Radical prostatectomy for localized prostate cancer

INTRODUCTION — Standard management options for men with clinically localized prostate cancer include radical prostatectomy; radiation therapy (RT), including external beam RT and/or brachytherapy; and, for appropriately selected patients, active surveillance. Patients treated with RT who were classified as high risk based upon pretreatment assessment and those managed with radical prostatectomy who have significant adverse pathologic findings (positive margins, seminal vesicle invasion, persistent elevation of serum prostate specific antigen [PSA]) may require a combined modality approach.

The role of radical prostatectomy in the treatment of clinically localized prostate cancer will be reviewed here. Overall treatment options for men with newly diagnosed prostate cancer and the factors influencing the choice of therapy are discussed separately based upon the risk of recurrence and the extent of disease:

●(See "Localized prostate cancer: Risk stratification and choice of initial treatment".)

●(See "Initial approach to low- and very low-risk clinically localized prostate cancer".)

●(See "Initial management of regionally localized intermediate-, high-, and very high-risk prostate cancer and those with clinical lymph node involvement".)

●(See "Overview of systemic treatment for recurrent or metastatic castration-sensitive prostate cancer".)

SURVIVAL IMPACT OF RADICAL PROSTATECTOMY — Randomized clinical trials provide evidence that radical prostatectomy improves overall survival or delays the development of metastatic disease compared with observation (watchful waiting) [1-5]. The trials did not include definitive therapy at the first evidence of disease progression, do not compare the impact of radical prostatectomy with other active treatment approaches, and need to be distinguished from active surveillance, where definitive therapy is delayed and instituted only when evidence of progression is present.

●In the Scandinavian Prostate Cancer Group 4 trial, 695 men with clinical stage T1 or T2 prostate cancer were randomly assigned to radical prostatectomy or watchful waiting, with active therapy deferred until advanced disease was present [3]. With a maximum follow-up of 23 years (median 13 years), men randomized to radical prostatectomy had a significantly lower incidence of death from all causes (56 versus 69 percent), death from prostate cancer (18 versus 29 percent), distant metastases (26 versus 38 percent), and use of androgen deprivation therapy (43 versus 67 percent) compared with those assigned to watchful waiting. The benefits were most pronounced in those less than 65 years of age at diagnosis and in those with intermediate-risk disease. In a later analysis with a maximum 29 year follow-up (median 23.6 years), the cumulative incidence of death from prostate cancer was 19.6 percent in the prostatectomy group and 31.3 percent with watchful waiting [6]. A mean of 2.9 extra years of life were gained with radical prostatectomy.

●In the PIVOT trial, 731 men with T1-T2NxM0 prostate cancer were randomly assigned to radical prostatectomy or observation [2,4,7]. Men assigned to observation were offered palliative therapy for symptomatic or metastatic progression. Although the difference in overall survival and prostate cancer mortality did not reach statistical significance, the trial did not complete its planned accrual and was underpowered; it also included predominantly older men with substantial comorbidities. In the latest analysis with a minimum follow-up of death or 15 years and a maximum follow-up of 22 years, 246 of 364 patients assigned to surgery had died, and 269 of 367 assigned to observation had died (hazard ratio [HR] for death 0.84, 95% CI 0.70-1.00) [7]. The restricted mean survival in the surgical group was 13.6 years, compared with 12.6 years with observation, with a mean of one year gained with surgery at a median 22 years of follow-up.

Disease progression (local, regional, or systemic) was significantly less frequent in those managed with radical prostatectomy (41 versus 68 percent, HR 0.39, 95% CI 0.32-0.48) [4]. Additional treatment for prostate cancer was eventually required in 33.5 percent of those managed with radical prostatectomy and 59.7 percent of those managed with observation. Erectile dysfunction and urinary incontinence were more frequent with surgery compared with observation (14.6 versus 5.4 and 17.3 versus 4.4 percent, respectively).

The outcomes following radical prostatectomy compared with other treatment approaches are based upon risk stratification. The only large-scale data came from the Prostate Testing for Cancer and Treatment (ProtecT) trial that is being conducted in the United Kingdom. Patients with prostate cancer detected at prostate-specific antigen (PSA) screening were randomly assigned to active surveillance, radical prostatectomy, or definitive radiation therapy [8,9]. In the initial report of this trial, there was no significant difference in the 10 year cancer-specific survival or overall survival rates between the different treatment modalities. However, there was an increased frequency of metastatic disease and clinical progression with active surveillance, and there were only a very limited number of deaths related to prostate cancer. Detailed results and limitations of the ProtecT trial are discussed separately. (See "Initial approach to low- and very low-risk clinically localized prostate cancer", section on 'ProtecT trial'.)

Radical prostatectomy also has a role in patients with more extensive local disease and may be associated with a survival advantage. (See "Initial management of regionally localized intermediate-, high-, and very high-risk prostate cancer and those with clinical lymph node involvement", section on 'Radical prostatectomy'.)

PATIENT SELECTION — Radical prostatectomy is a treatment option for patients with localized prostate cancer, along with external beam radiation therapy, brachytherapy, and, in some cases, active surveillance.

The choice of therapy depends upon an informed patient decision incorporating knowledge about the potential advantages and disadvantages associated with different treatment approaches.

Radical prostatectomy is generally not indicated for patients with distant metastases, although new clinical trials are evaluating its role as a part of a multimodal approach in men who present with oligometastatic disease [10]. Neither is prostatectomy indicated when there is tumor fixation to adjacent structures.

The factors influencing the choice of prostatectomy rather than external beam radiation therapy, brachytherapy, or active surveillance are discussed separately. (See "Initial approach to low- and very low-risk clinically localized prostate cancer".)

Preoperative preparation — Preoperative counseling that includes the spouse or partner is essential to address the practical and emotional issues surrounding radical prostatectomy. Presurgical psychosocial interventions including a focus on stress management may be useful in improving quality of life following surgery [11]. In addition, patients should be counseled regarding the importance of modifying health-related behaviors or risk factors, such as smoking and obesity [12].

One of the most important goals prior to treatment is to set reasonable expectations for the short-term and long-term effects of surgery on activity level, continence, and potency. Emphasis is placed on the type of anesthesia to be used, whether lymphadenectomy will be performed, and whether a nerve-sparing procedure is contemplated, as well as the anticipated length of hospital stay.

SURGICAL TREATMENT — Radical prostatectomy, which implies total removal of the prostate and the seminal vesicles, can be safely performed via a variety of approaches (open retropubic or perineal; laparoscopic transperitoneal or extraperitoneal; robotic transperitoneal, extraperitoneal, transvesical [through the bladder], or transperineal). The approach is mostly determined by the skill and experience of the surgeon, though disease extent is also important.

Radical prostatectomy — In resource-rich countries, such as the United States, radical prostatectomy is most commonly performed robotically [13-15]. When performed by experienced surgeons, robotic-assisted radical prostatectomy (RARP) has similar oncologic and functional results, but shorter hospital stay, shortened catheter times, and fewer major complications, compared with open radical prostatectomy [16,17].

A 2017 practice guideline jointly sponsored by the American Urological Association (AUA), American Society for Radiation Oncology (ASTRO), and Society of Urologic Oncology (SUO), and later endorsed by the American Society of Clinical Oncology (ASCO) in 2018, considers open and RARP to be similar in cancer control, continence recovery, and sexual recovery [12]. The advantages of minimally invasive techniques, aside from a smaller incision, mainly lie in perioperative outcomes such as reduced blood loss and fewer postoperative complications [18].

A 2017 Cochrane review of two randomized trials showed that minimally invasive and open prostatectomy resulted in similar urinary and sexual quality-of-life outcomes. Overall and serious complication rates were also comparable, while patients had shorter hospital stay and fewer blood transfusions after minimally invasive prostatectomy. However, oncologic outcomes were not addressed with high-quality data [19].

One of the trials included in the Cochrane review cited above was updated in 2018 [20,21]. In a report of early outcomes, there was no significant difference in urinary or sexual function scores through 12 weeks, nor was there a significant difference in the incidence of positive surgical margins [20]. At 24 months after surgery, there was also no difference in urinary function scores or sexual function scores between the two groups. And although there was a higher rate of biochemical recurrence after open surgery (9 versus 3 percent), the discrepancy may be due to different postoperative management and use of additional cancer treatment [21].

A 2015 Swedish prospective, controlled, nonrandomized trial (LAPPRO) reported that, at eight years after surgery, urinary incontinence was not significantly different between RARP and open prostatectomy (27 versus 29 percent). Erectile dysfunction was significantly lower in the RARP group (66 versus 70 percent). Prostate cancer-specific mortality was significantly lower in the RARP group (40/2699 versus 25/885; adjusted risk ratio 0.56, 95% CI 0.34-0.93). However, a causal relationship could not be inferred, due to the nonrandomized study design [17].

Although laparoscopic radical prostatectomy offers the benefits of minimally invasive surgery without the need for specialized equipment and high costs associated with the surgical robot, it is considered by many to be a difficult technique with a steep learning curve and therefore is not often adopted in North America. In a randomized, patient-blinded trial (LAP-01), RARP resulted in significantly better continence recovery than laparoscopic prostatectomy at three months (continence rate 54 versus 46 percent) [22].

The experience of the surgeon is a critical factor associated with a successful outcome following radical prostatectomy regardless of technique since the results with all surgical approaches are associated with a significant learning curve [23-28]. Conversely, large retrospective series comparing open, laparoscopic, and RARP performed by expert surgeons at high-volume centers showed no difference in functional outcomes [29].

In several reports, extraperitoneal single-port robotic radical prostatectomy has been performed as outpatient surgery or only required overnight observation [30-32].

Nerve-sparing approach — Erectile function following radical prostatectomy depends upon preservation of the autonomic cavernous nerves, located within the neurovascular bundles. Because a nerve-sparing approach is associated with better erectile function recovery than non-nerve-sparing approaches [12], every effort should be made to preserve the bilateral neurovascular bundles during proctectomy as long as cancer control is not compromised. (See 'Erectile dysfunction' below.)

For patients with no evidence of tumor involving the neurovascular bundle, we recommend that a nerve-sparing approach be incorporated into the radical prostatectomy. This approach is associated with faster return of urinary continence and a lower frequency of erectile dysfunction in men who were potent prior to surgery.

In a 2017 systematic review and meta-analysis of 124 mostly observational studies, the risk of incontinence was lower in nerve-sparing cases (relative risk [RR] 0.75, 95% CI 0.65-0.85 and RR 0.61, 95% CI 0.44-0.84) at 3 and 12 months, respectively. The relative risk of erectile dysfunction with nerve sparing was 0.77 (95% CI 0.70-0.85) at 3 months and 0.53 (95% CI 0.39-0.71) at 12 months [33]. Nerve sparing did not increase the risk of positive surgical margins in patients with pT2 or pT3 disease, due to appropriate patient selection.

Nerve-sparing radical prostatectomy can be performed safely in men with pathologic extraprostatic extension as long as the neurovascular bundles are not involved. The decision to perform a nerve-sparing approach is influenced by the size and location of the tumor based on preoperative magnetic resonance imaging (MRI) but ultimately made during surgery based upon visual inspection of the gland and its relationship to the nerve bundle. If there is a clinical suspicion of extraprostatic extension involving the neurovascular bundles, intraoperative frozen section analysis to ensure complete tumor excision may be useful.

Multiparametric MRI (mpMRI) of the prostate may also be useful in guiding the surgical approach. (See "The role of magnetic resonance imaging in prostate cancer".)

Retzius-sparing approach — Retzius-sparing robotic-assisted radical prostatectomy (RS-RARP) avoids dissection of the retropubic space of Retzius and instead dissects the posterior space of Douglas (rectovesical pouch) [34]. At least in theory, RS-RARP can improve postoperative urinary continence by preserving the bladder neck and urethral anatomy through a posterior plane of dissection [35]. However, RS-RARP has a more limited working space compared with standard RARP.

A 2020 Cochrane meta-analysis of five trials concluded that the Retzius-sparing approach resulted in a lower urinary incontinence rate at up to six months but a higher positive margin rate [36]. Longer-term oncologic and functional outcomes are required before Retzius-sparing radical prostatectomy can be recommended for wide-spread use.

Perineal radical prostatectomy — Perineal radical prostatectomy recapitulates the retropubic approach via a perineal, rather than abdominal, incision. It was the favored radical prostatectomy approach for many years until the description of the retropubic radical prostatectomy, whose advantages included a large working space and more familiar anatomy. The adoption and rapid diffusion of robotic technology brought a new interest in the perineal approach. Although originally an open procedure [37], perineal radical prostatectomy is being performed robotically using a single-port platform at specialized centers [38-42].

Perineal radical prostatectomy is a reasonable option for men with low-risk primary tumors and relatively small prostates (eg, Gleason score <6, serum prostate-specific antigen [PSA] <10 ng/mL, and a prostate gland <80 g) and in whom a pelvic lymph node dissection is not indicated. Perineal radical prostatectomy, open or robotic, may be advantageous in patients with prior abdominal surgery, though the robotic transvesical approach similarly avoids the abdomen and allows for more working room than the perineal approach. Perineal approaches are associated with longer times to recovery of erections [43,44].

Pelvic lymph node dissection — Prostatectomy may be combined with a pelvic lymph node dissection if there is significant risk of lymph node involvement.

Indications for lymph node dissection — Since the widespread introduction of PSA testing, most patients are diagnosed with localized disease, and there has been a concomitant decrease in the percentage of patients with regional lymph node involvement at diagnosis [45-47]. However, the decreased utilization of PSA screening due to changes in screening guidelines may be contributing to an increased incidence of men with metastatic disease (from 2010 to 2014) and a decreased incidence of men with low-risk prostate cancer [48-51]. (See "Screening for prostate cancer", section on 'PSA testing'.)

Key factors that are associated with an increased risk of occult lymph node metastases include a higher clinical tumor stage, percentage of Gleason pattern 4 tumor, presence of cribriform and/or intraductal morphology [52,53], and higher serum PSA. The need for pelvic lymph node dissection in conjunction with radical prostatectomy is determined by the risk of regional lymph node involvement, which is based upon the extent of the local tumor (T stage), serum PSA, and Gleason score. (See "Localized prostate cancer: Risk stratification and choice of initial treatment", section on 'Risk-stratified approach to treatment of adenocarcinomas'.)

In their 2022 guidelines, the American Urological Association (AUA) recognizes that pelvic lymphadenectomy provides staging information, which may guide future management, but does not have consistently documented improvement in metastasis-free, cancer-specific, or overall survival [54]. This is based on a 2017 systematic review and meta-analysis of 44 studies showing conflicting results on biochemical and clinical recurrence, no significant differences for survival, but greater adverse outcomes in terms of operating time, blood loss, length of stay, and postoperative complications with more extensive pelvic lymph node dissection (PLND) [55].

The AUA suggests that clinicians use nomograms to select patients for lymphadenectomy. Several such nomograms exist to facilitate selection of patients for PLND [56-59]. The National Comprehensive Cancer Network (NCCN) recommends performing PLND when the risk of lymph node metastasis is greater than 2 percent based on a nomogram [60]. The European Association of Urology (EAU) guidelines recommend PLND for men with high-risk and intermediate-risk disease having at least a 5 percent probability of nodal metastases [61].

The oncologic benefit of PLND for prostate cancer remains controversial. An improvement in survival from a PLND has not been demonstrated in randomized trials [62,63]. Although lymph node dissection provides important staging and prognostic information, it is unlikely to have major therapeutic benefit. (See 'Oncologic outcomes' below.)

Furthermore, newer imaging agents such as prostate-specific membrane antigen (PSMA) are refining risk assessment and may soon rewrite the indications for PLND [64,65]. There are also studies underway using intraoperative imaging to help tailor the extent of the PLND.

Extent of lymph node dissection — The extent of a PLND has a major impact on the frequency with which positive lymph nodes are detected as well as on the incidence of complications. The optimal extent of PLND is uncertain, but the available evidence suggests that an extended dissection is preferable, especially in patients with very-high-risk disease [47,66].

Historically, PLND was limited to the obturator fossa (limited) or associated with the external iliac vein (standard). However, the primary lymphatic drainage of the prostate often bypasses these nodes and goes directly to the common iliac, hypogastric, paraaortic, presacral, or perirectal lymph nodes. A more extensive dissection (extended) including internal iliac nodes not only yields greater numbers of positive nodes but also can identify lymph node involvement when the nodes within a more limited template are negative [47,67-69].

In a trial of 300 patients with intermediate or high-risk prostate cancer, extended PLND provided better pathological staging, but differences in early oncologic outcomes were not demonstrated. One subgroup analysis suggested a potential biochemical recurrence-free survival benefit in patients with higher-grade cancers [62] However, these findings should be considered hypothesis generating, and further randomized controlled trials with larger cohorts and longer follow-up are necessary to better define the role of extended PLND during radical prostatectomy.

In another trial of 1440 patients, extended PLND did not improve biochemical recurrence-free survival over limited PLND for men with clinically localized prostate cancer. However, there were smaller-than-expected differences in nodal count (12 versus 14 nodes) and the rate of positive nodes between the two templates (12 versus 14 percent) [63]. 

Patients should be counseled regarding the potential complications associated with PLND, such as lymphocele formation, and their treatment [12]. (See 'Surgical outcomes' below.)

Follow-up after surgery — Patients with adverse laboratory or pathology features following prostatectomy (ie, positive margins, seminal vesicle invasion, extracapsular extension, or detectable PSA) should consider postoperative adjuvant or early salvage radiation therapy. In contemporary practice, adjuvant therapy is mainly indicated for those with persistently detectable PSA.

Pathologic staging — Patients who are managed with radical prostatectomy are restaged after surgery based upon the extent of disease in the surgical resection specimen. Such patients may be reclassified, based upon the extent of the primary tumor and/or the presence of microscopic involvement of regional lymph nodes. The information from pathologic staging can provide important information regarding prognosis and help guide future therapy.

The management of patients with pathologic T3 disease, margin-positive prostate cancer, or microscopic lymph node involvement is discussed separately. (See "Prostate cancer: Postoperative management of pathologic stage T3 disease, positive surgical margins, and lymph node involvement following radical prostatectomy", section on 'Pathologic versus clinical staging'.)

Assessment of treatment efficacy — Following radical prostatectomy, the serum level of PSA should become undetectable since all normal prostate tissue as well as the tumor is removed. Although in principle this is a straightforward, definitive endpoint, in fact there is no consensus as to what constitutes a failure after surgery. Most series use a PSA >0.2 ng/mL, but ultrasensitive assays can reliably detect recurrences years earlier. Newer genomic classifiers can assess the risk of developing metastatic disease at the time of biochemical recurrence [70,71]. (See "Rising serum PSA following local therapy for prostate cancer: Definition, natural history, and risk stratification", section on 'After radical prostatectomy'.)

Surveillance strategies after treatment for localized prostate cancer are discussed separately. (See "Follow-up surveillance after definitive local treatment for prostate cancer".)

OUTCOMES

Functional outcomes

Erectile dysfunction — Most men experience at least temporary erectile dysfunction even after nerve-sparing procedures. Recovery of erectile function is influenced by multiple factors, including age, pretreatment sexual functioning, and type of surgery (nerve-sparing versus non-nerve-sparing). A validated model that may be useful in counseling patients has been developed to predict sexual function recovery at 12 and 24 months after radical prostatectomy [72].

Incidence and time course — The frequency of erectile dysfunction depends upon the definition of erectile dysfunction and source of information. Potency rates as high as 76 to 86 percent have been reported by individual surgeons and centers performing nerve-sparing surgery on carefully selected men who then use phosphodiesterase inhibitors such as sildenafil [73,74]. In contrast, sexuality problems (eg, poor erections, difficulty with orgasm) were a moderate or serious problem in 59 percent of men two months after in a series of 603 patients who had undergone radical prostatectomy [75]. Although there was some gradual improvement with time, 43 percent still reported such problems two years after prostatectomy.

The recovery of erectile function can be delayed and can continue even beyond two years [76,77]. For those men who recover function, the available evidence indicates that such benefit can be maintained for at least 10 years.

The likelihood of regaining potency following radical prostatectomy decreases with increasing age. 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 [73]. Older men experience higher rates of permanent erectile dysfunction after prostatectomy compared with younger men [12].

Management — Penile sensation and the ability to have an orgasm are preserved even if the erectile nerves are removed during radical prostatectomy, leaving several options for treatment of erectile dysfunction [78]. These include the use of oral phosphodiesterase 5 (PDE5) inhibitors, vacuum-assisted erection devices, penile self-injection (prostaglandin E1, papaverine, phentolamine), and intraurethral alprostadil. Sexual counseling should be recommended for men and their partners as it may increase the use of and satisfaction with medical therapies. (See "Treatment of male sexual dysfunction" and "Surgical treatment of erectile dysfunction".)

PDE5 inhibitors are most helpful in men who have undergone a nerve-sparing procedure. As an example, in one study of 91 men presenting with erectile dysfunction following radical prostatectomy, the response rates to sildenafil in men who had undergone bilateral nerve-sparing, unilateral nerve-sparing, and a non-nerve-sparing approach were 72, 50, and 15 percent, respectively [79].

The response to sildenafil increases with time following radical prostatectomy [80]. 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 [81].

Emerging treatment for erectile dysfunction after radical prostatectomy includes injection of stem cells into the corpus cavernosum [82] and low-intensity extracorporeal shock wave treatment (LI-ESWT) to induce neovascularization [83].

Penile rehabilitation — Penile rehabilitation beginning shortly after surgery with oral phosphodiesterase inhibitors, vacuum-assisted devices, or prostaglandin E1 injections has been advocated to minimize the long-term incidence of erectile dysfunction, although the effectiveness of this approach is uncertain [84-88].

Early penile rehabilitation with oral agents remains controversial. On-demand treatment with a PDE5 inhibitor appears to be as effective as penile rehabilitation following bilateral nerve-sparing radical prostatectomy.

Two large double-blind randomized trials have been conducted, one with vardenafil [89] and the other with tadalafil [90]. In both trials, patients were randomly assigned to a daily PDE5 inhibitor, on-demand PDE5 inhibitor, or placebo for nine months, followed by a two-month washout period. In both trials, there were no statistically significant differences between the two PDE5 inhibitor regimens, and both were superior to placebo. Furthermore, after the two-month washout period, there were no statistically significant differences between treatment groups in response to PDE5 inhibition.

Animal model data suggest that perioperative use of oral phosphodiesterase inhibitors helps recovery. In a pilot human trial, tadalafil started before nerve-sparing RARP has been found to lead to better recovery of erectile dysfunction than does postoperative penile rehabilitation [91]. The author's routine is to use tadalafil (2.5 mg for three days preoperatively and 30 days postoperatively), followed by sildenafil 100 mg two to three times per week along with sexual stimulation to orgasm as soon as the patient recovers continence. Injection treatment is added at eight weeks if desired by patients whose erections have not returned.

LI-ESWT, which can cause a biological change that induces neovascularization, has also been used as a treatment for erectile dysfunction after radical prostatectomy [83]. In a nonrandomized comparative study comparing early LI-ESWT plus daily tadalafil therapy with tadalafil only, the proportion of patients with erection hardness scores (EHS) ≥3 (4/39 versus 12/41) was significantly higher in the LI-ESWT plus tadalafil group [92].

Urinary incontinence — Damage to the urinary sphincter can lead to urinary incontinence following radical prostatectomy. Although complete urinary incontinence is uncommon following radical prostatectomy, most men do experience some degree of urinary incontinence after radical prostatectomy, particularly stress incontinence. Older men experience higher rates of permanent urinary incontinence after prostatectomy compared with younger men [12]. (See "Urinary incontinence after prostate treatment", section on 'Pathophysiology'.)

The incidence of incontinence depends upon its definition, the time elapsed since surgery, and the surgical approaches and techniques used. In a study that compared four different techniques of RARP, the 0 pad continence rates of anterior, posterior, hybrid posterior-anterior, and transvesical approaches were 15, 42, 45, and 8 percent at one week and 35, 66, 64, and 25 percent at one month [93]. Bladder neck preservation was the only significant predictor of total continence recovery in adjusted analysis. Another study reported that routine implementation of standard full functional-length urethral sphincter and neurovascular bundle preservation with intraoperative frozen section technique resulted in a long-term continence rate of 91 percent, compared with 63 percent in standard RARP [94].

Urinary incontinence typically improves with time following retropubic radical prostatectomy. In a multi-institution analysis that included 603 patients who had undergone radical prostatectomy, 52 percent of patients reported some urine leakage more than once a day two months after surgery [75]. By 12 and 24 months, this had decreased to approximately 15 percent. Approximately 7 percent continued to consider urinary symptoms to be a moderate or large problem at two years. A validated model that may be useful in counseling patients has been developed to predict continence recovery at 24 months after radical prostatectomy [95].

How long additional improvement in urinary function can be observed is uncertain. One longitudinal study of urinary continence in 1788 men suggested that there was no further improvement in the continence rate and that between 2 and 10 years there was a slight decrease in urinary continence [96]. By contrast, a second study of 1003 men with impaired urinary function at 12 months found that there was continued improvement at least through four years [77].

Pelvic floor muscle exercises can accelerate the recovery of urinary continence [97]. However, the use of such exercises prior to surgery does not appear to provide additional benefit [98]. Fewer than 1 percent of patients ultimately require surgical placement of a sling or an artificial sphincter. (See "Urinary incontinence after prostate treatment", section on 'Management of incontinence'.)

Urethral strictures — Urethral strictures following radical prostatectomy may be due to bladder neck contracture or narrowing of the urethra at more distal sites. Urethral stricture may be manifested by symptoms of decreased urinary stream, urinary retention, or overflow incontinence.

The incidence of urethral stricture or bladder neck contracture was between 8 and 11 percent in the era of open radical prostatectomy [99,100]. That rate is significantly lower after RARP than open radical prostatectomy (1.6 versus 8.3 percent) in contemporary series [16].

Most contractures can be easily managed with simple dilation. Dense strictures may require endoscopic incision [101] and rarely require open surgical repair. (See "Strictures of the adult male urethra".)

Lower urinary tract symptoms — Men who undergo radical prostatectomy for localized prostate cancer frequently have pretreatment lower urinary tract symptoms (LUTS) that are due to benign prostatic hyperplasia (BPH) rather than tumor. Radical prostatectomy may partially reverse or prevent the progression of such symptoms [102].

Although the natural history of BPH can be variable, the symptoms of BPH in some men appear to improve following surgery. In a prospective 15 year longitudinal study, the proportions of men with clinically significant LUTS were smaller at all time points after retropubic prostatectomy, except 3 months and 15 years, than at baseline [103]. Another prospective study found that the benefit of radical prostatectomy in men with obstructive or irritative urinary symptoms was greatest in those with large prostate size [75]. The potential impact of radical prostatectomy on such symptoms may be a factor when choosing the definitive treatment of localized prostate cancer [102], and for that reason radical prostatectomy may be favored over external radiation or brachytherapy in men with significant LUTS.

Surgical outcomes — Perioperative morbidity rates of radical prostatectomy are generally under 10 percent. Serious complications include myocardial infarction and thromboembolic, infectious, and neurologic events, but most complications are minor and resolve without sequelae. Operative mortality rates in most series are less than 1 percent, even in older men [16,104,105].

A 2017 systematic review of 50 studies reported the following perioperative complications (with incidence) [106]:

●Conversion to open surgery – 1.8 percent [107]

●Readmission – Open radical prostatectomy 5.5 percent, RARP 3.5 percent [108]

●Reoperation – Both open and robotic radical prostatectomy 1 percent [108]

●Venous thromboembolic events – 1.4 percent [109], lymphadenectomy increased incidence by four- to eightfold [105]

●Lymphocele – 0 to 8 percent [110]

●Urine (anastomotic) leak – Open radical prostatectomy 1 percent, RARP 2 percent [111-114]

●Bladder neck contracture/urethral stricture – Open radical prostatectomy 8 to 11 percent, RARP 1 to 2 percent (see 'Urethral strictures' above)

●Rare (<1 percent) – Obturator nerve injury, rectal injury or fistula, vascular injury, lower extremity compartment syndrome

A retrospective analysis of 13,924 radical prostatectomies at a single institution reported that 10.8, 7.9, 3.4, 2.6, and 0.9 percent of patients suffered a Clavien-Dindo class I, II, IIIa, IIIb, and IV/V complication, respectively (table 1). The most common minor (class I or II) complications were lymphoceles or lymph leak (6.0 percent), blood transfusions (3.6 percent), urological infections (3.4 percent), or acute urinary retention after removal of the catheter (2.0 percent) [115]. The most common serious (class III or above) complications were infected lymphocele, hematoma or abscess requiring percutaneous drainage (3.3 percent), or persistent lymphocele requiring laparoscopic marsupialization (1.3 percent). Life-threatening complications were rare (0.9 percent). Compared with open radical prostatectomy, RARP was associated with less blood loss, shorter catheter time, and lower risk of Clavien-Dindo Grade II and III complications.

In a 2022 prospective multicenter comparison of open and robotic radical prostatectomy by the PROST-QA/RP2 consortium, RARP was associated with less mean intraoperative blood loss (192 versus 805 mL); a shorter mean hospital stay (1.6 versus 2.1 days); and fewer blood transfusions (1 versus 4 percent), wound infections (2 versus 4 percent), other infections (1 versus 4 percent), deep venous thromboses (0.5 versus 2 percent), and bladder neck contractures requiring dilation (1.6 versus 8.3 percent) compared with open radical prostatectomy [16].

Oncologic outcomes — Histopathologic examination of the resection specimen permits pathologic staging, which may differ significantly from the pretreatment clinical stage (table 2 and table 3). The more accurate assessment of the extent of disease provides a better correlation with prognosis in determining whether further therapy is indicated. (See "Prostate cancer: Postoperative management of pathologic stage T3 disease, positive surgical margins, and lymph node involvement following radical prostatectomy", section on 'Pathologic versus clinical staging'.)

The relationship between pathologic staging and prognosis is illustrated by a multicenter series of 23,910 men who were managed with radical prostatectomy at four centers between 1987 and 2005 [116]:

●Prostate-cancer-specific mortality at 15 years was a function of the pathologic stage of disease (0.8 to 1.5 percent, 2.9 to 10.0 percent, 15 to 27 percent, and 22 to 30 percent for pT2, pT3a, pT3b, and pN1 disease, respectively).

●The 15 year prostate-cancer-specific mortality rates also correlated with higher Gleason score (0.2 to 1.2 percent, 4.2 to 6.5 percent, 6.6 to 11 percent, and 26 to 37 percent at 15 years for Gleason scores ≤6 or less, 3+4, 4+3, and 8 to 10, respectively).

●The identification of higher pathologic stage (pT3 or pT4), microscopic lymph node involvement (pN1), or Gleason score 8 to 10 in the resection specimen did not preclude prolonged survival in a majority of cases. Depending upon age, the approximate overall survival rates at 15 years for men with Gleason score 8 to 10 disease were 50 to 60 percent; for those with seminal vesicle invasion, 50 to 70 percent; and for those with microscopic lymph node involvement, 60 to 65 percent.

However, these results cannot be generalized to men who present with clinical T3 or T4 disease or clinical evidence of lymph node involvement.

In a study of 428 patients followed for a median of 15.5 years (interquartile range 14.6 to 16.6 years) after radical prostatectomy, adverse pathology (positive margins, seminal vesicle invasion, extracapsular extension, or detectable prostate-specific antigen [PSA]) was highly associated with distant metastasis (hazard ratio [HR] 12.30, 95% CI 5.30-28.55) and prostate-cancer-specific mortality (HR 10.03, 95% CI 3.42-29.47) [117].

Multiple molecular prognostic tests are emerging, with the goal of improving risk stratification beyond that of pathologic staging. In a study of 428 patients followed for up to 20 years after radical prostatectomy, the Oncotype DX Genomic Prostate Score (GPS) result was highly associated with oncologic outcomes. Per 20 unit increase in GPS, multivariable analysis estimated hazard ratios of 2.24 (95% CI 1.49-3.53) and 2.30 (95% CI 1.45-4.36) for distant metastasis and prostate-cancer-specific mortality, respectively [118]. (See "Molecular prognostic tests for prostate cancer".)

Importantly, the occurrence of an isolated PSA recurrence following radical prostatectomy is not necessarily associated with the rapid development of more extensive disease. (See "Rising serum PSA following local therapy for prostate cancer: Definition, natural history, and risk stratification", section on 'Risk of metastases or death'.)

SPECIAL CONSIDERATIONS DURING THE COVID-19 PANDEMIC — The COVID-19 pandemic has increased the complexity of cancer care. Important issues include balancing the risk from delaying cancer treatment versus harm from COVID-19, minimizing the number of clinic and hospital visits to reduce exposure whenever possible, mitigating the negative impacts of social distancing on delivery of care, and appropriately and fairly allocating limited healthcare resources. Specific guidance for decision-making for cancer surgery on a disease-by-disease basis is available from the American College of Surgeons, from the Society for Surgical Oncology, and from others. These and other recommendations for cancer care during active phases of the COVID-19 pandemic are discussed separately. (See "COVID-19: Considerations in patients with cancer".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Diagnosis and management of prostate cancer".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Choosing treatment for low-risk localized prostate cancer (The Basics)")

●Beyond the Basics topics

SUMMARY AND RECOMMENDATIONS

●Patient selection – In patients with clinically localized prostate cancer, the preferred approaches for definitive therapy include radical prostatectomy and radiation therapy (RT); the choice is largely a matter of patient preference. Radical prostatectomy is generally not indicated for patients with distant metastases or when there is tumor fixation to adjacent structures. (See 'Patient selection' above.)

●Surgical treatment – Radical prostatectomy is the standard approach for most patients who choose surgery for the definitive management of their prostate cancer. We recommend robotic-assisted radical prostatectomy over an open procedure due to improved perioperative outcomes (Grade 1A). Indeed, in resource-rich countries, such as the United States, radical prostatectomy is most commonly performed robotically. (See 'Surgical treatment' above.)

•Nerve-sparing approach – For patients with no evidence of tumor involving the neurovascular bundle, we recommend that a nerve-sparing approach be incorporated into the radical prostatectomy (Grade 1B). This approach is associated with faster return of urinary continence and a lower frequency of impotence in men who were potent prior to surgery. (See 'Nerve-sparing approach' above.)

•Perineal prostatectomy – Perineal prostatectomy is an alternative to retropubic prostatectomy 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 abdominal surgery. Perineal prostatectomy should be limited to centers with expertise in this technique. (See 'Perineal radical prostatectomy' above.)

•Pelvic lymph node dissection – For patients choosing radical prostatectomy as their primary definitive therapy, we suggest performing an extended pelvic lymph node dissection when the risk of lymph node metastasis is estimated to be greater than 2 to 5 percent (Grade 2C). This risk is estimated using one of the nomograms selected by individual surgeons/centers. Extended dissection may be especially beneficial to those with very-high-risk disease. (See "Localized prostate cancer: Risk stratification and choice of initial treatment" and 'Pelvic lymph node dissection' above.)

●Follow-up treatment – After radical prostatectomy, patients with adverse laboratory or pathology features (eg, positive margins, seminal vesicle invasion, extracapsular extension, or detectable prostate-specific antigen [PSA]) should consider postoperative adjuvant or early salvage radiation therapy. (See 'Follow-up after surgery' above and 'Oncologic outcomes' above.)

●Functional outcomes – The most important frequent complications associated with radical prostatectomy include urinary incontinence and erectile dysfunction. (See 'Functional outcomes' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Eric A Klein, MD, who contributed to earlier versions of this topic review.