Nephron-Sparing Surgery for Renal Cell Carcinoma: State of the Art and 10 Years of Multicentric Experience

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1 european urology supplements 5 (2006) available at journal homepage: Nephron-Sparing Surgery for Renal Cell Carcinoma: State of the Art and 10 Years of Multicentric Experience Giuseppe Martorana a, *, Alessandro Bertaccini a, Sergio Concetti a, Alessandro Franceschelli a, Riccardo Schiavina a, Enrico Severini a, Francesco Sanguedolce a, Claudio Giberti b, Emanuele Belgrano c, Giorgio Carmignani d a Department of Urology, University of Bologna, Bologna, Italy b Department of Urology, San Paolo Hospital, Savona, Italy c Department of Urology, University of Trieste, Trieste, Italy d Luciano Giuliani Department of Urology, University of Genoa, Genoa, Italy Article info Keywords: Kidney Minimally invasive Nephron-sparing surgery Renal cell carcinoma Survival rate Abstract Objectives: The natural history of renal cell carcinoma (RCC) has changed dramatically in the last two decades. The rising incidence of small renal lesions and advances in surgical techniques have led urologists to perform nephron-sparing surgery (NSS) more frequently and also to extend its indication to elective conditions. We review the state of the art of NSS for RCC and report a multicentric experience at four Italian urologic departments. Methods: We used the Medline database to collect relevant reports on NSS. We critically reviewed and evaluated the data of patients who underwent open partial nephrectomy between 1994 and 2004 at four Italian urologic centres, namely, Genoa, Bologna, Trieste, and Savona. A final cohort of 360 patients, with a mean follow-up of 55.3 mo who underwent NSS mainly for elective conditions (72.1%), was statistically evaluated. Results: NSS is a successful treatment for patients with localised RCC for both elective and imperative conditions, providing the same excellent long-term results as radical surgery in selected patients. The surgical complications of NSS have continued to decline in the last three decades. In our population, the 5- and 10-yr cancer-specific survival rates were 96.6% and 86.9%, respectively. Conclusions: Open conservative surgery represents a safe and effective treatment for small renal tumours. New minimally invasive nephronsparing techniques are currently being developed and will certainly evolve in the near future. # 2006 European Association of Urology. Published by Elsevier B.V. All rights reserved. * Corresponding author. Department of Urology, Policlinico S.Orsola Malpighi, Via Palagi 9, 40138, Bologna, Italy. Tel ; Fax: address: giuseppe.martorana@unibo.it (G. Martorana) /$ see front matter # 2006 European Association of Urology. Published by Elsevier B.V. All rights reserved. doi: /j.eursup

2 european urology supplements 5 (2006) Introduction In the past two decades significant changes have occurred in the natural history of renal cell carcinoma (RCC) because of advances in the knowledge of tumour biology, progress in surgical techniques and stage migration due to early detection [1]. However, in the absence of an effective medical therapy, only surgical resection can achieve longterm results [2,3] and remains the standard treatment for RCC. Nephron-sparing surgery (NSS) was originally developed in Europe to treat RCC in a solitary functioning kidney but has also been demonstrated to be an effective alternative to radical nephrectomy (RN) even in the presence of a normal opposite kidney [4 6]. In the present paper we review the state of the art of NSS for RCC and report a multicentric experience at four Italian urologic departments. 2. Indications for NSS The indications for NSS have changed significantly over time; in fact, with the widespread use of crosssectional imaging, the majority of renal tumours today are diagnosed incidentally and have a diameter of 3 5 cm [7 9]. Even in the absence of controlled randomised trials that compare NSS and RN, NSS has become increasingly accepted and today patients with single, small (<4 cm), clearly localised RCC and normal contralateral kidney represent the optimal candidates. In these patients, long-term retrospective results showed that RN and NSS are equally effective curative treatments [10]; however, NSS can be considered more appropriate because it may prevent potential hyperfiltration injury to the opposite kidney [11,12] or it may simplify the management of metachronous RCC. Thus, NSS is generally accepted for T1a patients (TNM 2002) [13]. In recent years, some authors have shown that NSS is equivalent to RN for tumours of 4 7 cm and proposed the extension of the indications for NSS to include all T1 stage lesions [14 16]; however, there is still few long-term data and this indication remains controversial at the moment. Furthermore, NSS for larger masses can be technically challenging and should only be performed by surgeons with extensive experience. Recently, Ficarra et al. [17] observed that, apart from tumour size, the presence of symptoms was an independent prognostic factor; they stated that the stratification of patients with localized RCC 5.5 cm into two subgroups, according to the absence or presence of symptoms, might allow the staging system to better identify patients suitable for elective NSS and proposed to integrate this variable into the TNM system. When renal function is under potential future threat (e.g., in case of hereditary cancer diathesis such as von Hippel- Lindau [VHL] disease, hypertension, or diabetes mellitus or when the contralateral kidney is affected by a threatening condition such as chronic pyelonephritis, arterial stenosis, nephrolithiasis, etc), NSS would be recommended. Regardless of tumour size, imperative indications for NSS include relatively rare cases in which RN would render the patient anephric (including synchronous bilateral RCC or a unilateral tumour arising in a solitary functioning kidney). Finally, because many small renal lesions are benign or low grade with risk of malignancy correlated to the size (the incidence of benign lesions is 46.3%, when tumour size is <1 cm in diameter, and 21% for lesions from 1 to 4 cm) [18],in very selected patients, such as elderly ones or those with severe comorbidities, these lesions may be managed expectantly with cross-sectional imaging. 3. Preoperative assessment Before the availability of cross-sectional imaging technique, the diagnosis of RCC at an early stage was rare and >30% of patients presented with large masses and metastatic disease [19]. Since the 1980s, with the widespread use of ultrasonography, the incidence of asymptomatic incidentally detected tumours increased over the years. Currently, the gold standard in detecting and characterising renal masses is computed tomography (CT); with the recent development of multislice helical CT, it is possible to obtain a large number of very thin-section axial CT images in a very short time. Furthermore, with the new sophisticated software, three-dimensional volume-rendered CT images provide a complete, one-step evaluation of tumour stage as well as its precise relationship to the vasculature, collecting system, and adjacent normal parenchyma; in addition, this format is more familiar to the surgeon and consistent with intraoperative findings, thereby obviating the need for mental reconstruction [20]. Magnetic resonance imaging (MRI) provides the same accuracy as CT in the diagnosis and staging of RCC but is generally reserved for patients with compromised renal function or with a history of allergic reaction to contrast media. However, it has

3 602 european urology supplements 5 (2006) been reported that MRI can be more informative in the characterisation of renal complex cysts [21]. 4. Surgical technique of NSS An extraperitoneal approach through flank incision to the 11th and 12th intercostal space is generally preferred for NSS, allowing optimal exposure of the kidney and avoiding peritoneal space. An anterior transperitoneal incision might be necessary in the case of bilateral surgery or in the presence of concomitant abdominal disease; in rare cases, a thoracoabdominal incision can be performed if there are large tumours arising from the upper pole. The Gerota fascia is opened, leaving perirenal fat around the tumour, then the entire surface of the kidney is inspected to detect the presence of secondary tumours [22]. Intraoperative ultrasonography has not been effective in the assessment of tumour multifocality but can increase the surgeon s confidence in guiding parenchymal resection and permit the preservation of as much healthy parenchyma as possible [23]. The vascular hilus is dissected to enable arterial clamping to reduce bleeding; this is often necessary in imperative conditions or with large tumours but, occasionally, it is also prudent during elective surgery. In case of arterial clamping for <30 min, quick hydration and forced diuresis permit decreased intracellular injury derived from the warm ischemia. By contrast, when an arterial occlusion for >30 min is likely, in situ hypothermia, with surface cooling using ice slush, permits the ischemic time to be safely prolonged to approximately 3 h [22]. There are various techniques for carrying out NSS, depending on tumour size, location, and surgical indication. Enucleoresection (tumour enucleation with a rim of healthy parenchyma) is the most common procedure performed for exophytic or partially intraparenchymal tumours; the segmental or partial (superior and inferior) nephrectomy is reserved for large polar tumours, the wedge resection for totally intraparenchymal tumours, and major transverse resection generally for large and centrally located tumours. The extracorporeal bench surgery with autotransplantation is performed in very rare cases of large tumours with complex anatomy [22]. Simple enucleation, defined as enucleation executed using the cleavage plane between the pseudocapsule and normal parenchyma, presents a high risk of positive surgical margins because of the frequent invasion of the pseudocapsule by the tumour, especially for large ones; thus simple enucleation is generally reserved for cases in which maximal preservation of renal parenchyma is necessary (VHL or bilateral multiple low-stage tumours). For this reason, it is accepted worldwide that surgical resection should be performed with a healthy margin of a few millimeters around the tumour [24]. Recently Lapini et al. [25] reported excellent results in 107 patients, with a mean follow-up of 88.3 mo, treated with elective simple enucleation for RCC (mean tumour size, 2.7 cm; range, cm) with 1.9% of local recurrence rate and a progressionfree and cancer-specific survival of 94.7% and 97.8%, respectively; however, the long-term safety of this experience with simple enucleation in RCC should be confirmed in a larger population. 5. Complications of NSS The overall complication rate after NSS ranges between 4% and 30% [14,26 30]. Surgical complications of NSS have continued to decline in the last decade because of better patient selection, operating techniques, perioperative care, and surgical experience. Recently Thompson et al. from the Mayo Clinic [31] reviewed the incidence of complications in their extensive experience of 823 open partial nephrectomies and demonstrated that the overall rate of early and late complications decreased significantly over time. Urinary leakage is one of the most common early complications, occurring in % of patients [14,26,28,29,31]. Most of the urinary fistulas recover spontaneously but, sometimes, can require endoscopic procedures such as ureteric stent placement or percutaneous drainage when urinoma develops. Acute or delayed hemorrhage occurs in about % of patients, as described in different series [14,27,30,31]. Sometimes renal arteriography may be helpful to localise bleeding, which may be controlled via embolisation. When severe bleeding continues, surgical reintervention is indicated. The incidence of acute renal failure is reported in 1.3% up to 12.7% of patients [26,30 32] and is obviously increased in patients with imperative indications for surgery. Renal failure is caused by reduction of functional parenchyma and by intraoperative ischemia. Postoperative renal insufficiency is generally mild and rarely requires dialysis in elective conditions; however, the overall risk of temporary or permanent dialysis is about 3 5% [26,28].

4 european urology supplements 5 (2006) The benefits of renal parenchyma preservation, moreover, include a decreased risk of progression to chronic renal insufficiency [11,12]. 6. Oncologic results of NSS for RCC RN has been considered for many years the only effective surgical treatment for RCC but many authors showed that NSS was a viable option in the management of renal carcinoma in patients with solitary kidney or bilateral tumours [33 35]. The risk of local recurrence of RCC is the most relevant concern regarding NSS. The incidence of local recurrence is widely reported in the literature and it varies from 0% to 10% [10,14,15,29,35 37]. This rate decreases to about 3% in small tumours [14,36]. Local tumour recurrence may be due to incomplete resection of the primary tumour, undetected microscopic multifocal disease, or development of a new focus of RCC. Although local recurrence due to incomplete local resection can be avoided, recurrence due to multicentric disease cannot. The risk of multifocal RCC has been estimated to be as high as 15% [38], but it is much lower among patients with smaller and lower stage tumours who may be candidates for elective NSS. This risk is also influenced by tumour grade and histologic subtype [39]. On the other hand, it is well known that primary nonhereditary RCC has a small but well-recognised risk of bilateral involvement and this may favour a conservative approach [40]. Fergany et al. [6] reviewed the Cleveland Clinic experience of 107 patients with 10 yr of follow-up treated with NSS for RCC before Even in the presence of imperative indications for surgery in 90% of patients and 45% of renal lesions >4 cm, the 5- and 10-yr cancer-specific survival (CSS) rates were 88% and 73%, respectively, and were 98% and 92% for tumours of <4 cm. Furthermore, only 11 local recurrences (10%) were observed and only 7 (6.5%) patients developed end-stage renal failure. The most important prognostic factors influencing survival in the Cleveland Clinic experience were tumour grade, tumour stage, bilateral disease, and lesions >4 cm. Because conservative surgery showed satisfactory results in imperative cases, many authors began to perform NSS more frequently and showed that outcomes of NSS were comparable with those of RN in terms of CSS with low local recurrence rate (Table 1) [10,14,15,29,36 37]. Butler et al. [36] compared NSS with RN in patients with small (<4 cm), localised, unilateral sporadic RCC. After a mean follow-up of 4 yr, CSS was 100% and 97%, respectively, without any significant difference in local and distant recurrence rate. In a larger population, Lerner et al. [29] showed similar outcomes for NSS and RN for tumours of 4 cm. Likewise Lee et al. [10] evaluated a patient cohort with renal tumours of <4 cm and showed that in these cases NSS was a safe alternative to RN. As a consequence of a low complication rate and excellent oncologic results for patients with a single, localised tumour <4 cm, many authors began to propose NSS as an alternative treatment to RN also for patients with a normal contralateral kidney. In Table 2 we report results in >700 patients who underwent elective NSS in several centres with different periods of follow-up. The CSS rate was always >95% and the local recurrence rate ranged from 0% to 5.5%, values similar to those reported in RN series [5,10,14,15,27,41,42]. Herr [5] reported the Memorial Sloan Kettering experience in elective NSS with a median follow-up of 10 yr. This paper confirmed that conservative surgery resulted in excellent overall, disease-free, and local recurrencefree survival (93%, 97%, and 98.5%, respectively). No randomised studies have yet demonstrated the oncologic equivalence of NSS and RN; the results of the European Organization for Research and Treatment of Cancer (EORTC) phase 3 randomised prospective study (protocol 30904), comparing RN Table 1 Results of cancer-specific survival and local recurrence of nephron-sparing surgery versus radical nephrectomy References Patients % CSS at 5 yr No. local recurrence (%) Mean follow-up (mo) RN NSS RN NSS RN NSS Butler et al. [36] (2.2) 48 Barbalias et al. [37] (7.3) NR Belldegrun et al. [14] (2.4) 4 (2.7) Lee et al. [10] Leibovich et al. [15] (2.3) 5 (5.5) NR Lerner et al. [29] (5.9) 51 CSS = cancer-specific survival; RN = radical nephrectomy; NSS = nephron-sparing surgery; NR = not reported.

5 604 european urology supplements 5 (2006) Table 2 Results of elective nephron-sparing surgery References No. of patients Mean tumour size (cm) % CSS No. local recurrence (%) Mean follow-up (mo) Van Poppel et al. [27] Belldegrun et al. [14] 63 NR a (3.2) 57 Herr [5] (1.5) 120 (median) Leibovich et al. [15] (range, 4 7) 98.3 b 5 (5.5) NR Filipas et al. [41] b 3 (1.6) 55 Lee et al. [10] b 0 38 Becker et al. [42] b 3 (1.4) 66 CSS = cancer-specific survival; NR = not reported. a 84% patients <4 cm. b CSS at 5 yr. and elective NSS for low-stage RCC (maximum diameter 5 cm), are awaited and will probably confirm this issue. In recent years, some authors evaluated the role of NSS in patients with localised RCC > 4 cm (but <7 cm) in diameter. Hafez et al. [43] studied the impact of tumour size on patient survival and tumour recurrence after NSS by comparing four different tumour sizes (<2.5, 2.5 4, 4 7, and >7 cm). In patients with tumours of 4 cm, the 5- and 10-yr CSS was significantly better than for those with larger tumours (96% and 90% vs. 86% and 66%, respectively) and a higher recurrence rate was observed when the tumour size was >4 cm. However, a criticism of this study was that there was not a control group who underwent RN to demonstrate better survival rates with this procedure. Belldegrun et al. [14] reviewed their experience: defining tumour stage according to the 1997 TNM system, they did not find a statistical difference in CSS and recurrence rate in T1 tumours treated with RN or NSS. Similarly, the CSS of T1 tumours of <4cm and tumours of 4 7 cm was comparable when treated with NSS or RN. On the contrary, for tumours other than T1, RN had a better CSS. The authors concluded that the indication for conservative surgery could be extended to treat patients with single, localised tumours with a maximum size of 7 cm. Leibovich et al. [15] compared 91 patients treated with NSS and 841 patients treated with RN for 4 7- cm RCC and a normal contralateral kidney. They found no statistically significant difference in 5-yr CSS and distant metastasis-free survival rate between the two groups, after adjusting for histologic subtype, nuclear grade, and tumour stage; they concluded that NSS for RCC of 4 7 cm has an excellent outcome in appropriately selected patients. Similarly, in a retrospective large multicentric series, Patard et al. [16] evaluated the safety and efficacy of NSS for pathologic T1 tumours. When comparing RN with NSS, they observed that treatment choice had no impact on CSS in either the T1a or T1b group (defined according to the 2002 TNM staging system). On the contrary, when comparing T1a and T1b, they noted a better CSS rate in the T1a group, regardless of treatment. They concluded that tumours of 4 7 cm have a worse prognosis than tumours of <4 cm but the type of surgery does not have any impact on the prognosis. As well as tumour dimension, the role of NSS has also been debated for centrally located tumours. Hafez et al. [44] did not find significant differences in biologic behaviour and CSS between centrally versus peripherally located small solitary RCC. Likewise Martorana et al. [45] found comparable results in the treatment of centrally located RCC, with no significant differences in CSS and local recurrence rate between centrally versus peripherally located tumours. However, performing NSS in centrally located tumours is surgically more demanding; in fact, it requires a longer renal ischemia time, often causes collecting system violation, and leads to a higher blood loss and transfusion. 7. Minimally invasive nephron-sparing treatments Open partial nephrectomy represents the standard treatment against which all other nephron-sparing approaches must be compared. Today many minimally invasive therapies for NSS are currently being applied and represent the new challenge in this field. Laparoscopic radical nephrectomy (LRN), since its introduction in 1990, has gained consensus worldwide and is now a standard of care for patients with T1 3a N0 M0 RCC in many centres; however, in presence of small peripheral RCC, where NSS is indicated, LRN seems to be an over-treatment even

6 european urology supplements 5 (2006) if it is a noninvasive procedure. Laparoscopic partial nephrectomy (LPN) is a more challenging surgical technique than LRN: the specific technical problems during LPN are to achieve renal hypothermia, parenchymal haemostasis, watertight pelvicaliceal repair, and renorrhaphy. LPN is also associated with a greater intraoperative complexity and potential complications in comparison with open partial nephrectomy and should be reserved for surgeons with adequate laparoscopic experience; recently the results in 100 patients treated with LPN at the Cleveland Foundation with a minimum follow-up of 3 yr were reported; overall survival and CSS were, respectively, 86% and 100%, without evidence of local/distant recurrence or port-site metastasis [46]. Even in the absence of long-term oncologic followup data, LPN is a promising alternative for the management of relatively small and peripheral renal tumours, but it must be performed at most experienced centres in minimally invasive surgery because of the high learning curve and high incidence of complications. The development of new energy sources for tumour ablation has introduced promising alternatives for minimally invasive NSS. These include cryoablation therapy, interstitial radiofrequency ablation (RFA), and high-intensity focused ultrasound (HIFU). Cryoablation has been the most studied minimally invasive modality for the treatment of small renal masses. Cryotherapy uses super-cooling energy sources by which target tissue is rapidly frozen in situ; during laparoscopic- or percutaneous-guided cryoablation, cytonecrosis of cancerous renal cells is achieved with a core temperature of at least 40 8C using a liquid nitrogen-based cryoprobe. In the largest series to date, Gill et al. [47] have reported encouraging results in 56 patients treated with laparoscopic renal cryoablation with a follow-up of 3 yr. This and other preliminary studies have shown that this technique is well tolerated and technically successful in experienced hands but longer-term results are necessary to determine the proper place of cryotherapy among minimally invasive NSS techniques. RFA uses a high-frequency current that flows from the needle electrode into the surrounding tissue, which in turn causes ionic agitation, molecular friction, and cellular warming with rapid desiccation and cellular death. Temperatures reached to effectively heat and coagulate the target tissue range from 60 to 100 8C. RFA is usually performed percutaneously under ultrasound or CT guidance, but electrodes could also be applied laparoscopically or during open surgery. At present there are no phase 3 studies that demonstrate equivalent effective outcomes of this technique compared to open partial nephrectomy [48]. The use of HIFU for the treatment of renal lesions has been recently introduced. Ultrasound waves, generated by a cylindrical piezoelectric element and focused by a paraboloid reflector, determine thermal destruction of the tumour lesion. At the moment HIFU is a promising but experimental procedure [49]. 8. An Italian multicentric experience with open partial nephrectomy We reviewed the series of open partial nephrectomy performed between 1994 and 2004 at four Italian urologic centers: Bologna, Genoa, Trieste, and Savona. A total of 467 patients underwent NSS for solid renal lesions. Patients records were reviewed: patients were excluded from the analysis if there was a benign histologic pattern, malignant non- RCC, or incomplete data. A final cohort of 360 patients (mean age, 60.2 yr; range, yr) with a mean follow-up of 55.3 mo (range, mo) treated with NSS for sporadic RCC was recorded for statistical evaluation (Table 3). RCC was classified according to the 2002 American Joint Committee on Cancer (AJCC) classification and the Heidelberg classification was used for histology. Related cancer symptoms were labeled as absent (asymptomatic) or present (gross hematuria, flank pain, weight loss, asthenia, fever). A total of 282 (78.2%) patients were asymptomatic at presentation. In 259 (72.1%) patients the treatment was performed for an elective indication. Enucleoresection was performed in 312 (86.8%) patients and partial nephrectomy in 48 (13.2%). Estimations of cumulative survival distributions were calculated according to the Kaplan-Meier method and the log-rank test was used to compare the differences between groups. The multivariate Cox proportional hazards model was used to analyse the independent predictive value of prognostic variables that were statistically significant in the univariate analysis. A p value of <0.05 was considered significant. The 5-yr and 10-yr CSS rates were, respectively, 96.6% and 86.9% for the whole population (Fig. 1). CSS was also analysed according to stage, grade, size and kind of presentation. Univariate analysis showed a significant p value for pathologic tumour stage and kind of presentation (Table 4). However, on multivariate analysis only kind of presentation remained an independent prognostic variable (Table 5).

7 606 european urology supplements 5 (2006) Table 3 Patient characteristics No. (%) Patients 467 Eligible 360 (77) Side Right 172 (48) Left 188 (52) Indication Elective 259 (72.1) Imperative 101 (27.9) Kind of presentation Asymptomatic 282 (78.2) Symptomatic 78 (21.8) Median cm tumour size (range) 3.38 (0.8 12) Histologic subtype RCC Conventional 335 (93.1) Papillary 17 (4.6) Chromophobe 8 (2.3) Tumour stage pt1 338 (93.8) a 295 (81.9) b 43 (11.9) pt2 11 (3.1) pt3a 11 (3.1) Histologic grade G1 112 (31.1) G2 216 (59.4) G3 32 (9.5) Complications Early (<30 d) 87 (24.3) Acute renal failure 51 (58.3) Hemorrhage 7 (8.3) Urinary fistula 3 (2.7) Other 26 (22.6) Late (up to 1 yr) 41 (11.5) Chronic renal failure 38 (82.3) Wound hernia 3 (17.7) Recurrence 42 (11.6) Local 14 (3.9) Systemic 20 (5.5) Local and systemic 8 (2.2) The results of cancer-specific and local and distant recurrence-free survival analysis, performed only among T1 patients (93.8% of the whole population), are showed in Table 6. On multivariate analysis only kind of presentation influenced independently cancer-specific and local and distant recurrence-free survival (Table 7). Our experience of 360 patients treated for sporadic RCC with NSS mainly in elective conditions confirms the excellent results reported in the literature. On univariate analysis, kind of presentation and pathologic tumour stage were the only important prognostic factors. Furthermore, we found better CSS rate for T1a compared to T1b but NSS for T1b was not affected by a more frequent Fig. 1 Cancer-specific survival of all patients. local recurrence compared to T1a patients. These observations suggest that NSS is effective for local disease control also for patients with lesions of 4 7 cm but these tumours are potentially more aggressive than those <4 cm. Moreover, kind of presentation on multivariate analysis was the only independent prognostic factor, suggesting that symptoms are an important prognostic factor and should be considered in the preoperative assessment of RCC, as recently reported [17]. Nevertheless, our results should be interpreted with caution because our population is highly selected and subgroups are very different in size. Table 4 Univariate analysis for 5-yr and 10-yr cancerspecific survival in the whole population 5-yr cancerspecific 10-yr cancerspecific Stage T1a T1b T T3a 77.0 Grade Size (cm) < > Kind of presentation Asymptomatic Symptomatic p

8 european urology supplements 5 (2006) Table 5 Cox regression model of cancer-specific survival for significant variables on univariate model Categories p HR 95%CI for HR Lower Upper Stage T1a vs T1b vs T2 vs T3a Kind of presentation Asymptomatic vs symptomatic HR = hazard ratio; CI = confidence interval. Table 6 Univariate analysis for cancer-specific and local and distant recurrence free-survival in T1 patients Cancer-specific Local recurrencefree Distant recurrencefree 5yr 10yr p 5yr 10yr p 5yr 10yr p Stage T1a T1b Kind of presentation Asymptomatic Symptomatic Table 7 Multivariate analysis for cancer-specific and local and distant recurrence-free survival in stage T1 Categories Cancer-specific Local recurrencefree Distant recurrencefree HR p HR p HR p Stage T1a vs T1b Kind of presentation Asymptomatic vs symptomatic HR = hazard ratio. 9. Conclusions Currently, open conservative surgery represents a safe and effective treatment for small (<4 cm), localised renal tumours for both elective and imperative conditions, with the same long-term results as radical surgery. Some recent series showed how this indication could be extended to larger (<7 cm) localised tumours, with similar survival and recurrence rates to RN; nevertheless this issue remains controversial. LPN is a challenging and promising procedure; other minimally invasive techniques (cryoablation therapy, RFA, HIFU) are currently being developed and will certainly evolve in the near future. References [1] Pantuck AJ, Zisman A, Belldegrun AS. The changing natural history of renal cell carcinoma. J Urol 2001;166: [2] Godley PA, Stinchcombe TE. Renal cell carcinoma. Curr Opin Oncol 1999;11: [3] Giberti C, Oneto F, Martorana G, Rovida S, Carmignani G. Radical nephrectomy for renal cell carcinoma: long-term results and prognostic factors on a series of 328 cases. Eur Urol 1997;31:40 8. [4] Herr HW. A history of partial nephrectomy for renal tumors. J Urol 2005;173: [5] Herr HW. Partial nephrectomy for unilateral renal carcinoma and a normal contralateral kidney: 10-year followup. J Urol 1999;161:33 5. [6] Fergany AF, Hafez KS, Novick AC. Long-term results of nephron sparing surgery for localized renal cell carcinoma: 10-year follow-up. J Urol 2000;163: [7] Gudbjartsson T, Thoroddsen A, Petursdottir V, Hardarson S, Magnusson J, Einarsson GV. Effect of incidental detection for survival of patients with renal cell carcinoma: results of population-based study of 701 patients. Urology 2005;66: [8] Ficarra V, Prayer-Galetti T, Novella G, et al. Incidental detection beyond pathological factors as prognostic predictor of renal cell carcinoma. Eur Urol 2003;43: [9] Beisland C, Medby PC, Beisland HO. Renal cell carcinoma: gender difference in incidental detection and cancer-specific survival. Scand J Urol Nephrol 2002;36: [10] Lee CT, Katz J, Shi W, Thaler HT, Reuter VE, Russo P. Surgical management of renal tumors 4 cm or less in a contemporary cohort. J Urol 2000;163:730 6.

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