Ablative therapy for renal masses: Present and future Current view and plans by the ESUT Ablative Group Prof. Dmitry Enikeev Sechenov University Institute for Urology and Reproductive Health Moscow (RU) dvenikeev@ gmail.com The ongoing quest for less invasive surgery remains one of the primary concerns of the medical community. The combination of trying to reduce the negative impact on the patient’s quality of life and developing precise volumetric imaging has resulted in the creation of image-guided ablative techniques. In 2006, renal cell carcinoma ablation was mentioned in the EAU guidelines for the first time: an ‘experimental approach with limited applicability’. Until 2010, a lack of adequate data made the transition to cryoablation and RFA problematic. Currently, the European guidelines strongly recommend performing tumour ablation (TA) only on patients with small renal masses who are for one reason or another ineligible for surgery. Since then, image-guided ablation procedures have become a feature of urological departments all over the world. Their safety and efficacy are constantly being verified. This article aims at keeping the medical community updated on recent developments and highlighting the future potential of ablation techniques. What is the state of play? As readers are probably aware, the two main techniques suggested by the European guidelines for the percutaneous ablation of kidney tumours are cryoablation (CRA) and radiofrequency ablation (RFA). The main principle underpinning these procedures is to apply extremely low or high temperatures to the tumour site directly. As you can imagine, this results in cell injury, tumour apoptosis as well as coagulative necrosis. In a BJU International meta-analysis of case studies published by El Dib et al. (2012), it was shown that the CRA and RFA complication and efficacy rates were comparable. [1] The mechanisms Cryoablation refers to the freezing of cancer lesions below -20°C. The technique is based on the JouleThomson effect – the temperature changes due to rapid expansion of gas. The stages of the procedure comprise the freezing of the tumour with argon (cooling probe up to -40 °C), and then rapid thawing with helium. [2] These two consecutive steps lead to cellular death as a result of its rupture with ice crystals. [3]
Despite tumour ablation’s long history, wellperformed RCTs are still hard to find. In fact, most of the available studies deal with comorbid and frail patients and thus there is quite a selection bias. Any future studies should ideally include other cohorts of patients - this would then lead to a more objective outcome. In recent decades, we have gained valuable experience regarding the CRA and RFA of kidney cancer, despite the lack of prospective randomised trials. This means that ablative techniques nowadays comprise a rather well-studied treatment modality, especially in some patient cohorts. Even though it is comparable to PN in terms of outcomes, ablative surgery remains of particular interest for the reason of its specific advantages over conventional partial nephrectomy. What are the advantages? One of the main advantages of ablation is that it is possible to carry it out in one day. Previously, Rivero et al. [8] reported a decreased hospital stay for those who were treated with ablation. These data on shorter hospitalisation periods are supported by the meta-analysis of Sanchez et al., which shows a lower complication rate after TA compared to PN [9], despite the shorter hospitalization length. Moreover, as with tumour biopsy, cryoablation can be performed under local anaesthesia. Kerviler et al. showed that the mean pain levels measured during the procedure were negligibly low. [10] No general anaesthesia means that the hospital stay can be reduced. And let’s not forget that general anaesthesia in elderly patients may cause a number of neurological disorders, including cognitive decline. Cost effectiveness Moreover, local anaesthesia and low complication rates allow us to treat weak and frail patients. Active surveillance might be an option for this group of people, but lower quality of life and increased anxiety in patients on active surveillance suggest that immediate treatment is advantageous. Another point which cannot be ignored is the cost effectiveness of TA for health care systems. For example, the median total costs were almost 3 times lower for TA than for PN [11] in Castle’s analysis. However, renal tumour biopsy is always required before the ablative treatment because TA doesn’t allow us to perform a histological evaluation of the treated site. Some prefer to perform a biopsy on the same day as the ablation, but the jury is out on this one. At Sechenov University, we prefer to perform a biopsy several weeks prior to ablation so intraprocedural imaging is not compromised and the risk of complications remains at a minimum.
What can we expect? What is mostly expected from TA relates to the expansion of the indications. Even now, we may see Radiofrequency ablation, on the other hand, works on studies with favourable oncological outcomes for the basis of temperature increase (> 50°C). This larger tumours (T1b). For example, Andrews et al. method is also based on the Joule effect. It is the found that local recurrence, metastases and deaths process by which the passage of an electric current from RCC were not statistically different between PN through a conductor (tissue) produces heat. [4] The and cryoablation for cT1b patients. [12] Another resulting hyperthermia leads to cellular damage due important issue to be borne in mind is that we can to the immediate protein denaturation and perform ablation in patients without comorbidities – subsequent coagulative necrosis. Delayed changes this data is supported by a growing body of evidence occur several days after heating just as with induction on 5 and 10-year outcomes after TA. We believe that of apoptosis and vascular injury. in the not too distant future ablative surgery will be recommended for use in all patient cohorts. Bias In the 2021 EAU guidelines, both CRA and RFA for TA’s future not only lies in the enhancement of renal cell carcinoma are recommended in weak and current modalities but also the development of new comorbid T1a patients. [5] Ablation was found to be energy-based techniques. As readers may be aware, safe, resulting in lower complication rates than evidence on percutaneous microwave ablation surgery, and the only uncertainty was long-term (MWA) is rapidly growing. Yu et al. showed no oncological efficacy. High long-term survival rates difference between MWA and PN in their cohort were demonstrated by several large studies. A study study involving 1,955 patients neither in local tumour on cryoablation published in 2015 (Larcher et al.) progression, cancer-specific survival nor in distant showed a 10-year recurrence-free survival rate of metastases. [13] Irreversible electroporation (IRE), 95%, disease relapse-free survival of 81%, cancerfirst used in prostate cancer became a subject of specific mortality-free survival rate of 100% and research in RCC ablation. Currently, the only results all-cause mortality-free survival rate of 61% [6] available are those of short 2-year follow-up by A controlled study by Thompson et al. published in Canvasser et al. in renal tumours: with 83% of local European Urology (2015) showed that 5-year recurrence-free survival [14]. Initial clinical studies on metastatic-free survival rate was better after PN in laser ablation of renal tumours by Kariniemi et al. comparison with RFA (p = 0.005) for T1a tumours. [7] showed preliminary efficacy with no local recurrence The authors explained these differences by during 20 months of follow-up [15], yet this result imperfections in TA and imaging protocols, resulting remains highly questionable in view of inferior in residual cancer. However, these specific studies are outcomes in other trials. Stereotactic ablative of limited use because of their bias in selecting radiotherapy (SABR) has been presented as a viable patients. option for inoperable T1A patients. In their metaanalysis, Correa et al. have shown encouraging results of SABR with local control rate of 97.2%. [16] EAU Section of Uro-Technology (ESUT) However, the absence of high-quality controlled August/September 2021
Fig. 1: Partial nephrectomy and ablative therapies
studies means that we should be careful in promoting these techniques, at least at the moment. Join the team Tumour ablation is undoubtedly an important treatment modality that is now becoming a feature of clinical practice. Obviously, ongoing and future studies will expand the range of indications for TA and develop this technique further. The ESUT group plans to deepen its work on tumour ablation of the kidneys. We hope that you will join our team in its efforts to broaden the knowledge of this procedure as more and more surgeons continue to show interest in the universe of ablative techniques. References 1. El Dib, R., Touma, N. J. & Kapoor, A. Cryoablation vs radiofrequency ablation for the treatment of renal cell carcinoma: A meta-analysis of case series studies. BJU Int. 110, 510–516 (2012). 2. Habash, R. W. Y., Bansal, R., Krewski, D. & Alhafid, H. T. Thermal therapy, Part III: Ablation techniques. Crit. Rev. Biomed. Eng. 35, 37–121 (2007). 3. Chu, K. F. & Dupuy, D. E. Thermal ablation of tumours: Biological mechanisms and advances in therapy. Nat. Rev. Cancer 14, 199–208 (2014). 4. Ahmed, M., Brace, C. L., Lee, F. T. & Goldberg, S. N. Principles of and advances in percutaneous ablation. Radiology 258, 351–369 (2011). 5. EAU Guidelines: Renal Cell Carcinoma | Uroweb. 6. Larcher, A. et al. Long-term oncologic outcomes of laparoscopic renal cryoablation as primary treatment for small renal masses. Urol. Oncol. Semin. Orig. Investig. 33, 22.e1-22.e9 (2015). 7. Thompson, R. H. et al. Comparison of partial
nephrectomy and percutaneous ablation for cT1 renal masses. Eur. Urol. 67, 252–259 (2015). 8. Rivero, J. R. et al. Partial Nephrectomy versus Thermal Ablation for Clinical Stage T1 Renal Masses: Systematic Review and Meta-Analysis of More than 3,900 Patients. J. Vasc. Interv. Radiol. 29, 18–29 (2018). 9. Sanchez, A., Feldman, A. S. & Ari Hakimi, A. Current management of small renal masses, including patient selection, renal tumor biopsy, active surveillance, and thermal ablation. J. Clin. Oncol. 36, 3591–3600 (2018). 10. de Kerviler, E. et al. The Feasibility of Percutaneous Renal Cryoablation Under Local Anaesthesia. Cardiovasc. Intervent. Radiol. 38, 672–677 (2015). 11. Castle, S. M. et al. Cost comparison of nephron-sparing treatments for cT1a renal masses. Urol. Oncol. Semin. Orig. Investig. 31, 1327–1332 (2013). 12. Andrews, J. R. et al. Oncologic Outcomes Following Partial Nephrectomy and Percutaneous Ablation for cT1 Renal Masses(Figure presented.). Eur. Urol. 76, 244–251 (2019). 13. Yu, J. et al. Percutaneous Microwave Ablation versus Laparoscopic Partial Nephrectomy for cT1a Renal Cell Carcinoma: A Propensity-matched Cohort Study of 1955 Patients. Radiology 294, 698–706 (2020). 14. Canvasser, N. E. et al. Irreversible electroporation of small renal masses: suboptimal oncologic efficacy in an early series. World J. Urol. 35, 1549–1555 (2017). 15. Kariniemi, J., Ojala, R., Hellstrm, P. & Sequeiros, R. B. MRI-guided percutaneous laser ablation of small renal cell carcinoma: Initial clinical experience. Acta radiol. 51, 467–472 (2010). 16. Correa, R. J. M. et al. The Emerging Role of Stereotactic Ablative Radiotherapy for Primary Renal Cell Carcinoma: A Systematic Review and Meta-Analysis. European Urology Focus vol. 5 958–969 (2019).
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