Best Practice Statement on Cryosurgery for the Treatment of Localized Prostate Cancer

Introduction 

The protracted natural history of clinically localized prostate cancer has confounded the development of a national consensus regarding the optimal treatment for this disease. In the AUA 2007 Guideline for the Management of Clinically Localized Prostate Cancer: 2007 Update, multiple treatment modalities are considered as options.1 This conundrum is further complicated by stage migration and lead time bias, both associated with PSA-based early detection strategies and the resultant increase in the detection of small volume clinically localized cancers.2 Since the majority of men currently diagnosed with prostate cancer are likely to have the disease eradicated by one of several treatment modalities, the clinical focus on HRQL associated with treatment has intensified.3 There are no published long-term data on the efficacy of cryosurgery on metastasis-free, prostate cancer-specific, or overall survival as there are with other more established forms of therapy; however, several large, single institution experiences, a pooled analysis, and several prospective evaluation studies report the efficacy and morbidity of cryosurgery of the prostate.4, 5, 6, 7 Additionally, prostate cryosurgery has been found to result in acceptable HRQL-based outcomes with a reduced cost when compared to other local therapeutic options.8, 9 Short-term PSA relapse-free survival outcomes following cryoablation of the entire prostate comparable to radiation therapy in men with intermediate- and high-risk disease have been reported.4, 7, 10, 11, 12, 13 Biochemical-free survival comparisons between RP and other nonextirpative therapies are difficult since the definitions for success are different.

The inherent treatment planning flexibility of cryosurgery lends itself to a targeted subtotal gland ablation approach for men with low-risk and/or small-volume cancers.14

Methodology 

As noted in the AUA Guideline for the Management of Clinically Localized Prostate Cancer: 2007 Update,1 insufficient information was available to include cryosurgery in data meta-analyses. As such, the AUA convened a Panel to develop a BPS addressing the use of cryosurgery for the treatment of localized prostate cancer. A BPS uses published data in concert with expert opinion, but does not employ formal meta-analysis of the literature. A Medline search was performed using the Medical Subject Headings (MeSH) index headings “prostate cancer,” and “cryosurgery,” “cryotherapy,” and “cryoablation,” from 2000 through 2008. Publications were selected for review by the Panel members. The Panel formulated recommendations based on review of all material and the Panel members' expert opinions and experience which includes the treatment of several thousands of patients. Recommendations presented herein were achieved through a consensus process and may not reflect a unanimous decision by the Panel members. Levels of evidence were assigned based on the recommendations of the U.S. Preventive Services Task Force (Appendix 1).15

This document was submitted for peer review, and comments from all 19 responding physicians and researchers were considered by the Panel in making revisions. The revised document was submitted for a second peer review, and responses from all 21 responding physicians and researchers were considered by the Panel when making final revisions to the document. The final document was submitted to the AUA PGC and Board of Directors for approval.

Funding of the Panel was provided by the AUA. Members received no remuneration for their work. Each Panel member provided a conflict of interest disclosure to the AUA.

Historical Development and Technological Advances 

Some of the earliest reports of cryotherapy date back to the 19th century, when cervical and breast cancers were treated with a crude salt and ice mixture resulting in reduction of tumor volumes in some patients and improvement in local control.16 In 1961, Cooper and Lee17 developed the first cryotherapy probe system (Appendix 2), involving the circulation of liquid nitrogen through a closed metal tube placed in direct contact with the target tissue.16 These early liquid nitrogen probes, which allowed rapid freezing of tissue to −200°C, led to the nitrogen based prostate cryosurgical procedures performed in the 1960s and 1970s. Soanes, and Flocks and others used liquid nitrogen probes placed either transurethrally or via an open perineal incision to treat both benign prostatic hyperplasia and prostate cancer.18, 19 Notably, the freezing process was monitored by direct visualization, which was unreliable and resulted in an unacceptably high complication rate.20, 21 Dreaded complications such as total urinary incontinence, rectourethral fistulas, urethral sloughing, and stricture were common.

In the early 1990s, adoption of urethral warmers22 was essential in reducing the risk of urethral sloughing,23 and the implementation of TRUS22 for percutaneous probe placement significantly advanced technology. Ice ball formation could now be monitored to ensure complete prostate ablation while reducing damage to adjacent tissue. On ultrasound imaging, the edge of the frozen tissue appears as a hyperechoic rim with acoustic shadowing.22, 24 The use of thermocouple devices introduced in the mid-1990s allowed the surgeon to determine the extent of cell damage and served as an endpoint to the freezing cycle when temperatures less than −40°C were reached. Thermocouples record when lethal temperatures are achieved in the prostate and when nondestructive, warmer temperatures are maintained in sensitive adjacent structures such as the rectum (Denonvilliers' fascia) and external sphincter.25 Next, a multiprobe system, allowing percutaneous placement under TRUS guidance, was developed. These probes were 3 mm in diameter, requiring dilation of the tract for placement.

Another technological advancement occurred when the original liquid nitrogen technology was replaced by argon based cryosurgery in which pressurized argon gas allows for rapid temperature drops by the free expansion of gas (Joule-Thompson effect). Real-time control of ice ball formation improved the precision of tissue ablation and further minimized harm to adjacent tissue. The transition to gas also permitted the advent of systems using thin (2.4 mm diameter) or ultrathin (17-gauge; 1.5 mm diameter) cryoneedles or smaller (2.4 mm diameter) cryoprobes that could be percutaneously passed through a brachytherapy-like template25 or freehand. Separate skin incisions and tract dilation were no longer necessary.26, 27 Helium gas, which warms when it expands, provided an active warming capability that was not available in the liquid nitrogen systems.28 The introduction of pinpoint thermocouples, another feature of argon based cryosurgery systems, further reduced procedural complications.28 In addition to the smaller needle system, computer software was developed that has the ability to generate preoperative isotherm maps based on theoretical cryoneedle placements. This latest strategy for ablation allows the surgeon to plan needle placement so as to best target diseased tissue and avoid damaging important structures.

The operative time averages two hours, and the majority of the cases can be performed as outpatient procedures with either a Foley or suprapubic catheter placed for 5 to 14 days. With the aforementioned technological advances, there has been a significant reduction in overall side effects, including urinary incontinence, rectal pain, and urethral sloughing.23

In summary, a review of the historical evolution of cryosurgery provides two overriding messages, the first being that there is evidence of therapeutic benefit, and the second, that treatment-associated morbidity has been reduced as technological refinements have emerged.

Scientific Background 

Clinically, cryosurgical procedures are grounded on well-recognized scientific principles supporting physician-managed destruction of clinically-localized tumors of the prostate.29, 30, 31 When performed with multiprobe devices and advanced imaging techniques, cryosurgery has yielded effective short-term biochemical disease-free results in the treatment of prostate adenocarcinoma.4, 7, 12 Prostate geometry dictates CN/P: CN/Ps are placed to support thermal homogeneity at approximately −40°C throughout the prostate. Following ultrasound-guided placement of CN/P, the physician directs freezing from anterior to posterior in the gland. This sequencing supports clear visualization and control of the ablative process.32, 33 Other CN/P placement strategies have also been reported showing similar ablative performance.4, 10, 14

Cryosurgery is a thermal therapy in that it extracts heat (thermal energy) from the targeted tissue resulting in a series of destructive effects. It is long recognized that the tissue response from cold injury, which can range from inflammation to total destruction, depends on the severity of freezing. The lesion created by freezing is characterized by coagulation necrosis in the central region with a surrounding, relatively thin, peripheral region in which cell death is apparent.34, 35

There are two scientific principles that underlie successful cryodestruction of tissue. The first relates to the cellular responses to freezing that induce cell death, including freeze rupture, necrosis and apoptosis. “Freeze rupture” is the term used to describe the cascade of events that leads to cell stress and death. With the onset of ice formation, water is “extracted” from the extracellular solution as pure crystalline ice, leaving an increasingly hyperosmotic solution. This hyperosmotic extracellular solution causes water to leave the cell, followed by cell shrinkage and damage to the intracellular matrix (especially protein) due to high-salt content. (NOTE: The extracellular osmolality of the prostatic tissue increases to approximately 8,000 mOsm by −15°C.) As the temperature approaches −15°C and below, lethal intracellular ice begins to form. In a structurally constrained organ (ie, encapsulated), the expanding ice front may destroy cells of the capillary endothelial lining, rendering the vascular tree impaired after thawing.

The first principle of cryoablation is promotion of apoptosis. Apoptosis (genetically-regulated [programmed] cell death) has recently been linked with thermal injury.36 Prostate cancer cells die from apoptosis following a freezing insult at temperatures consistent with the freeze-zone margin.37 Apoptosis induction has been linked to a mitochondria-induced intrinsic mechanism characterized by an upregulation of cellular levels of Bax, the pro-apoptotic protein, without a concomitant change in prosurvival Bcl-2.38 More recently, Clarke et al have demonstrated that apoptotic induction can be facilitated in prostate cancer cells through an extrinsic pathway involving the interaction of tumor necrosis factor-related apoptosis-inducing ligand with its receptor in the plasma membrane.39

The second principle of successful cryodestruction relates to procedural factors that maximize cancer cell kill (ie, freeze rate, end temperature, time, and freeze-thaw repetition). Contemporary cryosurgical technique provides precise “temperature management” of the targeted tissue with reliance on the combination of intraoperative ultrasound and temperature monitoring.5, 25, 40 The destruction of both benign cells and cancer cells is dependent on an array of physical freeze-related stresses. Prostate cell death follows a relatively precise temporal pattern. Cancer cells proximate to the CN/P or contained within the CN/P array are destroyed primarily by freeze rupture due to intracellular ice formation. The level of intracellular ice formation increases exponentially at temperatures less than −15°C. Throughout the frozen prostate, those cancers cells not destroyed by intracellular ice undergo either necrotic- or apoptotic-cell death depending on the extent of the stress experienced and the cell-cycle stage.41

Immediately postthaw, some cancer cells will have experienced partial physical damage and will then undergo a bout of primary necrosis within one hour. This event, along with the presence of cell fragments resulting from freeze rupture, is responsible for the launch of the inflammation cascade. Simultaneously, and extending over approximately 6 to 12 hours, surviving cancer cells experience the onset of apoptosis stimulated by the biochemical stresses associated with the freeze concentration of inorganic and organic solutes. With progressive vascular stasis caused by freeze rupture of the tumor capillaries, local hypoxia results causing the induction (24 to 48 hours) of another bout of secondary necrosis.42 These combined physical, structural, and biochemical insults render the prostate fully ablated.

In vitro and in vivo experiments demonstrate that human prostate cancer cells can be sensitized such that both apoptosis and secondary necrosis occur at greater rates when freezing is combined with cytotoxic agents.43, 44 This observation has been corroborated in other cancers.45, 46 Prostate cancer cells experiencing multiple molecular-targeted stressors (cytotoxic agents) succumb more readily to low temperature exposure. In fact, very recent data indicate that with appropriate paired combinations, even freezing at −1°C can be totally lethal.38, 47, 48 Neoadjuvant cryosurgery clinical trials will be needed to test these in vitro observations.

To both maximize the destructive effects of cryosurgery and to permit comparisons of outcomes among treatment centers, specific procedural requisites should be followed.29

Primary Cryosurgery (Evidence Level II-2/3) 

The consensus opinion of the Panel is that primary cryosurgery is an option, when treatment is appropriate, to men who have clinically organ-confined disease of any grade with a negative metastatic evaluation. High-risk patients may require multimodal therapy. There are even more limited data regarding the outcomes for clinical T3 disease, and the role of cryosurgery in this setting is currently undetermined.

Patient Selection 

Cryosurgery of the prostate is a locally ablative treatment option for the management of prostate cancer. Suitable candidates should have documented prostate cancer that is clinically confined to the prostate. Although cryosurgery is an option for low-, intermediate-, and high-risk patients, gland volume is a factor; the larger the prostate, the more difficult to achieve a uniformly cold temperature throughout the gland. After assessment of volume and gland configuration, technical considerations will need to be made followed by appropriate technical modifications. In some larger glands, neoadjuvant cytoreduction can be considered to overcome the technical limitations of treating a large gland. Neoadjuvant or concomitant hormonal therapy, however, has not been shown to have a positive impact on subsequent cryosurgical outcomes.

The role of lymph node dissection in patients being considered for cryosurgery is similar to that in patients receiving radiation therapy. Elevated PSA levels (greater than 20 ng/mL) or Gleason scores of 8 to 10 are associated with an increased incidence of lymph-node involvement. Men with a greater than 25 percent risk based on established nomograms or some other published criteria may warrant lymph node dissection prior to or concurrent with cryosurgery (Partin Table52).53 A prior history of TUR of the prostate is a relative contraindication for cryosurgery, especially if there is a large TUR defect present. These patients are at increased risk for urethral necrosis leading to sloughing and urinary retention due to failure of the urethral warming device to coapt to the mucosa. While many patients with elevated PSA levels have been treated with cryosurgery, the best results are achieved in patients with PSA levels less than 10 ng/mL.54, 55

Cryosurgery is a minimally invasive option when treatment is appropriate for men who either do not want or are not good candidates for RP because of comorbidities, including obesity, or a prior history of pelvic surgery. The latter is based on the opinion and experience of the Panel. Cryosurgery may also be a reasonable option in men with a narrow pelvis or who cannot tolerate EBRT, including those with previous nonprostatic pelvic radiation, inflammatory bowel disease, or rectal disorders. As cryosurgery is an outpatient procedure or may only require an overnight stay, it is an option for patients seeking shorter-duration treatment of clinically organ confined prostate cancer. For patients who desire minimally invasive therapy for their intermediate disease, defined as Gleason score 7 and/or Gleason score less than 8 with a PSA level greater than 10 ng/mL but less than 20 ng/mL and/or clinical stage T2b, cryosurgery is also an option.4, 6, 7, 32

Treatment Outcomes 

Physician Reported Complications 

Long term 

Fistula formation 

In the 1960s and 1970s, with the earlier forms of cryosurgery technology, fistula formation was the most significant complication and continued to be a concern in the early 1990s when cryosurgery was reintroduced. The patients at highest risk were those treated with salvage cryosurgery after radiation therapy. This is not a common complication in primary treated patients and, in the last 10 years, the incidence of this complication has become uncommon. The incidence reported in the literature ranges between 0 percent to 0.5 percent.4, 5, 6, 10 Thus, the risk of fistula formation is the same as the risk of rectal injury following RP, various forms of EBRT, and interstitial prostate brachytherapy.

Incontinence 

In complete gland cryosurgery, the external sphincter is inevitably affected by the freeze, although it is somewhat protected by the urethral-warming catheter, as is the prostatic urethral mucosa. Nonetheless, there is a risk of urinary incontinence, and when present, is usually limited to mild stress incontinence. The incidence of permanent physician reported incontinence (wearing a pad) in the literature ranges from less than 1 percent to 8 percent.12

Erectile Dysfunction 

During total gland cryosurgery, the ice ball extends outside the prostate capsule and in most cases encompasses both neurovascular bundles, commonly resulting in ED. The incidence of ED reported in the literature ranges from 49 percent4, 5 to 93 percent at one year. For this reason, cryosurgery is generally considered suitable as a treatment option in men who are not concerned with erectile function. A recent study of penile rehabilitation following total gland cryoablation reports a potency rate of 41.4 percent at one year and 51.3 percent at four years.12

Urethral sloughing 

The use of a urethral-warming catheter, currently a standard technique of the operative procedure during the freeze, has been shown to significantly reduce the risk of urethral sloughing.50, 59 On occasion, however, its protective effect can be overcome. Urethral sloughing is particularly likely to occur in the sulcus on either side of the verumontanum, which is frequently not in contact with the urethral-warming catheter surface. As a result, the prostatic mucosa can necrose, forming a linear ulcer, exposing the necrotic prostate tissue to urine flow. Severe dysuria and urinary retention can result and may require TUR of the necrotic tissue to overcome the problem, the outcomes of which have not been reported. The currently reported incidence of urethral sloughing in patients undergoing cryosurgery with the use of a urethral-warming catheter ranges from 0 percent to 15 percent.57, 59

Mouraviev and Polascik60 recently summarized in tabular form the more common complications associated with primary cryosurgery of the prostate (table 1).6, 13, 23, 54, 56, 60, 61, 62, 63 It is thought that the high morbidity presented in earlier series could be attributed to the use of liquid nitrogen based systems, older ultrasound techniques, and banning of the urethral warmer by the U. S. Food and Drug Administration.60 Cohen, using a large single-institution database, compared the complications of cryosurgery with the use of nitrogen and argon based equipment and showed that this technological change has led to a decrease in serious side effects such as incontinence and fistulas.13

Table 1. Complication rates after primary cryosurgery of the prostate

	Reference	Yr	No. Pts	Cryosystem	ED (%)	Incontinence (%)	Fistula (%)	Urethral Stricture (%)	Urethral Sloughing (%)	Perineal Pain (%)	Obstruction/ Retention (%)	UTI/Sepsis (%)
	Primary Cryosurgery
	Bahn et al63	1995	210	Cryocare	41	9.0	2.4	NA	NA	NA	3	NA
	Shinohara et al56	1997	102	NA	86	15.0	1.0	NA	23.0	3.0	23	3.0/3.0
	Cohen et al23	1995	239	Cryocare Seednet	4	0.4	2.2	NA	9.8	0.4	3	2.2/0.7
	Wake et al61	1996	100	Cryocare	NA	8.0	0	NA	1.0	NA	22	NA
	Long54	1996	145	Cryocare	88	2.0	1.3	3.4	8.9	2.3	17	2.3/Less than 1
	Badalament et al62	1999	290	Cryocare	85	4.3	0.4	NA	10.0	12.0	NA	NA
	Long et al6	2001	975	Cryocare	NA	7.5	0.5	NA	NA	NA	13	NA
	Cohen13	2004	865	Accuprobe (before 1996)	NA	8.6	2.0	NA	16.0	NA	NA	NA
				Cryocare (1996–2000)	NA	3.2	0	NA	14.0	NA	NA	NA
			98	Seednet	NA	0	0	NA	2.0	NA	NA	NA

No. Pts – number of patients; NA – not available; UTI – urinary tract infection. Adapted from Mouraviev and Polascik, reprinted in part with permission.60

Salvage Cryosurgery (Evidence Level II-3) 

It is the opinion of the expert Panel that salvage cryosurgery can be considered as a treatment option for curative intent in men who have failed radiation therapy. The most appropriate candidates have biopsy proven persistent organ-confined prostate cancer, a PSA less than 10 ng/mL, and a negative metastatic evaluation as determined by standard assessment tools such as imaging modalities.51

Introduction 

Radiation is a common form of therapy for patients with newly diagnosed and localized prostate cancer. It has been estimated that nearly one third of newly diagnosed prostate cancer patients will choose one form of radiation therapy as their primary treatment. Despite modifications of delivering radiation such as intensity modulation, 3-dimensional conformal, and computer-assisted brachytherapy, a number of these patients will have a rise in their serum PSA value sometime after radiation. Since rising PSA levels can occur with both local and metastatic disease, an elevation does not necessarily imply that a patient has local recurrence. In addition, a minimal PSA level elevation may be due to benign causes. These factors make it difficult to clearly define a locally salvageable population. After radiation therapy, a prostate biopsy will be positive in one third of patients with biochemical failure.65 If local recurrence is detected early, and occurs without clinical evidence of metastatic disease, salvage therapy is feasible. Recent advances in both technology and the technique of salvage cryosurgery have reduced treatment-associated morbidity and stimulated interest in this treatment option for curative intent in the setting of radiation failure.29, 51, 55, 66, 67, 68

Patient Selection 

Technical Considerations and Modifications 

Salvage cryosurgery can be performed in the patient with recurrent disease following EBRT as well as interstitial prostate brachytherapy. Previously placed radioactive seeds can be visualized quite well under TRUS and may cause some confusion as their sonographic appearance is similar to the tip of the cryoneedles, especially in the transverse view. Placing the needles in the sagittal plane can overcome this difficulty, since the length of the cryoneedles can be easily followed in this view. Due to previous radiation, the gland may be adherent to the anterior rectal wall, diminishing the thickness of Denonvilliers' fascia. This needs to be assessed by TRUS prior to freezing so the surgeon can determine how to appropriately place the posterior cryoprobes and the Denonvilliers' thermocouple. If the space between the anterior rectal wall and posterior prostatic capsule is less than 5 mm, it may not be possible to drive the temperatures down to –40°C safely, and freezing should be terminated when the leading edge of the ice ball has extended just beyond the capsule, even if the target temperature of –40°C is not reached. Double freeze-thaw cycles have better outcomes in terms of biochemical failure-free and local recurrence-free survival rates compared to a single freeze-thaw cycle.51

When counseling patients for any salvage procedure, the risks of urinary incontinence need to be addressed. Placement of a thermosensor to monitor the temperature of the external sphincter can reduce the potential of thermal injury to this muscle. The thermosensor is introduced through the perineal skin and advanced until the impression of the tip of the thermocouple can be seen in the sphincter. The placement can be documented by TRUS with/without cystoscopy.

There is no documented evidence of benefit from hormone therapy prior to salvage cryosurgery except for downsizing purposes.

Treatment Outcomes 

Physician Reported Complications 

Recent advances in technology have reduced the complication rates associated with salvage cryosurgery (table 228, 51, 60, 66, 87, 88). In the past, incontinence rates following salvage cryosurgery exceeded 70 percent,51 but current studies report rates less than 10 percent.28, 32, 66, 84 Despite these improvements, incontinence rates in the salvage setting are still higher compared to those following primary cryosurgery. A recent study reported an improvement in the incontinence rate following salvage cryosurgery by leaving the urethral warmer in place for 60 to 90 minutes.88 Rectourethral fistula was also reported to occur more frequently in salvage cases; however, recent studies report this serious complication has been significantly diminished (0 percent to 3 percent).28, 32, 84 Although rectal fistula is currently rare, rectal pain has been reported. In a series of 35 patients who underwent cryosurgery of the prostate with an argon based system, 37 percent who had prior radiation therapy had pain compared with 12 percent of patients who underwent primary cryosurgery.85 In a later study, Donnelly et al reported that rectal pain occurred in 17 percent (8 of 46) of salvage patients.67 The cause of the pain is unknown but may be related to an ischemic event that occurs near the anterior rectal wall. After radiation, there may be reduced blood supply to this area and introducing lethal ice may elicit further devascularization. Urethral sloughing and obstruction can be seen in 5 percent to 10 percent of patients.28, 32, 84 Even with the current technologies and techniques, ED rates remain high at greater than 80 percent.

Table 2. Complication rates after salvage cryosurgery of the prostate

	Reference	Yr	No. Pts	Cryosystem	ED (%)	Incontinence (%)	Fistula (%)	Urethral Stricture (%)	Urethral Sloughing (%)	Perineal Pain (%)	Obstruction/ Retention (%)	UTI/Sepsis (%)
	Salvage Cryosurgery
	Pisters et al51	1997	150	Accuprobe	72.0	73.0	1.0	NA	NA	NA	67.0	NA
	Chin et al66	2001	118	Cryocare	NA	6.7	3.3	0	5	NA	8.5	0
	Ghafar et al28	2001	38	Seednet	NA	7.9	0	0	0	NA	4.0	0
	Han and Bellegrun87	2004	29	Seednet NA	NA	9.0	0	0	0	NA	3.0	0
	Katz et al88	2005	157	Cryocare Seednet	NA	9.7	0	0	0	12.8	5.8/1.9	0

No. Pts – number of patients; NA – not available; UTI – urinary tract infection. Adapted from Mouraviev and Polascik, reprinted in part with permission.60

Summary 

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.

Subtotal Prostate Cryosurgery (Evidence Level III) 

While this minimally invasive technique of cryosurgery is attractive from a conceptual perspective, clinical experience is limited93 and long-term results are unavailable. The Panel's consensus is that cases of subtotal prostate cryoablation should be collected prospectively in a database for future analysis.

The criteria for patient selection for subtotal prostate cryosurgery have yet to be determined. This procedure may fill a void in the therapeutic options available to men who are potential candidates for active surveillance who prefer therapy or for men with clinically organ confined unilateral significant disease (yet to be defined).

Theoretically, this targeted approach has the potential to customize treatment and address the growing concerns of both over and under treatment. However, current data are insufficient to determine the incidence or consequences of treatment failure.

Overview Conclusions 

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 7- to 8-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 potency12 in association with the technological advances over the last 10 to 15 years.

Conflict of Interest Disclosures 

All panel members completed Conflict of Interest disclosures. Those marked with (C) indicate that compensation was received; relationships indicated by (U) indicate no compensation was received.

Consultant or Advisor: Richard J. Babaian, Endocare (C); Aaron Katz, Oncura (C), Endocare (C); Louis Pisters, Endocare (C); Martin Dineen, Abbeymoor Medical Inc. (C), Endocare (C); Bryan Donnelly, Endocare (C); Katsuto Shinohara, Nihon Mediphysics (C); Wilex AG (C); Investigator: Louis Pisters, Protox Therapeutics (C); Scientific Study or Trial: Martin Dineen, Oakwood Pharmaceuticals (C), Duramed (C), Amgen (C), National Cancer Institute – Johns Hopkins (C), Mentor (C), Sanofi (C), GlaxoSmith-Kline (C), AstraZeneca (C), Schering Plough (C), GTX (C); Katsuto Shinohara, KineMed (C), GlaxoSmithKline (U); Meeting Participant or Lecturer: John G. Baust, Galil Medical (C); Other: Richard J. Babaian, Gen-Probe (C); David Ellis, Endocare (C).