Radical Retropubic Prostatectomy for Prostate Cancer 

With the evolving techniques and improving knowledge of surgical anatomy, physicians can perform radical retropubic prostatectomy (RRP) with great efficacy and minimal morbidity. The authors believe that surgical treatment of prostate cancer is the best viable option for patients with clinically localized disease. However, its role may be expanded to locally advanced disease when used in combination with early adjuvant androgen ablative therapy in carefully selected patients who have low comorbidities and at least a 10-year life expectancy.

In 1947, Millin introduced the retropubic approach to prostatectomy. The operation had 2 distinct advantages over radical perineal prostatectomy (RPP):

• Urologists were more familiar with retropubic anatomy
• The retropubic approach permitted the performance of an extraperitoneal pelvic lymph node dissection (PLND) for staging purposes

Walsh deserves much credit for pioneering the technique of nerve-sparing RRP.^[1] Before anatomic characterization in the early 1980s and the description and anatomic characterization of the Santorini plexus, the operation was fraught with massive blood loss and morbidity.

Modifications in the technique of RRP and the introduction of the anatomic nerve-sparing method have dramatically decreased the frequency of the most worrisome associated morbidities—incontinence and impotence. As a consequence of these developments, most patients with prostate cancer have a high quality of life after undergoing radical prostatectomy.

RRP has been the criterion standard for the surgical approach, although RPP has been shown to be an equally efficacious surgical option.^[2] The explosion of minimally invasive surgery and the inherent morbidity associated with conventional open radical prostatectomy has led to the search for less invasive treatment options.

Pure laparoscopic radical prostatectomy has a steep learning curve and currently accounts for fewer than 1% of all prostatectomies in the United States. Laparoscopy was introduced to urology in the early 1990s, with the first series of laparoscopic retropubic prostatectomy reported by Schuessler et al in 1991.^[3] Most studies indicate longer operating times for laparoscopic retropubic prostatectomy than for RRP, but the former consistently seems to yield significantly decreased estimated blood loss and transfusion rates.

The authors have concluded that laparoscopic retropubic prostatectomy is well tolerated and provides short-term oncologic and functional results that are comparable with those of RRP.

The use of robotic technology offers many advantages over conventional laparoscopic retropubic prostatectomy, including 3-dimensional visualization, magnification, increased degrees of freedom, absence of the fulcrum effect, and robotic-wrist instrumentation. The hypothesis is that robotic-assisted laparoscopic prostatectomy (RALP) can successfully reduce the learning curve that even experienced surgeons face while performing laparoscopic retropubic prostatectomy.

The bar for functional recovery (potency and continence) after open RRP is set very high. However, the primary author's experience is that the robotic approach provides equivalent, if not superior, outcomes. This is in line with studies on potency after RALP.^{[4, 5]} At present, RALP is the primary author's preferred method of performing radical prostatectomy.

Prostate cancer overview

Adenocarcinoma of the prostate is the most commonly diagnosed cancer and the second leading cause of death in American males. A surge in the incidence of prostate cancer has most likely been due to the use of the serum prostate-specific antigen (PSA) test, which has also changed trends in clinical and pathologic aspects of prostate cancer.^[6]

PSA testing offers earlier detection, which means that patients with known prostate cancer are increasingly younger and have earlier-stage, clinically localized disease. As a result, more patients have potentially curable lesions and can benefit from radical prostatectomy.

The use of minimally invasive radical prostatectomy, particularly robotic prostatectomy, has surged. Minimally invasive approaches provide excellent visualization of the anatomy, cause less pain, permit earlier discharge, and have equivalent oncologic efficacy. Even so, a sound and fundamental knowledge of traditional open radical prostatectomy, with and without nerve sparing, remains a crucial component of the urologist's armamentarium.

Incidence

In the United States, prostate cancer, which is predominantly a disease of elderly men, is the second-most common malignancy in males after cutaneous malignancies and is the second-most common cause of cancer death in men.

Worldwide, the incidence of prostate cancer varies, but in general, it is higher in Western developed countries. For example, African American men (in whom the incidence of prostate cancer is highest) are 200 times as likely to develop prostate cancer as are Chinese men living in Asia (in whom the incidence of prostate cancer is among the lowest in the world). As worldwide life expectancy increases, the absolute number of prostate cancer cases is expected to grow.

Mortality

The American Cancer Society has estimated that in 2012, approximately 241,740 new cases of prostate cancer would be diagnosed, and approximately 28,170 prostate cancer deaths would occur.^[7]

Environmental risk factors

Migration studies have revealed increased prostate cancer rates among migrants who move from areas with low prevalence to areas of high prevalence. In one study, the incidence of prostate cancer in emigrants from Japan increased 4-9 times over the disease's incidence in Japan.^[8]

Such studies suggest that environmental factors (eg, diet) play an important role in prostate cancer. Researchers have found a positive correlation between higher consumption of fat, especially animal fat, and a higher prostate-cancer death rate. Higher fat consumption can increase the relative risk by a factor of 1.6-1.9.

Experts suggest certain dietary habits to lower the risk of prostate cancer. These include consumption of a low-fat, high-fiber diet, which lowers serum androgen levels. Researchers have investigated other dietary components, including selenium, lycopene, vitamin D, alpha-tocopherol, vitamin E, and large amounts of green tea, and have postulated that consumption of these substances may prevent prostate cancer.

Familial and genetic risk factors

Family history and genetics are important in the etiology of prostate cancer. Having a single first-degree relative with prostate cancer increases the risk of prostate cancer by a factor of 2.1-2.8. Having both a first-degree and a second-degree relative with prostate cancer increases the risk by a factor of 6.

Familial predisposition can be due to common environmental exposures; however, researchers have mapped a potential major prostate cancer susceptibility locus (1q24-25). This gene, called HPC1, is involved in 33% of hereditary prostate cancer cases.

Men with a family history of female breast cancer are also at an increased risk of prostate cancer. Specific mutations of the genes BRCA1 and BRCA2, both of which are involved in familial breast cancers, appear to confer an increased risk for prostate cancer.

Currently, nerve-sparing RRP remains a reasonable treatment option for men with clinically localized prostate cancer who have at least a 10-year life expectancy and low comorbidities. It is a well-tolerated procedure that is associated with low morbidity.

Although RRP is not limited to men younger than a certain age, the authors generally do not consider patients older than 73 years for prostatectomy. The authors believe that whereas all cases must be judged on an individual basis, it is difficult to justify a major operation in an elderly patient with prostate cancer who has alternatives to major surgery and in whom a 10-year overall survival is improbable.

Optimal management of higher-stage disease remains controversial, but radical prostatectomy is considered a viable treatment option in T3 disease for select patients. In patients with poorly differentiated disease, surgery may be supplemented with adjuvant hormonal therapy because monotherapy, in any form, is prone to failure.

Apparently, some cases of prostate cancer are clinically overstaged and can be cured with surgery alone. The remaining patients with locally advanced disease are identified and can be offered adjuvant therapy.

As noted, all patients selected for nerve-sparing RRP should have low comorbidities, at least a 10-year life expectancy, and clinically localized disease. Patients with locally advanced disease cannot undergo nerve-sparing RRP; because of the extent of the local tumor burden (especially posteriorly), the nerve-sparing procedure can compromise the adequacy of the operation.

Whether patients with preoperative erectile dysfunction can benefit from nerve-sparing procedures in the sildenafil era has not been extensively studied. Therefore, the authors still do not recommend the nerve-sparing approach in patients with preoperative erectile dysfunction.

Nerve-sparing RRP should not be performed to treat locally advanced prostate cancer. In that setting, the radical prostatectomy specimen should include both layers of Denonvilliers fascia, with wide excision of the lateral pelvic fascia and the neurovascular bundles en bloc with the prostate and ejaculatory organs.

Physicians must have a clear understanding of the anatomy pertinent to radical prostatectomy, including not only the gland itself but also the periprostatic anatomy. Such an understanding, coupled with achievement of vascular control and preservation of the neurovascular bundles, allows a safe and anatomic approach to the operation, with reduced morbidity.

The fascial investment of the bladder and the prostate, the endopelvic fascia (ie, pelvic fascia), sweeps down and off the pelvic sidewall, where it covers the levator ani.

The puboprostatic ligaments represent the anterior condensation of the fusion of the parietal and visceral pelvic fascia.

Incising the fascia at this point of fusion exposes the lateral surface of the prostate and the anterolateral rectal wall. At this point, the lateral periprostatic or lateral prostatic fascia becomes evident. This layer continues posteriorly to cover the neurovascular bundles and to become the lateral rectal fascia, and it continues distally over the membranous urethra to become the lateral periurethral fascia.

The lateral periprostatic fascia is continuous with the endopelvic fascia and is fused to the anterior and posterior Denonvilliers fascia. The rectal fascia (ie, posterior Denonvilliers fascia) covers the anterior surface of the rectum. The neurovascular bundles are invested in this posterior layer of Denonvilliers fascia laterally and are posterior and lateral to the prostate.

Anterior and posterior leaflets of the anterior Denonvilliers fascia envelop the seminal vesicles. Entering the posterior aspect of the anterior Denonvilliers fascia is essential for complete dissection of the seminal vesicles in RRP for localized prostate cancer.

The prostatic plexus of veins (ie, Santorini plexus) carries the venous return from the deep dorsal vein of the penis and the cavernosal veins. These venous effluents ultimately drain into the internal iliac veins.

The venous drainage may vary greatly and may be asymmetrical. Accordingly, great care must be taken in the dissection, especially at the prostatic apex, where blood loss could be massive. The superficial branch lies within the retropubic fat, between the puboprostatic ligaments.

The periphery of the glandular elements of the prostatic peripheral zone contains a fibromuscular rim referred to as the prostatic capsule. The base and the apex of the prostate have no well-defined capsule; the capsule is deficient as it merges with the smooth muscle of the bladder neck superiorly and with the striated muscle of the urethral sphincter inferiorly.

The striated urethral sphincter is directly beneath the dorsal venous complex. This sphincter is well-developed anterolaterally, creating a horseshoe-shaped appearance. Because the striated sphincter mechanism lies directly beneath the dorsal venous complex, care must be taken not to damage its fibers during vein control.

The cavernous nerves originate from the pelvic plexus on either side of the rectum. They travel posterolaterally to the prostate beneath the cover of the lateral periprostatic fascia. At the level of the membranous urethra, these nerves course anteriorly and lie directly lateral to the urethra. Branches of the nerves are located anteriorly close to the vessels of the penile hilum at the base of the membranous urethra, where the striated sphincter ends.

Experience with robotic and laparoscopic radical prostatectomy has led to identification and characterization of the vesicoprostatic muscle. This retrotrigonal layer, lying anterior to the ejaculatory organs, marks the posterior limit of dissection. It corresponds with the posterior longitudinal fascia of the detrusor and is divided after division of the bladder neck posteriorly, just before encountering the ampullae of the vas deferens. The description of this layer challenges the once-common belief that it is actually a layer of the anterior Denonvilliers fascia.

This section presents outcome analysis with respect to cancer control and survival data after radical prostatectomy and the role of radical prostatectomy in each clinical stage group.

The Partin tables are adjuncts for predicting prostate cancer spread and prognosis. The Kattan nomograms can be used to predict outcomes after different modalities for the treatment of prostate cancer.

Using readily available pocket software, the clinician can enter preoperative data and advise the patient concerning the likelihood of organ confinement and outcomes after radical prostatectomy. Chances for recurrence after radical prostatectomy can also be calculated by using the pathologic data. This guides the clinician in devising a treatment strategy.

Clinical stages T1a and T1b

Clinical stages T1a and T1b refer to prostate cancer incidentally detected during transurethral resection of the prostate (TURP). Stage T1a refers to low-grade or medium-grade cancer in fewer than 5% of the resected chips, and stage T1b refers to high-grade cancer or any grade cancer in fewer than 5% of the resected chips.

In a series from the Mayo Clinic, T1a and T1b tumors constituted 1.5% and 5.6% of all clinically organ-confined tumors, respectively.^[9] Eighty-eight percent of T1a tumors were pathologically organ-confined at the time of radical prostatectomy, as opposed to 68% of T1b tumors. Significant understaging was evident, especially in the T1b group.

Several series revealed that the likelihood of finding significant tumor on examination of the radical prostatectomy specimen for T1a disease ranges from 12% to 20%.

In one series, low-grade tumors (ie, Gleason score ≤3) were not associated with extracapsular extension, but 60% of those with a Gleason score of 7 or above had extracapsular extension. These clinical stages could represent clinically significant prostate cancers. A substantial portion of these patients could harbor cancer in the peripheral zone.

In one series, two thirds of patients had cancer distal to the verumontanum. Cause-specific survival differences in these 2 subcategories became more significant, especially after 10 years.

Currently, the authors recommend radical prostatectomy as a viable treatment option for young, healthy patients with a life expectancy of more than 10-15 years and T1a disease. Observation may be a viable option, along with careful follow-up, serial serum PSA testing, digital rectal examination (DRE), and ultrasonography with biopsy, when indicated. All cases of significant residual disease (ie, clinical stage T1b or high-grade T1a disease) warrant early treatment with radical prostatectomy.

Clinical stages T1c and T2

Since the advent of serum PSA testing, physicians have detected more prostate cancers at an earlier stage. In the authors' contemporary radical prostatectomy series, 45% of patients present with clinical stage T1c disease and 45% present with clinical stage T2 disease. On the basis of the relations among tumor volume, tumor grade, DNA ploidy, and likelihood of disease progression, previous studies have shown that 84-92% of c-T1c tumors are clinically significant and warrant definitive treatment.

In a Mayo Clinic study, the 7-year survival rates for clinical T1c, T2a, and T2b/c tumors free of systemic or local progression were 96%, 92%, and 89%, respectively, whereas the 7-year survival rates free of PSA progression for clinical T1c, T2a, and T2b/c tumors were 73%, 75%, and 66%, respectively.^[10]

The investigation compared PSA-detected, nonpalpable prostate cancers (c-T1c) and digitally palpable (c-T2) prostate cancers treated with radical prostatectomy in 4453 patients between 1987 and 1995.^[10] In all, 1041 patients had T1c disease, 1076 had T2a disease, and 2336 had T2b/c disease.

Overall, 76%, 71%, and 54% of patients with clinical stage T1c, T2a, and T2b/c lesions had organ-confined disease (less than p-T2c) at the time of prostatectomy, respectively.^[10] The pathologic stage, Gleason score, and DNA ploidy pattern were comparable in clinical T1c and T2a disease. Progression-free survival (systemic or local and PSA level progression [>0.2 ng/mL]) was also comparable in these 2 groups but was significantly worse in the c-T2b/c group (see the images below).

Certain clinical and pathologic factors of c-T1c tumors closely resemble those of c-T2b/c tumors, especially with regard to preoperative PSA level and margin positivity. The short-term 7-year cause-specific survival rates of 99.9%, 98.6%, and 97.6% in clinical T1c, T2a, and T2b/c prostate cancers, respectively, in the PSA era are a testament to the effectiveness of radical prostatectomy in this group of patients, who makes up 93% of the surgically treated patients at the Mayo Clinic.

Clinical stage T3

The role of radical prostatectomy in patients with locally advanced disease is controversial. Much of the controversy is based on earlier series, which reported poor 10-year survivals in patients undergoing RPP.^{[11, 12]} (It should be kept in mind that patients in the earlier series were incompletely staged.) Because of the high incidence of lymph node metastasis and the potential for incomplete excision, surgeons use monotherapy with androgen deprivation or radiotherapy.

Monotherapy with androgen deprivation therapy is associated with a 34% progression to metastatic disease and a 22% mortality within 2 years of therapy and therefore should be reserved for elderly patients or patients with significant comorbid disease.

Radiotherapy alone also yields a poor outcome, especially with regard to local control. Studies show that failure to control the primary tumor results in an increased risk of metastatic disease dissemination. Postirradiation biopsy results after definitive external beam radiation therapy (EBRT) have been positive in 55-93% of patients. The 5- and 10-year survival rates after EBRT are 60-72% and 41-47%, respectively.

The authors' approach to radical prostatectomy in locally advanced prostate cancer is based on the following principles:

• Wide excision of the neurovascular bundles
• En bloc removal of both layers of Denonvilliers fascia, the ampullae of the vas deferens, and the seminal vesicles
• Precise apical dissection with frozen-section analysis of the apical margins
• Wide excision of the circular smooth muscle fibers of the bladder neck, again based on intraoperative frozen-section analysis

Nerve-sparing radical prostatectomy has no role in clinical stage T3 disease. In the event of a cancerous margin, wider excision can be performed.

In reviewing the Mayo Clinic experience with radical prostatectomy for T3 disease, a prominent feature was inaccurate clinical staging. In 25% of the cases in the authors' reported series, prostate cancers were organ-confined pathologically (ie,

Operative and perioperative morbidities were comparable with those of clinically localized prostate cancers. Crude survival rates at 5, 10, and 15 years were 89%, 70%, and 50%, respectively, and the cause-specific survival rates at 5, 10, and 15 years were 93%, 84%, and 74%, respectively. At 10- and 15-year follow-up, 82% and 78% of patients, respectively, were free of local recurrence.

Review of the authors' contemporary radical prostatectomy series in 1107 patients treated for pathologic stage T3a/b disease revealed 9-year progression-free survival rates of 93% with early adjuvant hormonal therapy (ie, within 3 months of radical prostatectomy), 89% with adjuvant radiation therapy, and 85% with no adjuvant therapy. Early adjuvant hormonal therapy was shown to have a more striking advantage when local or systemic progression-free and PSA progression-free survival rates were considered.

The authors' experience with c-T3 disease reveals that excellent long-term survival rates with low treatment-related morbidity can be achieved with radical prostatectomy and adjuvant therapy for pathologically confirmed locally advanced disease; such results are not achieved by other treatment modalities. Neoadjuvant androgen deprivation does not alter the long-term recurrence rate in men with clinical stage T3 prostate cancer.