From its introduction in the late 1990s, focal ablation of small renal masses (SRMs) has evolved from innovative therapy in an experimental and development setting, with a significant body of emerging basic research during the first 10 years to implementation and expansion when preliminary case series on outcomes were published. While these 2 initial phases of the introduction of a new technology were successful, treatment evolved from open/laparoscopic approaches to percutaneous image-targeted treatments.¹ This has minimized the burden of surgery and has become the paradigm of a true minimally invasive therapy. However, the expansion of the technique has been challenged and at present the application of focal ablation of SRMs remains stable, representing not more than 10% of patients among the management options for localized renal cell carcinoma (RCC).

Not only have insights on the histology and aggressiveness of SRMs increased² questioning the need for treatment of all SRMs, but the aggressiveness and clinical relevance in the context of competing risk of death³ of small RCCs have also been the subject of investigations. Furthermore, implementation of robotic-assisted surgery facilitated the minimally invasive application of nephron-sparing surgery (NSS), and active surveillance (AS) management strategies with rising adoption and low rates of delayed intervention⁴ have expanded the options in patients with SRMs.

Among the available image-targeted therapies, cryoablation (CA) and radiofrequency ablation (RFA) have historically been the most widely used and reported. Despite basic research data, limited but evolving clinical data are available on other technologies such as microwave, irreversible electroporation, and high-intensity focused ultrasound.

Over the years, different semantics have been used to describe the concept of tumor ablation, eg, focal therapy, thermal ablation (TA), and local tumor destruction. The denomination “image-targeted therapy” seems to describe more precise and inclusively the current practice as image control is necessary for any successful modality of ablation.

Indications

Contemporary data from the National Cancer Database show that the choice for ablation therapy was mainly determined by patient’s age and comorbidity. As such, the proportion of focal ablation among the management options of SRMs increased notably for those aged ≥75 years and/or having a Charlson Comorbidity Index ≥2.⁵

Indications for image-targeted therapy of the SRM vary slightly across the different major guidelines. A brief review on the recommendations regarding image-guided therapy is provided in Table 1.

Table 1. Recommendations on Focal Ablation/Image-targeted Therapy of Kidney Tumors From Major Societies

With the aim to control cancer, preserve renal function, and minimize morbidity of the procedure when choosing treatment of an SRM, several modifiable and unmodifiable factors should be taken into account. Unmodifiable factors are mostly related to patient characteristics (eg, chronic morbidity, age, life expectancy, and renal function) and to the tumor characteristics (size, location, aggressiveness).⁶ Modifiable factors include transitory patient conditions (eg, medical, social) and structural factors such as health care systems and hospital resources and organization.⁶

Besides small differences, some clinical principles can be distilled from these recommendations: a careful assessment of patient frailty is critical in decision-making. Tumor biopsy becomes necessary to avoid unnecessary treatment and for follow-up purposes, although the clinician should be aware of the limitations of percutaneous renal tumor biopsy. Clinical outcomes are invariably associated with tumor size, location, and histology. Oncologic and functional outcomes are similar irrespective of the energy source used, and almost every image-ablation modality can be done by a percutaneous approach.

A further point to consider on percutaneous image-targeted therapy is that the mean effective and skin doses are higher in CA than in RFA due to the longer time of the procedure.⁷ Although likely irrelevant when considering the age at which the therapy is administered, these patients will require cross-sectional image follow-up with the consequent cumulative dose.

Follow-up should be risk adapted and personalized according to tumor characteristics and available guidelines. AUA guidelines recommend pre- and post-imaging at 6 months and from then onward follow-up as per intermediate risk,⁸ while others consider cT1a (low grade/nuclear grade 1-2) of low risk for follow-up purposes.⁹

Outcomes

Rather than considering the individual outcomes of image-guided therapy of the SRM, a comparison of perioperative or long-term functional and oncologic outcomes with the different management strategies of SRMs, namely radical nephrectomy (RN) vs NSS vs AS, becomes more informative.

Systematic reviews show similar oncologic outcomes among many treatment modalities (RN, NSS, and TA).^10-13 The median 5-year, cancer-specific survival approaches 95% for all management in cT1a RCC, and the metastasis-free survival is similar for all the management options after accounting for possible multiple treatments in image-targeted therapy. Conversely, local recurrence is higher in TA than after RN or NSS (see Figure). Overall survival is highly dependent on patient comorbidity and competing risks of mortality.^10,11

Overall, systematic reviews on comparative effectiveness of surgical management vs image-targeted therapy are consistently reporting weak evidence supporting image-targeted therapy of cT1a RCC. There is low strength of evidence for cancer-specific survival, overall survival, and categorical or evolutive renal function and harms. The evidence is at most moderate for local recurrence and perioperative outcomes.^10-13 In terms of quality of life, the latest data available suggest that differences among interventional treatments are only apparent up to 1-3 months after treatment, with better physical role for TA vs NSS and percutaneous approach benefits over open surgery.¹⁴ Lastly, no proper studies comparing outcomes between image-targeted therapy and AS exist.¹⁰

As series on kidney ablation mature, data from propensity-matched comparisons among managements have emerged. These series aim to overcome, albeit partially, the confounding factors driven by patient and tumor differences, by the use of different technologies, and by mixed and heterogeneous reporting. Table 2 gives an overview of the main conclusions of these studies.^15-19

Table 2. Propensity Score-matched Outcomes in T1a Renal Cell Carcinoma Comparing Nephron-sparing Surgery vs Thermal Ablation^15-19

Of note, recent population-based propensity score matched and adjusted for overall cause mortality and patient/tumor covariates shows association of local tumor destruction with higher cancer-specific mortality, relative to partial nephrectomy. The magnitude of the cancer-specific mortality disadvantage was more pronounced in tumors of size 3.1-4 cm²⁰ and 2-fold higher after heat-based TA than after CA.²¹

Data on cT1b tumors treated by image-targeted therapy are still scarce and of low strength of evidence. In most of these series CA has been used and more rarely RFA or microwave ablation. Higher rates of complications (15% to 50%), incomplete ablation (up to 13%), and local recurrence (23%-40%) compared to cT1a tumors have been reported, although not substantially different than those corresponding to NSS in this clinical stage.^23-26

In summary, comparative effectiveness evidence among image-targeted therapy and surgical treatments in small RCCs is low to moderate for clinical outcomes, with no definite superiority of any treatment definitively proven. Nonetheless, the claimed superiority for NSS is based on a single randomized controlled trial comparing radical vs partial nephrectomy not exclusive of bias. Acknowledging that the evidence and the clinical principles of NSS should prevail, there is still a definitive role for image-targeted therapy in the management of small RCCs. It entails a thorough assessment of the patient’s frailty and competing death risk, and counseling on the advantages and harms, considerations on follow-up, and the possibility of re-treatment to achieve optimal survival and oncologic outcomes.