This is consistent with the results of two large studies reporting the outcomes of NSS for
absolute indications. Fergany et al in 400 patients with unique kidney found a 9% urinary fistula rate [18]. Similarly, Ghavamian et al in the same setting reported 23.8% and 27% early and late complication rates, respectively [8]. This is consistent with our 16.4% and 20.4% surgical and medical complication rates. Similarly, Pasticier et al identified a 49.1% overall complication rate in the imperative compared to 17.6% in the elective setting [19]. Although the requirement for temporary dialysis was not recorded in our study, it is likely that it occurred more frequently for patients having a greater propensity for impaired renal function before surgery. Logically, it translated into a significantly increased postoperative serum creatinine levels in this subset. Finally, Ghavamian et al reported a 10.8% recurrence rate and an 80.7% 5-yr cancerspecific survival rate in his unique kidney series. These poor results are unusual in comparison to the elective setting. This, in addition to the increased morbidity that was previously reported, definitively supports the need to distinguish absolute from elective indications when reporting about cancer control and morbidity outcomes after using NSS techniques. In this study we also confirmed that elective NSS for small renal tumours is associated with minimal morbidity. By analyzing 600 tumours measuring <4 cm with both normal contralateral kidney and renal function, we found a 386 ml mean blood loss, along with 10.8% and 8.7% medical and surgical complications rates, respectively. Urinary fistula occurred in only 1.7% of the cases. Although these data ares not surprising, it is an important message to remind all urologists dealing with renal tumours, because it has been recently demonstrated that NSS still does not have the place that it deserves compared to radical nephrectomy even in patients with small tumours [20]. Although there is an increased morbidity in NSS performed for absolute indications, it must be acknowledged that alternative therapeutic choices are very limited in such cases. Conversely, it is not the case for patients with T1b renal tumours with a normal contralateral kidney because laparoscopic radical nephrectomy is, in such cases, an effective therapeutic approach with low morbidity [21,22]. Therefore, it may be a concern that expanding the indications of NSS could translate into an increased morbidity unfavourably comparing with other treatments. Previous studies have focused on NSS morbidity in relation to surgical technique [23] or to surgical period [24]. However, to our knowledge this is the first large study examining the relationship between tumour size and NSS morbidity. In this
european urology 52 (2007) 148–154
study, we could demonstrate that intraoperative and perioperative NSS morbidity as measured by blood loss, urinary fistula rate, and need for blood transfusion was significantly increased in tumours >4 cm in size. However, it is worth noting that our overall medical and surgical complication rates, as well as the length of hospital stay, were not significantly different when comparing patients with small and larger tumors. Moreover, the 12.3% and 10.8% surgical and medical complication rates, respectively, as well as the 5.4% urinary fistula rate that we reported in tumours measuring >4 cm are in the range of what is published overall for NSS. Uzzo et al in a review compiling 1129 patients reported a mean 13.7% major surgical complication rate (4–30%) along with a mean 7.4% urinary fistula rate [25]. Similarly, Stephenson et al in a large contemporary study reported an overall 19% complication rate for NSS [26]. Finally, Thompson et al recently reported about complications of NSS in relation to the period of surgery [24]. In addition to an overall complication rate, which decreased with time, the authors reported a mean intraoperative blood loss of 483 ml for recently operated patients. This result is comparable to the mean intraoperative blood loss of 510 ml that we mentioned for tumours measuring >4 cm. Interestingly, it also appeared that operating on larger tumors by NSS did not result in either the increased need to clamp the renal vessels or in prolonged warm ischaemic times, probably due to experienced case selection. Therefore, it can be assumed that elective NSS in well-selected cases of T1b tumors, by avoiding prolonged warm ischaemic times, is also able to achieve good preservation of renal function. Finally, it appears that although slightly increased in patients with larger tumours undergoing NSS, morbidity remains acceptable and not significantly different from that reported for overall morbidity in large contemporary series. Even though we have demonstrated that expanding elective NSS indications to larger tumours is associated with acceptable morbidity, it is obvious that some NSS-related complications could be particularly deleterious in elderly patients or in those presenting with significant comorbidities. In such patients, particularly when the tumour is deeply located in the renal parenchyma or close to the renal vessels, it is clear that laparoscopic radical nephrectomy may be considered as a preferable option. On the other hand, elderly patients, with comorbidities such as diabetes or hypertension, are at increased risk of altered renal function. Therefore, conservative surgery in such challenging cases should be considered on an individual decision-
153
making basis while understanding that minimally invasive treatments such as cryotherapy or radiofrequency do have a limited efficacy in larger tumours. Our study has some limitations. First, due to its retrospective character some information is obviously missing for an accurate reporting of complications. Thus, we were not able to present complications according to recognized grading scales. Particularly, we were not able to distinguish between minor and major complications. A second limitation is that our study was based on a multicentre experience during an extended period of time. Various surgical techniques may have been used according to centre and surgeon preferences. It is also likely that appreciation of complications may have differed among periods and centres. Surgeon and centre volume may have also affected NSS-related morbidity. This obviously was not uniform in our study and we were not able to take this variable into account. Finally, as suggested previously, an increasing experience with time has probably translated into a decreased complication rate even in the most complicated cases. This was not analysed in the present study. Nevertheless, we believe that our series reflects ‘‘the real life’’ experience and that as such it provides a useful message for the general community of urologists.
5.
Conclusions
When reporting about NSS results, absolute and elective indications should be clearly separated. Otherwise, excellent cancer control and outcomes can be achieved with elective NSS in carefully selected patients presenting with tumours >4 cm. Expanding size indications of NSS results in an increased but acceptable morbidity. However, it is important to counsel patients regarding these additional risks when deciding on a radical versus partial approach, especially in elderly patients or in those with significant comorbidities.
Conflicts of interest The authors have nothing to disclose. References [1] Lam JS, Shvarts O, Pantuck AJ. Changing concepts in the surgical management of renal cell carcinoma. Eur Urol 2004;45:692–705.
154
european urology 52 (2007) 148–154
[2] Patard J-J, Tazi H, Bensalah K, et al. The changing evolution of renal tumours: a single center experience over a twodecade period. Eur Urol 2004;45:490–3, discussion 493–4. [3] Belldegrun A, Tsui KH, deKernion JB, Smith RB. Efficacy of nephron-sparing surgery for renal cell carcinoma: analysis based on the new 1997 tumor-node-metastasis staging system. J Clin Oncol 1999;17:2868–75. [4] Lerner SE, Hawkins CA, Blute ML, et al. Disease outcome in patients with low stage renal cell carcinoma treated with nephron sparing or radical surgery. J Urol 1996;155:1868– 73. [5] Hafez KS, Fergany AF, Novick AC. Nephron sparing surgery for localized renal cell carcinoma: impact of tumor size on patient survival, tumor recurrence and TNM staging. J Urol 1999;162:1930–3. [6] Leibovich BC, Blute ML, Cheville JC, Lohse CM, Weaver AL, Zincke H. Nephron sparing surgery for appropriately selected renal cell carcinoma between 4 and 7 cm results in outcome similar to radical nephrectomy. J Urol 2004;171:1066–70. [7] Patard JJ, Shvarts O, Lam JS, et al. Safety and efficacy of partial nephrectomy for all T1 tumors based on an international multicenter experience. J Urol 2004;171:2181–5. [8] Ghavamian R, Cheville JC, Lohse CM, Weaver AL, Zincke H, Blute ML. Renal cell carcinoma in the solitary kidney: an analysis of complications and outcome after nephron sparing surgery. J Urol 2002;168:454–9. [9] Sobin LH, Wittekind C. TNM Classification of Malignant Tumors. UICC International Union Against Cancer. ed. 6 New York: Wiley-Liss; 2003. p. 193–5. [10] Kovacs G, Akhtar M, Beckwith BJ, et al. The Heidelberg classification of renal cell tumours. J Pathol 1997;183:131–3. [11] Fuhrman SA, Lasky LC, Limas C. Prognostic significance of morphologic parameters in renal cell carcinoma. Am J Surg Pathol 1982;6:655–63. [12] Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 1982;5:649–55. [13] Wolters U, Wolf T, Stutzer H, Schroder T. ASA classification and perioperative variables as predictors of postoperative outcome. Br J Anaesth 1996;77:217–22. [14] Becker F, Siemer S, Hack M, Humke U, Ziegler M, Stockle M. Excellent long-term cancer control with elective nephron-sparing surgery for selected renal cell carcinomas measuring more than 4 cm. Eur Urol 2006;49:1058–64.
[15] Carini M, Minervini A, Lapini A, Masieri L, Serni S. Simple enucleation for the treatment of renal cell carcinoma between 4 and 7 cm in greatest dimension: progression and long-term survival. J Urol 2006;175:2022–6, discussion 2026. [16] Dash A, Vickers AJ, Schachter LR, Bach AM, Snyder ME, Russo P. Comparison of outcomes in elective partial vs radical nephrectomy for clear cell renal cell carcinoma of 4–7 cm. BJU Int 2006;97:939–45. [17] Mitchell RE, Gilbert SM, Murphy AM, Olsson CA, Benson MC, McKiernan JM. Partial nephrectomy and radical nephrectomy offer similar cancer outcomes in renal cortical tumors 4 cm or larger. Urology 2006;67:260–4. [18] Fergany AF, Saad IR, Woo L, Novick AC. Open partial nephrectomy for tumor in a solitary kidney: experience with 400 cases. J Urol 2006;175:1630–3, discussion 1633. [19] Pasticier G, Timsit M-O, 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. [20] 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. [21] Wille AH, Roigas J, Deger S, Tu¨llmann M, Tu¨rk I, Loening SA. Laparoscopic radical nephrectomy: techniques, results and oncological outcome in 125 consecutive cases. Eur Urol 2004;45:483–8, discussion 488–9. [22] Janetschek G, Jeschke K, Peschel R, Strohmeyer D, Henning K, Bartsch G. Laparoscopic surgery for stage T1 renal cell carcinoma: radical nephrectomy and wedge resection. Eur Urol 2000;38:131–8. [23] Gill IS, Matin SF, Desai MM, et al. Comparative analysis of laparoscopic versus open partial nephrectomy for renal tumors in 200 patients. J Urol 2003;170:64–8. [24] Thompson RH, Leibovich BC, Lohse CM, Zincke H, Blute ML. Complications of contemporary open nephron sparing surgery: a single institution experience. J Urol 2005;174: 855–8. [25] Uzzo RG, Novick AC. Nephron sparing surgery for renal tumors: indications, techniques and outcomes. J Urol 2001;166:6–18. [26] Stephenson AJ, Hakimi AA, Snyder ME, Russo P. Complications of radical and partial nephrectomy in a large contemporary cohort. J Urol 2004;171:130–4.
available at www.sciencedirect.com journal homepage: www.europeanurology.com
Kidney Cancer
Morbidity and Clinical Outcome of Nephron-Sparing Surgery in Relation to Tumour Size and Indication Jean-Jacques Patard a,*, Allan J. Pantuck b, Maxime Crepel a, John S. Lam b, Laurent Bellec c, Baptiste Albouy d, David Lopes e, Jean-Christophe Bernhard f, Franc¸ois Guille´ a, Bertrand Lacroix g, Alexandre De La Taille e, Laurent Salomon e, Christian Pfister d, Michel Soulie´ c, Jacques Tostain g, Jean-Marie Ferriere f, Claude C. Abbou e, Marc Colombel h, Arie S. Belldegrun b a
Department of Urology, Rennes University Hospital, Rennes, France Department of Urology, University of California Los Angeles, Los Angeles, CA c Department of Urology, University of Toulouse, Toulouse, France d Department of Urology, University of Rouen, Rouen, France e Department of Urology, CHU Henri Mondor, Creteil, Creteil, France f Department of Urology, University of Bordeaux, Bordeaux, France g Department of Urology, University of Saint Etienne, Saint Etienne, France h Departement of Urology, University of Lyon, Lyon, France b
Article info
Abstract
Article history: Accepted January 9, 2007 Published online ahead of print on January 16, 2007
Objective: To analyse through a large multicentre series, morbidity of nephron-sparing surgery (NSS) in relation to tumour size and surgical indication. Methods: The study included patients from eight international academic centres. Age, sex, TNM stage, tumour size, Fuhrman grade, Eastern Cooperative Oncology Group performance status (ECOG-PS), surgical margins, local and distant recurrences, and overall and cancerspecific survival rates were collected and analysed. Indication for elective or mandatory NSS, medical and surgical complication rates, mean blood loss, blood transfusion, and length of hospital stay were specifically recorded for the purpose of this study. Groups were compared for qualitative and quantitative variables by using x2 (Fischer exact test) and Student t tests, respectively. Results: A total of 1048 NSS procedures were included in this study. Mean tumour size was 3.4 2.1 cm. In 730 elective procedures mean operative time ( p = 0.002), mean blood loss ( p = 0.01), the need for blood transfusion ( p = 0.001), and urinary fistula rate ( p = 0.01) were significantly increased for tumours >4 cm. However, these differences did not result in significantly increased medical ( p = 0.4), surgical complication rates ( p = 0.6), or length of hospital stay ( p = 0.9). Finally, in elective procedures for malignant tumours, positive surgical margins, local or distant recurrence rates, and cancer-specific survival were not significantly different in tumours 4 cm and >4 cm. Conclusion: Excellent cancer control and outcomes can be achieved with NSS in carefully selected patients with tumours >4 cm. Expanding the size indication of elective NSS results in an increased but acceptable morbidity.
Keywords: Carcinoma Morbidity Nephrectomy Renal cell
Please visit www.eu-acme.org/ europeanurology to read and answer questions on-line. The EU-ACME credits will then be attributed automatically.
# 2007 European Association of Urology. Published by Elsevier B.V. All rights reserved. * Corresponding author. Rennes University Hospital, Rennes, France. Tel. +33 2 99 28 42 70; Fax: +33 2 99 28 41 13. E-mail address: [email protected] (J.-J. Patard).
0302-2838/$ – see back matter # 2007 European Association of Urology. Published by Elsevier B.V. All rights reserved.
doi:10.1016/j.eururo.2007.01.039
european urology 52 (2007) 148–154
1.
Introduction
The use of partial nephrectomy has historically been limited to patients who would be rendered anephric following radical nephrectomy. Such patients include those with a solitary functioning kidney, bilateral renal cell carcinoma (RCC), or unilateral RCC with some compromise of the contralateral kidney [1]. Due to the increased use of routine body imaging, a greater number of small renal lesions are now being discovered, and elective partial nephrectomy has been adopted more frequently for the treatment of such tumours [2]. It has been extensively demonstrated that for tumours <4 cm in size, partial nephrectomy provides excellent survival and recurrence rates comparable to those achieved with radical nephrectomy [3–5]. However, other studies have demonstrated significantly better survival in patients undergoing partial nephrectomy for tumours 4 cm compared to those with tumours >4 cm in size [4,5]. As a result, 4 cm has served as a commonly accepted cut-off size for renal neoplasms that can be treated by elective partial nephrectomy. Recently, two studies have shown equivalent cancer control when comparing radical nephrectomy and partial nephrectomy in T1b tumours, thus suggesting that it may be safe to increase the indications of nephron-sparing surgery (NSS) from 4 to 7 cm [6,7]. Even though NSS has an acceptable morbidity in experienced hands even in patients with solitary kidneys [8], partial procedures are technically more challenging in large tumours and it may be a concern that broadening the indications may result in increased morbidity. Therefore, the primary objective of our study was to analyse through a large multicentre series the morbidity of NSS in relation to both tumour size and surgical indication. 2.
Methods
2.1.
Data collection
The study included patients from eight academic centres: Rennes, Saint Etienne, Cre´teil, Bordeaux, Lyon, Toulouse, and Rouen in France, and the University of California at Los Angeles (UCLA) in the United States. Partial nephrectomy accounted for at least 30% of the surgical management for renal tumours at each institution. Patient records were extracted from each institutional database to obtain data regarding age, sex, TNM stage, tumour size, Fuhrman grade, Eastern Cooperative Oncology Group performance status (ECOG-PS), symptoms at diagnosis, tumour histology, and overall and cancer-specific survival. Specific data collected for the purpose of this study included American Society of Anesthesiologists (ASA) score, medical and surgical complication rates, mean blood loss, the need for renal vessel clamping,
149
collecting system repair, blood transfusion, and length of hospital stay. Additionally, preoperative and postoperative serum creatinine levels as well as information regarding surgical margins and local and distant recurrence rates were also noted when available. Years of treatment ranged from 1984 to 2005. NSS was defined as elective when the contralateral kidney was anatomically normal with overall normal renal function. NSS was considered imperative in cases of solitary kidney, atrophic contralateral kidney, bilateral tumour, or compromised renal function with risk of end-stage renal disease in case of total nephrectomy. Tumour stage was determined according to the 2002 Union Internationale Contre le Cancer (UICC) revised TNM classification [9]. Tumour histology for malignant tumours was classified according to the Heidelberg classification and tumours were graded according to the Fuhrman grading scheme by pathologists at each of the eight institutions [10,11]. ECOG-PS was determined according to the original criteria set forth by Oken et al [12]. ASA score was determined according to the ASA risk score [13].
2.2.
Statistical analysis
Qualitative and quantitative variables were compared by using x2 (Fischer exact test) and Student t tests, respectively. All p values were two sided and a p < 0.05 was considered significant. All data analysis was processed through the SPSS 12.0 statistical software (Chicago, IL).
3.
Results
3.1.
Patients and tumours
A total of 1048 NSS procedures performed at eight academic institutions were included in this retrospective study. Patients included 694 men (66.2%) and 354 women (33.8%). Mean age at diagnosis was 59.1 12.9 yr and mean tumour size was 3.4 2.1 cm. Most tumours were discovered incidentally (76%) and were malignant at histology (80.1%). Poor ECOG-PS (1) was noted in only 16.8% of the cases. NSS was performed for a mandatory indication in 318 cases (30.3%) including 145 solitary kidneys cases (13.8%). The number of procedures from each institution was 104(9.9%), 79 (7.5%), 195 (18.6%), 53(5.1%), 59 (5.6%), 74 (7.1%), 127 (12.1%), and 357 (34.1%) from Rennes, Cre´teil, Bordeaux, Saint Etienne, Toulouse, Rouen, Lyon (France), and UCLA (United States), respectively. Main tumour characteristics regarding TNM stage, nuclear grade, and histology are described in Table 1. 3.2.
Procedures and morbidity
Mean operative time for the entire cohort was 155 59 min. Renal vessels were clamped in 61.8%
150
european urology 52 (2007) 148–154
Table 1 – Patient and tumour characteristics in 1048 partial nephrectomies including 839 procedures for malignant tumours Mean age, yr (SD) Sex, male (%) Mean tumour size, cm (SD) Tumour size 4 cm Incidental tumours (n = 724) ASA score 3 (n = 698) ECOG 1 (n = 567) Benign tumours Elective procedures Solitary kidney History of bilateral tumours No. of tumours >1 (n = 1007)
59.1 12.9 694 (66.2%) 3.4 2.1 801 (76.4%) 550 (76%) 212 (30.4%) 95 (16.8%) 209 (19.9%) 730 (69.7%) 145 (13.8%) 214 (20.4%) 140 (13.9%)
Histologic subtype in malignant tumours (n = 807) Clear cell carcinomas Papillary carcinomas Chromophobe carcinomas
590 (73.1%) 168 (20.8%) 49 (6.1%)
T stage in malignant tumours T1 T2 T3
743 (88.6%) 28 (3.3%) 68 (8.1%)
N stage 1 M stage: 1 Fuhrman grade in malignant tumours (n = 817) G1 G2 G3 G4
12 (1.4%) 31 (3.7%)
190 458 161 8
(23.3%) (56.1%) (19.6%) (1%)
ASA = American Society of Anesthesiologists; ECOG = Eastern Cooperative Oncology Group.
of the cases for a mean duration of 20.1 10.9 min. Overall, medical and surgical complications occurred in 131(12.5%) and 133(12.7%) cases, respectively. Urinary fistula was noted in 32 cases (3.1%). Blood transfusion rate was 15.3% and median blood loss was 350 ml (range: 0–4000 ml). Mean hospital stay was 8.3 6.2 d.
Table 2 shows that NSS performed for tumours 4 cm or >4 cm were significantly different for age ( p = 0.03), symptoms at presentation ( p = 0.0001), Fuhrman grade ( p = 0.002), and preoperative serum creatinine ( p = 0.01) reflecting a higher proportion of absolute indications (57.4%) and solitary kidneys (21.1%) in the group with larger tumours. Then, we focused on morbidity in elective indications. A total of 730 elective NSS procedures were analyzed, including 130 for tumours >4 cm. Detailed results are described in Table 3. Mean operative time ( p = 0.002), mean blood loss ( p = 0.01), the need for collecting system repair, blood transfusion ( p = 0.001), and urinary fistula rate ( p = 0.01) were significantly increased in patients with tumours >4 cm. However, these differences did not result in significantly increased medical ( p = 0.4) or surgical complication rates ( p = 0.6) or length of hospital stay ( p = 0.9). As expected, differences in term of morbidity were even more pronounced when comparing elective and mandatory procedures. Table 4 describes the details of this comparison. The two groups exhibited significantly different comorbidities and performance status as measured by ASA score ( p = 0.0001) and ECOG-PS ( p = 0.008). Additionally, mean operative time, mean blood loss, the need for blood transfusion, medical complication rate, and length of hospital stay were dramatically increased in the mandatory group ( p = 0.0001). Similarly, the risk for surgical complications ( p = 0.02), including urinary fistulas ( p = 0.03), was significantly increased in the mandatory group. 3.3.
Oncologic results
Finally, we compared in elective procedures oncologic results according to tumour size. Of the 730 elective procedures, 550 were performed for
Table 2 – Comparison of 1048 nephron-sparing surgical procedures for patient and tumour characteristics according to tumour size Variables No. of patients Mean age, yr SD Sex, male ASA 3 (n = 698) ECOG 1 (n = 567) Benign tumours Symptoms (n = 724) Fuhrman grade, G 3 (n = 817) Elective surgery Solitary kidney Mean preoperative serum creatinine, mM/l (n = 794)
Tumours 4 cm
Tumours >4 cm
801 59.5 12.7 538 (67.2%) 159 (29.2%) 63 (15%) 151 (18.9%) 110 (19.4%) 117 (18.4%) 600 (74.9%) 93 (11.6%) 100.2 46.2
247 57.6 13.5 156 (63.2%) 53 (34.6%) 32 (21.6%) 58 (23.5%) 64 (41%) 52 (28.7%) 130 (52.6%) 52 (21.1%) 110.1 49.8
ASA = American Society of Anesthesiologists; ECOG = Eastern Cooperative Oncology Group.
p 0.03 0.2 0.2 0.06 0.11 0.0001 0.002 0.0001 0.0001 0.01
151
european urology 52 (2007) 148–154
Table 3 – Comparison of operative characteristics and morbidity in 730 elective nephron-sparing surgical procedures Tumours 4 cm
Tumours >4 cm
600 146.8 49.4 205 (60.3%) 19.3 10.9 133 (39.2%) 386.0 369.0 65 (10.8%) 52 (8.7%) 36 (6.3%) 10 (1.7%) 7.7 6.0 103.0 52.1
130 165.4 61.4 40 (63.5%) 17.4 6.4 39 (62.9%) 510.5 502.7 16 (12.3%) 14 (10.8%) 19 (14.8%) 7 (5.4%) 7.6 6.3 109.8 71.4
No. of patients Mean operative time, min SD (n = 572) Clamping of renal vessels (n = 403) Mean warm ischaemic time, min (n = 240) Collecting system repair (n = 401) Mean blood loss, ml SD (n = 411) Surgical complications Medical complications Blood transfusion (n = 704) Urinary fistula Mean hospital stay, d SD, (n = 706) Mean postoperative serum creatinine, mM/l (n = 538)
p 0.002 0.6 0.2 0.001 0.01 0.6 0.4 0.001 0.01 0.9 0.3
Table 4 – Comparison of 1048 nephron-sparing surgical procedures for patient and tumour characteristics and morbidity according to the indication Elective indication
Nonelective indication
730 58.3 12.9 3.2 1.8 54 (13.9%) 121 (24.4%) 149.7 51.8 413.3 404.7 55 (7.8%) 81 (11.1%) 17 (2.3%) 66 (9.4%) 7.6 6.0 104.1 55.6
318 60.8 12.9 4.0 2.6 41 (22.9%) 91 (44.8%) 172.9 59.9 703.0 622.3 100 (32.7%) 52 (16.4%) 15 (4.7%) 65 (20.4%) 9.8 6.3 156.6 87.9
No. of patients Mean age, yr SD Mean tumour size, cm SD ECOG 1 (n = 567) ASA score 3 (n = 698) Mean operative time, min SD (n = 821) Mean blood loss, ml SD (n = 587) Blood transfusion (n = 1010) Surgical complications Urinary fistula Medical complications Mean hospital stay, d SD (n = 1009) Mean postoperative serum creatinine, mM/l, SD (n = 788)
p 0.004 0.0001 0.008 0.0001 0.0001 0.0001 0.0001 0.02 0.03 0.0001 0.0001 0.0001
ASA = American Society of Anesthesiologists; ECOG = Eastern Cooperative Oncology Group.
malignant tumours. Median follow-up for this group was 36 mo (range: 1–120 mo). In this subset, positive surgical margins, local or distant recurrences, overall or cancer-specific deaths as well as depth of surgical margins were not significantly different in tumours 4 cm and >4 cm. Detailed results are given in Table 5. Finally, when comparing cancerspecific survival curves in the elective subset no significant difference was found according to the 4-cm tumour size cut-off (log rank test, p = 0.8; Fig. 1).
4.
Discussion
Open NSS is considered to be the standard of care for small renal tumours. Currently, 4 cm is considered as a commonly accepted cut-off size for delineating the indications between NSS and radical nephrectomy. The 4 cm cut-off level was determined based on the knowledge that there was an increased risk for recurrence and progression beyond this arbitrary limit [4,5]. However, it has been shown recently from several independent
Table 5 – Comparison of 550 elective nephron-sparing surgical procedures for oncologic results according to tumour size
Positive margins (n = 542) Margin size, mm SD (n = 148) Local recurrence (n = 520) Distant recurrence (n = 506) Deaths (n = 500) Cancer-related deaths (n = 498)
Tumours 4 cm
Tumours >4 cm
7 (1.5%) 4.2 3.7 4 (0.9%) 7 (1.6%) 20 (4.7%) 9 (2.1%)
1 (1.3%) 5.3 4.9 1 (1.3%) 3 (3.9%) 7 (9.3%) 2 (2.7%)
p 0.9 0.2 0.7 0.2 0.1 0.8
152
european urology 52 (2007) 148–154
Fig. 1 – Cancer-specific survival according to tumor size in 550 elective nephron-sparing surgical procedures.
large series that the risk for dying from cancer beyond a 4 cm tumour size cut-off was increased both for radical and NSS. Subsequently, it was suggested that it was the inherent tumor biology rather than the surgical approach that dictated outcomes and that the tumour size limit of NSS could be expanded from 4 to 7 cm [6,7]. More recently, additional studies have challenged the validity of the 4-cm cut-off, confirming that it is safe for cancer control to expand the indications of NSS [14–17]. Although we previously reported that NSS and radical nephrectomy achieved comparable results for all T1 tumours [7], it is obvious that absolute indication represents an heterogeneous and nonselected group potentially containing poor prognostic tumours. Therefore, the additional strength of the present study was the ability to separate elective from absolute indications. Our data clearly suggest that in the highly selected population of elective NSS, surgical margins, local recurrences, and cancerrelated death rates are not affected by tumour size. Another important finding of the present study was that NSS for absolute indications carries significantly increased morbidity. Indeed, ‘‘imperative’’ tumours are different from the electives, being greater in size and occurring in patients with poorer performance status along with increased comorbidities. In this subset, intraoperative bleeding as well as urinary fistula rates were almost doubled. The need for blood transfusion was four times more frequent for absolute than it was for elective indications. This is consistent with the results of two large studies reporting the outcomes of NSS for
absolute indications. Fergany et al in 400 patients with unique kidney found a 9% urinary fistula rate [18]. Similarly, Ghavamian et al in the same setting reported 23.8% and 27% early and late complication rates, respectively [8]. This is consistent with our 16.4% and 20.4% surgical and medical complication rates. Similarly, Pasticier et al identified a 49.1% overall complication rate in the imperative compared to 17.6% in the elective setting [19]. Although the requirement for temporary dialysis was not recorded in our study, it is likely that it occurred more frequently for patients having a greater propensity for impaired renal function before surgery. Logically, it translated into a significantly increased postoperative serum creatinine levels in this subset. Finally, Ghavamian et al reported a 10.8% recurrence rate and an 80.7% 5-yr cancerspecific survival rate in his unique kidney series. These poor results are unusual in comparison to the elective setting. This, in addition to the increased morbidity that was previously reported, definitively supports the need to distinguish absolute from elective indications when reporting about cancer control and morbidity outcomes after using NSS techniques. In this study we also confirmed that elective NSS for small renal tumours is associated with minimal morbidity. By analyzing 600 tumours measuring <4 cm with both normal contralateral kidney and renal function, we found a 386 ml mean blood loss, along with 10.8% and 8.7% medical and surgical complications rates, respectively. Urinary fistula occurred in only 1.7% of the cases. Although these data ares not surprising, it is an important message to remind all urologists dealing with renal tumours, because it has been recently demonstrated that NSS still does not have the place that it deserves compared to radical nephrectomy even in patients with small tumours [20]. Although there is an increased morbidity in NSS performed for absolute indications, it must be acknowledged that alternative therapeutic choices are very limited in such cases. Conversely, it is not the case for patients with T1b renal tumours with a normal contralateral kidney because laparoscopic radical nephrectomy is, in such cases, an effective therapeutic approach with low morbidity [21,22]. Therefore, it may be a concern that expanding the indications of NSS could translate into an increased morbidity unfavourably comparing with other treatments. Previous studies have focused on NSS morbidity in relation to surgical technique [23] or to surgical period [24]. However, to our knowledge this is the first large study examining the relationship between tumour size and NSS morbidity. In this
european urology 52 (2007) 148–154
study, we could demonstrate that intraoperative and perioperative NSS morbidity as measured by blood loss, urinary fistula rate, and need for blood transfusion was significantly increased in tumours >4 cm in size. However, it is worth noting that our overall medical and surgical complication rates, as well as the length of hospital stay, were not significantly different when comparing patients with small and larger tumors. Moreover, the 12.3% and 10.8% surgical and medical complication rates, respectively, as well as the 5.4% urinary fistula rate that we reported in tumours measuring >4 cm are in the range of what is published overall for NSS. Uzzo et al in a review compiling 1129 patients reported a mean 13.7% major surgical complication rate (4–30%) along with a mean 7.4% urinary fistula rate [25]. Similarly, Stephenson et al in a large contemporary study reported an overall 19% complication rate for NSS [26]. Finally, Thompson et al recently reported about complications of NSS in relation to the period of surgery [24]. In addition to an overall complication rate, which decreased with time, the authors reported a mean intraoperative blood loss of 483 ml for recently operated patients. This result is comparable to the mean intraoperative blood loss of 510 ml that we mentioned for tumours measuring >4 cm. Interestingly, it also appeared that operating on larger tumors by NSS did not result in either the increased need to clamp the renal vessels or in prolonged warm ischaemic times, probably due to experienced case selection. Therefore, it can be assumed that elective NSS in well-selected cases of T1b tumors, by avoiding prolonged warm ischaemic times, is also able to achieve good preservation of renal function. Finally, it appears that although slightly increased in patients with larger tumours undergoing NSS, morbidity remains acceptable and not significantly different from that reported for overall morbidity in large contemporary series. Even though we have demonstrated that expanding elective NSS indications to larger tumours is associated with acceptable morbidity, it is obvious that some NSS-related complications could be particularly deleterious in elderly patients or in those presenting with significant comorbidities. In such patients, particularly when the tumour is deeply located in the renal parenchyma or close to the renal vessels, it is clear that laparoscopic radical nephrectomy may be considered as a preferable option. On the other hand, elderly patients, with comorbidities such as diabetes or hypertension, are at increased risk of altered renal function. Therefore, conservative surgery in such challenging cases should be considered on an individual decision-
153
making basis while understanding that minimally invasive treatments such as cryotherapy or radiofrequency do have a limited efficacy in larger tumours. Our study has some limitations. First, due to its retrospective character some information is obviously missing for an accurate reporting of complications. Thus, we were not able to present complications according to recognized grading scales. Particularly, we were not able to distinguish between minor and major complications. A second limitation is that our study was based on a multicentre experience during an extended period of time. Various surgical techniques may have been used according to centre and surgeon preferences. It is also likely that appreciation of complications may have differed among periods and centres. Surgeon and centre volume may have also affected NSS-related morbidity. This obviously was not uniform in our study and we were not able to take this variable into account. Finally, as suggested previously, an increasing experience with time has probably translated into a decreased complication rate even in the most complicated cases. This was not analysed in the present study. Nevertheless, we believe that our series reflects ‘‘the real life’’ experience and that as such it provides a useful message for the general community of urologists.
5.
Conclusions
When reporting about NSS results, absolute and elective indications should be clearly separated. Otherwise, excellent cancer control and outcomes can be achieved with elective NSS in carefully selected patients presenting with tumours >4 cm. Expanding size indications of NSS results in an increased but acceptable morbidity. However, it is important to counsel patients regarding these additional risks when deciding on a radical versus partial approach, especially in elderly patients or in those with significant comorbidities.
Conflicts of interest The authors have nothing to disclose. References [1] Lam JS, Shvarts O, Pantuck AJ. Changing concepts in the surgical management of renal cell carcinoma. Eur Urol 2004;45:692–705.
154
european urology 52 (2007) 148–154
[2] Patard J-J, Tazi H, Bensalah K, et al. The changing evolution of renal tumours: a single center experience over a twodecade period. Eur Urol 2004;45:490–3, discussion 493–4. [3] Belldegrun A, Tsui KH, deKernion JB, Smith RB. Efficacy of nephron-sparing surgery for renal cell carcinoma: analysis based on the new 1997 tumor-node-metastasis staging system. J Clin Oncol 1999;17:2868–75. [4] Lerner SE, Hawkins CA, Blute ML, et al. Disease outcome in patients with low stage renal cell carcinoma treated with nephron sparing or radical surgery. J Urol 1996;155:1868– 73. [5] Hafez KS, Fergany AF, Novick AC. Nephron sparing surgery for localized renal cell carcinoma: impact of tumor size on patient survival, tumor recurrence and TNM staging. J Urol 1999;162:1930–3. [6] Leibovich BC, Blute ML, Cheville JC, Lohse CM, Weaver AL, Zincke H. Nephron sparing surgery for appropriately selected renal cell carcinoma between 4 and 7 cm results in outcome similar to radical nephrectomy. J Urol 2004;171:1066–70. [7] Patard JJ, Shvarts O, Lam JS, et al. Safety and efficacy of partial nephrectomy for all T1 tumors based on an international multicenter experience. J Urol 2004;171:2181–5. [8] Ghavamian R, Cheville JC, Lohse CM, Weaver AL, Zincke H, Blute ML. Renal cell carcinoma in the solitary kidney: an analysis of complications and outcome after nephron sparing surgery. J Urol 2002;168:454–9. [9] Sobin LH, Wittekind C. TNM Classification of Malignant Tumors. UICC International Union Against Cancer. ed. 6 New York: Wiley-Liss; 2003. p. 193–5. [10] Kovacs G, Akhtar M, Beckwith BJ, et al. The Heidelberg classification of renal cell tumours. J Pathol 1997;183:131–3. [11] Fuhrman SA, Lasky LC, Limas C. Prognostic significance of morphologic parameters in renal cell carcinoma. Am J Surg Pathol 1982;6:655–63. [12] Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 1982;5:649–55. [13] Wolters U, Wolf T, Stutzer H, Schroder T. ASA classification and perioperative variables as predictors of postoperative outcome. Br J Anaesth 1996;77:217–22. [14] Becker F, Siemer S, Hack M, Humke U, Ziegler M, Stockle M. Excellent long-term cancer control with elective nephron-sparing surgery for selected renal cell carcinomas measuring more than 4 cm. Eur Urol 2006;49:1058–64.
[15] Carini M, Minervini A, Lapini A, Masieri L, Serni S. Simple enucleation for the treatment of renal cell carcinoma between 4 and 7 cm in greatest dimension: progression and long-term survival. J Urol 2006;175:2022–6, discussion 2026. [16] Dash A, Vickers AJ, Schachter LR, Bach AM, Snyder ME, Russo P. Comparison of outcomes in elective partial vs radical nephrectomy for clear cell renal cell carcinoma of 4–7 cm. BJU Int 2006;97:939–45. [17] Mitchell RE, Gilbert SM, Murphy AM, Olsson CA, Benson MC, McKiernan JM. Partial nephrectomy and radical nephrectomy offer similar cancer outcomes in renal cortical tumors 4 cm or larger. Urology 2006;67:260–4. [18] Fergany AF, Saad IR, Woo L, Novick AC. Open partial nephrectomy for tumor in a solitary kidney: experience with 400 cases. J Urol 2006;175:1630–3, discussion 1633. [19] Pasticier G, Timsit M-O, 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. [20] 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. [21] Wille AH, Roigas J, Deger S, Tu¨llmann M, Tu¨rk I, Loening SA. Laparoscopic radical nephrectomy: techniques, results and oncological outcome in 125 consecutive cases. Eur Urol 2004;45:483–8, discussion 488–9. [22] Janetschek G, Jeschke K, Peschel R, Strohmeyer D, Henning K, Bartsch G. Laparoscopic surgery for stage T1 renal cell carcinoma: radical nephrectomy and wedge resection. Eur Urol 2000;38:131–8. [23] Gill IS, Matin SF, Desai MM, et al. Comparative analysis of laparoscopic versus open partial nephrectomy for renal tumors in 200 patients. J Urol 2003;170:64–8. [24] Thompson RH, Leibovich BC, Lohse CM, Zincke H, Blute ML. Complications of contemporary open nephron sparing surgery: a single institution experience. J Urol 2005;174: 855–8. [25] Uzzo RG, Novick AC. Nephron sparing surgery for renal tumors: indications, techniques and outcomes. J Urol 2001;166:6–18. [26] Stephenson AJ, Hakimi AA, Snyder ME, Russo P. Complications of radical and partial nephrectomy in a large contemporary cohort. J Urol 2004;171:130–4.