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Keywords:

  • radiofrequency ablation;
  • renal tumour;
  • nephron-sparing surgery;
  • oncological outcomes

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Patients and Methods
  5. Results
  6. Discussion
  7. Conflict of Interest
  8. References

Objective

  • To report the long-term oncological and renal function outcomes in healthy adults treated with radiofrequency ablation (RFA) for small renal masses.

Materials and Methods

  • We retrospectively analysed the medical records of otherwise healthy patients (those with American Society of Anesthesiologists symptom score 1 or 2) with clinical T1a renal tumours who underwent RFA at our institution between March 2001 and July 2012.
  • Radiographic follow-up with contrast imaging was performed at 6 weeks, 6 months, 1 year and annually thereafter.
  • Local recurrence was defined as any new enhancing lesion (>10 HU) after the initial negative post-treatment computed tomography results.
  • The estimated glomerular filtration rates (eGFRs) before and after RFA were calculated using the Cockgroft–Gault equation.

Results

  • We performed RFA on 58 renal tumours in 52 patients. The mean tumour size was 2.2 cm with a median (interquartile range) follow-up of 60 (48–90) months.
  • Three (5.1%) of the treated masses had tumour recurrence after initial RFA. The 5- and 10-year recurrence-free survival rate was 94.2%. There were no recurrences after 3 years. Three (5.1%) patients died during the follow-up, which gave 5- and 10-year overall survival rates of 95.7% and 91.1%. No patient developed metastatic renal cell carcinoma (RCC) and none died from RCC.
  • Paired analysis showed that the eGFR values at a median follow-up of 40 months did not differ significantly from those before RFA.

Conclusion

  • With long-term follow-up, RFA provides durable oncological and functional outcomes for selected T1a renal tumours in otherwise healthy patients.

Abbreviations
RFA

radiofrequency ablation

RN

radical nephrectomy

PN

partial nephrectomy

CKD

chronic kidney disease

ASA

American Society of Anesthesiologists

IQR

interquartile range

Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Patients and Methods
  5. Results
  6. Discussion
  7. Conflict of Interest
  8. References

The number of incidentally discovered renal masses is increasing because of the widespread use of cross-sectional imaging. Most of these masses are small, slow-growing and confined to the kidney at the time of diagnosis [1]. Radical nephrectomy (RN) has historically been the ‘gold standard’ treatment in these cases, but has been shown to carry an increased risk of chronic kidney disease (CKD) and cardiac events compared with nephron-sparing approaches [2, 3]. Currently, nephron-sparing surgery, such as partial nephrectomy (PN), is the standard of care for small renal masses [4], but this surgery can be technically challenging and may be associated with significant peri-operative complications and morbidity [5, 6]. With this in mind, minimally invasive nephron-sparing techniques such as cryoablation and radiofrequency ablation (RFA) have been used in an effort to decrease complications, shorten the convalescence period and reduce ischaemic insult.

Based on the current AUA guidelines for T1 renal masses, thermal ablation treatment is reserved for tumours <4 cm in older patients with significant comorbidities. Within the three-tiered system implemented by the AUA, thermal ablation treatments have achieved a ‘statement of recommendation’ as a nephron-sparing strategy for unhealthy patients with a T1a renal mass [4]. For healthy patients, the panel stated that thermal ablation was ‘an option’, their lowest strength statement. The panel cited the relative lack of large cohorts and long-term oncological data as reasons for their conclusions. To help address these shortcomings, we report oncological and renal function outcomes after RFA for T1a renal masses in healthy patients with long-term follow-up (median of 5 years).

Patients and Methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Patients and Methods
  5. Results
  6. Discussion
  7. Conflict of Interest
  8. References

Institutional review board approval was obtained for this retrospective study. Between March 2001 and July 2012, all healthy patients (those with an American Society of Anesthesiologists [ASA] physical status classification score of 1 or 2) who underwent RFA were identified. Only those with >3-year follow-up were included in the study. Patients with an identified genetic disease predisposing them to RCC were excluded from the analysis, as were patients who had undergone a previous intervention in the ipsilateral kidney.

Radiofrequency Ablation Technique

We have described our technique for percutaneous and laparoscopic RFA previously [7]. Briefly, a radio frequency generator (model 1500; Angiodynamics, Latham, NY, USA) was used with a 14-G Starburst XL probe. Percutaneous approaches were performed using CT guidance and laparoscopic approaches were performed using ultrasound and tumour visualization to guide probe placement. An ablation zone of 0.5–1.0 cm beyond the maximum measured tumour diameter was created. The generator modulated the power up to 150 W to achieve an average ablative temperature of 105 °C. Two ablative cycles were applied with additional cycles at the surgeon's discretion if ablation was considered to be incomplete on immediate radiographic studies. A biopsy was performed in most cases at the time of RFA, if it had not been performed previously.

Follow-up after RFA included history, physical examination, chest radiograph, liver function tests and serum creatinine assessment. Contrast-enhanced CT or MRI studies were obtained at 6 weeks, 6 and 12 months and at least annually thereafter. Incomplete ablation was defined as persistent enhancement (>10 HU) in any portion of the treated lesion at the 6-week CT or MRI. Local recurrence was defined as any new enhancing portion within the ablation zone after the initial negative contrast-enhanced CT or MRI. Recurrence-free survival was defined as freedom from local recurrence. Cancer-specific survival was defined as freedom from death from RCC and overall survival was defined as freedom from death from any cause.

Estimated GFR (eGFR) values were calculated from serum creatinine concentrations, gender and weight using the Cockcroft–Gault equation. Changes in eGFR were calculated based on the eGFR before RFA. CKD stage progression was defined as any change in stage based on the National Kidney Foundation classification system [8].

Statistics

Mean and median values were calculated for continuous variables and frequencies were reported for categorical variables. Survival analysis was calculated using the Kaplan–Meier method. The paired t-test was used to compare eGFR before and after RFA. A P value <0.05 was considered to indicate statistical significance in all cases. Statistical analysis was performed using IBM spss v19 (Chicago, IL, USA).

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Patients and Methods
  5. Results
  6. Discussion
  7. Conflict of Interest
  8. References

Of the 354 patients who underwent RFA within the study period, 117 patients had an ASA score of 1 or 2. Of these, 54 patients had follow-up ≥3 years. Of the remaining patients, two patients were excluded because RFA was performed for PN recurrence. This left a total of 52 patients with ASA scores of 1 (n = 2) or 2 (n = 50) who were included in the analysis. Patient characteristics are shown in Table 1. One patient had bilateral tumours and five had multiple tumours. Laparoscopic RFA was performed for 24 tumours and percutaneous RFA for 34 tumours. The patients' median (interquartile range [IQR]) age at the time of ablation was 57 (51–63) years. The mean (sd) tumour size was 2.2 (0.8) cm. A slight majority (52.5%) of the tumours were exophytic. A procedural biopsy was performed in 55 tumours (95%) and RCC was confirmed in 41 (70%) tumours.

Table 1. Patient demographics and tumour characteristics
  1. *It was not possible to determine whether masses were benign or malignant.

No. of patients52
Male (%)35 (67.3)
Female (%)17 (32.7)
No. of masses58
Median (IQR) age, years57 (51–63)
Median (IQR) follow-up, months60.1 (48–90)
Mean (sd) tumour diameter, cm2.2 (0.8)
Treated side, n (%) 
Right20 (34.5)
Left37 (63.8)
Bilateral1 (1.7)
Tumour location, n (%) 
Exophytic31 (53.4)
Endophytic18 (31.0)
Mixed9 (15.5)
Approach, n (%) 
Percutaneous34 (58.6)
Laparoscopic24 (41.4)
RCC41
Angiomyelolipoma4
Oncocytoma4
Non-diagnostic*5
No biopsy4

Of the 58 treated renal masses, no incomplete ablations were identified. Local tumour recurrence was observed in three patients, all with RCC and all recurring within 3 years. No patients developed metastatic disease. Of the three patients with local recurrence, all underwent RN, two after re-ablation failure. One patient who underwent RN for persistent peripheral enhancement of CT showed no viable RCC, but rather a giant cell reaction.

The median (IQR) follow-up was 60 (48–90) months, with a 5- and 10-year recurrence-free survival of 94.2% (Figure 1). No patient developed metastatic disease and none died from RCC, which gave metastatic-free and cancer-specific survival rates of 100%. Three patients died in the follow-up period, but none from RCC. One died from congestive heart failure complications, one from an undefined cardiovascular event and one from acalculous cholecystitis. The 5- and 10-year overall survival rates were 95.7 and 91.1%, respectively (Figure 2).

figure

Figure 1. Kaplan–Meier estimates of recurrence-free survival (RFS) for healthy patients after RFA.

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figure

Figure 2. Kaplan–Meier estimates for overall survival (OS) in healthy patients after RFA.

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Renal function outcomes are shown in Table 2. The paired change in eGFR before (106.3 mL/min/m2) and after RFA (99.2 mL/min/m2) was not significantly different (P = 0.058). Eight patients had CKD stage progression and one patient had CKD stage improvement during follow-up.

Table 2. Estimated GFR of patients before and after treatment at a mean of 40 months after RFA
 Pre-treatment eGFR (sd)Post-treatment eGFR (sd)P
All patients106.3 (48.8)99.2 (39.2)0.058
CKD classification   
11913 
2813 
323 
4 and 500 

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Patients and Methods
  5. Results
  6. Discussion
  7. Conflict of Interest
  8. References

Renal tumour ablation has conventionally been reserved for patients with small tumours who are in general poor health, but the use of cryoablation and RFA has increased in recent years. Reasons for this increase may include the ease of use and relative lack of complications, along with reported excellent short- and intermediate-term oncological and renal function outcomes in selected patients [9, 10]. Nevertheless, RFA studies demonstrating oncological efficacy are limited by sample size and relatively short follow-up and these limitations are among the reasons that PN remains the preferred method of nephron-sparing treatment [4, 11].

When compared with that of PN, the oncological equivalence of RFA varies between reports and is largely based on cohort selection. In a large population-based study, Whitson et al. found there to be significant differences between tumours treated by PN and thermally ablated tumours in terms of disease-free survival [12]. This study, however, did not directly compare RFA with PN, rather it included RFA, cryoablation and other unspecified types of ablation. Furthermore, there were also significant differences between the study cohorts, with larger tumours and older patients included in the ablative group. Lastly, the era in which the ablative therapy was performed was considered by those authors to be a confounding variable, with the outcomes of more contemporary ablations rivaling those for PN. In a study comparing matched cohorts for PN and RFA, Olweny et al. [13] reported 5-year recurrence-free survival and cancer-specific survival to be similar, but that study was limited by small numbers in each arm (<50 patients) and a short mean follow-up in the RFA arm (30 months). Although the present study did not have a matched PN group of patients, it did show similar long-term results to those published for PN (Figure 1). Although local recurrence was detected in three patients, all were successfully retreated and all remained without evidence of disease on last follow-up. Furthermore, no patients developed metastasis or died from RCC.

When treating small renal masses with ablation techniques, their great dependence on tumour size should be considered. The current guidelines use a 4 cm threshold to distinguish between T1a and T1b stages. Despite studies confirming that outcomes for T1b tumours treated with RFA are significantly worse than those for T1a tumours [14], this may not be the most clinically relevant distinction when considering the technical success of RFA. A recent paper by Best et al. [15] showed a significant improvement in RFA success and disease-free survival in tumours <3 cm. In that study, patients with a tumour <3 cm had a 3-year 96% disease-free survival rate, while those with tumours >3 cm had a 3-year disease-free survival rate of 79%. Other studies have reported similar findings, with 3 cm seeming to be a clinically relevant threshold for tumour size for the success of both RFA and cryotherapy [16, 17]. In the current study, the only tumours that showed recurrence were >3 cm, again suggesting the sensitivity of RFA to tumour size, even within the T1a classification.

While oncological outcomes are of primary concern when treating RCC, recent evidence suggests that preservation of renal function is paramount as this can improve overall survival in this population. Thompson et al. [2] reported an age-dependent increased relative risk of mortality in patients undergoing RN vs PN. The age dependence was noted only in patients <65 years old, which would imply that a significant life expectancy after treatment was needed for the deleterious effects of RN to be seen. Examining this relationship further, Lucas et al. [9] compared renal function outcomes for several treatment methods and, on multivariate analysis, found that a significant increased risk for the development of CKD was associated with PN (hazard ratio 10.4) and RN (hazard ratio 34.3) compared with RFA. While this study did not specifically look at mortality, the development of CKD was used as a surrogate for potential morbidity as it has been linked to adverse cardiac events and death [18]. While no comparative group was available for the present study, we found that renal function based on eGFR measurements was preserved after RFA and included the three patients who underwent RN for suspected recurrence. Of the eight patients with CKD stage progression, six had a change in eGFR of <10 mL/min/m2, indicating that these patients were simply near a CKD cutoff point at the time of ablation. Furthermore, the patient population was relatively young; >75% of the patients in our study were aged <65 years. As suggested by Thompson et al. [2], this young, healthy population may gain the most benefit from nephron-sparing treatment. As such, the renal function data reported in the present study, in combination with the oncological outcomes, suggest that RFA of small renal tumours (especially those <3 cm) could be considered as a treatment option in younger, healthy patients. We acknowledge that this is the first long-term study of its kind and its results will require confirmation in a larger cohort. Nevertheless, our data may be useful in counselling healthier patients who want to avoid surgery or in whom PN may be exceedingly difficult, but where a nephron-sparing approach is preferred.

Several limitations are worth noting in this study, one being the use of the ASA score as a surrogate for patient health. Although this may be a somewhat simplistic system, previous studies have shown ASA score to correlate with postoperative patient outcomes [19]. Only three patients died from causes other than RCC over an extended study period (Figure 2), and those who did die were all >70 years, which validates our population as healthy at the time of RFA. Another limitation is the follow-up period. Despite being one of the longest reported series, RCC recurrences have been described in up to 3-6% of patients after 5 years [20, 21] and, although no recurrences were observed in any patient after 3 years in this series, late recurrence may be an important factor when considering healthy patients with prolonged life expectancy. Lastly, as this was a retrospective study, selection bias is an issue. Approximately 33% of the patients treated with RFA at our institution had ASA scores of 1 or 2, demonstrating the current trend of reserving this technique for patients with generally worse comorbidities and a shorter life expectancy. Prospective studies enrolling younger, healthy patients are needed in this field, with the caveat that patient counselling in this population must be performed carefully and thoroughly.

In conclusion, according to the available long-term oncological and renal function outcomes, the treatment of clinical T1a renal cancer with RFA in healthy patients appears favourable. Before recommending this as a treatment alternative in this population, larger confirmatory studies with comparable follow-up are needed.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Patients and Methods
  5. Results
  6. Discussion
  7. Conflict of Interest
  8. References
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