Radical Retropubic Prostatectomy for Prostate Cancer 

Updated: Feb 21, 2018
Author: David F Jarrard, MD; Chief Editor: Edward David Kim, MD, FACS 

Overview

Background

With the evolving techniques and improving knowledge of surgical anatomy, physicians can perform radical retropubic prostatectomy (RRP) with great efficacy and minimal morbidity. The procedure has evolved over the last several decades to remain an important approach for the treatment of prostate cancer.

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[2]  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 standard for the surgical approach.  However, the explosion of minimally invasive surgery has led to the search for less invasive treatment options and laparoscopic and robotic appear to provide equally efficacious surgical options in selected patients.[2]

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 and a longer learning curve, but the former consistently seems to yield significantly decreased estimated blood loss and transfusion rates. Laparoscopic retropubic prostatectomy is well tolerated and provides short-term oncologic and functional results that are comparable with those of RRP in the hands of experienced surgeons. 

Robotic technology began to be utilized more broadly after 2005 and the usage of a robot for RP increased from 4.5% in 2003 to 85.2% in 2009.[4] It 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. Robotic-assisted laparoscopic prostatectomy (RALP) can potentially reduce the learning curve that even experienced surgeons face while performing laparoscopic retropubic prostatectomy. However, there are still situations where open RRP may provide benefit including in patients with previous abdominal or pelvic surgery, and more extensive cancers where tactile information is an advantage. 

Functional recovery (potency and continence) after open RRP is high for experienced surgeons. However, the robotic approach provides equivalent outcomes in experienced hands.[5, 6] Oncologic outcomes appear similar in the shorter term for the majority of low and intermediate grade cancers when compared to open RRP.[7]

Minimally invasive approaches provide excellent visualization of the anatomy, cause less pain, permit earlier discharge, and have equivalent oncologic efficacy. Nevertheless, a sound and fundamental knowledge of traditional open radical prostatectomy, with and without nerve sparing, remains a crucial component of the urologist's armamentarium.  When choosing an approach, a major feature is the urologist’s experience and comfort with the robotic or open approach.

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 was noted in the 1980’s due to the wider use of the serum prostate-specific antigen (PSA) test, which has also changed trends in clinical and pathologic aspects of prostate cancer.[8]

Since the advent of serum PSA testing, physicians have detected more prostate cancers at an earlier stage. From 1998 – 2011, there was a twofold increased incidence of low risk prostate cancer from 14 – 28% and more than twofold decrease in the incidence of metastatic prostate cancer form 25% - 11%. During the same time period, the percentage of T1c disease increased from 36 – 71%, PSA levels between 4 and 6 ng/ml increased from 24% to 38%; T2 tumors decreased from 39% to 20% and PSA between 8 and 10 ng/ml decreased from 24% to 15%.[9]

In 2008, the United States Preventive Services Task Force (USPSTF) recommended against PSA-based screening in men aged ≥ 75 years. This recommendation was expanded to include all men in 2012. In 2013, the American Urological Association also issued a guideline statement for not screening men over the age of 70 years. These recommendations had widespread ramifications on age stratified outcomes.  The exclusion of PSA screening saw a further increase in aggressive disease and higher mortality rates in men over the age of 70.[10] Since 2012, consequent to USPSTF recommendations, there was a decrease in PSA screening and a decrease in the incidence of early stage prostate cancer in men of all ages. However, there was a stage and grade migration, with more men presenting with advanced disease at presentation.[11] Subsequently the USPSTSF revised its recommendation to screen men between ages 55 to 69 years in 2017 based on physician’s discussion about potential benefits and harms of prostate-specific antigen (PSA)–based screening for prostate cancer.[12]

The incidence of small, lower risk well-differentiated prostate cancer increased in the early PSA era and almost half of the patients with this diagnosis are candidates for active surveillance (AS) in an attempt to avoid overtreatment and morbidity associated with surgery or radiation.[13] The selection of men for AS has been traditionally guided by clinicopathological features that indicate the patient presents with an organ confined, well-differentiated tumor. Using strict selection criteria, patients with a life expectancy > 10 years, T1c, PSA ≤ 10, Gleason ≤ 6, ≤ 2 positive biopsy cores, ≤ 50% cancer in any core, and PSAD < 0.15 would be eligible for AS. Recent studies have shown that including intermediate risk disease for AS (4 or fewer cores with GS 6 cancer and/or only 1 core of Gleason 3+4 cancer <15%) did not adversely affect outcomes.[14] Discussion of risks and benefits of AS with patients and shared decision making is the key to successful surveillance.

15-year mortality of prostate cancer specific mortality rate based on a contemporary multiinstitutional data for pathological Gleason score 6 or less, 3+4, 4+3 and 8-10 was 0.2% to 1.2%, 4.2% to 6.5%, 6.6% to 11% and 26% to 37%.[15] The 15-year prostate cancer specific mortality risk was 0.8% to 1.5%, 2.9% to 10%, 15% to 27% and 22% to 30% for organ confined cancer, extraprostatic extension, seminal vesicle invasion and lymph node metastasis, respectively. 

Incidence

In the United States, prostate cancer, which is predominantly a disease of elderly men, is the second-most common malignancy in males. 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 2017, approximately 161,360 new cases of prostate cancer would be diagnosed, and approximately 26,730 prostate cancer deaths would occur generating a 1:6 ratio.[15]

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.[16]

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 increasing 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. However, a recently concluded metaanalysis of 12 international prospective cohort studies concluded that there were no statistically significant associations for advanced prostate cancer or prostate cancer mortality with any food group (including total fruits and vegetables, total fruits, total vegetables, fruit and vegetable juice, cruciferous vegetables, and tomato products), nor specific fruit and vegetables. Pooled multivariable relative risks comparing the highest versus lowest quantiles across all fruit and vegetable exposures and prostate cancer outcomes ranged from 0.89 to 1.09.[17]   However, this does not discount the impact that diet may have in subsets of susceptible patients and research on the association of genetics, ethnicity and diet will likely generate impactful findings in the future.

Familial and genetic risk factors

Family history and genetics can play a role 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.[18]

Researchers have mapped prostate cancer susceptibility loci including HPC1 (1q24-25), involved in 33% of hereditary prostate cancer cases.[19] Indeed, testing is now available using a number of these susceptibility loci that can help predict an individual’s risk for prostate cancer development.[20] However, the interplay of environment and these loci are complex making use of this test for one individual less reliable.

An estimated 10% of prostate cancer is due to mutations in BRCA1, BRCA2, HOXB13 and Lynch syndrome.[21] BRCA1 and 2 are associated with risk of breast, ovarian, pancreatic, prostate cancers and melanoma. Families with BRCA2 mutations appear to harbor aggressive variants of prostate cancer. Mutations of HOXB13 are associated with 2-8 fold increased risk of hereditary prostate cancer (HPC) among first degree relatives and early onset caner before 55 years of age. Patients with Lynch syndrome have a threefold elevated risk of prostate cancer, apart from colorectal, ovarian, upper tract urothelial and gastric cancers.[22]

At present, genetic testing can be performed for BRCA1 and BRCA2 mutations according to NCCN guidelines which include a personal history of Gleason ≥ 7 prostate cancer at any age with a first degree relative with early onset breast cancer (

Indications

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, patients older than 70 years should be carefully selected for prostatectomy. All cases must be judged on an individual basis, and 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.

Life expectancy calculators give an accurate prediction of mortality rates. Age, Charlson Comorbidity Index (CCI) and the type of treatment were used for predicting 10-year life expectancy after treatment for localized prostate cancer.[23] The model was 84% accurate in 10-year mortality prediction. The Memorial Sloan Kettering Cancer Center (MSKCC) model for predicting 10-year survival probability before treatment of localized prostate cancer is an online tool that is widely used by clinicians. https://www.mskcc.org/nomograms/prostate/pre-op/coefficients

In a large SEER based retrospective study done in 23,338 men with localized prostate cancer, the 10-year cancer specific mortality was only 2.8%, compared to 21% mortality due to other causes.[24] Coronary artery disease, stroke and other cancers were the leading cause of death in this age group.

Optimal management of higher-stage disease remains controversial, but RP is considered a viable treatment option in T3 disease for select patients. Patients with high risk of Extracapsular extension (ECE) and neurovascular bundle invasion are increasingly staged with multiparametric MRI before definitive therapy. A multiparametric MRI consists of a combination of T2 weighted imaging, diffusion weighted imaging and Dynamic Contrast Enhanced imaging and /or MR spectroscopy for functional details. A 3T MR imaging scanner is preferred and if using a 1.5 T MR imaging scanner, combining endorectal coil with an external phased array coil is preferred.[25] Cancer with invasion of the bladder, sphincter or rectum are better served by radiation therapy if clinically localized.

RP is being increasingly employed in patients with clinical T3 disease. The rates of RP vs radiation was 49.8% vs. 37.1% in one retrospective study from 2012.[26] Many studies comparing surgery versus radiation therapy for locally advanced disease have shown a trend towards better oncological outcomes with surgery.[27, 28] However, healthier earlier stage patients are often selected for surgery which may confound these results. An ongoing prospective randomized controlled trial NCT02102477 is expected to clarify the superiority of one modality over the other.

Contraindications

As noted, all patients selected for nerve-sparing RRP should have few to no comorbidities, at least a 10-year life expectancy, and clinically localized disease. Patients with locally advanced disease, detected by MRI or physical exam, may undergo non 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.  In this setting, the radical prostatectomy specimen should include both layers of Denonvilliers fascia, with wide excision of the lateral pelvic fascia and the neurovascular bundle on that side en bloc with the prostate and ejaculatory organs. In patients with obvious extension outside the prostate into the bladder or other structures radiation may be a preferred approach.

Technical Considerations

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 dissection of the seminal vesicles in RRP for localized prostate cancer.

The prostatic plexus of veins (i.e., 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. In general, the system trifurcates shortly after exiting under the pubic bone.  Accordingly, great care must be taken in the dissection, especially at the prostatic apex, where blood loss can be significant. The superficial branch lies within the retropubic fat, between the puboprostatic ligaments.

Visualization of the prostate and its fascia is critical and complete removal of investing fat is critical for the operation.  Using gentle bilateral digital or blunt dissection using scissors through the lateral aspects of periprostatic fascia develops a plane just above the urethra and leads to isolation of Santorini plexus which is then easily ligated and divided.[29]

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 and courses anterolaterally, creating a horseshoe-shaped appearance. Because the striated sphincter lies beneath the dorsal venous complex clear visualization is important to avoid injury.

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. 

Outcomes

Numerous papers have demonstrated the excellent long-term cancer control and survival data after this operation, however numerous factor impact these outcomes.  A significant portion of the outcome is driven by the Gleason Score of the cancer.  For organ confined prostate cancer, high grade tumor volume (as predicted by the percentage of cancer in biopsy), Gleason sum, PSA levels, margin positive status and bilateral disease were all significant predictors of outcome after RP.[30]

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 fewer than 5% and T1b refers to greater than 5% cancer in resected chips during TURP.  In a series from the Mayo Clinic, T1a and T1b tumors constituted 1.5% and 5.6% of all clinically organ-confined tumors, respectively.[31] Eighty-eight percent of T1a tumors were pathologically organ-confined at the time of radical prostatectomy, as opposed to 68% of T1b tumors.

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%. A substantial portion of these patients harbor cancer in the peripheral zone that can be detected by subsequent peripheral zone biopsy or MRI.

Radical prostatectomy is 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), peripheral zone biopsy, imaging with MRI and peripheral zone biopsy, when indicated. Significant residual disease (i.e., clinical stage T1b or high-grade T1a disease) may warrant early treatment with radical prostatectomy.

Clinical stages T1c and T2

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.[32] 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.

Clinical stage T3

The role of radical prostatectomy in patients with locally advanced disease is controversial. Much of the debate is based on earlier series, which reported poor 10-year survivals in patients undergoing RPP.[33, 34] Because of the high incidence of lymph node metastasis and the potential for incomplete excision, many surgeons use combination of surgery with radiotherapy with or without androgen deprivation therapy. Recent retrospective studies have suggested that a multimodality approach is associated with a better cancer specific and overall survival.[35]

Radical prostatectomy in locally advanced prostate cancer is based on the following principles:

  • Careful imaging with CT scan and bone scan to evaluate for metastatic disease.
  • mpMRI to assess local tumor extent and whether surgery is feasible in higher volume or higher risk disease
  • Wide excision of the neurovascular bundles if peripheral invasion of the nerves is suggested or large tumor bulk is seen in that area.
  • En bloc removal of both layers of Denonvilliers fascia, the ampullae of the vas deferens, and the seminal vesicles
  • Precise apical dissection

 

In reviewing radical prostatectomy for T3 disease, a prominent feature was inaccurate clinical staging.

Neoadjuvant androgen deprivation does not alter the long-term recurrence rate in men with clinical stage T3 prostate cancer.

 

Periprocedural Care

Patient Education and Consent

Informed consent must be obtained. Discuss the risks of the procedure, including erectile dysfunction, incontinence, risk of transfusion, infection, and other acute surgical morbidities, with the patient before the operation.

For patient education information, see the Prostate Health Center and Prostate Cancer.

 

 

Preprocedural Evaluation

Because radical prostatectomy is most effective when the cancer is organ- or specimen-confined, accurate preoperative characterization of the cancer is essential for a tailored, safe, and effective operation. Physicians can estimate successful outcomes of radical prostatectomy by using well-established nomograms that provide important prognostic information before therapy.[23, 36, 37, 38, 39]

Predictive nomograms

A model combining the preoperative prostate-specific antigen (PSA) level, the Gleason score, and the clinical stage has enhanced clinicians’ ability to predict the pathologic stage. This predictive model, initially proposed by Partin et al in 1997, made use of a multinomial log-linear analysis in three major institutions, including the John Hopkins Hospital, Baylor College of Medicine, and the University of Michigan.[40]

The sensitivity and specificity of the Partin tables were found to be similar when the validity of the Partin nomograms was tested at the Mayo Clinic. The test involved a large cohort of patients (2475 patients) treated with radical prostatectomy.[41]

The Cancer of the Prostate Risk assessment (CAPRA) score is based on age, serum PSA, Gleason score, Clinical stage and percentage of cancer in biopsy cores. It can predict an individual's likelihood of metastasis, cancer-specific mortality, and overall mortality.[42] The MSKCC risk calculator https://www.mskcc.org/nomograms/prostate/post-op/coefficients

can predict two, five, seven and ten year cancer recurrence free survival after radical prostatectomy and is the most widely used nomogram by clinicians for predicting recurrence after surgery. 

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 and patient in devising a treatment strategy.

Laboratory studies

Routine preoperative laboratory studies are performed, including a complete blood count (CBC), blood chemistry (ie, CHEM 7), and urinalysis.

The patient’s blood also is typed and screened. Autologous blood transfusion is not necessary with improved surgical techniques

Imaging studies

Electrocardiography and chest radiography are performed.

AUA guidelines recommend a bone scan if PSA levels are more than 20ng/dl. Bone scan may be considered in patients with PSA levels of Cross sectional imaging in the form of CT/MRI is indicated in patients with PSA levels of >20 ng/mL, Gleason score ≥8, or clinically advanced disease, as few patients without these parameters harbor metastatic lymphadenopathy. Patients with a risk of lymph node metastasis of >20% according to Partins’s tables should also be offered imaging.The Prostate Cancer Radiographic Assessments for Detection of Advanced Recurrence (RADAR) group recommends a bone scan and cross sectional imaging in newly diagnosed intermediate and high risk patients with any 2 of the 3 criteria are met, namely PSA >10 ng/ml, Gleason score greater/equal to 7 and palpable disease (³ T2a).[43] The NCCN guidelines recommend pelvic CT or MRI should be used in patients with T3–T4 disease or those with T1–T2 disease, if nomogram-predicted probability of lymph node involvement is >10%. European Urology guidelines mention the low sensitivity of cross sectional imaging for detecting lymph (<40%) and recommend for patients in whom curative treatment is planned and who have PSA levels of >10 ng/mL, Gleason score ≥8, or clinical stage ≥T3. Whether positron emission tomography (PET) is useful in prostate cancer is debatable. Prostate cancer is not an active metabolic malignancy, and uptake of 18-fluorodeoxyglucose (FDG) may be suboptimal. At present, the data do not support an additional role for PET scanning in the staging and evaluation of de novo or recurrent prostate cancer.Monoclonal antibody technology has been applied to the staging of prostate cancer. Indium (In)-111 labeled capromab pendetide (ProstaScint; EUSA Pharma [USA], Langhorne, PA) recognizes an epitope of the prostate-specific membrane antigen (PSMA) and can be useful for evaluation of nodal and distant metastases in prostate cancer. However the overall sensitivity is poor at 50-60%.[44] ProstaScint scanning can be used to detect recurrence in previously treated patients or to stage patients with poor prognostic parameters (high Gleason grade and PSA level with negative results on bone scan and CT scanning) prior to definitive local therapy. One area of clinical utility may be the detection of lymph node metastases before radical prostatectomy; studies in this area have reported a sensitivity of about 60% and a specificity of about 70% with positive and negative predictive values approximately 60% and 70%, respectively.[44] These values, although superior to those of CT for evaluation of lymph nodes, are not accurate enough to justify routine use of this modality.  Improved monoclonal imaging with alternate more sensitive tracers is currently in development.

Monitoring and Follow-up

In treating prostate cancer, physicians have the luxury of a very accurate marker for disease recurrence: the serum PSA level. Serum PSA is measured every 3 months for the first 2 years. If it is undetectable (or <0.2), the interval is increased to every 6 months until 5 years after the operation, at which point the serum PSA level can be measured yearly.

If serum PSA is detectable after radical prostatectomy, it is important to determine the timing of the PSA level rise. Abnormal PSA levels must be confirmed with a repeat measurement. A confirmed rise in the PSA level less than 1 year after prostatectomy is more indicative of occult distant metastases at the time of the operation.

A confirmed rise in the PSA level that occurs later, however, is more compatible with local recurrence. Imaging studies, such as bone scanning, can be repeated. In patients with a late PSA level rise in whom bone scan results are negative, a ProstaScint scan can be considered or performed to rule out distant metastases before local salvage therapy (radiotherapy) is contemplated.

In a study by Patel et al, 80% of patients with a PSA-level doubling time of 6 months or longer remained clinically disease-free, compared with 64% of patients with a PSA-level doubling time shorter than 6 months.[45] Regardless of the time of PSA level recurrence, a short PSA-level doubling time (high log slope) was strongly associated with clinical recurrence.

In a study by Pound et al, the PSA-level doubling time, along with the Gleason score, was also predictive of probability and time to development of metastatic disease.[46]

 

Technique

Retropubic Approach to Radical Prostatectomy

Before beginning a radical retropubic prostatectomy (RRP), antibiotics are given and measures are taken to avoid lower extremity deep venous clots. These include the application of a sequential compression device to the patient’s lower extremities and use of heparin 5000U subcutaneously.

Make a lower midline incision (see the first video below). Perform an extraperitoneal bilateral pelvic lymph node dissection if necessary (PLND; see the second video below).

Radical retropubic prostatectomy. Preparation, positioning, and incision. Video courtesy of Dennis G Lusaya, MD, and Edgar V Lerma, MD.
Radical retropubic prostatectomy. Bilateral pelvic lymph node dissection. Video courtesy of Dennis G Lusaya, MD, and Edgar V Lerma, MD.

Remove the retropubic fat, and isolate and cauterize the superficial branch of the dorsal venous complex. Bluntly incise the endopelvic fascia bilaterally (see the first video and the image below). Sweep all residual muscle fibers (ie, levator ani, pubococcygeus, and puborectalis) off the lateral aspect of the prostate laterally to expose the prostatic fascia and the dorsal venous complex. The puboprostatic ligaments will have to be divided (see the second video below).

Radical retropubic prostatectomy. Incision in endopelvic fascia. Video courtesy of Dennis G Lusaya, MD, and Edgar V Lerma, MD.
Fascial anatomy after division of endopelvic fasci Fascial anatomy after division of endopelvic fascia (EPF). Reprinted with permission from Ghavamian R, Zincke H. An updated simplified approach to nerve-sparing radical retropubic prostatectomy. BJU Int. Jul 1999;84(1):160-3. DDV = deep dorsal vein complex; PPL = puboprostatic ligaments; SDV = superficial dorsal vein.
Radical retropubic prostatectomy. Division of puboprostatic ligaments. Video courtesy of Dennis G Lusaya, MD, and Edgar V Lerma, MD.

Using a suture carrier, pass a 0 polyglactin suture just underneath the dorsal venous complex and anterior to the urethra in a figure-8 fashion and tie. Control backbleeding by placing 2 figure-8 sutures of 0 polyglactin (ie, bunching sutures) on the proximal aspect of the dorsal vein complex one at the bladder neck and another midway between the apex and bladder neck.

Radical retropubic prostatectomy. Bunching suture placement on edge of endopelvic fascia. Video courtesy of Dennis G Lusaya, MD, and Edgar V Lerma, MD.
Radical retropubic prostatectomy. Control of dorsal vein complex. Video courtesy of Dennis G Lusaya, MD, and Edgar V Lerma, MD.

Divide the dorsal venous complex sharply leaving a defect in the prostatic fascia (see below). Make an inverted-V incision in the exposed prostatic fascial edge, carrying the line of the incision distally and proximally (see the image below) using a right angle.  The complex may be further oversewn with a 3.0 Monocryl if needed.

Radical retropubic prostatectomy. Transection of dorsal vein complex. Video courtesy of Dennis G Lusaya, MD, and Edgar V Lerma, MD.
Incision in prostatic fascia (PF) from defect in P Incision in prostatic fascia (PF) from defect in PF after division of dorsal venous complex. Note neurovascular bundle (NVB) deep to PF. Reprinted with permission from Ghavamian R, Zincke H. An updated simplified approach to nerve-sparing radical retropubic prostatectomy. BJU Int. Jul 1999;84(1):160-3. DDV = deep dorsal vein; EF = endopelvic fascia; SDV = superficial dorsal vein.

Using a spreading maneuver with Satinsky scissors, carry the incision parallel to the neurovascular bundle toward the urethra and the bladder (see the image below). In this fashion, the lateral prostatic fascia containing the neurovascular bundles is mobilized posteriorly and out of harm’s way.

Incision in prostatic fascia (PF) is carried paral Incision in prostatic fascia (PF) is carried parallel to neurovascular bundle (NVB) toward bladder and membranous urethra (MU). Reprinted with permission from Ghavamian R, Zincke H. An updated simplified approach to nerve-sparing radical retropubic prostatectomy. BJU Int. Jul 1999;84(1):160-3.

Spread the clamp and sweep the right neurovascular bundle off the prostate cranially and posteriorly. Divide the membranous urethra at the apex of the prostate with the electrocautery (see the video below). Hold the electrocautery probe at a 45° angle toward the apex (see the image below). In this fashion, the residual delicate fibers of the external urethral rhabdosphincter complex, which cover the anterior aspect of the prostatic apex in a fan-shaped manner, are divided and preserved on the eventual urethral stump. In the manner of Walsh, 6 evenly placed absorbable sutures (eg, 2-0 poliglecaprone) are placed, 3 anterior and 3 posterior. These are tagged and covered with a towel. The posterior urethra is then incised as is Denonvilliers fascia and a finger gently inserted under the prostate to develop this plane.

The prostate is gently retracted with a sponge stick and mobilization of the prostate cephalad begins first on one side.  Ligate the lateral vascular pedicles close to the prostate with small hemostatic clips. Sweep the right neurovascular bundle off the prostate working cranially clipping and sharply dividing small perforators.  Divide the anterior layer of Denonvilliers fascia, and identify the ampullae of the vas deferens (Figure below).

 

Radical retropubic prostatectomy. Division of urethra. Video courtesy of Dennis G Lusaya, MD, and Edgar V Lerma, MD.
Division of membranous urethra (MU) just distal to Division of membranous urethra (MU) just distal to prostatic apex. Note angle of division (inset), allowing preservation of outermost fibers of external rhabdosphincter. Reprinted with permission from Ghavamian R, Zincke H. An updated simplified approach to nerve-sparing radical retropubic prostatectomy. BJU Int. Jul 1999;84(1):160-3.

Dissect the ampullae of the vas deferens off the medial aspect of the seminal vesicles, and divide them after mobilizing them distally. Using sharp dissection, mobilize the seminal vesicles to their tips. Careful dissection at this juncture prevents injury to the neurovascular bundles and the pelvic plexus, which lie close to the lateral aspect of the seminal vesicles.

Retract the seminal vesicles and the ampullae of the vas deferens cephalad and dissect them free of the bladder base and the posterior aspect of the bladder with the electrocautery. 

Cephalad retraction of prostate (P) and seminal ve Cephalad retraction of prostate (P) and seminal vesicles (SV) and ampullae of vas deferens. Reprinted with permission from Ghavamian R, Zincke H. An updated simplified approach to nerve-sparing radical retropubic prostatectomy. BJU Int. Jul 1999;84(1):160-3. B = bladder; MU = mucosal urethra; NVB = neurovascular bundle.

Taking care to preserve the circular fibers of the bladder neck, remove the surgical specimen en bloc.

With careful bladder neck preservation, extensive bladder neck reconstruction is not necessary. A 3-0 poliglecaprone suture is used to reconstruct the bladder neck and evert the mucosa.  Start the suture on the right side at the 7-o’clock position and run it, everting the bladder mucosa onto the parietal bladder fascia. 

Bladder neck reconstruction. (A) 3-0 poliglecapron Bladder neck reconstruction. (A) 3-0 poliglecaprone suture is placed, starting at 7-o'clock position. (B) Approximation and eversion of bladder mucosa to overlying bladder fascia anteriorly. Reprinted with permission from Ghavamian R, Zincke H. An updated simplified approach to nerve-sparing radical retropubic prostatectomy. BJU Int. Jul 1999;84(1):160-3.

Lock the suture at the 5-o’clock position, and incorporate the visceral bladder fascia in the suture between the 5- and 7-o’clock positions (see the image below). Perform a direct vesicourethral anastomosis using 6 evenly placed absorbable sutures (eg, 2-0 poliglecaprone) and a urethral sound (see the videos below). Alternatively, interrupted sutures placed at 12, 3, 6 and 9 o clock can also be used to advance bladder mucosa over the raw bladder neck muscle to ensure a mucosa to mucosa anastomosis. The urethral sutures are then placed through the bladder neck.  The anterior anastomotic sutures are tied first. There should be no tension. If there is, the bladder should be released from the peritoneum. The 12-, 10-, 2-, 4-, 8-, and 6-o’clock sutures are tied sequentially. A 20F Foley catheter is placed and inflated to 15cc. After the operative site is irrigated vigorously with saline, a small suction drain is placed next to the anastomosis. The fascia is closed with No. 2 Prolene and skin with metallic clips.

 

(A) Suture is locked at 5-o'clock position, incorp (A) Suture is locked at 5-o'clock position, incorporating visceral bladder fascia. (B) Completed bladder neck reconstruction is pictured. Reprinted with permission from Ghavamian R, Zincke H. An updated simplified approach to nerve-sparing radical retropubic prostatectomy. BJU Int. Jul 1999;84(1):160-3.
Radical retropubic prostatectomy. Placement of anterior anastomotic sutures. Video courtesy of Dennis G Lusaya, MD, and Edgar V Lerma, MD.
Radical retropubic prostatectomy. Placement of posterior anastomotic sutures. Video courtesy of Dennis G Lusaya, MD, and Edgar V Lerma, MD.

Intraoperative frozen-section analysis of the surgical margins is used in some situations. In the event of a positive margin, prostatic induration, or suspected locally advanced prostate cancer, the ipsilateral neurovascular bundle can be excised.

Postoperative Care

Ambulation is encouraged on the evening of procedure. Sips and a clear liquid diet is started on the same day evening and low fat diet is started on the next day. Narcotics are administered using a patient controlled pump overnight and in patients with normal renal function and low intraoperative blood loss, parenteral NSAIDs can be substituted for narcotics.

Postoperatively, drains are removed when output from suction drain falls below 50ml. In some patients, drain input increases initially. The drain is left in to prevent lymphocele formation. If drainage is significant, consider the possibility of urine leakage; if the increased drainage continues, suction drains are taken off bulb suction. This allows the anastomotic leak to seal in most cases. If this measure does not suffice (an extremely rare scenario), a Foley catheter can be hooked up to low wall suction through a drainage system to allow a seal at the anastomotic site.

The drainage fluid can be sent for creatinine measurement. A drainage-fluid creatinine level that approximates the serum creatinine level indicates lymphatic drainage rather than urine. Cystography is sometimes helpful for assessing the extent of the extravasation.

Other potential mechanical problems can occur. Clot retention can be managed with gentle bladder irrigation.

Management of a dislodged catheter depends on the timing of the event. At postoperative day 3, with a good anastomosis, a single attempt at reinsertion with a well-lubricated coudé-tip catheter is reasonable. However, if the attempt is possibly or certainly unsuccessful, flexible cystoscopy at the bedside with passage of a Councill-tip catheter over a wire under direct vision is the safest approach.

With a good anastomosis, if the catheter is dislodged after 1 week, the patient should be allowed to void; if he does so with no problems, a new catheter need not be inserted.  Urinary catheter removal should be done between 7 -14 days after surgery. 

Adjuvant Treatment

Hormonal therapy

The effect of neoadjuvant ADT on survival outcomes has been controversial. Several randomized trials failed to show a survival benefit with neoadjuvant hormonal therapy for localized prostate cancer. A prospective randomized trial showed no difference in biochemical recurrence rate in cT2B patients who received neoadjuvant hormonal therapy at 5 years of follow up.[47] Another phase III study analyzed effects of 3 months vs 8 months of neoadjuvant ADT. Positive margin rates were significantly lower in the 8 than in the 3-month group (12% versus 23%, respectively), but there was higher incidence of adverse events in the 8-month group.[48] A phase II SWOG trial included 62 patients with locally advanced disease (97% with T3, 3% with T4 and 39% with bulky nodal disease, a majority of whom would have been otherwise candidates for radiation. After a course of neoadjuvant hormonal therapy 55 (90%) of patients underwent surgery and had a 5 – year progression-free and overall survival of 70% and 90%.[49]

A recently concluded retrospective multiinstitutional study compared propensity matched high risk prostate cancer patients defined as clinical stage T3-4, PSA >20 ng / ml or biopsy Gleason score 8-10 treated with surgery alone or neoadjuvant ADT + surgery. Neoadjuvant ADT reduced the risk of prostate cancer related death (HR 0.5; 95% confidence interval (CI) 0.32-0.80; P=0.0014).[50] Further prospective studies with well-defined high risk population are needed to define the role of neoadjuvant hormonal therapy in localized PCa. 

Radiation therapy

The risk of local failure and biochemical progression depends on Gleason score, initial prostate-specific antigen (PSA) level, positive seminal vesicles, and positive margins.[51, 52] Radiation therapy is effective in reducing biochemical recurrence and for achieving local control in patients with local failure.[53, 54] There has been considerable debate about the timing of radiation therapy. Proponents of adjuvant therapy emphasize the adjuvant radiation therapy of 60–64 Gy administered soon after wound healing, typically within 3 months after surgery for pathologically confirmed predictors of recurrence like capsule penetration, seminal vesicle invasion, margin positivity or for high risk T3 disease. This approach reduces biochemical recurrence and improves local control, as evidenced from three large randomized trials.[53, 54, 55]  

Opponents of this approach cite the lack of improvement in survival indices at 5 years, (overall, cancer specific and metastasis free survival) and the increased rates of acute and late gastrointestinal toxicity, urinary stricture and incontinence as reasons for opting for a salvage approach. Salvage radiotherapy offers a chance of cure for patients with biochemical recurrence. Using ultrasensitive PSA for early detection and using dosages of up to 75 Gy,[56] 60% of the patients can reach an undetectable PSA and 80% of these can be progression-free after 5 years.[57, 58] PSA is a very sensitive marker of recurrence and to date no difference in radiation outcomes has been reported between patients with low versus lower PSA values.  

Thus, the literature would support adjuvant radiotherapy be reserved for infrequent patients at very high risk of local recurrence (e.g. multiple positive surgical margins), with the rest being monitored for recurrence and treated with salvage radiotherapy if needed.[59] Adding a short course of hormone therapy to salvage radiation therapy has recently been shown to improve biochemical progression and clinical progression at 5 years, compared to radiation alone in randomized phase III trial (GETUG-AFU16). No additional late adverse events occurred in patients receiving short-term androgen suppression compared with those who received radiotherapy alone.[60]

Complications

Intraoperative complications

Radical prostatectomy is a well-tolerated procedure that is associated with low morbidity and few intraoperative complications in experienced hands.

Hemorrhage is the most common intraoperative complication, with venous bleeding the most likely source. Venous bleed can occur during endopelvic fascia incision, puboprostatic ligament division and during exposure of the apex of the prostate with transection of the dorsal vein complex (DVC). Bleeding from the DVC can be profuse and difficult to control. Division of the DVC over the urethra and oversewing can is used to manage bleeding from DVC.

With improved surgical technique and experience, the incidence of hemorrhage has decreased with mean estimated blood loss ranging from 300-1000 ml in most of the contemporary prostatectomy cohorts.[61, 62]  

Transfusion rates vary from 2-20% for patients undergoing RRP. Autologous blood donation is an option to avoid transfusion risk.  An alternate approach has been to utilize epoetin alpha injection to stimulate and boost red cell production prior to the operation. 2 preoperative doses 600 IU/kg given on days (-14) and (-7) are safe for significantly increasing hematocrit in men before radical retropubic prostatectomy.[63]

Less common intraoperative complications are rectal injury, obturator nerve injury and ureteral injury.

Postoperative complications

Delayed hemorrhage is a rare complication of radical prostatectomy. Expectant management is employed, along with blood transfusion. However, large pelvic hematomas can drain through urethrovesical anastomosis causing bladder neck contracture or incontinence later.[64] Hence it is prudent to explore and drain large hematomas that require blood transfusion.

Thromboembolic events including deep vein thrombosis (DVT) and pulmonary embolism occur in the early post-operative period. Open radical prostatectomy (compared to RALP) and lymph node dissection increase the odds of thromboembolic events.[65] Using sequential compression devices, proper lower extremity positioning and early ambulation can prevent DVT development.   

Bladder neck contracture is reported in 1 – 5 % of contemporary prostatectomy series.[66, 67] Excessive blood loss, persistent urinary extravasation, prior radiation, prior bladder outlet procedures, BMI, age, and smoking status have all been suggested as factors contributing to BNC development.[68] Simple dilatation is tried initially typically in the clinic setting, followed by bladder neck incision at 3, 6, and 9 o clock positions if recurrent. Injection of steroid (triamcinolone acetate) after bladder neck incision can be effective for recurrent cases.[69]

Urinary incontinence

Urinary incontinence is a troubling complication of radical prostatectomy. Clinically incontinence symptoms can range from occasional stress leakage to total incontinence. Occasional stress incontinence is significantly more common. Comparison of its incidence across different series is difficult because of variations in how incontinence is defined. Most centers with expertise in RRP report a postoperative stress incontinence rates of less than 10%.

Incontinence after surgery depends on patient parameters including the patient’s body mass index (BMI), age, urethral length, preoperative continence status and prostatic volume. Surgeon factors like experience and surgical technique also correlate with incontinence rate.[70]   Striated sphincter damage during ligation and division of DVC can cause intrinsic sphincter deficiency and is a significant contributor to incontinence. Damage to intrinsic smooth muscle of urethra during vesicourethral anastomosis and functional hindrance by an altered bladder neck caliber are other etiologies for incontinence. Meticulous surgical technique can reduce the incidence and severity of incontinence. Tension free vesicourethral anastomosis and adequate mucosal cooptation between the bladder neck and urethra help preserve an adequate bladder neck function post operatively. Buttressing sutures to intussuscept bladder neck has been shown to improve continence rates at 1-year follow up.[71, 72]   

A study that used a novel cluster modeling technique to determine predictors of post prostatectomy urinary incontinence identified 3 distinct postoperative continence recovery patterns. The first group of patients had a significant postoperative decrease with only one third recovery of function at 1 year. The second group had moderately decreased urinary function at 3 months with improvement to 76.8% of optimum function at 1 year. Group 3 patients had minimum impairment of continence post-operatively. Old age, major depression, peripheral vascular disease, smoking history and comorbidities were predictors of poor continence recovery in group 1.[73] These findings have implications for preoperative patient counseling and early intervention for post prostatectomy urinary incontinence.

Management strategy of incontinence begins with quantification of incontinence by calculating number of pads used in a day and the extent to which the symptoms affect the quality of life.  Patients must be counselled about likelihood of improvement up to one year following surgery and deferring invasive treatment until at least 1 year has elapsed after RRP.[74] Life style modifications and pelvic floor exercises have been shown to be effective for early continence recovery. Biofeedback, pelvic floor stimulation, pharmacotherapy (duloxetine), and urethral bulking agents have limited evidence in this setting.[75] A large population based analysis of 16,348 men treated with radical prostatectomy showed only  1,057 (6%) had 1 incontinence procedure by a median of 20 months after the procedure, indicating that a majority of incontinence are minor and could be medically managed.[76]

Surgical options for management of post prostatectomy incontinence include artificial urinary sphincter and the male sling.[77] The artificial urinary sphincter has a success rate in the range of 58% to 90%. Potential complications include incontinence (due to poor compliance in neurogenic bladders), urethral atrophy, mechanical failure, device erosion, and infection.[78] The male sling is designed for men with low volume incontinence (1-3 pads/ day).[77] In properly selected patient population slings have a success rate of 40%-90% without the risk of device failure.[77]

Erectile dysfunction

Whether and to what degree erectile dysfunction develops after RRP is governed by numerous factors, including potency before the operation, the age of the patient, the stage of the tumor, and the preservation of the neurovascular bundles.

Preservation of the neurovascular bundles allows better postoperative potency rates. Surgical technique is of great importance in this regard, and the data on postoperative return of potency reported from centers of excellence differ substantially from those reported in population surveys. The goals of adequate cancer surgery and retained potency should be balanced to maintain negative surgical margins.

Return of erections is more common in patients who have undergone a bilateral nerve-sparing procedure than in those who have undergone a unilateral procedure. Generally, potency is retained in 68% of patients who have undergone bilateral nerve-sparing prostatectomy and in 13-47% of those who have undergone prostatectomy with unilateral neurovascular bundle preservation.[79]

Return of erectile function occurs gradually after RRP and depends to a large extent on the age and preoperative potency status. Sexual function returns gradually after surgery, with 38% potent at 3 months, 54% at 6 months, 73% at 12 months, and 86% at 18 months in large series.[72] Age has a critical role in the return of sexual function with 100 % of men in 30 -39 years age group and only 75% men above 60 – 67 years regaining sexual function after surgery in the same series.[72] There is some evidence for correlation for return of sexual function with the pathological stage. Erectile function returned at least partially in 70% of men with organ-confined disease who had bilateral neurovascular preservation, compared with 50% of men with seminal vesicle invasion.[80]

Management of impotence after RRP includes oral phosphodiesterase 5 inhibitors (PDE5I), intra corporeal injections, vacuum erection device, and penile prosthesis. In the absence of contraindications, an oral PDE5I should be the first agent administered in the treatment of post prostatectomy impotence. Sildenafil was efficacious in bilateral nerve-spared patients compared to unilateral and non-nerve sparing patients, with 72% of the patients reporting rigidity that was sufficient for penetration.[81] Only 50% of the patients in the unilateral nerve-sparing group responded to sildenafil. However, the response may be poor, depending on the operation performed and the presence of other comorbidities, such as vascular disease or diabetes.

Early combination therapy with intracavernosal injections and sildenafil may increase sexual activity and to facilitate the return of natural erections after radical prostatectomy but further research is needed. Combination therapy also allows a lower dose of intracavernosal injections, thereby decreasing morbidity and discomfort.[82]

The concept of erection rehabilitation has been proposed by researchers based on preclinical evidence of potential positive effect of PDE5I on erectile function recovery.[83] Two large double-blind placebo controlled trials assessed the effect of early administration of oral PDE5 inhibitors vardenafil and tadalafil for erection rehabilitation. Both studies showed that PDE5 inhibitors were only effective in potentiating erections post RP, with no clear positive effect on erection rehabilitation in the long term setting off drug.[84, 85] Improvements in morning erections and penile length were noted in the drug groups. Thus, oral PDE5 inhibitors have a role for on demand usage to improve erection quality post RRP.

Vacuum erection devices have shown promise for improving erectile function and for penile rehabilitation. In a prospective randomized trial, 80% of men using vacuum erection device daily after a nerve-sparing radical prostatectomy had erections sufficient for intercourse.[86] Of those patients who were unsatisfied with the device, the addition of sildenafil to device usage led to significant improvement in satisfaction in 77% of patients.

Penile prosthesis are used as last resort if above measures fail. Data from a population based study indicates penile implant utilization rate of 2.3% after RP.[87] Penile prosthesis have a high rate of patient satisfaction (86%) with acceptable complications (5%) of infection, revision, or mechanical failure.[88]