An increasing number of small renal masses (SRMs) with heterogeneous histology and clinical behaviour are being detected with modern radiologic imaging. Although surgical removal is the standard of care for small renal tumours, alternative minimally invasive and conservative treatment options are possible in selected patients with shorter life expectancy.
To systematically review indications, techniques, and outcomes of surgical and conservative treatments of SRMs.
A literature search of English-language publications was performed using the Medline database from January 2000 to February 2011 using the terms renal mass and renal carcinoma in conjunction with the evaluated management options. The articles that provided the highest level of evidence were selected with the consensus of all the authors and reviewed.
Only one randomised controlled trial comparing the results of elective nephron-sparing surgery and radical nephrectomy for low-stage renal tumours is available. Few comparative studies of different treatment options for SRMs have been published. The assessment of oncologic outcomes is therefore based mainly on observational studies. Most series of nonsurgical therapies have strong selection biases and relatively short follow-up. Treatment selection is based on the clinical and histologic characteristics of SRMs, on patient age and comorbidities, and on personal preferences and experience of the urologist.
Partial nephrectomy (PN) is the standard treatment for solitary SRMs whenever it is technically feasible. Laparoscopic PN is an alternative to open PN in experienced hands. The rationale of ablative treatments is to treat incidental cortical SRMs in patients at high surgical risk with potentially reduced morbidity. Active surveillance is considered an appropriate strategy for the elderly or for patients with significant comorbidity who have a shorter life expectancy. Percutaneous biopsies are increasingly being used to establish histology of SRMs and support treatment decisions, especially for patients who are candidates for nonsurgical treatment.
Keywords: Carcinoma, renal cell, Cryoablation, Nephron-sparing surgery, Partial nephrectomy, Renal mass, Renal tumour biopsy, Surveillance, Thermal ablation.
During the last two decades, a 2% annual increase in the incidence of renal cell carcinoma (RCC) has been observed both in Europe and in North America  and . This is largely the result of increased detection of localised RCCs as small renal masses (SRMs) in asymptomatic patients who undergo imaging for nonspecific abdominal or musculoskeletal complaints or follow-up of other unrelated malignancies . Most renal lesions are first detected by abdominal ultrasound, but in the presence of solid or complex cystic lesions a precise assessment of the size, shape, profile, and tissue enhancement by triphasic computed tomography (CT) or magnetic resonance imaging (MRI) scans with administration of contrast medium is necessary. A SRM is generally defined as a contrast-enhancing mass within the kidney with the largest dimension ≤4
The gold standard treatment for SRMs is surgical removal with preservation of the remainder of the kidney whenever technically feasible. Progress in technology has recently led to effective minimally invasive surgical approaches for renal tumour excision, including laparoscopy and robotic-assisted surgery.
However, the histologic features of SRMs are heterogeneous. Some small renal tumours harbour aggressive disease. An analysis of the Surveillance Epidemiology and End Results (SEER) database from 1998 to 2003 showed a 5.2% prevalence of metastasis at presentation among 8792 patients with RCCs ≤4
2. Evidence acquisition
A literature search of English-language publications was performed using the Medline database from 2000 to 2010 using the terms renal mass and renal carcinoma in conjunction with the evaluated management options. A total of 1135 articles were scrutinised to obtain a complete overview on the current management of SRMs. The 134 articles that provided the highest level of evidence were selected with the consensus of all the authors, analysed and included in this review.
3. Evidence synthesis
The current options for the treatment of SRMs are partial nephrectomy (PN) or radical nephrectomy (RN), minimally invasive ablative therapies (ATs), and AS. With the exception of a recently published prospective randomised European Organisation for Research and Treatment of Cancer (EORTC) intergroup phase 3 study assessing complications and oncologic results of elective PN and RN , randomised controlled trials comparing the results of different treatment options for small renal tumours are lacking. Few comparative studies are available, and the assessment of oncologic outcomes is based mainly on observational studies. The series reported in the literature are characterised by important differences in the demographics of the patient populations exposed to different treatments, reflecting strong selection biases that have to be acknowledged. Finally, the length of follow-up is frequently inadequate for most of the newer treatment modalities. Treatment selection for each individual case is based on the clinical and histologic characteristics of SRMs, on patient age and comorbidities, and on the personal preferences and experience of the urologist . Table 1 summarises the indications and contraindications of the principal treatment options for SRMs.
|Partial nephrectomy||Enhancing solid or complex cystic renal mass whenever technically feasible
Young and fit patients with limited medical comorbidity
Hilar tumours (contraindication to ablative treatments)
Indications for NSS (see section 3.1)
|Severe and irreversible coagulopathy
Abdominal scars (relative contraindication)
|Ablative treatment (cryoablation or radiofrequency ablation)||Renal masses <3 cm
Elderly patients or patients with medical comorbidities and high surgical risk who desire active treatment
Patients with solitary kidneys and baseline renal dysfunction
Informed younger patients who refuse surgery
Renal masses in a postsurgical renal remnant
|Healthy young patients (lack of long-term oncologic outcomes)
Severe and irreversible coagulopathy
Hilar tumours close to proximal ureter and central collecting system
Tumours with irregular shape and infiltrative appearance
Unwillingness to comply with a strict follow-up (imaging/biopsy)
|Active surveillance||Patients with limited life expectancy (elderly, severe medical comorbidities, high surgical risk)
Severe renal dysfunction
Informed younger patients who refuse active treatment
|Healthy young patients
Unwillingness to comply with a strict radiologic follow-up
3.1. Surgical treatment
3.1.1. Partial nephrectomy
Historically, the curative treatment for SRMs was RN, that is, removal of the entire tumour-bearing kidney within its fascia. Nephron-sparing surgery (NSS) was recommended when a SRM was detected (1) in anatomically or functionally solitary kidneys (absolute indications), (2) in patients with a contralateral functioning kidney affected by a condition that might impair renal function in the future, or (3) in the presence of multiple bilateral tumours or hereditary forms of RCC that pose a high risk of developing a tumour in the contralateral kidney (relative indications) . In the last few years the accumulating evidence derived from high-quality clinical research in the field of renal oncology has led to the increased use of PN in the presence of localised unilateral RCC with a healthy contralateral kidney (elective indications).
220.127.116.11. Oncologic outcomes
The recently published EORTC randomised phase 3 trial 30904 and several large retrospective nonrandomised studies showed comparable cancer-specific outcomes for PN and RN of low-stage renal tumours , , , and . In the EORTC study, 541 patients with small (≤5
18.104.22.168. Preservation of renal function
The expanding elective indications of PN are also due to the increased recognition of chronic kidney disease (CKD) as a public health problem worldwide. The adverse clinical effects of a decline in renal function has been confirmed by a large community-based study on 1 120 295 adults whose serum creatinine was measured between 1996 and 2000 and who had not undergone dialysis or renal transplant in the same time period. CKD, defined as estimated glomerular filtration rate (eGFR) <60
Preservation of the largest amount of healthy renal parenchyma is therefore paramount when the excision of a SRM is needed. Urologists must be aware that a proportion of men in the age groups of those who are commonly diagnosed with a renal tumour have baseline renal dysfunction even in the presence of normal serum creatinine levels. In fact, in a recently reported series of 1178 patients presenting for surgery for a solid renal mass, 23% were found to have CKD stage III or greater (eGFR <60
There is clear evidence that renal function is better preserved with NSS. Two retrospective studies from the Memorial Sloan-Kettering Cancer Center (MSKCC) and the Mayo Clinic observed that patients undergoing PN were less likely to have elevated serum creatinine levels during follow-up than those who underwent RN  and . Of note, serum creatinine was the measure of renal function in these studies. However, similar results with the use of eGFR (estimated with the Modification of Diet in Renal Disease study equation) were obtained by Huang et al, who retrospectively reviewed a series of 662 patients with normal serum creatinine levels and two normal kidneys who underwent PN or RN for renal tumours <4
A recent SEER analysis also showed that patients who underwent PN from 2000 to 2002 experienced fewer adverse renal outcomes compared with those who underwent RN (16.4% vs 21.8%; adjusted hazard ratio [HR]: 0.74; 95% CI, 0.58–0.94), including a trend toward less frequent need for dialysis services, dialysis access surgery, or renal transplant . Similar results were recently reported in an analysis based on a Canadian population that showed RN was associated with an HR of 1.75 (95% CI, 1.02–2.99) compared with PN for the development of renal-adverse outcomes .
Finally, in several studies the decreased risk of renal function decline and relative adverse effects on general health appear to provide a survival advantage to patients treated with PN , , and . Using SEER registry data linked with Medicare claims, Huang et al identified 2991 patients >66 yr of age who were treated with RN or PN for renal tumours <4
22.214.171.124. Current guidelines and diffusion of partial nephrectomy
Based on all the previously described observations on the oncologic and functional outcomes of PN, the current versions of the European Association of Urology and the American Urological Association (AUA) guidelines recommend NSS as the standard treatment for solitary renal tumours up to a diameter of 7
The complication rates of open partial nephrectomy (OPN) are slightly higher than those of open radical nephrectomy (ORN). A prospective randomised study compared the complications of elective OPN and ORN for solitary localised renal tumours. The rate of severe haemorrhage was slightly higher after NSS (3.1% vs 1.2%). Urinary fistulas were observed only after PN (4.4%). Pleural and spleen damage were observed with similar rates in both groups. Postoperative CT scanning abnormalities were seen in 5.8% of NSS and 2.0% of RN patients. Reoperation for complications was necessary in 4.4% of NSS and 2.4% of RN patients .
Three scoring systems have been recently developed to provide a better anatomic description and classification of renal tumours that are candidates for NSS , , and . The preoperative aspects and dimensions used for an anatomic classification (PADUA) score was applied to a series of 164 consecutive PNs and shown to be an independent predictor of the occurrence of any grade of complications at multivariate analysis . Bruner et al recently observed that the RENAL score appears to correlate with the risk of urine leak after PN . Finally, the centrality index (c index) was found to be an independent predictor of warm ischaemia time (WIT), which is a surrogate for technical complexity . Although these systems need to be further validated in larger series, they have the potential to be useful tools for patient counselling, treatment decision making, and clinical research.
126.96.36.199. Impact of ischaemia time on renal functional outcomes
Vascular clamping during OPN is significantly associated with a higher incidence of renal complications . In fact, the degree of kidney damage depends on the duration of ischaemia time. In a study of renal functional outcomes of PN in patients with normal contralateral kidney, Funahashi et al assessed the postoperative function of the operated organ by renal scintigraphy. Regional 99mTc-mercaptoacetyltriglycine-3 uptake was significantly higher for cases with WIT <25
In a large multicentre series of OPN in solitary kidneys, a WIT >20
188.8.131.52. Positive surgical margins
A complete resection of the renal mass, avoiding positive surgical margins with the potential risk of local recurrence, is essential in NSS. The thickness of negative margin around the tumour does not seem to influence oncologic outcomes . Carini et al retrospectively analysed 232 SRMs undergoing simple enucleation with a low complication rate and good intermediate-term oncologic outcomes. With a mean follow-up of 76 mo, 13 patients (6.4%) had disease progression, and none had local recurrence in the enucleation bed .
Over the short term, the presence of a positive surgical margin on the inked surgical specimen does not seem to increase the likelihood of local recurrence or decrease CSS  and . In a recent multicentre European retrospective study, 111 patients with a positive surgical margin were compared with a cohort of patients with negative margins. With a mean follow-up of 37 mo, patients with positive surgical margins had similar recurrence-free survival, CSS, and OS compared with those with negative margins. Indication and tumour location, but not margin status, were significant predictors of local recurrence . Although longer follow-up is needed, these data suggest that selected patients with positive surgical margins after PN may be reasonably managed conservatively without compromising survival outcomes, reserving further surgery for those with clear radiologic signs of local recurrence during follow-up . Nevertheless, unquestionably a primary intraoperative goal of any PN surgery is achieving negative surgical margins.
3.1.2. Laparoscopic partial nephrectomy
Laparoscopic partial nephrectomy (LPN) is an alternative to OPN in experienced hands . LPN can be performed either with transperitoneal or retroperitoneal access. The choice of approach is based on tumour location and surgeon's experience. Ng et al compared transperitoneal and retroperitoneal LPN and observed similar results in terms of analgesic use, blood loss, and perioperative complications. Renal masses managed with a transperitoneal approach were on average larger and more endophytic. This may in part explain the longer operative time, WIT, and hospital stay associated with this approach .
Long-term oncologic outcomes of LPN are still evolving, but CSS of series with intermediate-term follow-up are comparable with those achieved with OPN  and  (Table 2). Lane and Gill recently compared the outcomes of two cohorts of patients who underwent LPN and OPN with a median follow-up of 4 and 5.7 yr, respectively. Actuarial 7-yr OS and metastasis-free survival rates were 83.1–97.5% and 83.5–97.3% after LPN and OPN, respectively. At multivariate analysis, surgical approach was not an independent prognosticator of survival (p
|Study||Study period||Approach||Patients, n||Mean tumour size, cm||Mean follow-up, mo||Local recurrence, %||Cancer-specific survival, %|
|Becker et al ||1975–2002||Open||216||3.7||66||5.6||97.8|
|Patard et al ||1984–2001||Open||314*||2.5||50.7||0.8||97.8|
|Patard et al ||1984–2005||Open||600||3.4||36||0.9||97.9|
|Gill et al ||1998–2005||Open||1029||3.5||34||1.5||99.2|
|Gill et al ||1998–2005||Laparoscopic||771||2.7||15||1.4||99.3|
|Permpongkosol et al ||1996–2004||Laparoscopic||85||2.4||40.4||2.3||98.8|
|Lane and Gill ||1999–2008||Laparoscopic||145||2.5||74.4||2.4||97|
The rate of positive surgical margins after LPN is similar to that observed with OPN. A survey of 17 academic centres in the United States and in Europe identified 21 cases of positive surgical margins in an overall series of 855 LPNs (2.4%) . Permpongkosol et al reported a positive surgical margin rate of 1.8% in a series of 511 LPNs for RCC. Two patients underwent completion nephrectomy without finding residual tumour in the specimen. The remaining seven patients were managed expectantly, with one dying from metastatic disease 10 mo after LPN .
The largest comparative series of LPN and OPN reported 771 patients treated laparoscopically and 1028 treated with an open approach at three large referral centres. This study includes some of the initial patients undergoing LPN in the literature and therefore represents not only the learning curve but also the discovery curve of LPN. Although patients undergoing OPN were at higher risk with a larger tumour size and a greater proportion presenting with symptoms at diagnosis, impaired renal function, and tumour in a solitary kidney, this retrospective paper provides important information. LPN was found to be associated with significantly shorter operative times, decreased operative blood loss, and shorter hospital stay compared with OPN. However, the laparoscopic approach had a significantly higher chance of postoperative complications and need for subsequent procedures to manage complications. In particular, the risk of postoperative haemorrhage was found to be significantly higher after LPN (OR: 3.52; p
One of the major concerns with the earlier reported series of LPN is the longer WIT compared with OPN. In the previously mentioned multicentre series, mean WIT was 30.7
Porpiglia et al prospectively studied renal function with serum creatinine, creatinine clearance, and renal scintigraphy before and after LPN in 18 cases. The authors observed that significant kidney damage occurs with a WIT >30
3.1.3. Robot-assisted partial nephrectomy
Robot-assisted partial nephrectomy (RAPN) allows magnified stereoscopic visualisation and the use of articulated robotic instruments under precise control. RAPN may reduce the technical challenges associated with tumour dissection and parenchymal reconstruction during LPN. A matched cohort study comparing the perioperative outcomes of 186 LPNs and 75 RAPNs performed by a single surgeon was recently published. Mean estimated blood loss (EBL) was higher in the RAPN cohort. However, there was no significant difference with respect to operative time, WIT, length of hospitalisation, percentage change in eGFR, or adverse events . The largest multi-institutional comparison of the two approaches to date published describes the outcomes of 118 consecutive LPNs and 129 consecutive RAPNs performed between 2004 and 2008. Patient and tumour characteristics were comparable. Comparison of operative data revealed no significant differences in overall operative time (189 vs 174
Although the first experiences of RAPN are encouraging, oncologic outcomes are still immature, and larger series with longer follow-up are awaited to confirm the preliminary results. At present, the technique is still considered under evaluation by the major urologic guidelines .
3.1.4. Radical nephrectomy
RN has a very limited role in the management of SRMs and should be recommended only when an expert surgeon believes that NSS is not feasible or advisable based on tumour location or other radiographic characteristics  and . Before deciding on a RN, nonsurgical alternative options should be discussed systematically including AS and ablative techniques. Laparoscopic radical nephrectomy (LRN) has been shown to achieve similar long-term oncologic outcomes as ORN and to be superior to the open approach in terms of shorter recovery, shorter hospital stay, smaller blood loss, and lower analgesic requirements , , and . In the rare circumstance that a RN is finally chosen for the treatment of a SRM, the laparoscopic approach should therefore be favoured for kidney removal . However, the advantages of minimally invasive RN must not lead to decreased indications of NSS for SRMs. A recent population-based analysis in Canada indeed confirmed that the introduction of the laparoscopic approach for removal of the entire kidney has negatively affected the uptake and use of PN for RCC . The urologic community thus must be strongly advised that OPN and not LRN should be the treatment of choice for SRMs if LPN is not deemed an option at a particular centre.
3.2. Ablative therapies
Alternatives to surgical treatment of SRMs include image-guided percutaneous or laparoscopic minimally invasive ablative techniques such as radiofrequency ablation (RFA), cryoablation (CA), microwave ablation, laser ablation, radiosurgical ablation (CyberKnife), and high-intensity focussed ultrasound (HIFU) ablation.
The rationale of AT is to treat incidental cortical SRMs in patients at high surgical risk with potentially reduced morbidity. These procedures can be performed in an outpatient setting using a percutaneous image-guided approach. The best candidates for AT are elderly patients with serious medical comorbidities who desire active treatment. In selected patients with tumour in a solitary kidney and baseline renal dysfunction, at high risk of complete loss of renal function after surgical resection, tumour ablation may also be discussed . These patients have to accept the need for long-term radiographic surveillance after AT . Contraindications to AT are tumours with a low chance of successful treatment due to size >3
Intermediate follow-up data are available only for CA and RFA. HIFU ablation and the other proposed ATs are still experimental.
CA causes tumour cell destruction by rapid freeze-and-thaw cycles to a temperature below −20
CA can be performed either with a percutaneous or a laparoscopic approach. Perioperative morbidity of laparoscopic CA of SRMs with ultrathin probes was assessed in a European multicentre study including 148 procedures in 144 patients. Negative outcomes (defined as any deviation from the planned clinical course in the 30 d following CA) and complications were observed in 17% and 15.5% of cases, respectively. However, most complications (80%) did not require surgical, endoscopic, or radiologic intervention . A comparative study at a single tertiary referral centre showed that percutaneous CA is associated with a higher complication rate than laparoscopic CA (21.1% vs 13.9%). However, laparoscopic CA was associated with a higher rate of severe events that required active management .
Percutaneous CA seems to be characterised by decreased postoperative pain, shorter hospital stay, and shorter convalescence time  and . However, the advantage of lower invasiveness of the percutaneous approach is compromised by a higher primary failure rate. In the largest comparative study, Mues et al assessed the short-term outcomes of 99 percutaneous and 97 laparoscopic CAs for SRMs with comparable characteristics. The complication rate was similar, but treatment failure was significantly higher for percutaneous CA (9% vs 3.1%) .
Non-uniform criteria have been used to define treatment success and recurrence after CA. Most authors use radiographic loss of contrast enhancement on CT or MRI to assess treatment effect; routine postablation biopsy is rarely performed  and . However, Weight et al observed an adequate correlation between the results of radiographic imaging and pathology of needle biopsies performed 6 mo after CA in 192 SRMs .
Table 3 shows the oncologic outcomes of selected large series of CA. Most studies are limited by a relatively short follow-up. However, two urologic groups recently reported positive intermediate-term results of laparoscopic-assisted CA of SRMs. Aron et al reported the longest follow-up outcomes of 80 patients treated by a single surgeon (minimum follow-up: 5 yr). Mean tumour size was 2.3
|Study||No.||Biopsy-proven RCC, n (%)||Median size, cm||Approach||Follow-up, mo||CSS, %||Tumour recurrence, %|
|Aron et al ||80||55 (68.8)||2.3||Laparoscopic||93 (median)||92||14**|
|Guazzoni et al ||131||69 (56.1)||2.14||Laparoscopic||46 (mean)||100||0|
|Hegarty et al ||179||–||2.5||Laparoscopic||36 (median)||98||1.7*|
|Schwartz et al ||85||50 (58.8)||2.6||Open/laparoscopic||10 (mean)||–||2.4*|
|Beemster et al ||100||51 (51)||2.5||Laparoscopic||30 (mean)||100||8.2*|
|Davol et al ||48||38 (79.2)||2.6||Open/laparoscopic||64 (median)||100||12.5*|
* Local recurrence.
** Local and distant recurrence.
Guazzoni et al retrospectively reviewed the records of 131 laparoscopically assisted CAs in 123 patients. Mean tumour size was 2.14
3.2.2. Radiofrequency ablation
RFA is a thermal therapy that converts radiofrequency waves to heat in the target tissue. Temperatures >50
|Study||No.||Biopsy-proven RCC, n (%)||Median size, cm||Approach||Follow-up, mo||CSS, %||Tumour recurrence after one ablation, %|
|Zagoria et al ||125||125 (100)||2.7||Percutaneous||13.8 (mean)||98||13|
|Varkarakis et al ||56||27 (48.2)||2.2||Percutaneous||27.5 (mean)||–||19.5|
|Hegarty et al ||81||–||2.5||Percutaneous||12 (median)||100||11.1|
|Ferakis et al ||39||–||3.1||Percutaneous||61.2 (mean)||–||10|
|Tracy et al ||243||179 (73.7)||2.4||Percutaneous/Laparoscopic||27 (mean)||99||7|
Tracy et al recently published the largest series of RFA of renal tumours. The authors performed 243 treatments for SRMs in 208 patients over a period of 7.5 yr. Overall, mean tumour size was 2.4
As for CA, no standardised radiologic criteria for successful ablation are available for RFA. Lack of contrast enhancement at CT or MRI is generally used to define treatment success; posttreatment biopsies are rarely used. Three studies assessed the outcomes of thermal ablation by surgical removal of the tumour or the entire kidney after RFA , , and . In the largest and most recent of these studies, 17 SRMs with a mean size of 2.2
3.2.3. Comparison of cryoablation and radiofrequency ablation
The outcomes of laparoscopic CA and percutaneous RFA were compared in two retrospective single institutional studies. Hegarty et al reviewed their series of 164 laparoscopic CAs and 82 percutaneous RFAs and compared the results of the two techniques in terms of oncologic outcomes and complications. Radiologic evidence of tumour recurrence or persistence of disease was observed in three patients (1.8%) who underwent CA and nine (11.1%) who were treated with RFA. CSS was excellent, respectively 98% at a median follow-up of 3 yr for CA and 100% at a median follow-up of 1 yr for RFA. Complication rates were minimal in both groups, and no significant impact on renal function was observed. However, the two groups were not completely comparable, with fewer central tumours and fewer solitary kidneys treated with CA. The use of two different approaches for CA and RFA make it impossible to reliably compare the complications of the two ablative strategies .
Weight et al followed 109 renal lesions treated with percutaneous RFA and 192 lesions treated with laparoscopic CA with imaging. Lack of contrast enhancement at CT was observed at 6 mo in 85% and 90% of cases for RFA and CA, respectively. A total of 45% of renal lesions were biopsied 6 mo after the procedure. Histologically proven treatment success remained high for CA (93.8%) and decreased to 64.8% for RFA. Six of 13 patients (46.2%) with a postablation positive biopsy after RFA demonstrated no enhancement on posttreatment CT or MRI. Conversely, in patients treated with CA all positive biopsies were associated with posttreatment enhancement on imaging just before biopsy .
Finally, a meta-analysis of 99 studies of nonsurgical treatment of SRMs showed that local recurrence is overall more frequent after RFA (11.7%) than CA (4.6%). Both techniques have significantly increased local progression rates compared with NSS (relative risk 7.45 for CA and 18.23 for RFA). Progression to metastatic disease was described in 1.2% of cases after CA and 2.3% of cases after RFA, with no statistical difference compared with surgically treated SRMs .
In summary, CA and RFA are promising alternative techniques for treatment of SRMs, but long-term oncologic outcomes are still lacking. The definition and standardisation of accurate criteria to define treatment success after ATs are needed. The issue of poor correlation between lack of enhancement at imaging and persistence of viable tumour at biopsy after RFA remains unsolved. Although the clinical significance of these viable cells remains to be determined, routine use of postablation biopsies would allow a more accurate determination of true local recurrence rate after AT. Randomised prospective studies comparing the results of ATs with those of surgical excision and observation are needed to better determine the proper applications of these techniques in the management of SRMs.
3.2.4. Other ablative techniques
HIFU is a technique of thermal ablation that uses ultrasound waves that can be focussed on the tumour under imaging guidance to achieve a temperature sufficient for immediate thermal destruction of all tissues within the target zone. Ideally, HIFU should be performed with a percutaneous approach. However, the acoustic interference of intervening tissues and kidney mobility has made the percutaneous approach unsatisfactory . These problems are avoided if the HIFU transducer is placed in direct contact with the target tumour under laparoscopic approach. In 2008, Klingler et al published the first experience of laparoscopic HIFU of eight SRMs, followed by LPN in seven cases. There were no complications, and complete ablation of the tumour was obtained in four cases, confirming the feasibility of the technique . Very recently, another group reported the short-term outcomes of a series of 15 percutaneous HIFUs of SRMs. Five patients underwent surgery or an alternative ablative therapy during follow-up for the persistence of contrast enhancement at imaging. The remaining 10 masses remained in follow-up at a mean of 36 mo after HIFU, showing an average 30% decrease in tumour area and no enhancement in all cases .
Microwaves have also been tested as an ablative energy source for renal tumours . Liang et al reported 12 cases of percutaneous microwave ablation of pathologically proven small RCCs. The authors reported no residual tumour or radiologically detected recurrence at a median follow-up of 11 mo. Although the results of these newer ablative treatments are encouraging, further studies with longer follow-up and postablation biopsies to confirm treatment success histologically are needed before their efficacy can be confirmed. At present these techniques are still considered experimental .
3.3. Active surveillance
The rationale for conservative management of SRMs is based on the hypothesis that active treatment for small renal lesions may not influence OS in elderly patients and in those with comorbidities who have a shorter life expectancy. In fact, a significant proportion of SRMs are benign tumours or low-grade RCCs with relatively indolent biologic and clinical behaviour , , and .
Recent studies have shown that non-RCC–related mortality after surgical treatment for SRMs is significant and correlates with age and comorbidity. A population-based analysis of 26 618 patients who were surgically treated for locoregional kidney cancer between 1983 and 2002 showed that competing-cause mortality increases with increasing patient age irrespective of tumour size (reaching 28.2% for patients >70 yr of age) . In a retrospective review of 192 patients with clear cell RCC, Arrontes et al observed that a higher Charlson comorbidity score (>2) is significantly associated with a worse OS after surgical treatment (p
AS is defined as the initial monitoring of tumour size by serial abdominal imaging (ultrasound [US], CT, or MRI) with delayed intervention reserved for those SRMs that show progression during follow-up . Progression of a SRM during AS is generally defined as tumour volume doubling time
Initial experiences have shown that the growth rate of SRMs under surveillance is variable, overall slow, and does not correlate with initial tumour size , , , , , and  (Table 5). Chawla et al carried out a meta-analysis of eight active surveillance series including 234 renal masses with a mean size at presentation of 2.6
|Study||Patients (SRMs), n||Mean tumour size, cm||Available histology, n (%)||Histologically proven RCC, n (%)||Mean follow-up, mo||Growth rate, cm/yr||Progression to metastasis, n (%)|
|Bosniak et al ||37 (40)||1.73||26 (70.3)||22 (85)||39||0.36||0|
|Volpe et al ||29 (32)||2.48||9 (31)||8 (89)||27.9||0.1||0|
|Chawla et al ||49 (61)||2.97||21 (42.9)||17 (81)||36||0.2||1 (2)|
|Abou Youssif et al ||35 (44)||2.2||8 (23)||6 (75)||47.6||0.21||2 (5.7)|
|Abouassaly et al ||110 (–)||2.5||9 (8)||3 (33)||24||0.26||0|
|Crispen et al ||154 (172)||2.5||68 (44.2)||57 (84)||31||0.28||2 (1.3)|
|Rosales et al ||212 (223)||2.8||40 (18.9)||37 (92.5)||35||0.34||1 (0.5)|
Some authors have shown that delaying intervention for SRMs did not limit or compromise the feasibility of NSS and the laparoscopic approach and did not lead to an increased risk of local or metastatic progression  and .
The main limitations of AS series are the relatively short follow-up and the lack of pathologic diagnosis in a significant number of cases. Almost all studies have been retrospective and single institutional. However, the first results of a prospective phase 2 multicentre clinical trial of AS of 209 SRMs in 178 elderly and/or infirm patients were recently reported. Mean tumour size at diagnosis was 2.1
At the present time, AS is considered an appropriate strategy for elderly patients or patients with significant comorbidities who are not good surgical candidates  and . Gill et al recently suggested that AS also seems a reasonable option for masses ≤1
|20–30% SRMs have benign pathology; 70–80% of RCCs <4
|SRMs typically grow slowly (2–3 mm/yr)|
|Progression to metastatic disease during AS is infrequent|
|Delayed surgery after an initial period of AS does not seem to increase oncologic risk|
|75% SRMs grow during AS; a significant number are removed with delayed surgical intervention (approximately 40% of patients on AS crossover to surgery within 2 yr)|
|Abdominal imaging cannot conclusively identify either malignant pathology or high-grade disease|
|No significant clinical predictor of future renal tumour growth and disease progression has been identified|
|Absence of tumour growth does not necessarily mean absence of malignancy|
|Small increases in tumour diameter increase the tumour volume exponentially, implying considerably greater tumour burden. For example, a spherical 1-cm tumour has a volume of 0.5
|Rarely, a SRM can progress to metastatic disease during AS and lead to cancer-specific death in absence of curative systemic treatment|
|AS series are limited by small sample size, short follow-up duration, and inadequate corroboration with histologic data|
|AS implies strict follow-up imaging with potential cumulative radiation risk and cost implications|
There is no clear consensus about the best imaging technique and the optimal follow-up schedule that should be adopted in AS protocols . CT and MRI are generally preferred for their superior accuracy and lower variability in determining tumour size, but there are no studies showing their superiority over abdominal US. The typical recommendation is to perform repeat imaging at an interval of 6–12 mo that is a balance between oncologic safety and the risks associated with serial radiation exposure .
Counselling of patients who are candidates for AS should include a balanced discussion of the small but real risk of cancer progression, lack of curative salvage therapies if metastases develop, possible loss of window of opportunity for NSS, and substantial limitations of the current AS literature. Larger tumours (3–4
3.4. Percutaneous tumour biopsy
The role of percutaneous biopsy in the management of SRMs is expanding. Historically, renal tumour biopsies were rarely used because of concerns about their safety and accuracy . Several large series of renal tumour biopsies have been recently published, confirming that the procedure is characterised by low morbidity in centres with expertise , , , and . Clinically significant bleeding is reported in <1% of cases, and only six cases of renal tumour seeding after biopsy have been reported in the literature . All cases of renal tumour seeding occurred before the advent and widespread use of modern biopsy techniques implying the use of a coaxial cannula through which biopsy cores are taken, thereby minimising the contact between tumour cells and tissues intervening between skin and tumour surface. All recent series of renal tumour biopsies reported high diagnostic rates and excellent accuracy for the diagnosis of malignancy (Table 7) , , , , , , , , and . In a series of 100 percutaneous biopsies of SRMs, Volpe et al observed that a larger tumour size and a solid pattern are significant predictors of a diagnostic biopsy .
|Study||Tumours biopsied, n||Imaging guidance||Needle size, gauge||Nondiagnostic biopsies, %||Outcomes|
|Lechevallier et al ||73||CT||18 G||21||Concordance biopsy and surgical diagnosis 89%|
|Neuzillet et al ||88||CT||18 G||9.1||Accuracy 92%|
|Vasudevan et al ||100||CT/US||16 G||30||Accuracy 100%|
|Schmidbauer et al ||78||CT||18 G||3||Sensitivity 93.5%
|Lebret et al ||119||CT||18 G||21||Accuracy 86%|
|Maturen et al ||152||CT/US||18 G||4||Sensitivity 97.8%
|Volpe et al ||100||CT/US||18 G||16||Accuracy 100%|
|Blumenfeld et al ||81||US/CT||18 G||2.5||Accuracy: 88%|
|Wang et al ||110||US/CT||18 G||10.1||Accuracy 100%|
|Veltri et al ||150||US/CT||18 G||14||Accuracy 92%|
The aims of biopsy are to determine malignancy, histotype, and grade of SRMs to support treatment decisions . Needle biopsy can avoid unnecessary surgery for benign renal tumours that cannot be accurately identified by modern abdominal imaging, such as oncocytomas and fat-free angiomyolipomas. Percutaneous biopsy can also be useful to guide surveillance strategies . Histologically proven high-grade RCCs may not be optimal candidates for AS for their higher risk of progression during follow-up, whereas benign tumours can be followed with a less rigorous imaging schedule. Finally, percutaneous biopsy is always indicated before ablative treatment without previous confirmation of the histology of a SRM  and  and is useful to confirm the success of ablative therapies in combination with CT and MRI.
However, several issues with renal tumour biopsies still must be resolved. Overall, 3–30% of biopsies still fail to provide a diagnosis (Table 7). Further improvements in biopsy techniques and in the definition of optimal patterns of biopsy are required. Moreover, a standardised classification of biopsy failures is needed to allow the comparison of different series and enable an accurate determination of biopsy accuracy. At present, when the biopsy of a radiologically suspicious renal mass is negative or nondiagnostic, surgical exploration or repeat biopsy should be recommended.
The diagnosis of histologic subtype is possible in most renal tumour biopsies. In a study of interobserver variability, pathologic subtyping on needle biopsy was found to be overall highly reproducible with the exception of chromophobe RCC . In fact, the differential diagnosis between oncocytoma and chromophobe RCC is challenging on biopsy specimens. The use of immunohistochemistry panels, fluorescent in situ hybridisation, and reverse transcriptase-polymerase chain reaction can increase the accuracy of diagnosis in uncertain cases  and . Finally, Fuhrman grading is challenging on renal tumour biopsies and its accuracy is not optimal (70–83%)  and . This can be partially explained by interobserver variability and by the presence of grade heterogeneity. However, a better accuracy in the assessment of Fuhrman grade can be obtained when tumours are simply classified as low (Fuhrman I–II) or high (Fuhrman III–IV) grade .
In summary, renal tumour biopsies have an increasing role in the management of SRMs. Adequate biopsies provide histologic information that can be combined with clinical tumour and patient characteristics to select the best treatment option for each individual patient. However, further improvements in biopsy techniques and in the histologic assessment of biopsy specimens are needed. In the future, molecular and cytogenetic information from renal tumour biopsies may be integrated with other histologic and clinical variables in algorithms and nomograms to be used for counselling and treatment decision making for SRMs.
An increasing number of SRMs today are detected in asymptomatic patients by noninvasive abdominal imaging. Surgical removal is the standard of care for small renal tumours. NSS achieves equivalent oncologic outcomes and better preservation of renal function compared with RN and is therefore the primary treatment choice whenever technically feasible. LPN is an alternative to OPN in experienced hands. Careful patient selection is needed in the early phase of a surgeon's experience with LPN to reduce WIT and morbidity. RAPN can reduce the technical challenges associated with LPN. However, although the first experiences are encouraging, oncologic outcomes are still immature, and the technique is still under evaluation.
The observation that a significant proportion of SRMs are benign tumours or low-grade RCCs with relatively indolent clinical behaviour has led to less invasive treatment options for selected patients who have a shorter life expectancy, including minimally invasive ATs and AS. The rationale of AT is to treat incidental cortical SRMs in patients at high surgical risk with potentially reduced morbidity. CA and RFA are promising ATs, but standardisation of accurate criteria to define treatment success and long-term follow-up are needed to better determine the oncologic outcomes of these techniques.
AS is a reasonable option to manage SRMs in elderly patients or patients with significant comorbidities who are not good surgical candidates, with delayed intervention reserved for those tumours that progress during follow-up. However, long-term results of prospective series of AS in patients with histologically proven RCCs are needed to confirm the safety of this conservative approach. Prospective randomised studies comparing the outcomes of excision, ablation, and observation of SRMs are warranted to better define the clinical role and indications of nonsurgical treatment modalities.
Renal tumour histology obtained by percutaneous needle biopsy can be useful in selected patients to make treatment decisions and guide surveillance strategies. The integration of clinical and histologic information has the potential to increase our ability to select the best treatment option for each individual patient diagnosed with a SRM.
Study concept and design: Volpe, Cadeddu, Cestari, Gill, Jewett, Joniau, Kirkali, Marberger, Patard, Staehler, Uzzo.
Acquisition of data: Volpe.
Analysis and interpretation of data: Volpe, Cadeddu, Cestari, Gill, Jewett, Joniau, Kirkali, Marberger, Patard, Staehler, Uzzo.
Drafting of the manuscript: Volpe.
Critical revision of the manuscript for important intellectual content: Volpe, Cadeddu, Cestari, Gill, Jewett, Joniau, Kirkali, Marberger, Patard, Staehler, Uzzo.
Statistical analysis: None.
Obtaining funding: None.
Administrative, technical, or material support: None.
Supervision: Volpe, Cadeddu, Cestari, Gill, Jewett, Joniau, Kirkali, Marberger, Patard, Staehler, Uzzo.
Other (specify): None.
Financial disclosures: I certify that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/ affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: None.
Funding/Support and role of the sponsor: None.
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a Department of Urology, University of Eastern Piedmont, Maggiore della Carità Hospital, Novara, Italy
b Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA
c Department of Urology, University Vita-Salute, San Raffaele Hospital, Milan, Italy
d USC Institute of Urology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
e Division of Urology, Department of Surgery and Surgical Oncology, Princess Margaret Hospital and the University Health Network, University of Toronto, Ontario, Canada
f Department of Urology, University Hospitals Leuven, Leuven, Belgium
g Division of Kidney, Urologic and Hematologic Diseases, NIDDK, National Institutes of Health, Bethesda, MD, USA
h Department of Urology, Medical University of Vienna, Vienna, Austria
i Department of Urology, Bicêtre Hospital, Paris XI University, Paris, France
j Department of Urology, University of Munich, Klinikum Grosshadern, Munich, Germany
k Department of Urologic Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA
Dr. Kirkali is participating in his personal capacity. The views and opinions expressed by Dr. Kirkali do not represent any position of policy of the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institutes of Health, the US Department of Health and Human Services, or the US government.
© 2011 Published by Elsevier B.V.