Focal and ablative therapies have become an accepted treatment option for select patients with renal cell carcinoma.
Contemporary thermal ablation techniques are administered percutaneously, with less morbidity or risk than traditional surgical treatment.
There has been no prospective trials or level 1 evidence comparing to surgery, but retrospective data suggests good efficacy in the right patient and the right tumour.
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Ablative therapies (RFA/cryo) |
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| Pros | Cons |
| · Can be done under LA/sedation
· Less morbidity than PNx/Nx (percutaneous approach) · Day case / quick recovery · Less effect on kidney function cf. nephrectomy · Can be repeated if recurrent disease · Acceptable oncological control (good long term survival) especially in patients with competing co-morbidities |
· Higher risk of recurrence cf. surgery (i.e. oncologically inferior)
· Unclear long term survival data · Imaging interpretation after difficult · Active surveillance probably suitable for many of these patients · Not all tumours are suitable |
Indications for thermal ablative therapies:
The ideal patient for thermal ablation or focal therapy is someone with a small tumour, that needs or desires treatment, but is unable to have surgery
- T1a tumours ideally < 3 cm
- Advanced age
- Significant co-morbidities
- Solitary kidney but not fit for partial nephrectomy
- ?CKD
- ?Familial syndromes / multifocal tumours
Poor candidates for thermal ablation:
- Hilar tumours (risky, heat-sink)
- Endophytic lesions
- Medial / difficult to access tumours (incl anterior tumours with bowel in front)
- Larger than 3 cm
- Cystic masses (never been studied)
Radiofrequency ablation (RFA)
- High frequency electrical currents -> excitation of ions -> frictional forces and heat -> denaturing of proteins and melting of cellular membranes
- Temperatures of up to 100° at tips of probes, but this rapidly dissipates further from the tip -> multiple probes or tines used to achieve adequate heating of entire lesion
- Difficult to monitor in ‘real time’ to ensure adequate coverage
Cryotherapy
- Rapid freezing, followed by gradual thawing, then repetition of the freeze-thaw cycle -> disruption of organelles and cell membrane -> delayed microcirculatory occlusion causes cellular hypoxia
- Complete reliable tissue necrosis at temperatures of -19.4° or lower – this occurs 3 mm inside the “ice-ball” seen on real time sonography – therefore iceball must extend preferably > 5mm outside the tumour
Both ablative methods share the “heat sink” effect – where large vessels in or near the treatment area dissipates thermal energy due to blood flow, meaning tissue near the vessels may not reach the desired temperature, and do not die
Success rates and follow up
- 5 year disease free / recurrence free survival is 85 – 90 % (NB definition of recurrence varies)
- 5 year metastasis free and cancer specific survival is over 95 %
- Oncological outcomes appear equivalent between RFA and cryo
- Most local recurrences are amenable to repeat ablation
- Recurrence rates are higher than partial or radical nephrectomy
- As a general rule, central or nodular enhancement on contrast imaging > 6 months after treatment has generally been used as diagnostic or supportive of local recurrence
- Other considerations are increasing size of tumour, new nodularity in or around the tumour, failure of the lesion to regress over time, or satellite lesions
- Biopsy can be considered if there are concerns on imaging
- Recurrences can be observed, undergo repeat ablation, or undergo surgery, depending on discussions with the patient
- Surveillance – best done with contrast enhanced CT if able, 3 – 6 monthly initially
- Routine post treatment biopsies are controversial and unsupported by evidence
Biopsy prior to treatment
- EAU guidelines have a strong recommendation to perform biopsy of the lesion prior to, and not concomitantly with thermal ablation, as a proportion of tumours will be benign
Complications from thermal ablation
- Up to 20 % total complication rate, but the vast majority are minor, and less than partial nephrectomy
- Bleeding (incl mild haematuria)
- Rare serious effects on adjacent organs have been reported – bowel injury, pneumothorax, pancreatitis, PUJ stricture
- Failure / recurrence
- No significant drop in renal function / eGFR – appears similar to partial nephrectomy
Experimental ablative techniques:
- HIFU
- High intensity ultrasound primarily causes cell death by thermal effects (coagulative necrosis secondary to heat) but also has some mechanical effects (cavitation)
- Microwave ablation
- Microwaves propagate through tissue causing the oscillation of polar molecules, producing frictional heat, generating tissue necrosis
- Creates higher temperatures, faster, with larger ablations zones cf. RFA – ?may be better for T1b tumours
- Irreversible electroporation
- Non thermal – delivery of high voltage short pulse electrical currents creating cellular membrane nanopores, leading to apoptosis
- All of these techniques are in their infancy and should be considered experimental.
Stereotactic radiotherapy (SABR / SBRT)
- SABR is an emerging treatment which has shown promising early results in treating renal masses not suitable for surgery
- RCC has traditionally thought to be radio-resistant – however this was at low doses per fraction
- Delivery of high dose radiation therapy from multiple directions in a small number of fractions using advanced imaging to ensure precision and accuracy
- It aims to achieve high “ablative” doses to the target, sparing surrounding normal tissue
- IROCK meta-analysis – 3 % local failure rate with mean tumour size 4.6 cm
- eGFR drops around 5 – 10 ml/min – similar to other focal Rx and partial Nx
Well tolerated and minimal side effects with no need for anaesthetic at all.