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Initiatives Improving outcomes following
Radical Prostatectomy
The Walsh anatomic nerve-sparing radical retropubic prostatectomy has dramatically improved both the intraoperative and the quality-of-life outcomes, leading to a greater acceptance of surgical intervention for the treatment of clinically localized prostate cancer. At present, I perform over 200 radical prostatectomies a year. The operation is typically performed in less than 2 hours, and 98% of patients experience no intraoperative or perioperative morbidity. The mean hospital stay is slightly less than 2 days, and men return to unrestricted physical activity by 3 weeks. For men without significant comorbidities, the complications associated with radical retropubic prostatectomy compare favorably to those from external-beam or interstitial-seed radiation. Nevertheless, there are still opportunities to improve outcomes following radical prostatectomy. Selecting candidates To identify the best candidates for radical prostatectomy, one must know the life expectancy of the patient, the natural history of the disease, and the curability of the malignancy.1 These parameters can be estimated from life tables, survival data from cohorts of untreated men presenting with localized disease, and nomograms correlating clinical parameters with pathologic stage. However, life tables often do not take into account comorbidities. Relevant natural-history studies are from the pre-PSA era and have inherent problems related to selection bias. Pathologic stage as a predictor of cure has serious limitations, since a significant proportion of men with pathologically localized disease develop systemic metastasis, and men with extraprostatic extension and/or positive margins do not have disease recurrences. Even if the survival advantage of surgical intervention could be predicted with precision, the surgeon and patient must ultimately weigh these benefits relative to the risks of surgery. Therefore, the decision-making process for managing localized prostate cancer will never be reduced to an algorithm, since the priorities of the patients are highly relevant. Despite the inherent limitations of clinical staging, the ability to predict pathologic stage is of some value in selecting candidates for radical prostatectomy. Several investigators have recently reported immunohistochemical staining for neovascularity, tumor suppressor genes, oncogenes, genes and proteins that regulate the cell cycle, and reverse transcription polynerase chain reaction assays for the mRNA of PSA or PSMA (prostate specific membrane antigen) to predict pathologic stage. In my opinion, none of these assays is of clinical utility in selecting candidates for radical prostatectomy. Further research is required to identify clinically useful markers for predicting pathologic stage and the aggressiveness of the tumor. Decreasing the risk of blood transfusion The Walsh anatomic approach to radical retropubic prostatectomy has diminished the risk of life-threatening hemorrhage. Nevertheless, significant bleeding can occur, resulting in the need for allogeneic transfusion. Strategies to decrease the risk of allogeneic blood exposure include autologous blood donation, hemodilution, the use of the cell saver, and preoperative recombinant erythropoietin (epoetin alfa) therapy. Koch and Smith recently reported that blood-management strategies are not justified, based upon a personal allogeneic transfusion rate of only 3 percent.2 To the contrary, Skinner and Catalona have reported allogeneic transfusion rates of 21% when no blood-management strategies are adopted.3,4 It is reasonable to assume that transfusion rates in community practice, where urologists perform an average of six radical prostatectomies per year, is higher than the 21% reported by surgeons who limit their practice to genitourinary malignancies. It is my opinion that the extent of bleeding associated with radical retropubic prostatectomy justifies implementation of blood-management strategies. Over the past one-and-a-half years, I have recommended preoperative therapy with erythropoietin exclusively for reducing the risk of allogeneic blood exposure. A randomized single-blind study performed at NYU Medical Center demonstrated that allogeneic transfusion rates were comparable (9.6%) for men undergoing preoperative autologous blood donation and preoperative epoetin alfa therapy.5 While multi-center randomized double-blind studies are necessary to determine the most cost-effective dosing regimen, I currently recommend 600 units per kg SQ (subcutaneously) 14 and 7 days prior to radical prostatectomy, providing the baseline hematocrit level is less than 48%. Iron supplements must be administered to support the erythrocytosis response. In 283 consecutive cases managed with this epoetin alfa dosing regimen, the mean increase in hematocrit was 3 percentage points, which is equivalent to over one unit of packed red blood cells. Only one of the 283 men experienced any vascular complication (myocardial infarction, cerebral vascular accident, deep venous thrombosis, or pulmonary embolus.) Preoperative erythropoietin therapy is a cost-effective strategy to minimize allogeneic blood exposure for men undergoing radical retropubic prostatectomy. It should be considered a convenient alternative to autologous blood donation. We are presently investigating a lower dosing regimen of 300 unit per kg SQ on preoperative days 14 and 7 in order to decrease the cost of erythropoietin therapy. Prevention/treatment of incontinence Stress urinary incontinence is a complication of radical prostatectomy with a reported incidence varying between 2% and 30%.1 This wide range of reported incontinence rates most likely reflects varying levels of surgical expertise and definitions of continence. The precise mechanism for post-prostatectomy incontinence is not well understood. The capacity of the distal sphincter mechanisms to function following radical prostatectomy is likely influenced by the relationship between the prostatic apex and the rhabdosphincter. Because all prostate tissue must be extirpated, a prostate that encroaches upon the membranous urethra and rhabdosphincter presumably is more apt to be associated with stress urinary incontinence. Based upon my experience of performing over 1,000 radical retropubic prostatectomies, I feel it is important to make every effort to maximally preserve the rhabdosphincter. Therefore, meticulous control of the dorsal venous complex is essential. After incising the lateral pelvic fascia and dividing the puboprostatic ligaments, I recommend dividing the dorsal venous complex between suture ligatures. Two suture ligatures are placed 2 cm proximal to the prostatourethral junction. The plane between the dorsal venous complex and rhabdosphincter is palpated and pierced with a McDougal clamp. With traction on the closed McDougal clamp, a suture ligature is placed 1 cm distal to the prostatourethral junction. (When the distal suture is placed under direct vision, the dorsal venous complex is controlled without entrapping the rhabdosphincter.) The dorsal venous complex is then sharply divided. With cephalad traction on the prostate, the anterior rhabdosphincter and urethra are divided. Six 2-0 monocryl sutures are placed into the urethra, incorporating a small portion of the adjacent rhabdosphincter. The Foley catheter is divided. The catheter and prostate are retracted cephalad and the posterior urethra is sharply divided. The posterior elements of the rhabdosphincter and the Denonvillier's reflection over the anterior rectal wall are divided over a right angle clamp. The final two posterior anastomotic sutures are placed after completion of the prostatectomy. An effort is made to preserve the bladder neck while recognizing that this most likely does not contribute significantly to continence. In the absence of any intervention, over 85% of men will gain 100% continence under any level of strenuous activity. Approximately 10% of men will wear a small, single padÑwhich is typically dry throughout the dayÑand be continent with heavy activity, but not always. Less than 5% of men will require more than a single pad per day. Elucidating the mechanism for stress urinary incontinence will allow the surgeon to make further refinements in surgical technique. For those men experiencing troublesome post-prostatectomy stress incontinence, I advise periurethral collagen injections for mild incontinence and an artificial sphincter for more severe levels of incontinence. In the more than 800 prostatectomies that I have performed over the last 5 years, only 4 men have undergone placement of an artificial sphincter. Prevention/treatment of erectile dysfunction Nerve-sparing radical retropubic prostatectomy has dramatically improved quality of life for men undergoing radical prostatectomy. Initial concern that the nerve-sparing technique compromises the ability to cure cancer has been dispelled by very favorable long-term biochemical disease-free survival data. While there are no validated guidelines for performing a nerve-sparing radical prostatectomy, I generally excise the ipsilateral nerve in the presence of high-volume, high-grade disease or a large palpable nodule. It is my practice to obtain 12 biopsy cores from the prostate and to individually process the cores obtained from the right and left prostatic lobes. I am reluctant to perform a nerve-sparing procedure when greater than 50% of the ipsilateral biopsy cores are involved with cancer. Rather than arbitrarily excising the entire nerve, I often send for analysis an intraoperative frozen section from the portion of the neurovascular bundle that was adjacent to the surgical specimen, and I perform a complete excision of the bundle if the frozen section shows prostatic tissue. There are at least five factors that influence the preservation of erectile function following nerve-sparing radical prostatectomy. The first and most important is whether the surgeon is truly familiar with the nerve-sparing technique. The other important factors are age, extent of the disease (which might influence the decision to excise a portion or the entire neurovascular bundle), baseline erectile function, and the quality of the patient's sexual relationship. The ability to preserve erectile function has been favorably affected by the availability of sildenafil (Viagra). Our preliminary experiences indicate that Viagra is most effective when there is some remaining erectile function. This is consistent with Viagra's mechanism of action, which is to decrease the breakdown of cGMP. If there is no nerve function, then there is no cGMP to potentiate. At times, it is difficult to precisely visualize the neurovascular bundle. The neurovascular bundle is often preserved by assuming its location based upon published anatomic observations.6 The CaverMap is a device marketed by Blue Torch that is designed to assist the surgeon's intraoperative localization of the cavernous nerves. The device involves a handpiece that delivers an electrical stimulus to the tissues and a mercury-filled sensor that fits circumferentially around the penis. During radical prostatectomy, the location of the cavernous nerve is confirmed by delivering an electrical stimulus and measuring an increase in penile circumference. The probe delivers an increasing current between 8-20 mAmp and the sensor is able to detect a 0.5% change in penile circumference. The only way to unequivocally define the impact of the CaverMap on the preservation of erectile function is to perform a randomized study where radical prostatectomy is performed with and without the CaverMap. Ideally, the patient should not know the treatment-group assignment, and the surgeon should not assess the erectile-function outcome. At the present time, this study is not available. Klotz and Herschorn reported a preliminary experience with the CaverMap in 23 men, 19 of whom were potent preoperatively.7 Of the 17 potent men who showed an intraoperative tumescence response, 16 (94%) reported some erectile function one year postoperatively, and 5 (29%) became fully potent. The same surgeons reported a 30% recovery rate of full or partial erections when the CaverMap was not used. Six surgeons in the United States have embarked on a study to examine the utility of the CaverMap (Walsh, Lepor, Steiner, Catalona, Meyers, and Scardino). One of the goals of the study is to enroll 120 patients and to determine whether intraoperative responses correlate with subsequent return of erectile function. One of the initial problems encountered by the investigators was spontaneous erectile activity. It was felt that false positive responses were due to background erectile function during the surgical procedure. The CaverMap software was improved to inform the surgeon if the patient is generating tumescence activity. This modification has made a positive response to the nerve stimulation a far more reliable indicator of nerve location. I have performed over 80 radical prostatectomies using the CaverMap. It is too early to determine whether the intraoperative responses correlate with the return of erectile function. This correlation must be demonstrated in order to determine whether the device has a legitimate role in the surgical management of prostate cancer. If a correlation exists between the nerve-stimulation studies and erectile function, then a randomized study will be required to determine the CaverMap's overall impact on preserving erectile function. It is my opinion that intraoperative nerve stimulation is a reasonable concept. CaverMap is a promising device whose ultimate role and utility have yet to be defined. While further technological refinements are required, there are definitely some cases where the CaverMap device provided information that was clinically relevant. Summary Radical prostatectomy has come a long way over the last 18 years since Walsh described the anatomic nerve-sparing technique. Intraoperative complications are exceedingly rare, and the post-operative course is typically uneventful. Clinical understaging, bleeding requiring allogeneic blood exposure, incontinence, and erectile dysfunction are the primary limitations of radical prostatectomy performed in the modern era. A preoperative assessment that includes life expectancy, as well as the natural history and curability of the malignancy, is essential to select candidates for the procedure. Preoperative administration of erythropoietin, meticulous dissection of the prostatic apex, and the use of sildenafil are ways to further improve the outcome.Erectile dysfunction is the most common complication of radical prostatectomy. While promising, the role of the CaverMap for improving preservation of potency requires further investigation. References: (Click on images for Bio)
Initiatives is a serial newsletter focusing on emerging techniques and technologies in the treatment of prostate cancer. Initiatives is distributed free-of-charge to health professionals and is published by Saxe Healthcare Communications. Initiatives is funded through an education grant from UroMed Corp. The opinions expressed in Initiatives are those of the authors and not necessarily of the editorial staff or the advisory board. The publisher disclaims any responsibility or liability for such material. We welcome opinions and subscriptions requests from our readers. Please direct your correspondence to:
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