Radical prostatectomy for localized prostate cancer – UpToDate Authors: Eric A Klein, MD Section Editors Nicholas Vogelzang, MD W Robert Lee, MD, MS, MEd Jerome P Richie, MD, FACS Deputy Editor Michael E Ross, MD Last literature review version 18.2: May 2010 | This topic last updated: April 1, 2010 INTRODUCTION — Prostate cancer is the sixth most common cancer in the world, and it is the most common non-skin malignancy in the United States where it represents about 30 percent of all cancers diagnosed in men each year. Widespread screening with prostate specific antigen (PSA) has led to increased detection of prostate cancer when the tumor is localized and therefore potentially curable. (See "Screening for prostate cancer", section on 'Evidence from observational studies'.) Standard management options for men with clinically localized prostate cancer include radical prostatectomy (RP), radiation therapy (RT), including external beam and/or brachytherapy, and active surveillance (watchful waiting). RP is an effective option for localized prostate cancer, based upon long-term cancer control rates, perioperative morbidity and mortality rates, and the associated profiled of long-term adverse effects. For men choosing RP, surgical options include both the retropubic and perineal approaches, as well as minimally invasive (robotic or laparoscopic) surgery. The uncertainty about optimal therapy for early prostate cancer is reflected in the lack of definitive recommendations from both the American Urological Association (AUA) task force on treatment for early stage prostate cancer and the National Comprehensive Cancer Network (NCCN) guidelines [1,2]. The 2007 AUA guidelines concluded that the available data are insufficient to recommend any one form of treatment over another for any risk category of disease (table 1) [1]. The surgical approaches to the treatment of clinically localized prostate cancer will be reviewed here. The issues and data that compare surgery with other treatment modalities are addressed elsewhere. (See "Overview of treatment for clinically localized prostate cancer".) PATIENT SELECTION — PSA-based screening has increased the frequency with which patients are diagnosed with localized disease so that most newly diagnosed men are candidates for definitive therapy. The best candidates for RP are those with a life expectancy of 10 years or more and no or minor comorbidities. The probability of long-term disease control following RP is highest in patients with cancers confined to the prostate gland (clinical stage T1 or T2). Additional prognostic information is derived from the pretreatment serum PSA level and the biopsy Gleason score, and this information has been combined into the anatomic stage prognostic groups of the 2010 TNM staging system (table 2 and table 3). In the Partin model, this information has been used to construct tables that estimate the likelihood of organ-confined cancer with various combinations of these values (table 4) [3]. (See "Early stage prostate cancer: Predicting the pathologic extent of disease and clinical outcome", section on 'Predictive tools'.) RP is also an accepted treatment option for men with locally advanced (T3) and high-risk prostate cancer, many of whom will have lymph node involvement. The role of surgery in the management of patients with T3 prostate cancer is discussed elsewhere. (See "Clinical stage T3 prostate cancer", section on 'Radical prostatectomy'.) Commonly encountered comorbidities such as diabetes mellitus, hypertension, or coronary heart disease (CHD) are not contraindications to surgery in otherwise healthy patients with well-controlled blood glucose and blood pressure and normal exercise capacity. Patients with known CHD and those deemed to be at increased risk should undergo routine preoperative cardiac risk assessment. (See "Estimation of cardiac risk prior to noncardiac surgery".) RETROPUBIC RP: PROCEDURE Preoperative preparation — Preoperative counseling that includes the spouse or partner is essential to address the practical and emotional issues surrounding RP. Presurgical psychosocial interventions including a focus on stress management may be useful in improving quality of life following surgery [4]. One of the most important goals is to set reasonable expectations for the shortterm and long-term effects of surgery on activity level, continence, and potency. Special emphasis is placed on the type of anesthesia to be used, whether or not lymphadenectomy will be performed, and whether or not a nerve-sparing procedure is contemplated, as well as the anticipated length of hospital stay. Many men choose to donate autologous blood preoperatively. However, in our experience, the non-autologous transfusion rate is identical (about 5 percent) whether or not autologous blood is available. In addition, many of these units will be unused and therefore discarded [5]. Refusal of blood storage or transfusion on religious grounds is not a contraindication to RP. (See "Preoperative autologous blood donation".) The diet is restricted to clear liquids on the day prior to surgery, and a Fleet enema is administered the evening before or morning of surgery. Patients are admitted directly to the operating room (OR) on the day of surgery. A secondgeneration cephalosporin is routinely administered intravenously on call to the operating room and for two doses postoperatively. Anesthesia considerations — Retropubic RP can be safely performed under general, epidural, or spinal anesthesia. Epidural anesthesia is our preferred technique for all patients undergoing retropubic RP. Epidural anesthesia avoids the need for ventilatory support and virtually eliminates pulmonary complications. In our experience, epidural anesthesia alone is associated with better postoperative analgesia (as assessed by patient self-report using validated instruments), less sedation, lower opiate use, fewer transfusions, and less expense compared to epidural plus general anesthesia (table 5). Low thoracic epidural catheters are placed preoperatively and dosed with 0.1 percent bupivacaine and morphine sulfate (0.05 mg/mL) upon arrival in the operating room. This approach promotes early return of intestinal function [6]. Analgesia is maintained intraoperatively and postoperatively with morphine sulfate or fentanyl, and anxiolytics are administered parenterally as needed. This regimen has been associated with a high degree of patient acceptance and few complications, with approximately 5 percent requiring conversion to general anesthesia. Surgical technique — For a retropubic RP, the patient is placed in the supine position with slight hyperextension at the iliac crest. A Foley catheter is placed prior to incision. A midline incision is carried from the umbilicus to the top of the pubis, usually 10 to 15 cm in length depending upon individual patient anatomy. The space of Retzius is developed bluntly and the bladder is mobilized off the pelvic sidewall bilaterally. The peritoneum is mobilized superiorly, exposing the psoas muscles bilaterally. Dissection and removal of the prostate — The apical dissection is the most challenging part of a retropubic RP because of the close anatomic relationship with the dorsal vein complex, neurovascular bundles, and the distal sphincter. A meticulous apical dissection can limit blood loss. Modifications in the technique of apical dissection significantly affect the approach to nerve sparing and can improve the return of urinary control and potency. After incision of the endopelvic fascia, the puboprostatic ligaments are routinely divided along the posterior aspect of the pubis to obtain better exposure of the dorsal vein complex. The puboprostatic ligaments support the proximal pendulous urethra and attach the membranous urethra and the striated sphincter to the underside of the pubis [7]. This urethral suspensory mechanism may play an important role in maintaining effective distal sphincter function. In at least two reports, preservation of the puboprostatic ligaments was associated with earlier return of urinary control, less blood loss, and did not compromise margin status [8,9]. A variety of methods have been proposed for division and control of the dorsal vein [10-12]. Control of the dorsal vein complex is critical for achieving hemostasis and for exposure of the prostatic apex. Preservation of the striated urethral sphincter, which lies just underneath the dorsal vein and envelops the urethra and prostatic apex, is essential for the return of continence. We use a modified technique of apical dissection, which results in a typical blood loss of 100 to 300 mL from the dorsal vein prior to suture ligation, urethral exposure and preservation of urethral length, and excellent visualization of the neurovascular bundles at the apex prior to their dissection [13]. This technique involves initial incision of the endopelvic and lateral pelvic fascia, sparing of the puboprostatic ligaments, mobilization of the neurovascular bundles away from the prostate, and mobilization of the prostate off the anterior rectal surface prior to urethral transection [14]. The remainder of the procedure is similar to other published techniques and includes division of the urethra, placement of the vesicourethral anastomotic sutures, division of the bladder neck, dissection of the seminal vesicles, and completion of the vesicourethral anastomosis. A detailed description of our technique has been published elsewhere [13]. Others have used similar surgical modifications and reported comparable results [15-17]. Following completion of the vesicourethral anastomosis, closed suction drains are placed through separate incisions through the body of the rectus muscle and left in the obturator fossa. Only a single drain is used for patients in whom a pelvic lymphadenectomy is not performed. The incision is closed in a single layer with running nonabsorbable suture and the skin is approximated with clips. Average operative time (skin incision to skin closure) for RP without and with pelvic lymphadenectomy is 110 and 125 minutes, respectively. The average blood loss with a retropubic RP is 800 to 1200 mL [18-21]; massive blood loss is rare. Because of improvements in surgical technique and reduction in transfusion triggers, intraoperative blood transfusion is needed in 20 percent of cases or fewer [20,22-24]. Nerve-sparing approach — Erectile function following RP depends upon preservation of the autonomic cavernous nerves, located within the neurovascular bundles, immediately posterolateral to the prostate capsule, within the periprostatic fascia [25]. In order to maintain potency, every effort should be made to preserve the bilateral neurovascular bundles as long as cancer control rates are not adversely affected. (See 'Impotence' below.) Oncologic outcomes are not compromised by the use of the nerve-sparing approach if the tumor is confined to the prostate [26,27]. The decision of whether or not to perform a nerve-sparing approach is made during surgery based upon visual inspection and palpation of the gland and its relationship to the nerve bundle. Various preoperative parameters (eg, clinical stage, Gleason score, preoperative serum PSA) may help predict whether a nerve-sparing approach is likely to be feasible [28]. Dynamic endorectal coil MRI may also be useful for preoperative identification of neurovascular bundle involvement [29,30]. (See "Clinical stage T3 prostate cancer".) Some series suggest that nerve-sparing RP can be performed safely in men with pathologic extraprostatic extension as long as the neurovascular bundles are not involved. The posterolateral margin is one of the least common sites of involvement in men with positive margins, being positive in only 10 to 17 percent of cases [31-33]. If there is a clinical suspicion of extraprostatic extension, intraoperative frozen section analysis of the posterolateral margin can be used to predict tumor involvement of the neurovascular bundle and the advisability of a nerve-sparing approach [34]. If the posterolateral margin is histologically negative, the neurovascular bundles are usually uninvolved. For men who are unsuitable for a nerve-sparing procedure, sural or genitofemoral nerve grafts may restore potency in some patients who undergo resection of both neurovascular nerves [35-37]. Pelvic lymph node dissection — The role and extent of pelvic lymph node dissection (PLND) in men undergoing RP for prostate cancer is controversial. PLND is the standard approach for assessing regional lymph node status, which can provide important information about prognosis. Whether or not PLND offers a therapeutic benefit is unclear, and its prognostic value must be balanced against potential complications. The techniques for regional lymph node assessment and the management of patients with positive nodes are discussed separately. (See "Evaluation of regional lymph nodes in men with prostate cancer" and "Management of prostate cancer patients with positive regional lymph nodes".) Postoperative care — Patients are ambulated on the evening of or the morning following retropubic RP. A clear liquid diet is begun on postoperative day 1 and advanced as tolerated. Analgesia is maintained with continuous and on-demand morphine sulfate plus bupivacaine via epidural catheter for 24 hours, followed by oral ketorolac and ibuprofen as needed. The drains are removed after 48 hours unless there is clinical suspicion of a urine leak. Most patients are discharged after two nights of hospitalization, returning five to seven days later for the removal of incisional staples and the Foley catheter. This accelerated postoperative regimen is well tolerated by patients, and reduces the cost associated with retropubic RP without compromising the quality of care based upon the frequency of acute complications, hospital readmissions, or mortality [38]. RETROPUBIC RP: OUTCOME — Several institutions have published long-term efficacy data for patients with prostate cancer treated with retropubic RP [39-45]. The most widely reported clinical end point is the incidence of a detectable serum PSA level following surgery, the absence of which is expressed as the biochemical relapse-free survival rate (bRFS). Although results vary, approximately 70 percent of men undergoing RP for clinically localized disease have control of disease for at least 10 years based upon this criterion. Significance of biochemical failure — PSA-defined biochemical recurrence is a widely accepted endpoint in analyzing outcomes following RP. Although various definitions of biochemical recurrence have been proposed, the most widely accepted criterion for patients who have undergone RP is that of the American Urological Association (AUA) [46]. According to AUA guidelines, a biochemical recurrence is defined as a serum PSA ≥0.2 ng/mL, which is confirmed by a second determination with a PSA ≥0.2 ng/dL. Biochemical failure after definitive local treatment antedates metastatic progression and prostate cancer-specific mortality by an average of 7 and 15 years, respectively [47-49]. The complex relationship between biochemical recurrence and long-term outcome is illustrated by the following observations: In a consecutive series of 1132 men with clinically localized disease, 19 percent had a biochemical relapse, one-fourth of whom developed metastases at 10 years [47]. However, the 10-year survival rate in those with a PSA recurrence was similar to that in men without biochemical failure (88 and 93 percent, respectively). A second report of 1197 men observed a biochemical relapse after RP in 15 percent, of whom 34 percent developed metastatic disease at a median of eight years [48]. The median time to death after the development of metastases was five years. Men with a rising serum PSA within two years were less likely to be free of clinically evident metastases at seven years compared with those who failed after two years, both for Gleason score 5-7 disease (47 versus 77 percent), and Gleason score 8-10 disease (21 versus 47 percent). In a third series of 2809 men undergoing RP for ≤T2 disease (table 2), biochemical failure developed in 31 percent, at an average of 2.9 years posttreatment [49]. Among men with a biochemical failure, 91 percent remained free of systemic progression 10 years after a rising PSA was first detected. Effect of pathologic features — The prognosis following retropubic RP depends upon pathologic characteristics of the tumor, such as seminal vesicle or nodal involvement, margin status, and the presence of extraprostatic extension [39,41,42,44,50]. The importance of these factors is illustrated by the outcomes in our series of 906 men undergoing retropubic RP at the Cleveland Clinic for clinically localized disease [44]. In this cohort, 43 percent had extraprostatic extension, 56 percent had Gleason score ≥7 disease, 23 percent had positive margins, 9 percent had seminal vesicle invasion, and 2 percent had nodal metastases [44]. At an average follow-up of 44 months, the five- and eight-year cancer-specific survival rates for the entire cohort were 97 and 95 percent, and the biochemical relapse-free survival (bRFS) rates were 81 and 76 percent, respectively. Results based upon the presence or absence of various pathologic features included the following: Men with organ-confined disease (no extraprostatic extension and negative surgical margins) had a 100 percent cancer-specific survival and a 92 percent bRFS rate at both five and eight years. In men with extraprostatic extension who had negative or positive margins, the eight-year bRFS was 77 and 50 percent, respectively. Men with seminal vesicle invasion or lymph node metastases had the worst outcomes (34 and 0 percent bRFS at eight years, respectively). Combining all pathologic parameters, six prognostic groups could be identified to define risk groups for biochemical failure following RP (figure 1) [44]. These observations permit the identification of men at higher risk for treatment failure who might be candidates for immediate hormone ablation or other therapies. (See "Initial hormone therapy for metastatic prostate cancer".) Cause-specific mortality — Although most series utilize biochemical relapse-free survival (bRFS) as the clinical end point, disease-specific mortality provides important insights into outcomes following radical prostatectomy. The relationship between disease-specific mortality and various clinical and pathologic variables was evaluated in a multi-institutional cohort series of 12,677 men who underwent RP for clinically localized disease between 1987 and 2005 [51]. The 15-year disease-specific and overall mortality rates were 12 and 38 percent, respectively, for the entire cohort. The main factors affecting cancer-specific mortality at 15 years included: Clinical stage: - Stage T1 — 6 percent - Stage T2a — 7 percent - Stage T2b — 14 percent - Stage T2c — 12 percent - Stage T3 — 38 percent Pretreatment serum PSA (ng/mL): - <4 — 4 percent - 4 to 10 — 9 percent - 10.1 to 20 — 11 percent - 20.1 to 50 — 22 percent Biopsy Gleason score: - 2 to 6 — 6 percent - 7 — 17 percent - 8 to 10 - 34 percent Because of change in pathologic criteria, Gleason scores are now consistently higher than when these data were generated. Thus, the Gleason score results from this study cannot be directly applied to current practice. (See "Interpretation of prostate biopsy", section on 'Gleason score'.) There was a statistically significant improvement in prognosis for patients diagnosed more recently. Whether this reflects an improvement in treatment, changes in Gleason grading, or an effect of PSA screening is uncertain. These data have been used to generate a nomogram to assist in treatment planning for newly diagnosed patients. (See "Early stage prostate cancer: Predicting the pathologic extent of disease and clinical outcome", section on 'Predictive tools'.) PSA kinetics — A short PSA doubling time or a rapid PSA velocity prior to RP correlate with increased mortality from prostate cancer in men managed with retropubic RP. This correlation was illustrated by a series of 1095 men, in which a PSA velocity of 2 ng/mL per year or higher was associated with significantly shorter time to recurrence, and higher rates of death from prostate cancer (relative risk [RR] 12.8, 95% CI 3.7 to 43.7) relative to those with a PSA velocity <2 ng/mL per year [52]. Surgeon experience — Long-term oncologic results are influenced by the experience of the surgeon. The correlation between surgical experience and long-term oncologic outcomes was illustrated in a series of 7765 men who underwent RP by one of 72 surgeons at four US academic medical centers between 1987 and 2003 [53]. The learning curve was steep and did not start to plateau until a surgeon had performed 250 retropubic RPs. The predicted probability of biochemical recurrence at five years was significantly lower when the surgeon had performed 250 prior operations (10.7 versus 17.9 percent when the surgeon had performed 10 prior operations). The benefit from increasing surgical experience was present for men whose prostate cancer was at low, medium, and high risk of recurrence [54]. These observations suggest that men wanting the best chance for cure should seek the most experienced available surgeon. Predicting recurrence — A number of nomograms to predict long-term individual outcomes following retropubic RP have been developed and validated in both Caucasian and African-American men [55]. These nomograms can incorporate demographic data such as age, Gleason score, clinical stage, and treatment plans to help estimate the risk of recurrence or progression in a variety of clinical scenarios. A number of these nomograms developed by the Memorial Sloan-Kettering group are accessible on line at www.mskcc.org/mskcc/html/10088.cfm RETROPUBIC RP: QUALITY OF LIFE — The complications of most concern to men who undergo retropubic RP are urinary incontinence and impotence, which are due to operative damage to the urinary sphincter and penile nerves, respectively. On the other hand, removal of the prostate may partially reverse or prevent the progression of symptoms due to antecedent benign prostatic hyperplasia, potentially improving quality of life. Perioperative complications — Perioperative morbidity rates are generally under 10 percent. Serious complications include myocardial infarction, and thromboembolic, infectious, and neurologic events [18-20,39,56]. Operative mortality rates in most reported series are less than 1 percent, even in older men [16,19,40,41,57]. The perioperative complication rate in our most recent series of 306 consecutive retropubic RPs was 8.2 percent (table 1) [18]. Most complications were minor and resolved without sequelae. Patient age — Perioperative complications are more common in older men, although this may be due in part to comorbidities. The effect of age on the incidence of complications is illustrated by the following examples: In a series of 1870 men managed with retropubic RP by one surgeon, the perioperative complication rates among men in their 40s, 50s, 60s and 70s were 4, 9, 11, and 14 percent, respectively [19]. In a report of 11,010 men who underwent RP in Ontario, Canada between 1990 and 1999, comorbidity was a stronger predictor than age of almost all categories of early complications [57]. Even when adjusted for comorbidity and year of surgery, age was associated with a significantly increased risk of 30-day mortality (odds ratio 2.04 per decade of age). Nevertheless, the absolute 30-day mortality risk was low, even in men aged 70 to 79 (0.66 percent versus 0.58 and 0.19 percent in men 60 to 69 and <60 years of age, respectively). Hospital volume — Hospitals with higher volumes of RPs tend to have shorter lengths of hospital stay, lower perioperative morbidity and mortality rates, and a reduced risk of serious treatment-related complications [58,59]. This relationship was illustrated by a series that used the Surveillance, Epidemiology and End Results (SEER)-Medicare linked database, in which perioperative morbidity rates were significantly different (27 versus 32 percent) when very high volume hospitals (114 to 252 procedures per year) were compared to low volume institutions (fewer than 33 procedures annually) [58]. Similar results were noted when very high volume surgeons were compared to low volume surgeons. Furthermore, significant differences were also apparent between very high and low volume institutions when the rates of long term urinary complications (but not urinary incontinence) were compared. Urinary incontinence Incidence — Complete urinary incontinence is uncommon following retropubic RP. The use of bladder neck sparing and nerve-sparing approaches has decreased the incidence of urinary incontinence from bladder neck contracture to 1 to 2 percent [8,10,11,18,60-62]. Nevertheless, the majority of men experience some degree of urinary incontinence after RP, particularly stress incontinence. The incidence of incontinence depends upon the source of the data (physicianreported versus patient-reported symptoms), the definition of continence, the time elapsed since surgery, and whether or not a nerve-sparing approach was used. In physician-reported series from single institutions, the reported rates of continence (typically defined as no or minimal urinary leakage) ranges from 88 to 100 percent at 6 to 24 months following surgery [11,12,60,63,64]. In one of the largest reports, which included 581 men who were continent prior to RP, independent factors associated with higher rates of regaining continence were younger age, preservation of both neurovascular bundles, and absence of an anastomotic stricture [11]. In patients operated on after 1990, the median time to regain continence was 1.5 months and the rate of continence at 24 months was 95 percent. The influence of nerve-sparing versus non-nerve-sparing surgery was illustrated in a report in which the median time to recover continence (patient-defined as the absence of any urinary leakage) was significantly shorter in men undergoing nerve-sparing surgery (5.3 versus 10.9 months) [65]. Patient-reported data suggest that the frequency of incontinence is higher. In the Prostate Cancer Outcomes Study, results from 1291 men aged 39 to 79 who underwent retropubic RP for localized prostate cancer over a one year period (1994 to 1995) were analyzed [66]. At 24 months after surgery, 1.6 percent reported no urinary control (compared with 0.7 percent at baseline prior to surgery), while 7 and 42 percent reported frequent and occasional leakage, respectively (compared with 2 and 9 percent at baseline) (table 6). The incidence of incontinence increased with age (14 percent in men ages 75 to 79 compared with 0.7 to 4 percent in younger age groups). Time course — Urinary incontinence typically improves with time following retropubic RP [62,67-70]. Most men achieve continence within three to six months, although it can take up to 18 to 24 months. In our experience, continence without the need for absorptive pads is achieved by 90 percent of men at a median of six weeks, with stress incontinence requiring one or two pads per day in 10 percent. Less than 1 percent require surgical placement of an artificial sphincter. In a series of 25,651 men in the Medicare population who underwent RP in 1991, urinary incontinence was reported in 22 percent after surgery, but only 8 percent continued to carry that diagnosis ≥12 months later [67]. Centers in which retropubic RP is performed in large numbers by one or only a few surgeons generally report better outcomes than those seen in the Medicare-based survey. Management — Options available for the management of urinary incontinence include conservative maneuvers, periurethral injections of collagen, the urethral sling procedure, and the artificial urinary sphincter. Conservative management options (eg, pelvic floor muscle training, biofeedback, electrical stimulation using a rectal electrode, transcutaneous electrical nerve stimulation) are often used in the first months following RP in an effort to control symptoms while sphincter function is returning. Data supporting these approaches are limited [71-73]. One randomized trial has observed a significant decrease in the rates of incontinence with pelvic floor reeducation (PFR) during the first months following RP in men who were incontinent 15 days after RP [72]. Compared to a placebo procedure, the use of PFR was associated with a significant decrease in the rate of incontinence at three (10 versus 44 percent) and 12 months (4 versus 17 percent). Periurethral injection of collagen offers a minimally invasive approach for the treatment of men with incontinence following RP, but success rates with this approach are limited [74-77]. As an example, in one series of men with postprostatectomy incontinence, 8 of 41 (20 percent) treated with collagen injections were at least socially continent, requiring one pad daily or less [75]. More invasive options for patients with severe incontinence include the insertion of an artificial urinary sphincter and the urethral sling procedure: Artificial urinary sphincter — The artificial urinary sphincter (AUS) is a surgically implanted device that circumferentially occludes the urethra, thereby preventing urinary leakage [74]. The device consists of a reservoir that is connected to a pump inserted in the scrotum, which the patient can activate to temporarily relieve the pressure, thereby permitting voiding. Pressure on the urethra can cause ischemia, which may necessitate revision or removal of the AUS. The most extensive experience reported with the AUS comes from the Mayo Clinic [78]. At an average follow-up of 6.5 years, the rate of continence following placement of an AUS was 88 percent in 323 patients with severe incontinence (70 percent due to RP). Revisions to the AUS were needed in about one-third of cases. Urethral sling procedure — The urethral sling procedure involves the insertion of a noncircumferential support that compresses the urethra [74]. The amount of pressure on the urethra is adjusted at the time of surgery such that the detrusor activity of the bladder can overcome this obstruction to permit voiding. Several series have evaluated this procedure in men with severe incontinence [79-81]. One report, for example, included 48 men with severe incontinence following RP at a median follow-up of 48 months [79]. The outcome was excellent (no use of pads) in 31 (65 percent) and another seven patients (15 percent) had substantial improvement. The AUS is preferred in patients who have had a prior procedure for urinary incontinence, patients who have had prior RT, and those who have poor bladder detrusor activity [74]. A sling procedure is preferable in men who are unable to manipulate the AUS reservoir. Retropubic RP versus RT — The relative frequency with which incontinence occurs following retropubic RP compared to radiation therapy is discussed separately. (See "Overview of treatment for clinically localized prostate cancer", section on 'Complications of EBRT'.) Bladder neck contracture — Urethral strictures following radical prostatectomy may be due to bladder neck contracture or narrowing of the urethral at more distal sites. Urethral stricture may be manifested by symptoms of decreased urinary stream or overflow incontinence. In a series of 3310 men from the CaPSURE database managed with radical prostatectomy, urethral stricture was diagnosed in 8 percent [82]. In contrast, urethral strictures were diagnosed in approximately 1 percent of patients managed with watchful waiting. In another series of 1289 men who underwent radical prostatectomy between 1998 and 2004, 138 (11 percent) developed a bladder neck contracture [83]. The incidence was significantly higher among men who had urinary retention within seven days after catheter removal. Most contractures can be easily managed with simple dilation. Dense strictures may require endoscopic incision [84]. Impotence — The frequency of impotence following retropubic RP depends upon patient age, preoperative sexual function, and whether or not nerve-sparing surgery was performed. (See 'Nerve-sparing approach' above.) Incidence — Potency can be preserved in many men with normal preoperative erectile function who undergo bilateral nerve-sparing RP [17,18,38,62,63,85]. Using phosphodiesterase inhibitors such as sildenafil, potency rates as high as 76 to 86 percent have been reported from individual surgeons and centers performing nerve-sparing surgery on carefully selected men [63,85]. In contrast, the potency rate was substantially lower in an American College of Surgeons survey of hospital tumor registry data of multiple hospitals with varying expertise [86]. Only 28 to 30 percent of men undergoing RP between 1990 and 1993 maintained erectile function adequate for intercourse after surgery. Patient estimates of the frequency of impotence may differ substantially from physician-reported single-center data. For example, in the Prostate Cancer Outcomes Study, 42 percent of men undergoing RP reported that their sexual performance was a moderate to large problem at 24 months (compared with 18 percent at baseline), and 60 percent were not able to have erections firm enough for sexual intercourse (compared with 16 percent at baseline) (table 7) [66]. The return of potency is gradual. In a report of 647 previously potent men undergoing retropubic RP at a tertiary referral center between July 1998 and July 2003, the probabilities of recovering potency at the end of postoperative years 1 and 2 were 37 and 62 percent, respectively [87]. The likelihood of potency following RP is age related. In one series, the potency rate after surgery was 86 percent in men in their 40s, and 80, 60, and 42 percent for men in their 50s, 60s, and 70s, respectively [63]. Retropubic RP versus radiation — The relative frequency with which impotence occurs following RP compared to RT as primary therapy for localized prostate cancer is discussed separately. (See "Overview of treatment for clinically localized prostate cancer", section on 'Complications of EBRT'.) Management — Penile sensation and the ability to have an orgasm are preserved even if the erectile nerves are removed during RP, leaving several options for treatment of erectile dysfunction (ED) in these men [88]. The treatment approaches for ED are discussed separately. (See "Treatment of male sexual dysfunction" and "Surgical treatment of erectile dysfunction".) The success of medical treatments for men with ED who are long-term survivors of prostate cancer is limited. Men prefer noninvasive treatments although invasive treatments (intracavernosal injection therapy, penile implants, prostheses) are more effective [89]. Sexual counseling should be recommended for men and their partners, as it may increase the use of and satisfaction with medical therapies. Phosphodiesterase inhibitors such as sildenafil are most helpful in men who have undergone a nerve-sparing procedure [85,89-92]. As an example, in one study of 91 men presenting with ED following RP, the response rates to sildenafil in men who had undergone bilateral nerve-sparing, unilateral nerve-sparing, and a nonnerve sparing approach were 72, 50, and 15 percent, respectively [92]. The response to sildenafil increases with time following RP. In a study in which 95 percent of men had undergone nerve-sparing procedures, 60 percent reported benefit from sildenafil at 18 to 24 months after surgery, significantly higher than the 29 percent who reported benefit in the first six months after surgery [93]. Nightly treatment with a phosphodiesterase inhibitor beginning after radical prostatectomy has been advocated to improve erectile function long term [94], However, on-demand treatment appears to be equally effective. In a randomized, double-blind trial, 628 men were randomly assigned to nightly vardenafil, ondemand vardenafil, or placebo for nine months [95]. After a two-month washout period, there were no differences in sexual performance between the two vardenafil regimens, and on-demand vardenafil was better than placebo throughout the trial. Inguinal hernia — The incidence of inguinal hernias appears to be increased following retropubic RP, due both to the detection of preexisting hernias that were not diagnosed preoperatively as well as alterations of inguinal anatomy during surgery [96,97]. This was illustrated by a consecutive series of 1130 patients, in whom 13 percent had a preexisting hernia and 8 percent developed a new hernia postoperatively [96]. In contrast, the incidence of inguinal hernia appears to be much lower following perineal RP (5 of 285 [1.8 percent] versus 32 of 311 [10.3 percent] following retropubic RP) [98]. BPH symptoms — Men who undergo RP for localized prostate cancer frequently have pretreatment lower urinary tract symptoms that are due to benign prostatic hyperplasia (BPH) rather than tumor. RP may partially reverse or prevent the progression of such symptoms. The impact on lower urinary tract symptoms was assessed in a study of 453 men who underwent an RP for localized prostate cancer and who completed the American Urological Association symptom score (AUASS) at baseline, and 12 and 48 months after surgery (table 8) [99]. Overall, 36 percent of patients had moderate or severe symptoms at baseline (AUASS ≥8), while 64 percent had no or mild symptoms (AUASS ≤7). Among men with moderate to severe symptoms at baseline, there was a clinically and statistically significant decrease in symptoms at 12 months, which was maintained at 48 months (AUASS -5.0 versus baseline and -6.3 versus baseline at 12 and 48 months, respectively). The improvement in symptoms occurred despite the discontinuation of medical therapy for symptomatic BPH in all patients after RP. In men with mild symptoms, there was an initial slight worsening of symptoms in the first 12 months without further subsequent deterioration (AUASS +2.0 versus baseline and +1.7 versus baseline at 12 and 48 months, respectively). Although these increases from baseline were statistically significant, they were not clinically relevant. These results were derived from a nonrandomized series. Although the natural history of BPH can be variable, the symptoms of BPH in some men appear to improve following surgery. A prospective study found that the benefit of RP in men with obstructive or irritative urinary symptoms was greatest in those with large prostate size [62]. The potential impact of RP on such symptoms should be considered when choosing definitive treatment of localized prostate cancer [99]. (See "Clinical manifestations and diagnosis of benign prostatic hyperplasia", section on 'Natural history'.) MINIMALLY INVASIVE RP — Minimally invasive RP (laparoscopic or robotic) has been developed as an alternative to retropubic RP [100-107]. This approach uses a smaller incision and provides magnification of the surgical field for the operator. Postulated advantages of a minimally invasive RP include fewer complications and quicker recovery. There are no randomized trials that compare minimally invasive RP to retropubic RP for prostate cancer. The most extensive data come from an analysis of 8837 men identified from the Surveillance, Epidemiology and End Results (SEER) Medicare database who underwent RP [100]. Key results from this study included the following: Utilization of minimally invasive RP increased from 9 percent of cases in 2003 to 43 percent in 2006-2007. Compared to retropubic RP, minimally invasive RP was significantly associated with shorter hospital stays (2.0 versus 3.0 days), less frequent blood transfusions (2.7 versus 20.8 percent), fewer respiratory complications (4.3 versus 6.6 percent), and fewer anastomotic strictures (5.8 versus 14.0 percent). Compared to retropubic RP, minimally invasive RP was associated with a significantly increased risk of genitourinary complications (4.7 versus 2.1 percent), incontinence (15.9 versus 12.2 per 100 person-years), and erectile dysfunction (26.8 versus 19.2 per 100 person-years). There are conflicting data about whether or not there is a higher rate of positive surgical margins following minimally invasive RP compared to retropubic RP: In a series of 400 patients from Vanderbilt, lower rates of positive margins were observed in patients treated with minimally invasive RP compared to those undergoing retropubic RP (9 versus 24 percent for pathologic T2 disease and 50 versus 60 percent for pathologic T3 disease) [101]. However, the better results with minimally invasive RP may have been due to more favorable patient characteristics in this group (lower Gleason scores, lower PSAs, and lower clinical stage). In addition, the observed rates of margin positivity with minimally invasive RP were much higher than those reported by other groups with retropubic RP [108]. Indirect evidence supporting a higher incidence of margin positivity comes from an analysis of 2702 men in a Medicare database, which found that those treated with a minimally invasive RP were significantly more likely to require salvage RT or injectable hormonal treatment within six months after their RP (28 versus 9 percent after open RP) [105]. There is a significant learning curve associated with laparoscopic and robotic RP [102,109,110]. As an example, the rates of complications and the need for salvage treatment in a Medicare database analysis were substantially higher for both minimally invasive and open RPs compared to those reported from highvolume institutions [102]. PERINEAL RP — A perineal approach for RP is a reasonable alternative for appropriately selected men with localized prostate cancer. This approach can be combined with preservation of the neurovascular bundles, but is not suitable for patients in whom pelvic lymph node dissection is required. Perineal versus retropubic RP — Perineal RP has been compared to retropubic RP in one randomized trial and several retrospective observational studies [111113]. These reports indicate that perineal RP has similar oncologic outcomes in carefully selected patients with localized prostate cancer, although there are differences in the frequency of side effects with the two procedures. The two approaches were compared in an Italian trial, in which 200 men with clinical stage T1 or T2 prostate cancer and a prostate gland weighing less than 80 g were randomly assigned to either a perineal RP or a retropubic RP [111]. Surgery for all patients was performed by a single surgeon who was trained in both techniques. The following findings were noted: At a mean follow-up of 60 months, there was no difference in biochemical relapse-free survival, with 12 and 11 percent having a serum PSA >0.2 ng/mL with perineal and retropubic RPs, respectively. There was also no difference in the incidence of positive surgical margins (14 and 15 percent, respectively). The incidence and timing of return of urinary continence was the same with both surgical approaches (74 versus 76 and 96 versus 95 percent, at 6 and 24 months, respectively). Perineal RP was associated with significantly less blood loss, a shorter hospital stay, and a shorter duration of catheterization compared to retropubic RP (100 versus 400 mL, 8 versus 13 days, and 7 versus 12 days, respectively). In contrast to these benefits, recovery of potency was significantly less common with perineal RP (potency 30 versus 45 and 42 versus 60 percent, at 6 and 24 months, respectively). In reports from observational series, rectal injury and fecal incontinence have also been reported following perineal RP [112,113]. Summary — In men with localized (T1-2) prostate cancer and a relatively small prostate gland, perineal RP is associated with less blood loss than open retropubic RP and is associated with a similar frequency of positive margins and biochemical relapse. However, recovery of potency is delayed and less frequent with the perineal approach, even with a nerve-sparing procedure. There also is a small, but increased risk of rectal injury and fecal incontinence. There are no data comparing perineal RP with laparoscopic RP, which can also decrease blood loss and shorten the duration of hospital stay. Perineal RP is a reasonable option for men with low-risk primary tumors and relatively small prostates (eg, Gleason score <6, serum PSA <10 ng/mL, and a prostate gland <80 g). In these men, the likelihood of lymph node disease is under 5 percent, making pelvic lymph node dissection unnecessary [114,115]. Perineal RP may be particularly useful in men who have had prior pelvic surgery and in those for whom minimizing short-term toxicity is a priority. ADJUVANT AND NEOADJUVANT THERAPY Neoadjuvant ADT — Men with locally advanced prostate cancer have worse outcomes after RP than do those with organ-confined disease (table 9). Although neoadjuvant androgen deprivation therapy (ADT) decreased the rate of surgically positive margins, no survival advantage was demonstrated with this approach. (See "Clinical stage T3 prostate cancer".) Several prospective trials of ADT before RP in men with organ-confined disease have also noted a decrease in rates of margin positivity and improvements in tumor size, serum PSA, final pathologic stage, risk of progression, and time to progressive disease [116-120]. However, the few series with long-term follow-up suggest no benefit in terms of overall or cancer-specific survival, or biochemical relapse-free survival (bRFS): In a randomized trial, 138 men with clinical stage T2b disease received three months of leuprolide plus flutamide prior to RP while 144 were assigned to immediate RP [118]. Although the positive margin rate was significantly lower with neoadjuvant ADT (15 versus 48 percent), there was no difference in the fiveyear bRFS (serum PSA ≤0.4 ng/mL in 65 versus 68 percent of men undergoing neoadjuvant ADT or surgery alone, respectively). Similar results were noted in a European trial that randomly assigned 402 men with cT2-3 N0 prostate cancer to three months of goserelin plus flutamide followed by RP or immediate RP [119] and a Canadian trial that randomly assigned 213 men to three months of neoadjuvant cyproterone followed by RP or RP alone [120]. Neoadjuvant chemotherapy with or without ADT — Newer approaches to locally advanced prostate cancer consist of neoadjuvant or induction chemotherapy or combined chemotherapy plus ADT. While chemotherapy was previously considered to be relatively ineffective in prostate cancer, drugs such as docetaxel produce higher rates of both objective and biochemical response, and prolonged survival when compared to mitoxantrone. (See "Chemotherapy in castrate-resistant prostate cancer".) These data have led to the design of phase II trials exploring neoadjuvant chemotherapy or chemotherapy plus ADT prior to RP in men who have adverse pretreatment tumor characteristics. Although the ultimate goal is improved local control and survival, initial studies were designed to demonstrate the safety of retropubic RP following induction therapy, and to examine treated specimens for histologic evidence of antitumor effect. At least six trials have been reported; they included men without overt evidence of metastases who were at high risk for extraprostatic extension and subsequent biochemical failure by having the following characteristics [121-127]: Pretreatment PSA >15 to 20 ng/mL OR Clinical stage T2b, T2c, or T3 (table 2) OR Biopsy Gleason score ≥8 All of these trials demonstrated that RP is feasible with acceptable surgical and postoperative morbidity following neoadjuvant therapy. However, most of the drug regimens explored (estramustine/etoposide, weekly docetaxel with or without mitoxantrone, or combined ADT with alternating cycles of ketoconazole, doxorubicin, vinblastine and etoposide) had no significant antitumor effect as assessed by histologic changes in the RP specimens or a reduction in the incidence of adverse pathologic features. A single preliminary report of a phase II trial of weekly docetaxel plus ADT noted two complete pathologic responses among 64 men (3 percent) [127]. Adjuvant antiandrogen monotherapy — Thus, the available evidence does not support the use of antiandrogen monotherapy after resection of localized prostate cancer. Adjuvant antiandrogen monotherapy was extensively evaluated in the Early Prostate Cancer program. In these trials, 8113 men with localized (T1, T2) or locally advanced (T3, T4) nonmetastatic prostate cancer were randomly assigned to bicalutamide or placebo in addition to standard care (watchful waiting, RP, or RT) [128]. At a median follow-up of 10 years, patients with locally advanced disease had an improvement in progression-free but not overall survival. In men with localized (T1, T2) disease, there was no statistically significant improvement in either progression-free or overall survival. (See "Pathologic stage T3 and margin positive prostate cancer", section on 'Adjuvant hormone therapy without RT'.) Adjuvant chemotherapy — The activity of docetaxel and other cytotoxic chemotherapy agents in patients with advanced disease has led to the evaluation of adjuvant chemotherapy in men with resected prostate cancer. The role of adjuvant chemotherapy following definitive local therapy of prostate cancer is discussed separately. (See "Clinical stage T3 prostate cancer", section on 'Adjuvant therapy'.) SUMMARY AND RECOMMENDATIONS In patients with clinically localized prostate cancer, the preferred approach for definitive therapy (ie, radical prostatectomy [RP] or radiation therapy [RT]) is largely a matter of patient preference. Taken together, the available data suggest that surgery and RT offer fairly equivalent survival outcomes, at least for the first 10 years after therapy. (See "Overview of treatment for clinically localized prostate cancer".) For patients who choose surgery, we suggest a retropubic RP (Grade 2C). (See 'Patient selection' above and 'Retropubic RP: procedure' above.) Minimally invasive RP is an alternative in situations where there is adequate expertise with this approach. This approach has been associated with fewer short-term complications, transfusions, and shorter hospital stays. However, there are no comparative trials, and long term equivalence on oncologic results has not been demonstrated. (See 'Minimally invasive RP' above.) Perineal RP is an alternative to retropubic RP for men with clinical stage T1-2 disease, a relatively small prostate gland, and no indication for a lymph node dissection. This approach may be particularly useful in men who have had prior pelvic surgery and in those for whom minimizing short term toxicity is a high priority. (See 'Perineal RP' above.) We recommend that a nerve-sparing approach be incorporated into the RP when there is no evidence of tumor involving the neurovascular bundle (Grade 1B). 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