Does Renal Mass Ablation Provide Adequate Long-term Oncologic Control?

Renal ablation (RA) is no longer used exclusively in patients with limited life expectancy. There are few studies reporting a minimum follow-up of 5 years. Biases and discrepancies within the literature are abundant. The outcomes of any series must be interpreted in the context of median follow-up time, reported tumor characteristics, ablation technique and training background of the practitioner, and the definition of tumor recurrence. The long-term oncologic efficacy of radiofrequency ablation (RFA) and cryoablation appear similar, although the percutaneous RFA technique may necessitate reablation in more cases. RA is associated with slightly higher rates of local recurrence compared to surgical excision.

Although radiofrequency ablation (RFA) and cryotherapy were first described more than 10 years ago, large patient series are only now maturing with long-term follow-up. Because these techniques are still new, evidence and expert opinion are constantly evolving. For instance, a Cochrane Review comparing RFA with cryoablation was initially published in 2009 and withdrawn shortly thereafter, in May 2011, possibly because the evidence had already become outdated. There are no randomized studies comparing renal ablation (RA) with surgery or active surveillance. A few meta-analyses have been published in the last 5 years, most comparing surgery with RA and a few comparing RFA with cryoablation. Most of the evidence exists in the form of individual case series and cohort studies. With these limited and biased sources, this article focuses on the ablation series with the longest reported follow-up, and discusses some of the pitfalls in interpreting the literature. Although several different ablation modalities have been described ( Box 1 ), only RFA and cryoablation are widely used and have sufficient data to comment on oncologic efficacy. They are the focus of this article.

Box 1

▪

RFA
▪

Cryotherapy
▪

High-intensity focused ultrasound (HIFU)
▪

Laser interstitial thermotherapy (LITT)
▪

Microwave thermoablation (MWT)
▪

Pulsed cavitational ultrasound (PCU)
▪

Chemoablation
▪

Radiosurgery

Ablation modalities

The rationale for RA

RA has garnered increasing interest with the increase in detection of small renal masses (SRMs). Although 20% to 25% of SRMs prove to be benign, even the malignant neoplasms tend to be less aggressive and of lower grade than their larger counterparts. Although younger patients have traditionally been counseled to undergo surgical treatment of these masses, active surveillance alone is associated with low rates of metastasis. RA might be considered to be on a continuum between surgical excision and surveillance, offering the opportunity for treatment and minimizing patient morbidity.

RA has several advantages compared with partial nephrectomy (PN), including decreased morbidity and better preservation of renal function. Percutaneous ablation is performed as an outpatient procedure with minimal recovery time. In comparative studies with PN, laparoscopic cryoablation (LCA) had reduced blood loss and complication rates, and RFA had better preservation of renal function.

Indications for RA

RA has traditionally been reserved for patients who are poor candidates for surgery or in whom renal preservation is paramount ( Box 2 ). However, with some reports of oncologic efficacy approaching that of PN, some centers are now considering RA as a first-line option for young and healthy patients with small tumors. Although the American Urological Association (AUA) “Guideline for Management of the Clinical Stage 1 Renal Mass” lists RA as an option for T1b tumors in patients with comorbidities, the authors and others think that tumors larger than 4 cm should seldom be treated with RA, even in patients with comorbidities, because of significantly higher rates of treatment failure and recurrence. The focus of this article is oncologic efficacy for SRMs (ie, cT1a), which is the target population of most series in the literature.

Box 2

▪

Well-accepted indications: T1a tumor and
- •
  
  Elderly patients
- •
  
  Comorbidities/not surgical candidates
- •
  
  Renal impairment
- •
  
  Multiple bilateral renal masses
▪

Controversial indications:
- •
  
  Small tumors in young/healthy patients
- •
  
  Cytoreduction
- •
  
  T1b tumors
▪

Contraindications:
- •
  
  Relative
  - ○
    
    Central or hilar tumors
  - ○
    
    Acute illness or infection
  - ○
    
    Unstable cardiovascular status
  - ○
    
    Poor life expectancy
- •
  
  Absolute
  - ○
    
    Uncorrected coagulopathy

Indications and contraindications for renal mass ablation

Indications for RA

Box 2

▪

Well-accepted indications: T1a tumor and
- •
  
  Elderly patients
- •
  
  Comorbidities/not surgical candidates
- •
  
  Renal impairment
- •
  
  Multiple bilateral renal masses
▪

Controversial indications:
- •
  
  Small tumors in young/healthy patients
- •
  
  Cytoreduction
- •
  
  T1b tumors
▪

Contraindications:
- •
  
  Relative
  - ○
    
    Central or hilar tumors
  - ○
    
    Acute illness or infection
  - ○
    
    Unstable cardiovascular status
  - ○
    
    Poor life expectancy
- •
  
  Absolute
  - ○
    
    Uncorrected coagulopathy

Indications and contraindications for renal mass ablation

What constitutes long-term oncologic success?

In general, long-term oncologic success requires 5-year and 10-year survival data that encompass the period in which most recurrences present. However, there are few series with a minimum 5 years of follow-up: 2 LCA series, and 1 RFA series from our institution that has been submitted for publication. The focus of this review is therefore series with the longest available follow-up, although many of these series would be strictly defined as having intermediate follow-up.

Oncologic success encompasses local recurrence rates as well as the incidence of metastasis, cancer-specific deaths, and overall survival. Local recurrence is widely defined as new nodular enhancement of the treated lesion on imaging. Although lesions treated by cryoablation generally shrink, RFA-treated lesions may remain stable in size. Furthermore, empiric renal biopsy immediately following RA is generally not performed. In particular, biopsy soon after RFA may have a high false-positive rate. Several studies have suggested residual tumor early after RFA treatment (either on biopsy or PN specimens), whereas others using vitality stains or delayed biopsy more than 12 months after treatment showed that cross-sectional imaging reliably predicted RFA efficacy. Because early biopsy results and variable changes in lesion size seen after cryoablation do not accurately reflect RA efficacy, treatment success is defined by contrast-enhanced imaging.

To further complicate this definition, there is inconsistency in how local recurrence rates are reported in the literature. The AUA guidelines and several ablation series define local recurrence as any radiographic enhancement at any time after initial therapy. Other series do not consider incomplete treatment as a local recurrence. Instead, these patients are defined as treatment failures that are immediately reablated. In the evaluation of long-term oncologic success, the rate of initial ablation failure requiring retreatment is less relevant than the rate of de novo detection after negative postablation imaging. Although retreatment is inconvenient, costly, and may increase overall complication rate, the necessity to reablate has not be shown to predispose to delayed recurrence, metastasis, or decreased cancer-specific survival, which are the most important oncologic outcomes for the patient.

Making sense of differing efficacy rates between RA series

Reports of oncologic efficacy of RA may vary widely between series. For example, a cohort study by Turna and collegeaues found disease-free survival rates for laparoscopic partial nephrectomy (LPN), cryoablation, and RFA to be 100%, 69.6%, and 33.2% respectively ( P <.001). In contrast, another cohort study by Takaki and collegeaues found 5-year disease-free survival rates of 95% and 98% for RFA and radical nephrectomy respectively. How can there be such wide variability in reported success between series? Box 3 outlines several potential explanations.

Box 3

▪

Selection bias
- •
  
  Variable pretreatment renal biopsy practices
- •
  
  Variable tumor location or mean tumor size
▪

Variable reporting of treatment failure:
- •
  
  Controversial distinction between local recurrence versus treatment failure
- •
  
  Definition of local recurrence (ie, whether based on imaging, biopsy, and so forth)
▪

Technical variations:
- •
  
  Radiologist versus urologist performed
- •
  
  Approach (laparoscopic vs percutaneous vs open)
- •
  
  Center experience
- •
  
  Tumor targeting: computed tomography versus ultrasound guidance
- •
  
  Type of sedation: general versus intravenous sedation
- •
  
  Variations in ablation technique:
  - ○
    
    Number of electrodes
  - ○
    
    The number of ablation cycles/length of ablation cycle

Variations between RA series that contribute to conflicting reports of oncologic efficacy

RA studies can be riddled with biases because there are no randomized studies to control for confounding variables. Different series contain different tumor locations and mean tumor sizes, both of which are known predictors of ablation success. In one study, tumors greater than 3.7 cm were associated with higher rates of incomplete ablation and tumor recurrence. Centrally located tumors also have lower efficacy, possibly related to their proximity to vessels that may act as heat sinks. In a cohort study comparing RFA with cryoablation, Hegarty and colleagues reported higher rates of incomplete ablation following RFA, although the RFA-treated tumors were more likely to be central (37% vs 6% for cryoablation). In addition, some series correctly report oncologic outcomes only for tumors with a positive pretreatment biopsy, whereas other series include all outcomes, of which 20% to 25% may have benign masses. One meta-analysis showed that pretreatment biopsies were performed in only 82.3% and 62.2% of lesions undergoing cryoablation and RFA respectively.

Oncologic success can also be affected by ablation technique. A lack of standardization makes it difficult to compare series with different ablative technologies, surgical approaches, and levels of experience. For percutaneous RA, many practitioners, including ourselves, also think the type of patient anesthesia affects success. Compared with intravenous sedation, general anesthesia may allow better targeting by controlling respiratory movement.

The procedural approach (laparoscopic vs percutaneous) may affect oncologic success for several reasons. Laparoscopic-assisted RA is performed exclusively by surgeons, whereas the percutaneous approach is performed by both surgeons and interventionalists. It has been postulated that surgeons may be more aggressive in treating renal cancer, translating to better outcomes for neoplasms treated by a laparoscopic-assisted approach. A meta-analysis of RFA and cryoablation that compared laparoscopic and percutaneous approaches showed higher rates of primary treatment success in the laparoscopic versus percutaneous group (94% vs 87% respectively, P <.05). RFA is more often performed percutaneously, whereas most cryoablation series describe a laparoscopic approach. This discrepancy may explain why one meta-analysis found higher rates of incomplete ablation for RFA compared with cryoablation.

Long-term outcomes of RFA

For many years there were only 2 small RFA series with long-term follow-up. These series date back to the early experience with RFA when only patients with significant comorbidities were considered candidates. One-third of the patients in both series died of other causes before long-term oncologic follow-up could mature. In one of these series, Levinson and colleagues reported on 18 patients with pathologically proven renal cell carcinoma (RCC) and a mean follow-up of 57.4 months (range 41–80 months). Recurrence-free survival was suboptimal at 80%, although the actuarial cancer-specific and metastasis-free survival were both 100%. McDougal and colleagues reported a 91% recurrence-free survival in 16 patients with histologically confirmed RCC less than 5 cm in diameter and a minimum of 4 years follow-up. Again, there were no cases of metastasis or cancer-specific deaths.

More recently, Tracy and colleagues reported their RFA series of 243 SRMs with mean tumor size of 2.4 cm and mean follow-up of 27 months (range 1.5–90 months). Considering only the 179 tumors with histologically confirmed RCC, actuarial 5-year survival analysis revealed recurrence-free, metastasis-free, and cancer-specific survival rates of 90%, 95%, and 99% respectively. Similarly, Ferakis and colleagues reported on 31 patients with 39 tumors undergoing percutaneous RFA. Initial ablation success rate was 90% but, when reablation was allowed, the 3-year and actuarial 5-year recurrence-free survival rates were 92% and 89% after a mean follow-up of 61 months (range 36–84 months). These survival estimates likely overestimate the true RCC treatment success because no tumors were biopsied. Furthermore, although the investigators state that the results are comparable with nephron-sparing surgery, recurrence-free rates for PN are widely thought to be greater than 95%. Coupled with the wide confidence intervals that are common in RA series limited by small numbers, comments regarding equivalency to partial nephrectomy cannot be made with any certainty.

Zagoria and colleagues reported their series of 48 histologically proven RCC in 41 patients with median follow-up of 56 months. There were 3 treatment failures (7%), 2 delayed local recurrences (4%), and 3 patients who developed metastasis (7%), 1 of whom died a cancer-related death. There were no recurrences in patients with neoplasms less than 4 cm in diameter. The investigators defined local recurrence as any radiologic enhancement after 1 ablation, yielding local recurrence-free and disease-free survival rates of 88% and 83%.

In summary, the rate of local recurrence after RFA depends partially on definition. If primary treatment failures are considered a local recurrence (ie, patients requiring immediate reablation for persisting enhancement), local recurrence-free survival rates range from 33.2% to 88%. When only the cases of recurrence following satisfactory ablation are considered, local recurrence-free survival generally increases to 90% to 95%. Metastasis-free and cancer-specific survival are high, consistently greater than 90% across series. Table 1 summarizes RFA series with intermediate-term and long-term follow-up.

Table 1

Only gold members can continue reading. Log In or Register to continue