Salvage Cryosurgery--How I Do It

MANAGEMENT OF RADIATION FAILURE IN PROSTATE CANCER Salvage Cryosurgery—How I Do It Bryan J. Donnelly, MB, FRCSC, MSc, MCh, John C. Saliken, MD Tom Baker Cancer Center and Calgary Prostate Institute, Calgary, Alberta, Canada Prostate cryosurgery has advanced over the last decade, and is now recognized as a treatment option for patients who have failed radiotherapy. Appropriate patient selection is imperative for successful salvage. Because the treatment is a local therapy, the recurrent cancer must be confined to the prostate and its immediate area, and up to half of patients who undergo salvage cryotherapy may eventually fail treatment because of occult synchronous metastases. Yet some patients with poor prognosticators may still benefit from salvage treatment. [Rev Urol. 2002;4(suppl 2):S24–S29] © 2002 MedReviews, LLC Key words: Cryoablation • Transrectal ultrasound • Prostatic acid phosphatase • Gleason score • Radiation failure lmost a decade has passed since Doctors Onik and Cohen revived prostate cryosurgery, introducing transrectal ultrasound (TRUS) into the modern procedure.1 Since that time, the procedure has continued to advance both in its application and indication.2,3 This report updates the reader as to our current practice, specifically in the salvage of patients from failed radiotherapy. Appropriate patient selection is imperative for successful salvage. Because the treatment is a local therapy, the recurrent cancer must be confined to the prostate and its immediate area for full therapeutic benefit. Kuban and colleagues4 report that of those patients whose cancer recurs after radiotherapy, only 24.3% have isolated local recurrence without distant disease. Identifying this population of patients is very difficult even with the diagnostic aids available today. A positive A S24 VOL. 4 SUPPL. 2 2002 REVIEWS IN UROLOGY Salvage Cryosurgery prostatic biopsy and negative bone scan are the minimal requirements. We also use prostatic acid phosphatase (PAP) as an aid. There are also various qualifying criteria intended to improve selection and reduce the probability of failure. patients have only two potentially curative options and are often desperate for treatment. Salvage radical prostatectomy is an option for some, perhaps in particular younger men, but the majority of men receiving radiation are older and for one reason Appropriate patient selection is imperative for successful salvage cryoablation. Chin and others5–7 use a prostate-specific antigen (PSA) level of above 10 ng/mL as a cutoff point. Kuban and others4,8 have advocated a PSA level of above 20 ng/mL as an indicator of risk of distant disease, and we accept patients with PSA levels at or under 20 ng/mL if other requirements are fulfilled. A high Gleason score (Gleason 8 or higher) before or after radiation has been shown to be a poor prognostic sign5,7,9 and is correlated with a high risk of failure. Because approximately half of the patients with recurring cancer after radiation will show increases in Gleason score,11,10 we do not use the postradiation Gleason as an absolute contraindication. Patients with Gleason 9 and 10 are counseled on the very high risk of failure. Bulky T3 cancer and T4 disease are contraindications owing to the high risk of both local and distant failure and rectal injury. ProstaScint scans, magnetic resonance imaging (MRI), and computed tomography have not proven efficacious for routine application, although we do apply these tests on an individual basis if clinical suspicion dictates.12–14 Despite our best efforts, we assume that up to half of our patients who undergo salvage cryotherapy may eventually fail treatment because of occult synchronous metastases. Although these guidelines help, it must be remembered that these or another are not good candidates for radical surgery. Yet it must be recognized that some patients with poor prognosticators may still benefit from salvage treatment, and we urge flexibility in applying selection criteria. Several of our patients with poor prognostic indicators have done well, with persistently undetectable PSA following the procedure. Technique Our technique is a modification of that originally described by Onik and colleagues1 and follows revisions previously introduced.15 All cases are treated by a team consisting of a urologist and a radiologist. Patients are admitted to hospital on the morning of the procedure, fasting. An intravenous line is started and cefazolin, gentamicin, and metronidazole (Flagyl) using a brachytherapy arm and computer treatment planning system. A low lithotomy is used. The perineum is placed level with the end of the operating table to allow unimpeded access. If the pubic arch is low, an exaggerated lithotomy position can be used to improve transperineal access to the prostate. The entire perineum and suprapubic area is prepped with povidone-iodine solution (Betadine), and the patient is draped as for an endoscopic procedure. A flexible cystoscope is used to visualize the prostate and bladder, to fill the bladder, and to guide the placement of a suprapubic 10 French pigtail catheter. We prefer a suprapubic to a urethral catheter because we feel it is easier for the patient, it avoids irritation of the urethra and prostate during the recovery, and it is easily managed by patients at home. The catheter is removed once the postvoid residual is consistently below 100 cc, typically at around 2 weeks postoperatively. A guidewire is next inserted into the bladder through the scope, and the scope is removed. A well-lubricated urethral warming catheter (Endocare, Inc., Irvine, CA) is introduced over the guidewire. This is left in place throughout the treatment and for 30 minutes after the end of Some patients with poor prognosticators may still benefit from salvage treatment, and we urge flexibility in applying selection criteria. are given intravenously 1 hour preoperatively. A Fleets enema is administered to empty the rectum. The patient is offered either spinal or general anesthesia and is placed in the lithotomy position. We use sequential compression devices preoperatively. Patient positioning is important to allow good access to the perineum, especially if one is freezing. Water at 38.5ºC is circulated through the warming catheter with a warmer pump system, circulating at 400 to 500 mL/minute. We add methyl blue to this circulating water to aid in rapid identification of any leakage. Some operators insert a Foley catheter initially, replacing it with the warming catheter once the cryoprobes are in place, to reduce the risk of VOL. 4 SUPPL. 2 2002 REVIEWS IN UROLOGY S25 Salvage Cryosurgery continued 1 1 2 2 < 3cm <1cm 3 <1cm 4 5 6 RNVB LNVB RNVB LNVB Rectum 1 2 <2 cm cm <2 3 Rectum <1cm 1 4 2 3 <1cm 4 <2 cm 5 x < 2cm 1 x 2 RNVB RNVB LNVB 6 <2 cm LNVB Rectum Rectum Figure 1. Schematic representation of probe placement, viewed in transverse plane. Thermocouples are placed at left and right neurovascular bundles (LNVB, RNVB) and in the midline at the apex, posteriorly. puncturing the warming catheter during cryoprobe introduction. A biplane TRUS probe (Aloka, Japan) is inserted into the rectum to visualize and measure the prostate. Intermittent instillation of water into the rectum facilitates good visualization and distends the rectum to eliminate the wrinkles in the anterior rectal wall that can falsely imply that there is much more to freeze, even as ice encroaches on the rectal mucosa within the collapsed rectal folds. Usually we will use six cryoprobes, but more or fewer can be used if the prostate is exceedingly large or small or unusually shaped. For easy reference we refer to the probes using the same numbering system each time (Figure 1). This system is used because probes will be operated sequentially from anterior to posterior, ie, probes 1 and 2 are operated first, followed by 3 and 4, and then 5 and 6. This sequencing is utilized to maximize the S26 VOL. 4 SUPPL. 2 2002 TRUS visualization during the procedure. Using this as a guide, the two anterior sheaths are inserted first. We have recently adopted a coaxial rapid-access needle/dilator/sheath system (FastTrac, Endocare, Inc., CA) to place the introducer sheath directly. This replaces the original Seldinger technique and significantly reduces operator time. Using the FastTrac, the two anterior sheaths (1 and 2) are initially placed as in Figure 1. The cryoprobes must be less than 10 mm from the edge of the gland to ensure adequate freezing of the periphery. The temperature between the probes will fall more rapidly than the temperature at the edge of the iceball, so these probes can be up to 3 cm apart if necessary. Axial TRUS scanning is used to confirm spatial separation of the cryoprobes, and coronal plane scanning is used to ensure proper positioning of the cryoprobe tip at the base of the prostate. Once in REVIEWS IN UROLOGY place, the probes are “stuck" while the remaining probes are inserted. “Sticking" refers to lowering the temperature of the probes to just below the freezing point, which results in the probes becoming frozen in place without growing a large iceball. This effect is similar to sticking your tongue on cold metal in winter. The posterolateral probes (3 and 4) are placed next. As the prostate is an inverted cone, these probes can be directed a little laterally from the apex to the base while being inserted, to match the shape of the gland. Again, these must be less than 10 mm from the peripheral edge of the gland. There should be no more than 2 cm between probes 1 and 3 and between probes 2 and 4 to ensure adequate freezing between the probes (Figure 1). The posteromedial probes (5 and 6) are placed last. Because this placement can come close to the warmer, we typically use the coronal plane to place these probes, with the transverse view to fine-tune positioning and ensure adequate separation between cryoprobes. These probes can also be directed a little laterally to conform to the shape of the gland. The iceball generated on these probes is closest to the rectum, and its growth will often dictate the end of the freeze. It is important, therefore, that these probes are placed far enough away from the rectal wall. I like to position them no more than 2 cm apart and to orient the cryoprobe in the coronal plane closer to the midline than to the posterior margin of the gland. This ensures good freezing across the midline before the iceball reaches the rectum. In placing probes, we feel that lateral placement is the key, because the temperature between probes is much lower than the temperature at the edge of the iceball. We are always mindful of achieving sufficiently Salvage Cryosurgery A B Figure 2. Ultrasound images of saline injection. (A) Coronal view of saline being injected, separating the prostate from the anterior rectal wall. (B) Transverse view of saline, showing the extent of separation between prostate and rectum. cold temperatures around the gland margin, especially adjacent to the neurovascular bundles. A treatment planning system is under final development that can be used to aid in the placement of cryoprobes within the prostate (Cryoguide, Endocare, Inc.). Similar to brachytherapy planning systems, a volumetric study is used to determine appropriate cryoprobe placements. The system can also be used to guide the probes to the locations by using area that is easy to freeze inadequately and, as all surgeons know, is an area of high risk for a positive margin. Other thermocouples can be placed anterior to the gland or at any spot where specific temperatures need to be achieved. The cryoprobes are suspended from a supporting arm (eg, a Buchwalter arm) using a Penrose drain to ensure stability during the procedure. Before initiating the freeze, we inject 30 –50 mL of sterile saline Thermocouples are a critical part of the procedure, because ultrasound alone is unreliable to ensure adequate freezing. overlays of the planned probe placement and real-time TRUS images. Thermocouples are a critical part of the procedure, because ultrasound alone is unreliable to ensure adequate freezing.16 A minimum of three and up to five thermocouples can be placed. One is placed in the region of each neurovascular bundle (Figure 1), and one at the gland apex in the midline, just anterior to the rectum. This is an into the space between the rectum and prostate to expand this region. This is a very important step and greatly facilitates an aggressive freeze posteriorly. Although some of the saline is dispersed during the treatment, it does cause good separation and also appears to induce hyperemia and edema (Figure 2). This facilitates a more prolonged freeze posteriorly and at a slow rate, thereby “sculpting" the iceball to the shape of the anterior rectal wall. The freeze is begun with the two anterior probes. The posterolateral cryoprobes (3 and 4) are turned on when the initial iceballs reach the posterolateral cryoprobes and the iceballs coalesce anterior to the urethra. We like to run the anterior probes for about 2 minutes before turning on the next. It is best to begin the freeze slowly, using a machine setting of 50% of maximum freeze for the first 2 minutes and then increasing to 75% or 100%. The posteromedial (5 and 6) probes are turned on last. We initially run these at 25% and modify the posterolateral probes at the same time. The temperature of the posterolateral probes (3 and 4) impacts how rapidly the iceball forms on the posteromedial probes. This is the critical part of the procedure and it is better to proceed slowly, allowing the iceball to grow slowly and therefore shape to the gland and rectal wall. The operator must beware that once ice bridges across the posterior prostate between the urethra and the rectum, the tem- VOL. 4 SUPPL. 2 2002 REVIEWS IN UROLOGY S27 Salvage Cryosurgery continued perature and behavior of this ice directly anterior to the mid-rectum are influenced by cryoprobes 3 and 4 as well as 5 and 6. At all times, but especially at this part of the procedure, the iceball must be monitored closely to ensure adequate freezing and yet protect the anterior rectal wall. The thermocouples are very important because they report temperature much more accurately than does the appearance of the iceball. As the iceball approaches the rectal wall, intermittent digital rectal examination (DRE) is a very useful adjunct to TRUS, allowing the surgeon to palpate the anterior rectal wall. It is important to ensure that the mucosa feels soft over the hard iceball. On many occasions, TRUS has misled us into believing that there was a large region of safety when DRE revealed the rectum to be very thin but redundantly folded on itself. There will be occasions when the iceball will extend posteriorly to the rectum before the apical thermocouple reaches at least —20ºC. In those cases, the edematous reaction of the first freeze will facilitate a more aggressive freeze on the second cycle. Finally, it has been our experience that the operator should continue the freeze longer than he or she might think necessary in order to achieve a truly adequate freeze. As long as the rectum is safe, the operator should strive to achieve an iceball that becomes distinctly flat or even concave to palpation on DRE as it begins to extend laterally. Once the first cycle is complete, the argon (the freezing agent) is turned off, and occasionally we will run helium (the thawing agent) for 1–2 minutes, especially following an aggressive freeze. We leave one of per urethra, the suprapubic tube is closed throughout the day, but we leave it open at night until its removal, because nocturia is common initially. Once the postvoid residual is below 100 mL, we remove At all times … the iceball must be monitored closely to ensure adequate freezing and yet protect the anterior rectal wall. the anterior probes “stuck" to hold the position while the other probes then passively thaw for 20 –30 minutes. We wait for a complete thaw before initiating the second cycle. Before starting the second freeze, we check that none of the cryoprobes have slipped or need repositioning. The second freeze is executed in the same manner as the first. We consistently observe that the second freeze progresses faster than the first because of diminished thermal capacity in the previously frozen tissue. On completion, the cryoprobes are thawed and withdrawn. The urethral warming catheter is left in place for 30 minutes to protect the urethral mucosa against latent freezing. It is withdrawn in the recovery room. The patient is admitted overnight and discharged the following morning. Follow-Up The suprapubic tube is left open until postoperative day 4, when the patient is instructed to close the tap and try voiding per urethra. Once voiding the catheter. PSA monitoring and DRE are performed at 6 weeks postoperatively, every 3 months thereafter in the first 2 years, then every 6 months. We do not perform routine follow-up biopsies, and if a biopsy is required, we use the transperineal route. MRI is a useful tool to assess the freeze, if done using gadolinium enhancement. We perform this at 3 weeks postoperatively. It is a very good form of quality control in an institution that is beginning to use cryosurgery. References 1. 2. 3. 4. 5. Onik GM, Cohen JK, Reyes GD, et al. Transrectal ultrasound guided percutaneous radical cryosurgical ablation of the prostate. Cancer. 1993;72:1291–1299. Lee F, Bahn DK, McHugh TA, et al. US-guided percutaneous cryoablation of prostate cancer. Radiology. 1994;192;769–776. Pisters LL, von Eschenbach AC, Scott SM, et al. The efficacy and complications of salvage cryotherapy of the prostate. J Urol. 1997;157:921–925. Kuban DA, el-Mahdi AM, Schellhammer PF. Potential benefit of improved local tumor control in patients with prostate carcinoma. Cancer. 1995;75:2373–2382. Chin JL, Pautler SE, Mouraviev V, et al. Results of salvage cryoablation of the prostate after radiation: identifying predictors of treatment failure and complications. J Urol. Main Points • Prostate cryosurgery can be a successful salvage therapy for patients with recurrent cancer after radiotherapy, but the cancer must be confined to the prostate and its immediate area. • Of those patients whose cancer recurs after radiotherapy, around 25% have isolated local recurrence without distant disease. • A positive prostatic biopsy and negative bone scan are the minimal requirements to identify this population of patients. • Qualifying criteria to improve selection include prostate-specific antigen level, Gleason score, and absence of bulky T3 cancer and T4 disease. S28 VOL. 4 SUPPL. 2 2002 REVIEWS IN UROLOGY Salvage Cryosurgery 6. 7. 8. 9. 2001;165:1937–1942. Pisters LL, Perrotte P, Scott SM, et al. Patient selection for salvage cryotherapy for locally recurrent prostate cancer after radiation therapy. 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