Cast the die for randomised evidence comparing percutaneous ablation with surgery and prepare for the flood of renal cell carcinoma patients

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Christopher S Morris

Despite the well-known obstacles, it is time for a prospective, randomised clinical trial comparing percutaneous ablation (PA) and partial nephrectomy for the treatment of small renal cell carcinomas— and re-thinking the common practice of watching and waiting, rather than intervening, is long overdue, writes Christopher S Morris (Larner College of Medicine, University of Vermont, Burlington, USA).

Current studies with a moderate level of evidence have already confirmed decreased complications and similar effectiveness of PA compared to surgery in treating small renal tumours. Interventional radiologists (IRs) everywhere should be prepared for an increasing influx of patients seeking treatment of their small renal cell carcinomas with PA.

In developed countries, the incidence of renal cell carcinoma has increased over the past 20 years, mainly due to the increase in cross-sectional imaging and improving life expectancies. More than 50% of these tumours are diagnosed incidentally. In 2021, it is estimated that there will be more than 76,000 new kidney cancers diagnosed and almost 14,000 deaths attributed to kidney cancer in the USA alone. Like many solid malignancies, renal cell carcinoma is most effectively treated while small and prior to local and regional invasion, and certainly before the progression to distant metastatic disease.

Although the standard treatment of renal cell carcinoma is nephrectomy and partial nephrectomy, IRs have been treating small T1a (<4cm) renal cell carcinomas with PA, either cryoablation, radiofrequency ablation (RFA), or microwave ablation (MWA) for more than 20 years. Despite the proven safety and efficacy of PA for small renal tumors, less than 10% of these lesions are treated with PA. In addition, studies have shown that patients with small renal cell carcinomas are often surveilled with imaging, rather than treated with PA. Therefore, better awareness of the advantages and utility of PA in treating T1a renal cell carcinomas is needed.><4cm) renal cell carcinomas with PA, either cryoablation, radiofrequency ablation (RFA), or microwave ablation (MWA) for more than 20 years. Despite the proven safety and efficacy of PA for small renal tumors, less than 10% of these lesions are treated with PA. In addition, studies have shown that patients with small renal cell carcinomas are often surveilled with imaging, rather than treated with PA. Therefore, better awareness of the advantages and utility of PA in treating T1a renal cell carcinomas is needed.

Last year, the Society of Interventional Radiology published a Position Statement on the role of PA in renal cell carcinoma, which was endorsed by the Canadian Association for Interventional Radiology and the Society of Interventional Oncology.1 The writing group consisted of a multidisciplinary collection of experts who reviewed the pertinent literature. Although currently there are no randomised controlled trials comparing PA with surgery in renal cell carcinoma, the writing group found many population-based registry studies and systematic reviews of small cohort studies. The writing group concluded that PA is an acceptable treatment option for stage T1a renal cell carcinomas in carefully selected patients and can be offered over active surveillance. Of the three different PA modalities, the writing group found no significant differences in safety and efficacy between cryoablation, RFA, and MWA.

Regarding efficacy, four large database studies have shown that patients with small renal tumours treated with PA had acceptable, but mostly lower overall survival rates than those patients treated with surgery.2,3,4,5 However, when looking at cancer specific survival, two of the four studies showed no significant difference between PA and surgery. One study reported no difference in five-year overall survival between PA and surgery. These results reiterate the necessity for a randomised controlled trial comparing PA and surgery for small renal cell carcinomas, as these database studies may be biased by patient selection and other confounders. Despite the fact that a randomised clinical trial is often hampered by funding restraints, difficulties in recruitment of eligible patients, and political obstacles, it will be essential in further establishing safety and efficacy of PA.

Wind-down “watch and wait”

Multiple database studies have demonstrated the utility of adopting PA in lieu of active imaging surveillance.4,6,7 All studies showed that cancer-specific survival was higher for patients treated with PA than those subjected to surveillance and one study also demonstrated significantly greater overall survival rates for PA over active surveillance. These results seem to argue against the common practice of active imaging surveillance of small renal tumours, which would present large numbers of patients who would be more appropriately treated with PA. One of the greatest advantages of PA compared with surgery is its safety. Simply put, PA is associated with significantly fewer complications than surgery. Multiple cohort, registry-based studies, and systematic reviews have confirmed that complication rates and post-procedure renal function outcomes are better with PA than surgery in treating small renal tumours.3,4,8,9,10

As PA is often performed as an outpatient procedure, the length of stay is shorter for PA than surgery. In the cohort and registry-based analyses, significantly lower complication rates were found for PA than surgery in the treatment of small renal cell carcinomas, with complications following PA ranging from 6 to 21% and the complications from surgery ranging from 29 to 40%. In one study, patients treated with PA had lower rates of acute renal failure when compared to surgery. Acute renal failure associated with PA was 3%, whereas it was 7% with partial nephrectomy and 11% with radical nephrectomy.

A systematic review of 107 studies demonstrated lower rates of urine leak, acute kidney injury, and other urologic complications, as well as shorter median hospital stay and decreased median blood loss in patients treated with PA vs. surgery.9 Another systematic review of 15 studies reported lower perioperative complications with PA than surgery.10 In addition, the surgery (partial nephrectomy) group was associated with decreased renal function at six-month and one-year follow up, compared to the PA patients.

A large registry database study of 773 patients compared outcomes of PA of T1a tumours performed with cryoablation vs. thermal PA (either RFA or MWA)6. No significant difference in cancer-specific survival was found between cryoablation or thermal PA.

The writing group also determined that a biopsy of a small renal tumour should be performed prior to PA at any time, either during the first part of the PA procedure or as a separate prior procedure. In addition, there may be a role for PA in treating some T1b (between 4 and 7cm in diameter) renal cell carcinomas and distant oligometastatic renal cell carcinoma in selected patients.

Overall, PA appears to offer similar cancer-specific survival with fewer complications compared to partial nephrectomy for the treatment of small renal cell carcinomas. In addition, patients with T1a renal cell cancers tend to fare better when treated with PA compared to management with active surveillance. Although a randomised controlled trial is needed to further confirm the promising results of these population-based registry studies and systematic reviews of small cohort studies, IRs should expect a greater demand for PA of small renal tumours in the future.

Christopher S Morris is a professor of Radiology and Surgery at Larner College of Medicine at the University of Vermont, Burlington, USA. He has reported no relevant disclosures.

References:

1: Morris CS, et al. Society of Interventional Radiology position statement on the role of percutaneous ablation in renal cell carcinoma: Endorsed by the Canadian Association for Interventional Radiology and the Society of Interventional Oncology. J Vasc Interv Radiol 2020, 31:189–94
2: Zhou M, et al. SEER study of ablation versus partial nephrectomy in cT1A renal cell carcinoma. Future Oncol 2018, 14:1711–9
3: Talenfeld AD, et al. Percutaneous ablation versus partial and radical nephrectomy for T1a renal cancer: A population-based analysis. Ann Intern Med 2018, 169:69–77
4: Xing M, et al. Comparative effectiveness of thermal ablation, surgical resection, and active surveillance for T1a renal cell carcinoma: A surveillance, epidemiology, and end results (SEER)–medicare-linked population study. Radiology 2018, 288:81–90
5: Uhlig J, et al. Ablation versus resection for stage 1A renal cell carcinoma: National variation in clinical management and selected outcomes. Radiology 2018, 288:889–97
6: Uhlig A, et al. Treatment for localized T1a clear cell renal cell carcinoma: survival benefit for cryosurgery and thermal ablation compared to deferred therapy. Cardiovas Interv Radiol 2018, 41:277–83
7: Larcher A, et al. Population-based assessment of cancer-specific mortality after local tumour ablation or observation for kidney cancer: A competing risks analysis. BJU Int 2016, 118:541–6
8: Larcher A, et al. Mortality, morbidity and healthcare expenditures after local tumour ablation or partial nephrectomy for T1A kidney cancer. Eur J Surg Oncol 2017, 43:815–22
9: Pierorazio PM, et al. Management of renal masses and localized renal cancer: systematic review and meta[1]analysis. J Urol 2016, 196:989–99
10: Hu X, et al. Partial nephrectomy versus ablative therapies for cT1a renal masses: A Systematic Review and meta-analysis. Eur J Surg Oncol 2019, 45:1527–35

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