CRYOABLATION AS A PRIMARY PROSTATE CANCER TREATMENT FOLLOWED BY PENILE REHABILITATION

1. CRYOABLATION AS A PRIMARY PROSTATE CANCER TREATMENT FOLLOWED BY PENILE REHABILITATION DAVID S. ELLIS, MD, UROLOGY ASSOCIATES OF NORTH TEXAS A summary of results published in Urology, 2007 Feb;69(2):306-10 INTRODUCTION Although cryoablation was first studied in the 1960s, it has only recently been accepted as definitive treatment for prostate cancer1. This is due, in large part, to technical advances in the procedure that have made the procedure safer and consistently efficacious2. Both ultrasound4 and temperature monitoring are now used to monitor the procedure and the development of argon based technology improved the consistency of cryoprobe performance. Greater understanding of cryobiology as well as animal and human investigations have led to the definition of clinical endpoints for effective ablation and treatment planning3-5. As well, consistent use of an approved urethral warmer has decreased urethral complications including sloughing and incontinence10. Lastly, the use of two posterior-medial cryoprobes rather than a single posterior-central cryoprobe has reduced the fistula rate to <0.5%6-8. We report a consecutive series of patients who underwent modern prostate cryoablation by a single surgeon as a primary therapy for localized prostate cancer. Those patients potent at the time of intervention were encouraged to regularly utilize penile vacuum therapy after treatment in hopes of preserving or recovering erectile function. RESULTS Between December 2000 and 2005, 416 consecutive patients underwent cryoablation as primary therapy for localized prostate cancer. Patient demographics are summarized in Table 1. Of patients whose continence status was known prior to cryoablation, 97.1 % (384/395) were continent. Potency status was known for 325 patients prior to cryoablation, 127 of whom (39.1%) were potent. Mean follow-up of all patients was 20.4±14.7 months (range: 1.5 to 60, median: 60). Sufficient follow-up to determine biochemical survival was available for 291 patients with a mean follow-up of 25.9±13.1 months (range: 9 to 60, median:25). The procedure was well tolerated with no post-operative deaths and no rectal fistulas. Of the 384 patients continent at the time of treatment 327 had 6 month follow up with known continence status; thirteen of which were incontinent (4.0%). Stratifying by severity, two (0.6%) had total incontinence (requiring use of absorbent pads) and eleven (3.4%) had stress incontinence. All patients were impotent immediately following cryoablation. Kaplan-Meier analysis demonstrating the time dependent return to potency is shown in Figure 1. At one, two and four years, the probability a patient who was potent at the time of intervention regaining their ability to have intercourse with or without oral pharmaceutical assistance was 29.1±4.3%, 48.5±5.0% and 51.3±5.9%, respectfully. The mean and median PSA nadirs were 0.45 and 0.1ng/ml, respectively. A PSA nadir <0.4ng/ml was achieved by 79.7% of the population. Kaplan-Meier analysis revealed a four-year BDFS of 79.6±.24% for the entire population (Figure 2a). When stratified by risk group 83.6±3.8%, 82.3±3.6% and 69.1±5.5% of low, moderate and high-risk patients, respectively, remained disease free at four years (Figure 2b). The mean time to biochemical failure according to the scientific definition was 4.2 months with a mean time to being clinically evident of 14.2 months. Post therapy, 168 patients underwent biopsy, seventeen were positive (10.1%) at a mean of 10.2 months post-treatment. This yields a positive biopsy rate for the entire population of 4.1% (17/416). Figure 2: Kaplan-Meier Survival Curves for (a) all patients and (b) patients stratified by risk group COMMENT Past studies have shown that incontinence, when modern cryotechnology is used, ranges from 1.3%7 to 7.5%8. The 4.0% incontinence rate (0.6% total; 3.4% stress) from the current series fits well within previously recorded ranges. No rectourethral fistula occurred in our series. This is not surprising as reports utilizing argon based cryoprobes have stressed (and we echo) that urethral fistulas are no longer a morbidity expected post cryoablation3. What is different from previous cryoablation reports is the potency rate observed in the current series. Impotence is expected immediately following cryoablation. However, for some patients it proves to be transient with recovery noted as far as five years post-treatment. In a prospective study Robinson et al found recovery of erectile function with time9. Within 3-years of the procedure 47% of men who were having intercourse prior to cryoablation returned to intercourse with or without the use of oral or device ED aids. Our series, which encouraged patients to engage in a penile rehabilitation effort with regular use of a vacuum therapy device without constriction ring, shows a potency rate of 29.1±4.3% at one-year and 51.3±5.9% at four-years. This is substantially higher recovery than any other series published to date and the return appears to be expedited compared with that of Robinson9. We believe that the manner in which the procedure was presented to the patients as well as the use of penile rehabilitation was instrumental in helping our patients regain sexual function. Patients were told at initial consultation and again immediately pre-treatment that (based on the results of Robinson9) they would be impotent immediately following cryoablation but it was not necessarily true that they would remain impotent. This may have created a hopeful atmosphere for the patient increasing their probability of regaining erectile function This, we believe, in concert with regular use of a vacuum device without a constriction ring in attempt to both oxygenate the penis and prevent atrophy, is responsible for the rapid and high rate of return of sexual function. Brachytherapy has reported potency rates, ranging from 49%-100%10. This study demonstrates that potency rates within the range of brachytherapy’s may be achieved following cryoablation. It is important to note that in this study all prostates were aggressively and treated with total gland (i.e., non-focal) cryoablation. METHODS All procedures were performed with the Cryocare System (Endocare, Inc., Irvine, CA) with ultrasound guidance. Temperatures in and around the gland were monitored with thermosensors. A felxible urethral warming catheter was used to protect the urethra and adjacemnt structures such as the bladder neck and external sphincter. Patients potent at the time of intervention were strongly encouraged to utilize a vacuum therapy device (Firma Medical, Mansfield, TX) without constriction ring to create and maintain erection for 5 minutes at least once per day beginning six weeks post cryoablation and continuing until erections returned. They were also instructed to take oral ED pharmaceuticals once every other day beginning six months after cryoablation and until the return of satisfactory erections, then when necessary for intercourse. For the purposes of this study, incontinence was defined as any patient experiencing any leakage of urine regardless of number of pads worn (if any) six-months following cryoablation. Potency, evaluated every 6 months, was defined as the ability to achieve an erection sufficient for intercourse with or without oral pharmaceutical assistance. Patients utilizing a vacuum device for intercourse were not considered potent. Only those patients continent and potent, respectively, at time of intervention were included in the post-treatment potency and continence analysis. Biochemical disease free survival (BDFS) was determined using a modified American Society of Therapeutic Radiation Oncology (ASTRO) definition of three successive rises in PSA with a final value > 1.0 ng/ml. To determine biochemical survival a minimum of four post treatment PSA measurements are needed. Only patients with sufficient follow-up were included in the Kaplan-Meier analysis of biochemical survival. All patients treated in the first twelve months of our experience (n=93) underwent a 12 core biopsy 1 year post treatment. Subsequent to this, due to the very high negative biopsy rate of this group15, patients were biopsied if their PSA exceeded 1.0 ng/ml. If biopsies were negative, a bone scan was performed. Table 1:Patient demographics CONCLUSION Modern cryoablation as a primary intervention performed in a community hospital setting is an effective and safe primary therapy for localized prostate cancer. The effect of cryoablation on erectile function appears to be minimized when a patient is correctly informed that recovery of erectile function is possible. Also, use of a penile rehabilitation program after cryoablation may expedite the return of erectile function. Figure1: Kaplan-Meier prediction of potency recovery REFERENCES 1. Whyte, J. J., Bagley, G. P., and Kang, J. L.: The Health Care Financing Administration cryosurgery decision: a timely response to new data. J Urol, 162: 1386-7, 1999; 2. Katz, A. E. and Rewcastle, J. C.: The current and potential role of cryoablation as a primary therapy for localized prostate cancer. Curr Oncol Rep, 5: 231-8, 2003; 3. Lee, F., Bahn, D. K., Badalament, R. A., Kumar, A. B., Klionsky, D., Onik, G. 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