BJUI. Active surveillance of small renal masses offers short-term oncological efficacy equivalent to radical and partial nephrectomy

Transcription

1 BJUI Active surveillance of small renal masses offers short-term oncological efficacy equivalent to radical and partial nephrectomy Nilay Patel, David Cranston, M. Zeeshan Akhtar, Caroline George, Andrew Jones, Aaron Leiblich, Andrew Protheroe and Mark Sullivan Department of Urology, Churchill Hospital, Headington, Oxford, UK Accepted for publication 20 December 2011 Study Type Therapy (case series) Level of Evidence 4 OBJECTIVE To compare the oncological outcomes of active surveillance (AS), radical nephrectomy (RN) and partial nephrectomy (PN) in the management of T1a small renal masses (SRMs). What s known on the subject? and What does the study add? Active surveillance of small renal masses has traditionally been reserved for elderly patients deemed unfit for surgery or ablation. There is increasing evidence showing the safety of active surveillance in the management of small renal masses. In this retrospective study we compared outcomes for patients with small renal masses managed with active surveillance, radical nephrectomy and partial nephrectomy. We showed that active surveillance was safe and appeared as effective as immediate surgery in the management of small renal tumours. RESULTS CONCLUSIONS PATIENTS AND METHODS At present AS is used in the treatment of SRMs in elderly patients with multiple co-morbidities or in those who decline surgery. We identified all patients with T1a SRMs managed with RN, PN or AS. Retrospective data were collected from patient case records with survival data and cause of death cross-referenced with the Oxford Cancer Intelligence Unit. A total of 202 patients with 234 T1a SRMs (solid or Bosniak IV) were identified; 71 patients were managed with AS, 41 with an RN and 90 by PN. Over a median follow-up of 34 months the mean growth rate on AS was 0.21 cm/ year with 53% of SRMs managed with AS showing negative or zero growth. No statistically significant difference was observed in overall (OS) and cancer-specific (CSS) survival for AS, RN and PN (AS-CSS 98.6%, AS-OS 83%; RN-CSS 92.6%, RN-OS 80.4%; PN-CSS 96.6%, PN-OS 90.0%). Active surveillance of SRMs offers oncological efficacy equivalent to surgery in the short/intermediate term. The results of this study support a multicentre prospective randomized controlled trial designed to compare the oncological efficacy of AS and surgery. KEYWORDS active surveillance, renal carcinoma, small mass INTRODUCTION The incidence of renal cancer has been increasing in Europe and the USA since the 1980s [ 1 3 ]. An increase in the use of cross-sectional imaging over this period has resulted in a downward stage migration at presentation with an increasing proportion of patients presenting with small renal masses (SRM) < 4 cm in size [ 4 6 ]. Increased detection rates of early stage disease have resulted in increased rates of surgery for SRMs, the benefits of which remain unclear. There are conflicting reports on improvements in mortality rates for renal cancer over the past few years [ 5,7 ], suggesting that increased detection and earlier treatment may not necessarily be improving the survival of patients with T1a renal cancer. Numerous treatment options have been available to patients presenting with SRMs inclding radical nephrectomy (RN), partial nephrectomy (PN), ablative therapies (cryotherapy, radiofrequency ablation, high-intensity focused ultrasound) and active surveillance (AS). The current guidelines for the treatment of T1 renal cancer from the AUA and the European Association of Urology have suggested performing a PN whenever possible in the surgically fit patient [ 8,9 ]. A recent study from the USA has shown the increased use of nephron-sparing techniques over the past decade; however, in 2007 only 32.2% of T1 renal masses were managed with a PN, 57.7% with an RN, 6.8% with ablative therapy and 3.3% with AS [ 10 ]. A significant number of SRMs are diagnosed as incidental tumours often in elderly 2012 doi: /j x x 1

2 PATEL ET AL. patients. As life expectancy continues to improve, the number of patients with incidentally detected renal masses is likely to increase further, as will the number of patients being offered surgical intervention. There is increasing evidence to suggest that surgical intervention may not be needed in all SRMs because the risk of metastases and death from RCC is low regardless of treatment modality [ 11 ]. Active surveillance has traditionally been reserved for the treatment of SRMs in elderly patients with multiple co-morbidities or in those who decline surgery. It has not been proposed as the treatment of choice in young fit patients because of the small but real risk of developing incurable metastatic disease while on surveillance. In this paper we present the results of a single-centre retrospective audit in which we compared the oncological outcomes of AS, PN and RN in the management of SRMs. The main objective of the study being to determine if there is adequate evidence to support a randomized trial and to inform any proposed trial design of potential inclusion/exclusion criteria and triggers for intervention. METHODS We used our local Cancer Research Uro-Onocology Database [ 12 ] to identify all patients that presented to our department between 1 January 2005 and 31 December 2010 with suspected T1 renal tumours. Upon presentation, each patient was definitively staged with either a triple-phase CT scan of the chest and abdomen or a dedicated renal MRI scan. All images were reviewed by a urological surgeon and a uro-radiologist. Patients were subsequently counselled regarding their treatment options, which included RN (open or laparoscopic), PN (open, laparoscopic or robotic), ablative therapy (cryotherapy, radiofrequency ablation or high-intensity frequency ultrasound) and AS. The choice of treatment was based on tumour characteristics and patient factors, including age, associated co-morbidities and overall surgical risk. Predefined selection criteria for each treatment option had not been established at the commencement of this study. We only included patients with solid enhancing or cystic enhancing T1a small renal masses managed by RN, PN or AS. T1a Active Surveillance No. of patients 71 Sex Male 52 Female 19 Number of masses 93 Nature of masses Solid enhancing 76 Cystic enhancing 17 Biopsy Yes 7 Renal cell carcinoma 2 Oncocytoma 2 Non diagnostic 3 No 86 Mean annual growth rate (cm/year) 0.21 Mean duration of follow-up (months) 34 Mean growth rate (cm/year) All patients 0.21 Positive growth 0.35 Mean growth rates (cm/year) All patients 0.21 Negative or zero growth, n (%) 49 (53) cm/year, n (%) 19 (21) cm/year, n (%) 13 (14) > 0.5 cm/year, n (%) 11 (12) Positive growth 0.35 Patients progressing to intervention, n / N (%) 14/71 (19.7) Increase in size, n (%) 9 (64) Patient choice, n (%) 4 (29) Change in diagnosis, n (%) 1 (7) A follow-up surveillance protocol for patients managed with AS had not been prospectively established before this study. Patient assessment and follow-up were dependent upon individual physician preferences. Patients were followed up with CT, MRI or ultrasound scans of the abdomen and chest every 3 6 months. Routine percutaneous renal biopsy of T1 lesions has not been part of our practice. Patients on AS were advised to have definitive treatment if their tumours grew to > 4 cm in maximal diameter or had rapid tumour growth rates. Patients managed with an RN or PN were followed up postoperatively every 6 12 months with a CT scan of the chest and abdomen. Retrospective data were collected from patient case records including; radiological tumour characteristics at presentation, radiological tumour characteristics during follow-up, surgical pathology, incidence of local and metastatic recurrence and survival. Renal masses were staged according to the 2009 TNM classification for kidney tumours. Survival data and cause of death were cross-referenced with the Oxford Cancer Intelligence Unit. Statistical analysis was performed using Microsoft E XCEL and G RAPH P AD P RISM 4; using the following tests; chi squared, Student s t test and Kaplan Meier curves. RESULTS TABLE 1 Demographics and outcomes of patients managed with active surveillance A total of 71 patients with 93 small renal masses < 4 cm in maximal diameter (76 solid, 17 enhancing cystic Bosniak IV) were managed with AS ( Table 1 ). Four patients with a total of seven tumours were known to have Von Hippel Lindau disease. The mean age of patients on AS was 71.9 years (24 93) with a mean tumour size at presentation of 2.2 cm. The mean duration of follow-up was 34 months

3 A C T I V E S U R V E I L L A N C E O F S M A L L R E N A L M A S S E S FIG. 1. A waterfall plot illustrating the annual growth rate for each small renal mass managed with active surveillance. The dashed line represents a growth rate of 0.5 cm/year. This could be used as a trigger for intervention for patients being managed with active surveillance. Growth rate, cm/yr Patient Number Over this period the average annual growth rate for all 93 tumours was 0.21 cm/year. A percutaneous renal biopsy was performed in 7/93 (7.5%) tumours of which two showed renal carcinoma, two oncocytoma and three were non-diagnostic. We observed that 49/93 (53%) masses had negative or zero growth during the course of their follow-up. Tumours that did increase in size were observed to have variable growth rates: cm/year, 19/93 (21%); cm/year, 13/93 (14%); > 0.5 cm/year, 11/93 (12%) ( Fig. 1 ). Overall 14/71 (19.7%) patients managed with AS subsequently went on to receive definitive therapy; RN (2/14), PN (7/14), radiofrequency ablation (3/14) and high-intensity focused ultrasound (2/14). The trigger for intervention in these patients was an increase in size (9/14), patient choice (4/14) and a change in radiological diagnosis (1/14). The annual growth rate for patients that went on to receive treatment after a period of surveillance was significantly higher than those that remained on AS (0.32 cm/year vs 0.14 cm/year, P < 0.05). The mean time from commencement of AS to delayed intervention was 29 months. Metastatic progression was observed in only one patient of 71 (1.4%) managed with AS. This patient had a history of RCC and presented with two tumours within a solitary kidney, which measured 5.3 cm and 1.5 cm in maximal diameter. A total of 12 deaths occurred in the active surveillance cohort of which one was attributed to metastatic RCC, giving an overall survival (OS) rate of 83% and a cancer-specific survival (CSS) rate of 98.6%. Tumours 0 4 cm Tumours 4 7 cm Number of tumours Sex Male Female Operation Radical nephrectomy Partial nephrectomy Tumour characteristics Solid Solid (multifocal) 15 3 Cystic Tumour histology CCRCC CHROMO 8 5 ONCO 10 6 PAP PAP PAP 1 & SPINDLE 0 1 Tumour stage T1a T1b 0 67 T3a T3b 0 1 Furhman grade I 12 7 II III IV 3 7 x 10 6 Surgical margin Negative Positive 10 (PN = 9; RN = 1) 1 (RN = 1) Patients managed with AS and deferred definitive treatment had an OS rate of 78.5% and a CSS rate of 100%. Surgical pathology data were available in 9/14 patients, with no statistically significant upstaging of disease after a period of active surveillance; T1a, 6/8; T3a, 2/8. Pathology data were not available for the five patients who underwent tumour ablation. Over the study period, 131 patients with 141 SRMs < 4 cm in size were managed surgically by either a radical nephrectomy (43 patients) or a partial nephrectomy (98 patients). Over the same period 102 patients with T1b tumours were also managed with extirpative surgery ( Table 2 ). Four patients with six tumours with known Von Hippel Lindau disease underwent surgery for T1a tumours. TABLE 2 Patient demographics and pathological features of T1 tumours managed with surgery PN, partial nephrectomy; RN, radical nephrectomy. Patients managed with AS were significantly older than those managed with either RN or PN (mean age, AS 71.9 years, RN 65.4 years, PN 58.9 years; P < 0.05). There were no statistically significant differences in tumour size between the three treatment groups (AS 2.2 cm, RN 2.66 cm, PN 2.67 cm) ( Table 3 ). Local recurrence within the renal remnant or renal bed after surgery was observed in 2/41 patients after an RN and 7/90 patients after a PN (7.7%). Four of the seven patients who developed local recurrences after PN had multifocal disease and 2/7 had positive surgical margins. Positive surgical margins were noted in 10/141 (7%) SRMs (PN 9, RN 1); of whom only 2/10 went on to develop a local recurrence and 1/10 went on to develop metastatic disease. Metastatic progression was observed after surgery in 15/131 patients (11.4%). Of these patients,

4 PATEL ET AL. TABLE 3 Comparison of patient characteristics and oncological outcomes for patients with T1 renal masses managed with Active Surveillance (AS), Radical Nephrectomy (RN) and Partial Nephrectomy (PN) Variable < 4 cm AS < 4 cm RN < 4 cm PN < 4 cm surgery > 4 cm surgery No. of patients Mean age (years) Mean tumour size (cm) Mean follow-up (months) Local recurrence, n / N (%) N/A 2/41 (4.8) 7/90 (7.7) 10/131 (7.6) 5/102 (4.9) Metastatic progression, n / N (%) 1/71 (1.5) 4/41 (9.7) 11/90 (12.2) 15/131 (11.4) 18/102 (17.6) Overall survival, n / N (%) 59/71 (83) 33/41 (80.4) 81/90 (90.0) 113/131 (87.0) 85/102 (83.8) Cancer-specific survival, n / N (%) 70/71 (98.6) 38/41 (92.6) 87/90 (96.6) 125/131 (95.4) 95/102 (93.1) 8/15 had clear-cell RCC, 1/15 type 1 papillary RCC, 3/15 type 2 papillary RCC and 1/15 chromophobe RCC; 11/15 T1a, 4/15 T3a/b; G1/2 4/15, G3/4 11/15; mean size 2.36 cm ( ). Overall 114/131 patients managed with surgery were alive, equating to an 87.0% OS rate and a 95.4% CSS rate. Kaplan Meier curves comparing oncological outcomes for AS, RN and PN showed no statistically significant difference in OS or CSS between the groups ( Fig. 2 ). A sub-group analysis compared outcomes of AS and surgery in patients over the age of 70. In total, 60 tumours in 47 patients were managed with surveillance and 43 with surgery (PN 23, RN 20). No statistically significant difference was seen in the OS or CSS rate (surgery, 76.7% OS, 97.6% CSS; AS, 76.5% OS, 97.8% CSS). Surgical pathology was reviewed for all patients who underwent surgery for a T1 renal mass. The incidence of high-risk locally advanced disease (stage T3a) was significantly higher in patients with tumours 4 7 cm in maximal diameter than those with tumours < 4 cm in maximal diameter ( < 4 cm 11/141 (7.8%); > 4 cm 38/102 (37.3%), P < 0.001) ( Fig. 3 ). A similar difference was observed for tumours cm in size: /36 (25%); < 3.5 cm 8/105 (7.6%); P < These differences were not replicated when comparing smaller tumours; /40 (5%); < 3.0 6/76 (7.8%); P > DISCUSSION In this study we compared oncological outcomes for patients with T1a SRMs managed by either AS, RN or PN. The study has a number of inherent weaknesses; it is a retrospective single-centre study, the three treatment arms have unmatched patient characteristics that can introduce case selection bias between surgery and active surveillance, there is a low diagnostic biopsy rate for the active surveillance group and a lack of predetermined criteria for intervention in the AS group. Despite these weaknesses much can be gleaned from the results of this study. One of the main aims of this study was to evaluate the oncological safety of AS in comparison with surgical intervention. This was initially evaluated by determining the natural history of the SRMs within the study cohort. We observed an average growth rate for SRMs < 4 cm in size of 0.21 cm/year (mean follow-up 34 months). This compares with data from the pooled analysis by Smaldone et al. [ 13 ], which showed that T1a tumours have a growth rate of 0.31 cm/ year. Jewett et al. [ 14 ] noted an annual growth rate of 0.13 cm/year for T1a masses in the prospective Canadian Small Renal Mass Trial. Numerous studies have previously shown variability in the growth rates of T1 renal masses. In our experience 53% of T1a SRMs showed zero or negative growth and none of the patients subsequently developed metastatic disease. Other studies have shown that 23 36% of T1 SRMs have zero or negative growth rates [ ]. The pooled analysis of 880 patients with SRMs by Smaldone et al. [ 13 ] observed that metastatic progression was not observed in any patient who had negative or zero growth on follow-up, which is potentially of great importance when counselling patients being managed with AS. FIG. 2. Kaplan Meier curves comparing overall survival (OS) and cancer-specific survival (CSS) for all patients with T1a tumours managed with active surveillance (AS), radical nephrectomy (RN) and partial nephrectomy (PN). Percent survival Percent survival Months Months FIG. 3. Comparison of surgical pathology for T1 renal tumours. PN OS RN OS AS OS PN CSS RN CSS AS CSS 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% >4 cm <4 cm <3.5 < T3a (%) T1a (%)

5 A C T I V E S U R V E I L L A N C E O F S M A L L R E N A L M A S S E S Triggers for intervention for patients on an AS protocol are yet to be clearly defined in the management of SRMs. At present, rapid tumour growth and progression beyond a maximal size are the most commonly used triggers for intervention. The principle aim being to distinguish between high-risk tumours and low-risk SRMs. The identification of rapid growth rates in an active surveillance protocol for SRMs may act as a marker of aggressive disease in a similar way to that in which PSA doubling time is used in active surveillance protocols for prostate cancer. The use of growth rate in differentiating SRMs seems well founded, Smaldone et al. [ 13 ] showed that SRMs that progressed to metastatic disease had significantly higher growth rates than tumours that did not metastasize (0.8 cm/ year vs 0.4 cm/year). In our study, 12% of patients had an annual growth rate > 0.5 cm/year whereas 9% of patients showed an annual growth rate > 0.8 cm/year. Our data and that of Smaldone et al. [ 13 ] suggest that a linear growth rate of > 0.5 cm/year could be proposed as a trigger for intervention in an AS protocol. Use of the linear growth rate however may not be the most accurate means of assessing tumour growth as the linear growth rate is dependent upon tumour size at presentation. Evaluation of tumour volume may be a more sensitive means of assessing tumour burden and risk. Jewett et al. [ 14 ] used a doubling of tumour volume within 12 months as a trigger for progression in their prospective observation study. It is unclear which of these approaches is better at identifying high-risk disease. Tumour size beyond a predetermined limit such as 4 cm is often used alongside growth rate as the trigger for intervention for patients on AS. Our study justifies this approach, as we showed that tumours > 4 cm in size had significantly higher rates of high-risk disease (T3a) than tumours < 4 cm in size ( > 4 cm 37% vs < 4 cm 7.8%). Our study suggested that the trigger point should be lowered to 3.5 cm as a significant proportion of patients with cm tumours have T3a disease (25%). Others have suggested a trigger point as low as 3 cm, because tumours > 3 cm are associated with increased aggressive potential [ 17 ]. During the course of our study 14/71 (19%) patients went on to receive definitive therapy for their SRMs. Other groups have reported intervention rates of between 4.5 and 45.4% [ 13,14,18 20 ], most of these studies did not report predetermined intervention criteria for patients on AS. As would be expected the tumours of our patients who underwent definitive treatment had higher annual growth rates than tumours of patients who continued on AS (0.32 cm/year vs 0.14 cm/year, P < 0.05) an observation mirrored by Smaldone et al. [ 13 ]. Delayed intervention did not appear to adversely affect surgical approach or oncological outcome. Patients who went on to receive definitive treatment in our study were managed with nephron-sparing surgery in 85% of cases. There was no upstaging of disease or there were no adverse oncological outcomes in contrast to patients managed with surgery initially. Having determined the natural history of SRMs managed with AS we subsequently compared the oncological outcomes of tumours < 4 cm in size treated with AS, RN or PN. In our series only 1/71 patients managed with AS developed metastatic RCC (1.4%). In this patient it was unclear if the T1a SRM was the cause of the metastatic disease because the patient had a history of renal cancer and a synchronous T1b tumour within his remaining kidney. Interestingly metastatic disease occurred more frequently after surgery than after active surveillance (AS 1/71, RN 4/41, PN 12/90), though this may be a result of increased tumour size in both surgery groups and the potential for benign pathology in the non-biopsied AS group. Metastatic progression rates for T1a SRMs managed with AS are reported to be between 1 and 2% [ 13,14,21 ]. Kunkle et al. [ 11 ] performed a meta-analysis of oncological outcomes for over 6000 SRMs and concluded that no significant differences were detected in the incidence of metastatic progression regardless of whether lesions were excised, ablated or observed. No significant differences in CSS rates at a mean follow-up of 34 months were observed when comparing the outcomes of SRMs treated with AS, RN or PN. Evaluation of the overall survival rates suggested a benefit in favour of PN, although this was not significant (AS 83%, RN 80%, PN 90%). These are striking observations when it is considered that most AS patients are enrolled to surveillance on account of significant co-morbidities. Numerous groups have shown an overall survival benefit of PN over RN in the treatment of the SRMs [ ], an effect that may be attributable to the significantly greater incidence of chronic kidney disease after RN [ 25 ]. Our work and other recent studies have started to show the safety of AS as a treatment modality for SRMs. It is becoming increasingly clear that all SRMs do not need immediate surgical treatment. Many SRMs are incidental low-grade, low-risk tumours akin to Gleason 6 prostate cancer and are unlikely to result in the development of metastatic disease or cancer-related death. As a consequence, to treat all SRMs may be over-treatment and may unnecessarily expose patients to the perioperative risks of surgery and the long-term risks of chronic kidney disease and cardiovascular disease [ 25 ]. Further research in the diagnostic work up of patients may help to identify high-risk SRMs that are more likely to progress or metastasize. An example of clinically applicable advances in imaging is the R.E.N.A.L. nephrometry scoring system which has recently been shown to predict malignancy and high-grade pathology [ 26 ]. The ability to accurately identify vascular invasion (T3a) may be of particular importance in identifying patients suitable for AS. The past few years has seen a significant increase in the use of percutaneous renal biopsies in the diagnostic setting. Routine renal biopsy results in an 80% diagnostic rate with minimal associated complications [ 27,28 ]. The importance of renal biopsies may increase with the development and adoption of biomarkers that may help to personalize treatment of SRMs [ 27,29 ]. The results of this study support the development of a multi-centre prospective randomized controlled trial comparing active surveillance with delayed intervention versus immediate partial nephrectomy or ablation. The randomized controlled trial would aim to determine the oncological efficacy of these differing approaches in patients with biopsy-proven RCC. We would propose recruiting patients over 70 years of age as our study and that of Lane et al. [ 30 ] has shown the safety of AS in patients older than years. Based on our results we would propose intervention when tumours

6 PATEL ET AL. being managed with AS are > 3.5 cm in size or have growth rates > 0.5 cm/year or show doubling of tumour volume in less than 12 months. CONFLICT OF INTEREST None declared. REFERENCES 1 Ferlay J, Parkin DM, Steliarova- Foucher E. Estimates of cancer incidence and mortality in Europe in Eur J Cancer 2010 ; 46 : Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin 2011 ; 61 : Mathew A, Devesa SS, Fraumeni JF, Chow W-H. Global increases in kidney cancer incidence, Eur J Cancer Prev 2002 ; 11 : Cooperberg MR, Mallin K, Ritchey J, Villalta JD, Carroll PR, Kane CJ. Decreasing size at diagnosis of stage 1 renal cell carcinoma: analysis from the National Cancer Data Base, 1993 to J Urol 2008 ; 179 : Hollingsworth JM, Miller DC, Daignault S, Hollenbeck BK. Rising incidence of small renal masses: a need to reassess treatment effect. J Natl Cancer Inst 2006 ; 98 : Kane CJ, Mallin K, Ritchey J, Cooperberg MR, Carroll PR. Renal cell cancer stage migration: analysis of the National Cancer Data Base. Cancer 2008 ; 113 : Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, CA Cancer J Clin 2009 ; 59 : Campbell SC, Novick AC, Belldegrun A et al. Guideline for management of the clinical T1 renal mass. J Urol 2009 ; 182 : Ljungberg B, Cowan NC, Hanbury DC et al. EAU guidelines on renal cell carcinoma: the 2010 update. Eur Urol 2010 ; 58 : Cooperberg MR, Mallin K, Kane CJ, Carroll PR. Treatment trends for stage I renal cell carcinoma. J Urol 2011 ; 186 : Kunkle DA, Egleston BL, Uzzo RG. Excise, ablate or observe: the small renal mass dilemma a meta-analysis and review. J Urol 2008 ; 179 : ; discussion Charlesworth PJS, Kilbey N, Taylor M et al. Automated uro-oncology data collection: the Cancer Research Uro-Oncology Database. BJU Int 2010 ; 105 : Smaldone MC, Kutikov A, Egleston BL et al. Small renal masses progressing to metastases under active surveillance: a systematic review and pooled analysis. Cancer 2011 ; 118 : Jewett MAS, Mattar K, Basiuk J et al. Active surveillance of small renal masses: progression patterns of early stage kidney cancer. Eur Urol 2011 ; 60 : Crispen PL, Viterbo R, Boorjian SA, Greenberg RE, Chen DYT, Uzzo RG. Natural history, growth kinetics, and outcomes of untreated clinically localized renal tumors under active surveillance. Cancer 2009 ; 115 : Kunkle DA, Crispen PL, Chen DYT, Greenberg RE, Uzzo RG. Enhancing renal masses with zero net growth during active surveillance. J Urol 2007 ; 177 : ; discussion Remzi M, Ozsoy M, Klingler HC et al. Are small renal tumors harmless? Analysis of histopathological features according to tumors 4 cm or less in diameter. J Urol 2006 ; 176 : Haramis G, Mues AC, Rosales JC et al. Natural history of renal cortical neoplasms during active surveillance with follow-up longer than 5 years. Urology 2011 ; 77 : Rosales JC, Haramis G, Moreno J et al. Active surveillance for renal cortical neoplasms. J Urol 2010 ; 183 : Kouba E, Smith A, McRackan D, Wallen EM, Pruthi RS. Watchful waiting for solid renal masses: insight into the natural history and results of delayed intervention. J Urol 2007 ; 177 : ; discussion Chawla SN, Crispen PL, Hanlon AL, Greenberg RE, Chen DYT, Uzzo RG. The natural history of observed enhancing renal masses: meta-analysis and review of the world literature. J Urol 2006 ; 175 : Kates M, Badalato GM, Pitman M, McKiernan JM. Increased risk of overall and cardiovascular mortality after radical nephrectomy for renal cell carcinoma 2 cm or less. J Urol 2011 ; 186 : Huang WC, Elkin EB, Levey AS, Jang TL, Russo P. Partial nephrectomy versus radical nephrectomy in patients with small renal tumors is there a difference in mortality and cardiovascular outcomes? J Urol 2009 ; 181 : ; discussion Thompson RH, Boorjian SA, Lohse CM et al. Radical nephrectomy for pt1a renal masses may be associated with decreased overall survival compared with partial nephrectomy. J Urol 2008 ; 179 : ; discussion Huang WC, Levey AS, Serio AM et al. Chronic kidney disease after nephrectomy in patients with renal cortical tumours: a retrospective cohort study. Lancet Oncol 2006 ; 7 : Kutikov A, Smaldone MC, Egleston BL et al. Anatomic features of enhancing renal masses predict malignant and high-grade pathology: a preoperative nomogram using the RENAL Nephrometry score. Eur Urol 2011 ; 60 : Ph é V, Yates DR, Renard-Penna R, Cussenot O, Roupret M. Is there a contemporary role for percutaneous needle biopsy in the era of small renal masses? BJU Int 2012 ; 109 : Leveridge MJ, Finelli A, Kachura JR et al. Outcomes of small renal mass needle core biopsy, nondiagnostic percutaneous biopsy, and the role of repeat biopsy. Eur Urol 2011 ; 60 : Yates DR, Roupret M. Small renal mass and low-risk prostate cancer: any more for active surveillance? Eur Urol 2011 ; 60 : Lane BR, Abouassaly R, Gao T et al. Active treatment of localized renal tumors may not impact overall survival in patients aged 75 years or older. Cancer 2010 ; 116 : Correspondence: Nilay Patel, Department of Urology, Churchill Hospital, Old Road, Headington, Oxford OX3 7LJ, UK. n1laysp@googl .com Abbreviations : SRM, small renal mass ; RN, radical nephrectomy ; PN, partial nephrectomy ; AS, active surveillance ; OS, overall survival ; CSS, cancer-specific survival