Coverage Policy Manual
Policy #: 2003002
Category: Surgery
Initiated: August 2017
Last Review: June 2018
  Whole Gland Cryosurgical Ablation of Prostate Cancer

Description:
Cryoablation is a minimally invasive surgical technique that involves in-situ freezing by applying extremely cold temperature to destroy prostate tissue and reduce the size of the gland.  A cryogen is delivered to the prostate gland through multiple cryoprobes inserted via a transperineal percutaneous approach.  Probe placement is guided by transrectal ultrasound.  To prevent freezing of the urethra a warming device is simultaneously employed.  Multiple freeze-thaw cycles may be performed.
 
Perioperative mortality and acute life-threatening consequences of cryoablation appear to be minimal.  Studies have shown a greater likelihood of impotence following cryoablation as compared to radical nerve sparing prostatectomy for localized disease.
 
Focal Treatments for Prostate Cancer is addressed in a separate policy # 2015016.
 

Policy/
Coverage:
Cryosurgery of the prostate meets member benefit certificate Primary Coverage Criteria as a primary treatment option for carcinoma of the prostate that is clinically confined to the prostate. Patients with large prostates may not respond appropriately as it may be more difficult to achieve a uniformly cold temperature throughout the gland.  A  prior history of transurethral resection is a relative contraindication for cryosurgery.
 
Cryosurgery of the prostate meets member benefit certificate Primary Coverage Criteria for salvage when done as a curative intent in men who have failed radiation therapy, and have no identified metastatic disease as determined by radiological imaging and other standard assessment tools.
 
Cryoablation of the prostate for any other indication, including, but not limited to subtotal prostate cryosurgery, is not covered by Group Contracts or Individual Contracts which have Primary Coverage Criteria, as these uses have not been proven to be effective.
 
For members with individual contracts issued prior to July 1, 2004 (contracts without primary coverage criteria), cryoablation of the prostate for any indication other than those listed as covered  is considered investigational.  Investigational services are an exclusion in the member certificate of coverage.

Rationale:
There were no studies that compared outcomes of cryoablation to outcomes of radical prostatectomy or conformal external beam radiotherapy in randomized or otherwise similar patient populations. In addition, follow-up times were limited to 2 years or less in most cryoablation studies. Available studies reported only surrogate outcomes: prostate-specific antigen (PSA) and biopsy failure rates, and rates of second treatment.
 
Of 34 studies reporting efficacy outcomes after prostate cryoablation, only 6 (total n=2,352) met the Assessment’s inclusion criteria. Problems with available evidence included short follow-up times, heterogeneous patient populations, and insufficient information on baseline characteristics of enrolled patients. Where data were available, outcomes appeared to be generally comparable across treatment methods. However, data from cryoablation studies were sparse, and comparison of patient populations that may have had different risk distributions, both within and across treatment methods, did not permit conclusions.
 
One study presented a retrospective comparison of data from the CaPSURE database, a longitudinal observational database of patients with prostate cancer. Adjusted overall rates of second treatment indicated that patients receiving cryoablation were 1.9 times more likely to have a second treatment than patients who received radical prostatectomy, and 1.4 times more likely than patients who received external-beam radiotherapy (EBRT). When rates of second treatment were stratified by prognostic factors, the rates for cryoablation compared to radical prostatectomy tended to be significantly increased for low-risk disease but not for high-risk disease. The same was true for EBRT compared to radical prostatectomy, but to a lesser extent. Thus, these results did not suggest an advantage for cryoablation, and may have indicated poorer outcomes for low-risk disease.
 
Perioperative mortality and acute life-threatening consequences of cryoablation appeared to be negligible. Patients had the highest likelihood of impotence after cryoablation, compared to radical prostatectomy or 3-dimensional conformal radiation therapy (3D-CRT). The frequency of incontinence appeared similar to that after 3D-CRT, and potentially less than that after radical prostatectomy. However, there were other genitourinary complications unique to cryoablation. Adverse gastrointestinal consequences typical of 3D-CRT were not noted after cryoablation. Long-term consequences of cryoablation were uncertain because follow-up was inadequate.
 
In 2003  a MEDLINE search was performed for studies reporting outcomes of cryoablation for either primary treatment or clinically localized prostate cancer. Eight publications reporting primary analyses of outcomes data were reviewed and are summarized below. The data in these studies, individually or collectively, were insufficient to permit conclusions on health outcomes following cryoablation.
 
Eight studies reported on approximately 1,000 patients.  While some, but not all, studies collected data prospectively in consecutive patients, none included a concurrent comparison group treated with an established alternative. In addition, it was unclear whether “consecutive” meant patients meeting eligibility criteria or those consenting to enroll in a study. Furthermore, retrospective comparisons used historical data collected using different guidelines to assign risk groups or monitor for recurrence (e.g., frequency of follow-up PSA measurements and PSA thresholds for recurrence). Last, the largest single institution series reported the 7-year actuarial rate of biochemical disease-free survival of 590 consecutively treated patients. ) However 59% of the patients were treated using an older, liquid nitrogen system, which the authors asserted  “… yields inferior results compared with the argon-based cryomachines we now use… .” Even so, reported results combined outcomes obtained with both systems.
 
In 2005 Merrick et al stated cryotherapy had not been demonstrated to be as effective, or less morbid, than radical prostatectomy, external beam radiotherapy, or brachytherapy.  In 2006 Bahn et al reported results of cryoablation in 31 men, mean age 63 years, with a mean follow-up of 70 months.  Biochemical disease-free status was maintained by 92.8% of the patients and potency was maintained by 48.1%.
 
2006 – 2007 Update
A literature review was done through December 2006. Ball and colleagues reported on quality of life outcomes on a subset of 719 patients with localized prostate cancer treated with a variety of techniques including cryosurgical ablation.  They reported that in an older population, the tissue destruction resulting from cryoablation appeared to relieve obstructive and irritative urinary symptoms but at the sacrifice of sexual function compared with (103) Pd brachytherapy. Bahn and coworkers reported on use of focal prostate cryoablation with “less-than-complete” ablation of the gland with ice, which spares contralateral prostate tissue and surrounding structures.  Results on 31 men with a mean follow-up of 70 months showed biochemical disease-free status of 92.8%. Potency (either with or without oral medications) was 88.9%. The authors indicate that further investigation is needed.
 
2008 Update
The American Urological Association submitted a “Best Practice Policy Statement” to the Agency for Healthcare Research and Quality National Guideline Clearinghouse in October 2008.  The policy reads, in part: 1) “While there is no Level I evidence from prospective, randomized trials to support the role of cryosurgery over other therapeutic options in the treatment of prostate cancer, the literature contains documentation reporting the seven- to eight-year biochemical disease free results of cryosurgery. The literature reports that the morbidity profile associated with cryosurgery has improved in all aspects, including continence, rectal/urethral fistula formation, urethral sloughing, and potency in association with the technological advances over the last 10 to 15 years”; and 2) “Cryosurgery guided by ultrasound and temperature monitoring is an option for recurrent clinically organ-confined prostate cancer after radiation therapy. As with other salvage therapies for curative intent, cryosurgery should be considered early for patients defined as radiation failures.  Refinements in the surgical technique and equipment have resulted in significantly less morbidity than previously reported as well as encouraging short-term PSA results. Economic modeling is needed to assess the cost effectiveness of salvage cryosurgery relative to alternative treatments”.
 
2012 Update
 A literature search was conducted through May 2012. The literature identified did not prompt a change in the coverage statement. The following is a summary of the relevant literature identified.
 
In October 2011, a systematic review of localized prostate cancer treatments prepared for AHRQ to update the 2002 U.S. Preventive Services Task Force Recommendation was published ( Chou, 2011). The review found no studies comparing cryoablation with watchful waiting and no randomized trials or cohort studies evaluating OS or prostate cancer-specific mortality outcomes. The available evidence was mostly from uncontrolled studies and found to be very limited and not sufficiently reliable to estimate the benefits or harms of cryoablation.
 
In a 2012 comparative effectiveness report from the international Prostate Cancer Results Study Group (PCRSG), PSA-free survival following various prostate cancer treatments, including cryoablation, was noted to be difficult to evaluate, since very few studies comparing results from treatment options were identified (Grimm, 2012).  Additionally, variations in methods of evaluating outcomes and reporting results complicated the analysis. No recommendations for cryoablation were made by the PCRSG.
 
Salvage prostate cryoablation
In 2012, Mouraviev and colleagues reviewed literature published between 1991 and 2012 to compare salvage cryoablation for radio-recurrent prostate cancer to other salvage treatments (Mouraviev, 2012). The authors reported comparisons were difficult to make since no prospective, randomized studies were identified and PSA failure is defined in various ways. However, the authors noted studies have reported salvage cryoablation outcomes that are comparable to salvage radical prostatectomy on an intermediate term. PSA level less than 10 ng/mL, Gleason score less than or equal to 8, and clinical stage T1c or T2 before salvage cryoablation therapy were identified as favorable prognostic factors.
 
Subtotal (Focal) Prostate Cryoablation
There is minimal evidence for use of the technique of subtotal prostate cryoablation for treatment of localized disease. In one representative publication on focal therapy, Truesdale and colleagues reported on a retrospective chart review of 77 patients with unilateral prostate cancer treated with primary focal cryosurgery between 2002 and 2009 (Truesdale, 2010). Using D'Amico risk classifications, 44 patients were considered low-risk, 31 were intermediate-risk, and 2 were high-risk disease. Patients were followed for a median time of 24 months, and the biochemical (PSA) progression-free survival rate was 72.7% overall. Prostate cancer was confirmed by biopsy in 10 of 22 patients suspected of having recurrent disease (2 ipsilateral, 7 contralateral, and 1 bilateral disease). The overall pathologic progression-free survival rate was 87%. Disease progression was correlated with pretreatment PSA levels, pretreatment Gleason scores, number of positive cores, and total tumor lengths. Comparative data from studies with longer follow-up are needed to evaluate this technology.
 
Bahn and coworkers reported on use of focal prostate cryoablation with “less-than-complete” ablation of the gland with ice, which spares contralateral prostate tissue and surrounding structures (Bahn, 2006). Results on 31 men with a mean follow-up of 70 months showed biochemical disease-free status of 92.8%. Potency (either with or without oral medications) was 88.9%. The authors indicated that further investigation is needed. Bahn and colleagues subsequently reported on a retrospective review of 73 patients with low-intermediate risk, unilateral prostate cancer followed for a median of 3.7 months (range 1-8.5 years) after focal cryotherapy. (30) Mean PSA level decreased 70% from 5.9 ng/mL to 1.6 ng/mL after cryoablation of one lobe (p<0.001). Prostate biopsy was performed in 48 patients after focal cryotherapy and was negative in 36 (75%) patients. Incontinence was not documented in any patient, and impotence was noted in 14% of patients.
 
Ward and Jones reported on a retrospective review of 1,160 patients with localized prostate cancer treated with focal cryoablation between 1997 and 2007 from the national Cryo On-Line Database (COLD) Registry (Ward, 2011).  At 36 months, the biochemical recurrence-free rate (bDFS) was 75.7%. Prostate biopsy was positive in 43 (26.3%) of 164 patients biopsied for suspected cancer recurrence or 3.7% of all cryoablation patients. Incontinence and impotence were each documented in 1.6% of patients. Six patients (1.1%) experienced urinary retention for more than 30 days.
 
Ongoing Trials
An search of the online site clinical trials.gov identified 5 studies on cryotherapy for prostate cancer. Biochemical failure and quality-of-life outcomes will be evaluated in an estimated 800 patients in the prospective, multicenter registry of salvage cryotherapy in recurrent prostate cancer (SCORE) trial (NCT00824928A). This study began in January 2007 and is currently recruiting patients. A Phase III study that began in July 2011 will randomize high-risk localized prostate cancer patients to receive cryoablation either with or without androgen deprivation therapy (NCT01398657). Two single-institution studies (NCT00774436 and NCT00877682) will evaluate the effectiveness of focal cryotherapy in clinically-localized prostate cancer in 50 and 100 patients. These studies have completion dates of October 2011 and April 2012, respectively. A Phase I study on the safety of focal cryotherapy in 100 low-risk, localized prostate cancer patients is being conducted in Italy and is enrolling patients by invitation only (NCT00928603).
 
2013 Update
A search of the MEDLINE database was conducted through May 2013. There was no new information identified that would prompt a change in the coverage statement. The following is a summary of the key identified literature.
 
Chin and colleagues reported on a randomized trial of cryoablation compared to EBRT in patients with clinical stage T2C-T3B prostate cancer (Chin, 2008; Chin, 2012). These patients had node-negative disease and also received 6 months of hormonal therapy, starting 3 months before treatment. Only 64 of the planned 150 patients were accrued; entry was limited due to changes in practice and difficulty beginning cryosurgery at one of the sites. Twenty-one of 33 (64%) in the cryoablation group and 14 of 31 (45%) in the EBRT-treated group were classified as treatment failure. The mean biochemical disease-free survival (bDFS) was 41 months for the EBRT group compared to 28 months for the cryoablation group. The 4-year bDFS for EBRT and cryoablation groups were 47 and 13%, respectively (Chin, 2008). The 8-year bDFS for EBRT and cryoablation groups were 59.1% and 17.4%, respectively. Disease-specific survival (DSS) and OS for both groups were very similar and at 8-years follow-up, were not significantly different (Chin, 2012). Serious complications were uncommon in either group. EBRT patients exhibited adverse gastrointestinal (GI) effects more frequently. The authors concluded that taking into account the relative deficiency in numbers and the original trial design, this prospective randomized trial indicated that the results of cryoablation were less favorable compared to those of EBRT and that cryoablation was suboptimal primary therapy in locally advanced prostate cancer.
 
Wenske and colleagues reported on salvage cryoablation in a series of 396 consecutively treated patients who had failed cryoablation or radiotherapy (Wenske, 2012). Data was analyzed from 328 patients with a median follow-up of 47.8 months (range: 1.6-203.5). Fifty-five (16.7%) of these patients received subtotal (focal) salvage cryoablation. At 5- and 10-years follow-up, DFS was 63% and 35%, disease-specific survival (DSS) was 91% and 79%, and OS was 74% and 45%, respectively. After salvage cryoablation, median PSA nadir was 0.2 ng/ml (range: 0.01-70.70 ng/ml) at a median follow-up of 2.6 months (range: 2.0-67.3 months). PSA nadir was the only predictor of recurrence and DSS in multivariate analyses (p<0.001 and p=0.012, respectively). Complications occurred in 0.6-4.6% of patients. In the 55 patients that received subtotal (focal) salvage cryoablation, median PSA nadir was 0.44 ng/ml (range: 0.04-20.1 ng/ml) and recurrence was seen in 27 patients (49%). At 5- and 10-years follow-up, DFS was 47% and 42%, DSS was 100% and 83%, and OS was 87% and 81%, respectively.
 
2014 Update
A literature search conducted through May 2014 did not reveal any new information that would prompt a change in the coverage statement. The key identified literature is summarized below.
 
Durand and colleagues completed a clinical trial on treatment options for men with unilateral low-risk prostate cancer (Durand, 2014). From January 2009 to March 2012, patients with localized PCa who refused active surveillance were assigned to a FC protocol. This was a prospective, single-arm cohort study. Inclusion criteria were: unilateral disease, clinical stage T1c to T2a, prostate-specific antigen (PSA) concentration <10 ng/mL, low volume index lesion and Gleason score ≤6 (3+3). Hemi-ablation was carried out using the Precise(TM) cryoablation system (Galil Medical, Inc., Arden Hills, MN, USA). Oncological (PSA values) and functional (International Prostate Symptom Score and International Index of Erectile Function (IIEF)-5 score) outcomes were analysed at 3-, 6- and 12-month follow-up. The primary endpoint for oncological efficacy, no cancer in ipsilateral side, was based on the 12-month mandatory biopsy.
 
A total of 48 consecutive patients with a mean age of 67 years were included. The median (interquartile range) follow-up was 13.2 (7.4-26.5) months. Follow-up prostate biopsies were negative for the treated lobe in 86% of patients. The mean PSA concentration dropped significantly at 3 months (by 55%) but did not correlate well with positive biopsy results. Urinary symptoms were unchanged. A slight decrease in the IIEF-5 score was present at 3 months, but did not differ significantly from baseline at 6-month follow-up. There were 15% grade 1 and 4% grade 2 complications (Clavien classification).
 
Focal cryoablation is a low-morbidity option in selected patients with low-risk PCa. We showed PSA concentration to be an unreliable marker for monitoring FC and recommend a protocol of mandatory biopsies for follow-up. A multicentre randomized controlled trial is necessary to confirm the low-morbidity and the biopsy-proven PCa cure rates.
 
In a retrospective analysis Ahmad and colleagues studied 283 consecutive patients with RRPC treated by SCT in three independent U.K. centres (between 2001 and 2011) (Ahmad, 2013). Two freeze-thaw cycles of transperineal cryotherapy were performed under transrectal ultrasound guidance by a single surgeon in each of the 3 sites; analysed clinico-pathological factors against tumour response. Functional outcomes were assessed by continence status and IPSS questionnaire. Predictive factors for SCT-induced micturition symptoms were analyzed in a sub-group (n=42) of consecutive cases.
 
They found that nadir post-SCT PSA levels strongly associated with DFS. The DFS rates at 12- and 36-month were 84% and 67% for the ≤ 1 ng/ml group and 56% and 14% for the >1 ng/ml group, respectively (p<0.001). Correlative analysis revealed highly significant association between patients' post-SCT micturition status with prostate gland and iceball lengths following SCT. Finally, in a reduction model, both gland length and maximal length of iceball were highly associated with patients' IPSS outcome (p<0.001).
 
Ahmad and colleagues reported the largest European patient cohort treated with SCT for RRPC. Oncologic outcome guided by nadir PSA of <1 ng/ml is consistent with earlier single-centre series. For the first time, physical parameters were identified to predict micturition symptoms following SCT. The data will directly assist on-going and future trial design in cryotherapy in prostate cancer.
 
2015 Update
A literature search conducted through May 2015 did not reveal any new information that would prompt a change in the coverage statement. The key identified literature is summarized below.
 
A network meta-analysis published in 2014 evaluated the comparative efficacy and safety of radical prostatectomy, several regimens of EBRT, cryotherapy, and observational management (Xiong, 2014). This analysis incorporated 21 randomized controlled trials (N=7350) that reported OS and prostate CSS at 5 years and, late GI and late genitourinary (GU) toxicities at 3 years. It used Bayesian network analysis with informative prior distributions based on external evidence for heterogeneity variances to compute odd ratios (ORs) with 95% confidence intervals (CIs) for all pair-wise comparisons of interventions. The rank order of superiority of each intervention was compared against all others using the Surface Under the Cumulative Ranking (SUCRA) statistic. The latter is expressed as a percentage that ranges from 0% if an intervention is certainly the worst to 100% if an intervention is certainly the best. If all interventions are equal, all SUCRA values would approximate 50%. Overall, the network analysis showed no evidence of superiority of any treatment for OS, based on SUCRA values that ranged from 18% (observational management) to 69% (conformal low-dose EBRT). Cryotherapy had a SUCRA value of 50%, which yielded a ranking of fourth best treatment. However, the SUCRA values for late GI (99%) and GU (77%) events with cryotherapy placed this intervention in first place for those specific outcomes. These analyses are consistent with a positive balance of benefits and harms associated with total cryotherapy compared with radical prostatectomy, external beam radiotherapy (EBRT) and observational management.
 
2017 Update
A literature search conducted through May 2017 did not reveal any new information that would prompt a change in the coverage statement. The key identified literature is summarized below.
 
In 2016, Gao and colleagues reported results of a systematic review and meta-analysis comparing cryoablation to radiotherapy (RT) and radical prostatectomy for treatment of localized prostate cancer (Gao, 2016). The search included articles published up to December 2015. Because the pooled estimates combined primary and salvage treatment, we present the individual studies in the following sections and do not present pooled data here. Six studies described primary treatment (2 RCTs [Chin, 2008; Chin, 2012], 2 prospective observational [Ball, 2006; Elkjaer, 2014], 2 retrospective [Gould, 1999; Hubosky, 2007]). Cryotherapy had similar OS and disease-specific survival (DSS) rates as RT and radical prostatectomy in trials of primary treatment. There was significantly more sexual bother for cryoablation compared to RT at all times reported (p<0.01).
 
The Cryo Online Data (COLD) registry is a database established and supported by a cryoablation manufacturer. The data are maintained independently. Physicians submit standardized forms to the database and participation is voluntary. The registry contains case report forms of pretreatment and post-treatment information for patients undergoing whole gland or partial gland (focal) prostate cryoablation. Patients are stratified into low-, intermediate-, and high-risk groups. Jones and colleagues reported initial outcome for 1198 men with primary whole gland prostate cryoablation (Jones, 2008). Mean follow-up was 24.4months; 136 men had 5-year data. The 5-year bDFS (Phoenix definition) for the entire population was 73%; 91%, 79%, and 62%, for the low-, intermediate-, and high-risk groups, respectively. The rectal fistula rate was 0.4%. Incontinence was reported by 5% of men, with 3% of men using pads. Twenty-five percent of men reported having sexual intercourse but only 9% did so without pharmaceutical or device assistance. In 2016, outcomes for 300 men registered in COLD who underwent primary whole gland cryotherapy for high-grade (Gleason score ≥8), localized prostate cancer were published (Tay, 2016). Mean follow-up was 28.4 months. The estimated 2- and 5-year bDFS rates were 77% (95% CI, 71% to 88%) and 59% (95% CI, 50% to 67%), respectively. At 12-month follow-up, complete continence was reported by 91% of men and potency by 17% of men. The incidence of recto-urethral fistulae was 1.3%. Urinary retention requiring intervention beyond temporary catheterization was reported by 3% of men.
 
Section Summary: Primary Prostate Cryoablation
Evidence for the use of whole gland cryoablation for treatment localized prostate cancer comes from several systematic reviews, 2 RCTs, and many comparative and non-comparative observational studies. High-quality data comparing cryoablation to other treatments are lacking, but available data suggest similar OS and DSS rates compared to radical prostatectomy and EBRT.
 
Nonrandomized Comparative Studies
Peters and colleagues reported results of retrospective data from 129 men from 5 high-volume Dutch centers (Peters, 2013). Forty-four men underwent salvage prostatectomy, 54 underwent salvage cryoablation, and 31 underwent salvage brachytherapy. Mean follow-up was 29 months, 22 months, and 14 months, respectively. Biochemical failure occurred in 25 (81%) men in the brachytherapy group, 29 (66%) men in the prostatectomy group, and 33 (61%) men in the cryosurgery group. Severe GU and GI toxicity (grade >3) using Common Toxicity Criteria for Adverse events (v.3.0), definition was observed in up to 30% of patients in all 3 groups. There were 12 (27%), 5 (9%), and 14 (45%) deaths, respectively.
 
Pisters and colleagues compared retrospective data for 38 men who underwent salvage radical prostatectomy at the Mayo Clinic between 1990 and 1999 and for 34 men who underwent salvage cryoablation at M.D. Anderson Cancer Center between 1992 and 1995 (Pisters, 2009). Mean follow-up was 7.8 years in the prostatectomy group and 5.5 years in the cryoablation group. The bDFS rate was 42% for cryoablation and 66% for prostatectomy at 5 years (p=0.002). OS rate at 5 years was 85% for cryoablation and 95% for prostatectomy (p=0.001). There was no significant difference in DSS at 5 years (96% cryoablation vs 98% prostatectomy, p=0.283).
 
Nonrandomized Noncomparative Studies
In 2016, Siddiqui and colleagues reported long-term outcomes for 157 men undergoing salvage cryoablation for biopsy-proven, localized radio-recurrent prostate cancer at a single institution from 1995 to 2004 (Siddiqui, 2016). Median follow-up was 117 months (interquartile range, 55-154 months). OS rates at 5 and 10 years were 93% and 76%, respectively. The bDFS rates at 10 and 15 years were 35% and 23%, respectively. Rectourethral fistula developed in 2.5% of patients and successfully repaired in all cases. Fifty-two percent of men reported no incontinence while 44% required 0 or 1 pad per day.
 
Registry Studies
Friedlander and colleagues compared salvage cryoablation to salvage radical prostatectomy in 440 men retrospectively identified in the SEER database who were treated between 1992 and 2009 (Friedlander, 2014). The authors used propensity score analyses to compare overall and prostate cancer􀀐specific mortality. Overall mortality was significantly higher (21.6 vs 6.1 deaths/100 person years, p<0.001) for prostatectomy than for cryoablation. Prostate cancer􀀐specific death rates were numerically higher for prostatectomy than for cryoablation (6.5 vs 1.4 deaths/100 person years, p=0.061).
 
In 2013, Spiess and colleagues reported outcomes for 156 men who underwent salvage cryoablation without neoadjuvant hormonal ablative therapy from the COLD registry (Spiess, 2013). The bDFS rates at 1, 2, and 3 years were 89.0%, 73.7%, and 66.7%, respectively. For men with presalvage PSA levels less than 5 ng/mL, the bDFS rates were 95.3%, 86.7%, and 78.3% versus 81.4%, 58.4%, and 52.9% for those with PSA levels of 5 ng/mL or more.
 
Section Summary: Salvage Prostate Cryoablation
The evidence for use of salvage prostate cryoablation in men with localized, recurrent prostate cancer following RT includes primarily noncomparative case series. A small number of retrospective comparative studies have compared salvage cryoablation to salvage prostatectomy but with contradictory findings. Men in this group have few other options and prostatectomy can be difficult in tissue that has been irradiated.
 
SUMMARY OF EVIDENCE
For individuals who considering initial treatment for localized prostate cancer who receive whole gland cryoablation, the evidence includes several systematic reviews, 2 RCTs and many comparative and non-comparative observational studies. Relevant outcomes are overall survival, disease specific survival, symptoms, functional outcomes, quality of life, treatment-related morbidity. High quality data comparing cryoablation to radiotherapy, radical prostatectomy, or active surveillance is lacking but available data suggest similar OS and DSS compared to radical prostatectomy and EBRT. Along with clinical input, the evidence is sufficient to conclude that cryoablation leads to improvement in net health outcome
 
For individuals needing salvage treatment for recurrence of localized prostate cancer following radiotherapy for localized prostate cancer who receive whole gland cryoablation, the evidence includes primarily noncomparative case series and a few retrospective comparative studies comparing salvage cryoablation to salvage prostatectomy. Relevant outcomes are overall survival, disease specific survival, symptoms, functional outcomes, quality of life, treatment-related morbidity. High quality data comparing cryoablation to prostatectomy is mixed and evidence comparing cryotherapy to brachytherapy is lacking.
Men in this group have few other options and prostatectomy can be difficult in tissue that has been irradiated. Based on the limited data available and clinical input, the evidence is sufficient to conclude that cryoablation leads to improvement in net health outcome.
 
ONGOING AND UNPUBLISHED CLINICAL TRIALS
Some currently unpublished trial updates that might influence this review are listed below:
 
Ongoing
(NCT01398657) Cryotherapy with or without Short-term Adjuvant Androgen-Deprivation Therapy for High-Risk Localized Prostate Cancer – Open-Label Randomized Clinical Study; planned enrollment 182; projected completion date June 2016; status unknown.
 
 
Unpublished
(NCT00824928) an industry-sponsored or cosponsored trial. A Prospective Multicenter Registry of Salvage Cryotherapy in Recurrent Prostate Cancer Study (SCORE); planned enrollment 60; projected completion date December 2012; status terminated.   
 
2018 Update
A literature search conducted through January 2018 did not reveal any new information that would prompt a change in the coverage statement. The key identified literature is summarized below.
 
European Association of Urology et al
In 2017, the European Association of Urology published joint guidelines on prostate cancer with the
European Society for Radiotherapy and Oncology and the International Society of Geriatric Oncology (Mottet et al, 2017). For nonmetastatic prostate cancer, the guidelines have recommended that cryotherapy and high-intensity focused ultrasound be offered only in a clinical trial.

CPT/HCPCS:
55873Cryosurgical ablation of the prostate (includes ultrasonic guidance and monitoring)

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