Kunkle et al. in 2008, performed a meta-analysis comparing cryoablation (19 studies, 372 lesions) to partial nephrectomy , RFA and active surveillance [31]. The authors found that patients undergoing cryoablation were significantly older than those undergoing partial nephrectomy (mean age: 65.7 vs. 60.1 years old; p < 0.001). The mean tumor size was significantly smaller for patients undergoing cryoablation compared to partial nephrectomy (2.56 vs. 3.40 cm; p < 0.001) but similar when compared to patients undergoing RFA (2.56 vs. 2.69 cm; p = 0.40). The mean follow-up was significantly shorter for both thermal ablation options when compared to partial nephrectomy (cryoablation, RFA, partial nephrectomy: 18.3 vs. 16.4 vs. 54.0 months respectively; p < 0.001), further highlighting the need for studies with longer follow-up for patients undergoing thermal ablation. When assessing local recurrence, the study found a recurrence rate of 2.6% following partial nephrectomy compared to 4.6% for cryoablation and 11.7% for RFA . Progression to metastatic disease was described in 5.6% of patients undergoing partial nephrectomy, 1.2% in patients undergoing cryoablation and 2.3% in patients undergoing RFA.

The panel for the AUA 2009 Guideline for the Management of the Clinical T1 Renal Mass performed a meta-analysis which included 15 studies (644 patients) on cryoablation compared to other treatment options including active surveillance, RFA, open partial nephrectomy (OPN) , laparoscopic partial nephrectomy (LPN) , open radical nephrectomy (ORN) and laparoscopic radical nephrectomy (LRN) [26]. The mean age for patients undergoing cryoablation was 67.0 years compared to 68.5, 59.5, 60.4, 62.7 and 60.7 years for patients undergoing RFA, OPN, LPN, ORN and LRN respectively. The mean tumor size for patients undergoing cryoablation was 2.6 cm compared to 2.7, 3.2, 2.6, 4.9, and 4.8 cm for patients undergoing RFA, OPN, LPN, ORN and LRN respectively. The complication rate for patients undergoing cryoablation was 4.9% (95% CI: 3.3–7.4%) compared to 6.0%, 6.3%, 9.0%, 1.3% and 3.4% for patients undergoing RFA, OPN, LPN and LRN respectively. ORN complication rates were significantly lower than all other groups (p < 0.05). The complication rates for cryoablation, RFA and OPN were indistinguishable (p > 0.05). The local recurrence free survival rates for cryoablation and RFA (90.6% and 87.0% respectively) were significantly lower than LPN, OPN, LRN and ORN (98.4%, 98.0%, 99.2%, 98.1% respectively) (p < 0.05).

A multi-institutional study by Johnson et al. defined the complications associated with cryoablation (139 cases) and RFA (132 cases) for small renal masses (181 percutaneous, 90 laparoscopic) [32]. The rate of major and minor complications for patients undergoing cryoablation were 1.8% (n = 2) and 9.2% (n = 17) respectively. Reported complications for cryoablation included: Minor: probe site pain or paresthesia (n = 10, 7.2%), post-operative urinary tract infection (n = 2, 1.4%), post-operative pneumonia (n = 1), minor hemorrhage (n = 1), elevated serum creatinine (n = 1), wound infection (n = 1), respiratory difficulty (n = 1); Major: significant hemorrhage (n = 1), open conversion (n = 1) due to inability to access the tumor laparoscopically. There were no deaths in patients undergoing cryoablation and the study showed a decrease in the rate of complications with increased experience. Other potentially significant complications that can occur with percutaneous renal cryoablation include: ureteral stricture—related to the proximity of the ureter to the ablation site, urine leak—as manifest by contrast extravasation outside the collecting system on the delayed phase of post-procedure CT scan imaging, bowel injury and pneumothorax—which can occur when treating upper pole renal tumors (post-procedure CT scans should include the lower lung and viewed with lung windows to exclude pneumothorax) [33–35]. Ice ball fracture is a rare complication associated with renal cryoablation that can be associated with significant hemorrhage requiring prompt intervention. Some risk factors for ice ball fractures include the use of large-diameter cryoablation probes (those used for laparoscopic cryoablation), use of multiple probes and premature removal of the cryoablation probes before the ice ball has completely thawed [36].

Contemporary clinical series have shown that flank pain (cryoprobe site pain or parethesia) continues to be the most common complication reported for renal cryoablation (9.8–10.8%) [37, 38]. In a series of 162 patients by Sidana et al. treated with renal cryoablation, the size of the lesion (p = 0.001), the number of cryoablation probes (p < 0.001) and chronic anticoagulation (p < 0.05) were associated with an increased incidence of significant hematoma.

Vricella et al. in a retrospective study of 52 patients treated with percutaneous renal cryoablation found that Charlson comorbidity index score (p = 0.02) and the number of cryoprobes used (p < 0.005) both significantly correlated with an increase in post-operative complications [39]. Okhunov et al. performed a retrospective analysis of 190 patients undergoing percutaneous renal cryoablation for T1a renal tumors [40]. They observed an 8.4% complication rate with 14 Clavien Grade I complications (6 large renal/retroperitoneal hematomas, 2% pneumothoraxes, 1% UTIs, 1% atrial fibrillation). There were 2 (1%) Clavien Grade II complications (intestinal perforations). Multivariable analysis showed that larger tumor dimension (OR = 2.85; p = 0.006) and more cryoablation probes (OR = 1.94, p < 0.001) were independently associated with higher risk of major complications.

The use of nephrometry scores (such as RENAL score [radius, exophytic/endophytic properties of the tumor, how close the deepest portion of the tumor is to the collecting system or renal sinus, anterior/posterior descriptor, location relative to polar line], PADUA score [pre-operative aspects and dimensions used for an anatomical score ) may be helpful to predict complications after renal cryoablation, as the size of the lesion and higher nephrometry scores have been associated with a higher risk of complications [41, 42].

Ozkhunov et al. retrospectively reviewed their experience with salvage percutaneous renal cryoablation for biopsy proven renal cell carcinoma recurrence following primary cryoablation procedures [43]. Their study included 20 patients who underwent repeat cryoablation for 21 locally recurrent tumors, with a mean tumor size of 2.4 cm. All salvage cryoablation procedures were completed successfully without any complications and had a median follow-up of 30 months (range: 7–63 months). Three patients (15%) had local recurrence, occurring at 6, 13 and 35 months. Salvage percutaneous cryoablation after primary cryoablation failure is thus a feasible option with a low complication rate and acceptable short term oncologic outcomes.

The definition of therapeutic success following percutaneous renal cryoablation is based on the radiographic appearance of post-ablation axial imaging. Either contrast CT scan or MRI may be used to radiographically follow patients post-ablation [44]. Post-cryoablation lesions should decrease in size as the resultant inflammatory reaction following the thawing of the ice ball will lead to resorption of the necrotic cellular debris [45]. Though contrast enhancement of the lesion and/or growth of the lesion post-procedure can both signal local recurrence it is important to be aware that persistent contrast enhancement can be present up to 9 months post-cryoablation. Shortly after ablation, the ablated tumor may exhibit slight enlargement in size likely due to inflammation with gradual shrinkage over time [46]. Gill et al. reviewed the MRI appearance of tumors treated via cryoablation in 56 patients and found gradual involution of the ablation zone by up to 75% after 3 years [47]. Stein et al. showed that in a series of 30 patients (32 cases) treated with laparoscopic renal cryoablation, 84% of treated renal masses showed no contrast enhancement at the site of treatment at 3 month imaging follow-up [48]. However 16% percent of the ablation sites showed enhancement at 3 months with three (9%) persisting by 6 months and only one displayed enhancement at 9 months. The patient with persistent enhancement at 9 months underwent a partial nephrectomy which demonstrated no recurrence of cancer. Porter et al. studied the MRI characteristics of patients undergoing renal cryoablation and also found 8 of 23 lesions imaged within 6–36 hours after ablation enhanced on MRI [49]. Seven of the eight lesions exhibited no enhancement at 6 month follow-up imaging. The authors concluded that it may thus be reasonable to wait 6 months after technically successful renal cryoablation before performing contrast-enhanced MRI. The exact cause of the persistent post-ablation enhancement in treated tumors is not known. Immediately post-ablation, tumor enhancement may be due to delayed coagulative necrosis, persistent enhancement beyond this time may be due to persistent flow in large intratumoral vessels after cryotherapy [49]. Bolte et al. assessed the MRI appearance of renal ablation sites post-cryoablation and noted peripheral rim enhancement as a common finding (7/18 patients) within 3 months of follow-up [46]. Though four of the seven patients had resolution of the rim enhancement on follow-up imaging, patients with peripheral rim enhancement with an increase in lesion size or nodular enhancement were found to have local recurrence (Fig. 15.3). Rim enhancement of these lesions may be due to viable tissue at the border of the iceball (since the peripheral edge of the ablation zone only reaches 0 °C) [46]. In cases where there is peripheral rim enhancement with an increase in lesion size or nodular enhancement of the lesion, one should consider biopsy of the ablation site. Local recurrences post-cryoablation may be treated with repeat cryoablation or surgical management [43, 50].

We have come a long way since James Arnott’s usage of a mixture of crushed ice and salt for the first therapeutic use of cryoablation. The technologic innovations in cryotherapy, the development of smaller cryoprobes as well as a better understanding of cryobiology have led to the development of percutaneous renal cryoablation. With the advantages of minimal invasiveness, reproducibility and rapid patient recovery, percutaneous renal cryoablation can be a nephron sparing alternative to partial nephrectomy for the treatment of small renal tumors in select patients. Despite promising short/intermediate term outcomes, a larger number of studies with longer follow-up are required to assess its long term efficacy.