SEARCH

SEARCH BY CITATION

Keywords:

  • nerve sparing;
  • prostate cancer;
  • radical prostatectomy;
  • surgical technique

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Laparoscopic versus open radical prostatectomy: Is there an advantage?
  5. The role of the surgeon and surgical experience
  6. Impact of the surgeon on oncological outcomes after RP
  7. Technique to improve oncological outcomes after radical prostatectomy
  8. Techniques to improve the recovery of potency after RP
  9. RP in men with high-risk prostate cancer
  10. Identifying patients with high-risk disease
  11. Oncological outcomes of radical prostatectomy for high-risk cancers
  12. Pelvic lymph node dissection
  13. Conclusion
  14. References

The surgical treatment of prostate cancer ideally removes the entire cancer, avoids excessive blood loss or serious perioperative complications, and results in complete recovery of continence and potency. To achieve this, the surgeon must excise sufficient periprostatic tissue to cure the cancer while preserving the cavernosal nerves required for erectile function and the neuromusculature required for normal urinary and bowel function. Here we will examine recent trends in radical prostatectomy, focusing on surgical technique.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Laparoscopic versus open radical prostatectomy: Is there an advantage?
  5. The role of the surgeon and surgical experience
  6. Impact of the surgeon on oncological outcomes after RP
  7. Technique to improve oncological outcomes after radical prostatectomy
  8. Techniques to improve the recovery of potency after RP
  9. RP in men with high-risk prostate cancer
  10. Identifying patients with high-risk disease
  11. Oncological outcomes of radical prostatectomy for high-risk cancers
  12. Pelvic lymph node dissection
  13. Conclusion
  14. References

Men with clinically localized prostate cancer face a variety of treatment choices, including watchful waiting; active surveillance with deferred treatment if the cancer shows signs of local growth; brachytherapy, external beam irradiation therapy, or both, with or without hormonal therapy; cryotherapy; high-intensity focused ultrasound; and radical prostatectomy (RP). The choice of treatment is complex and, for the individual patient, is based on the threat to quantity and quality of life posed by the cancer, the potential effectiveness and complications associated with treatment, and the patient's life expectancy. Early detection programs, based primarily on serum prostate-specific antigen (PSA) testing, are identifying cancers much earlier in their natural history, when the individual patient has a longer life expectancy. Therefore, the patient and physician must weigh the potential benefit of a particular treatment against the risk of treatment-related complications that would detract from the patient's quality of life.

Laparoscopic versus open radical prostatectomy: Is there an advantage?

  1. Top of page
  2. Abstract
  3. Introduction
  4. Laparoscopic versus open radical prostatectomy: Is there an advantage?
  5. The role of the surgeon and surgical experience
  6. Impact of the surgeon on oncological outcomes after RP
  7. Technique to improve oncological outcomes after radical prostatectomy
  8. Techniques to improve the recovery of potency after RP
  9. RP in men with high-risk prostate cancer
  10. Identifying patients with high-risk disease
  11. Oncological outcomes of radical prostatectomy for high-risk cancers
  12. Pelvic lymph node dissection
  13. Conclusion
  14. References

Laparoscopic radical prostatectomy (LRP) with or without robotic assistance (robotic-assisted laparoscopic prostatectomy; RALP) can be performed with excellent results. The enthusiasm for LRP and RALP is based on the idea that a magnified surgical image and less bleeding would markedly improve patient outcomes in terms of cancer control and functionality. To date, this promise has not been realized. While many results may be comparable to those after open RP, overall they have not resulted in the anticipated benefits to patients.1–3

Open RP and LRP/RALP each have advantages and disadvantages. Because no prospective, randomized trials comparing the two techniques have been performed, and it is unlikely that they will be, outcomes must be assessed from published series by centers that focus on either open RP or LRP/RALP. Although patient selection and varying definitions of ‘outcome’ make direct comparisons difficult, outcomes such as the rate of positive surgical margins, recovery of urinary continence, and recovery of potency can be examined.

A common assumption is that LRP/RALP results in less postoperative pain than open RP, but the only published study making a direct comparison found no difference. Webster et al. compared 314 patients undergoing open RP to 154 men undergoing RALP by the same surgeon.4 Perioperative narcotic use and patient-reported pain were similar regardless of surgical approach.

A recent study suggests that oncological outcomes after LRP and/or RALP may actually be inferior to outcomes obtained with open RP. Hu et al. studied 2702 men undergoing either minimally invasive (LRP or RALP) or open RP from 2003 to 2005, using a national 5% sample of Medicare beneficiaries.5 The investigators determined that men undergoing a minimally invasive RP were over 3.5 times more likely to require salvage therapy (radiation and/or hormonal therapy) within 6 months of surgery than men treated with open RP (minimally invasive RP: 28%; open RP: 9%; odds ratio, 3.67; 95% confidence interval [CI], 2.81–4.81). This difference narrowed as minimally invasive surgeons gained experience (salvage therapy ranged from 40% for low-volume surgeons to 19% for high-volume surgeons), but the use of salvage therapy remained higher for men treated with a minimally invasive approach.

LRP and RALP are technically demanding, requiring a significant learning curve. Various authors have concluded that in order to become proficient at LRP or RALP (defined as achieving outcomes comparable to their open surgical experience) a surgeon must perform anywhere from eight to 12 cases6 to as many as 200 cases.7 A surgeon opting to transfer open surgical skills to RALP must go through a significant learning curve that is conservatively estimated at 100 cases. Simple math suggests that while a surgeon is learning a new technique, a number of patients may achieve outcomes inferior to what they might otherwise have obtained. In addition, some surgeons do not have the patient volume to ever complete their learning curve.

Open, laparoscopic, and robotic-assisted laparoscopic RP can be performed safely with acceptable oncological and functional outcomes. Current data suggest that the most significant outcomes – cancer control, continence, and potency – are no better with LRP or RALP than open RP. Despite the fact that there is no proven long-term benefit to using a minimally invasive approach, there has been a dramatic increase in the percentage of men undergoing robotic-assisted rather than open or even laparoscopic RP. Despite this trend, current data suggest that results ultimately depend more on surgical technique than on surgical approach or the tools used in surgery.

The role of the surgeon and surgical experience

  1. Top of page
  2. Abstract
  3. Introduction
  4. Laparoscopic versus open radical prostatectomy: Is there an advantage?
  5. The role of the surgeon and surgical experience
  6. Impact of the surgeon on oncological outcomes after RP
  7. Technique to improve oncological outcomes after radical prostatectomy
  8. Techniques to improve the recovery of potency after RP
  9. RP in men with high-risk prostate cancer
  10. Identifying patients with high-risk disease
  11. Oncological outcomes of radical prostatectomy for high-risk cancers
  12. Pelvic lymph node dissection
  13. Conclusion
  14. References

RP ranks among the most challenging and complex operations urologists perform. Research has repeatedly documented how the success of RP and the incidence of complications vary not only among surgeons with widely disparate levels of experience, but also among the subset of highly experienced surgeons.5,8–12 Begg et al. evaluated health-related outcomes after RP using the Surveillance, Epidemiology, and End Results (SEER) Medicare database.8 The rate of postoperative complications, late urinary complications (defined as strictures or fistulas arising 31 to 365 days after the procedure), and long-term incontinence (defined as incontinence persisting for more than 1 year after surgery) were inferred from the Medicare claims records of 11 522 patients who underwent RP between 1992 and 1996. Complication rates were analyzed in relation to hospital volume (number of procedures performed within a single hospital) and surgeon volume (number of procedures performed by individual surgeons). Significant trends in the relation between volume and outcome were observed with respect to postoperative morbidity and late urinary complications. Postoperative morbidity was lower in very-high-volume hospitals than in low-volume hospitals (27% vs 32%, P = 0.03). Morbidity was also lower when the RP was performed by very-high-volume surgeons as opposed to low-volume surgeons (26% vs 32%, P < 0.001). A similar pattern was found in the rate of late urinary complications.

A more detailed analysis of the study by Begg et al. examined clinical outcomes among the 159 surgeons who performed a high or very high volume of procedures.8 There was wide surgeon-to-surgeon variation, greatly exceeding any that could be predicted based on chance or variations in the case mix. These findings suggest that the incidence of early postoperative morbidity and urinary complications are lower among surgeons who perform a high volume of RP. The unanticipated variability in outcome among surgeons with the highest volume of RP strongly suggests that variations in surgical proficiency have a significant effect on results.

Impact of the surgeon on oncological outcomes after RP

  1. Top of page
  2. Abstract
  3. Introduction
  4. Laparoscopic versus open radical prostatectomy: Is there an advantage?
  5. The role of the surgeon and surgical experience
  6. Impact of the surgeon on oncological outcomes after RP
  7. Technique to improve oncological outcomes after radical prostatectomy
  8. Techniques to improve the recovery of potency after RP
  9. RP in men with high-risk prostate cancer
  10. Identifying patients with high-risk disease
  11. Oncological outcomes of radical prostatectomy for high-risk cancers
  12. Pelvic lymph node dissection
  13. Conclusion
  14. References

A successful RP requires that the cancer be completely removed. A positive surgical margin (cancer cells at the inked margin of resection) has been associated with up to a fourfold increased risk of biochemical recurrence even after adjusting for other known risk factors, including the pretreatment serum level of PSA and the clinical stage, grade, and pathological features at the time of RP (level of extracapsular extension, seminal vesicle invasion, and status of the pelvic lymph nodes).2,9 To examine the extent to which the surgeon's skill determines the risk for a positive surgical margin, Eastham et al. examined the incidence of positive surgical margins among 4629 men who underwent RP for clinically localized prostate cancer.9 The procedures were performed by 44 different surgeons. Patients who received either androgen deprivation therapy or pelvic radiation therapy were excluded from the analysis. In multivariable analysis, the surgeon was associated with surgical margin status after controlling for all other clinical and pathological variables. After further adjustment for surgical volume, individual surgeons remained associated with surgical margin status. The results suggest that experience and careful attention to surgical details can decrease positive surgical margin rates and improve cancer control outcomes.

While a positive surgical margin is a predictor of oncological outcome, biochemical recurrence after RP is perhaps the best model for examining the association between surgeon characteristics and oncological outcome, as there is no standard adjuvant therapy for prostate cancer and recurrence is not significantly affected by other aspects of postoperative care. To study the association between surgeon experience and biochemical recurrence, Vickers et al. performed a retrospective cohort study on consecutive patients treated from 1987 through 2003 at four academic medical centers in the USA.10 Patients who had received neoadjuvant therapy were excluded from analysis. The cohort comprised 7850 patients with clinically localized prostate cancer who underwent open RP performed by one of 72 surgeons. Total number of RP conducted before the incident case was used to define surgeon experience. Biochemical recurrence, as indicated by a confirmed rise in serum PSA level >0.4 ng/mL, was used to define cancer control. After adjustment for tumor characteristics and the year in which the surgery was performed, the results demonstrated that biochemical recurrence decreased with increasing surgeon experience. The learning curve for cancer control after RP was steep and did not start to plateau until the surgeon had completed approximately 250 operations (Fig. 1).10 The 5-year probability of biochemical recurrence was 17.8% when RP was performed early in the surgeon's career (10 previous RP) compared to 10.9% among surgeons who had performed 250 RP (absolute risk difference 6.9%; 95% C.I.: 4.3%, 9.5%). The investigators saw no evidence that features of the cancer attenuate the learning curve: in all analyses there was a statistically significant association between biochemical recurrence and surgeon experience. Treatment by a surgeon who had performed 10, rather than 250, previous RP was associated with a relative risk of 2.5 for low-risk patients, 1.8 for medium-risk patients, and 1.3 for high-risk patients. Although this study specifically focused on open RP, similar results would likely be found for LRP or RALP.

image

Figure 1. The surgical learning curve for cancer control after radical prostatectomy. Predicted probability (black curve) and 95% confidence intervals (gray curves) for freedom from biochemical recurrence 5 years after RP are plotted against increasing surgeon experience. Probabilities are for a patient with typical cancer severity (mean prostate-specific antigen level, pathological stage, and grade) treated in 1997 (approximately equal numbers of patients were treated before and after 1997). Adapted from reference 10.

Download figure to PowerPoint

Technique to improve oncological outcomes after radical prostatectomy

  1. Top of page
  2. Abstract
  3. Introduction
  4. Laparoscopic versus open radical prostatectomy: Is there an advantage?
  5. The role of the surgeon and surgical experience
  6. Impact of the surgeon on oncological outcomes after RP
  7. Technique to improve oncological outcomes after radical prostatectomy
  8. Techniques to improve the recovery of potency after RP
  9. RP in men with high-risk prostate cancer
  10. Identifying patients with high-risk disease
  11. Oncological outcomes of radical prostatectomy for high-risk cancers
  12. Pelvic lymph node dissection
  13. Conclusion
  14. References

From an oncological standpoint, obtaining negative surgical margins at the time of RP is paramount. In the following section we provide technical suggestions for one approach to RP, with an emphasis on reducing the likelihood of positive margins.9,11–13 Although the technique described here is not the only successful approach, the hope is that readers will discern the important anatomical and surgical principles that will allow them to improve their own technique.

In order to perform a successful RP, whether open or minimally invasive, the surgeon must achieve adequate hemostasis before beginning dissection of the prostate. The pneumoperitoneum associated with LRP and RALP markedly decreases bleeding, one advantage of the minimally invasive approach. Maximizing hemostasis allows the surgeon to focus on complete excision of the cancer, preservation of the external sphincter mechanism, and appropriate sparing of the neurovascular bundles (NVB). In open surgery, we suggest passing a 22-gauge surgical wire beneath the dorsal venous complex (DVC), anterior to the urethra just distal to the prostatic apex (Fig. 2).13 The wire serves as a template for dividing the DVC sharply with a knife. Proper placement of this wire in patients with large anterior tumors will ensure a clear and safe cleavage plane between the prostate and DVC (Fig. 3). Care must be taken to avoid incising into the prostatic apex while dividing the DVC. This is facilitated by placing a sponge stick on the anterior surface of the prostate to retract the gland cephalad and by using the tip of the sucker to further retract the apex away from the wire. In minimally invasive RP, the puboprostatic ligaments can be traced from their insertion on the pubic bone back to the prostate to identify an appropriate plane to divide the DVC (Fig. 4). We prefer direct division of the DVC with scissors and/or electrocautery rather than staples to ensure that an adequate margin of resection is obtained under direct vision.

image

Figure 2. Control of the dorsal venous complex. The superficial dorsal vein complex (DVC) is suture ligated at the bladder neck, approximately 1 cm cephalad to the junction of the prostate and bladder (a). A deeper suture is placed around the superficial and deep DVC midway toward the apex, extending from one cut edge of endopelvic fascia to the other (a). These sutures limit back bleeding on transection of the DVC. A right-angled clamp is passed beneath the DVC anterior to the urethra just distal to the prostatic apex (b). The clamp is used to grasp a 22-gauge surgical wire, which is brought around the complex and will later serve as a template when dividing the DVC sharply with a knife. Prior to dividing the complex, the wire is retracted gently cephalad to expose the DVC as it passes through the pelvic floor. A third suture, placed in a figure-of-eight fashion, is placed around the DVC at the pelvic floor. Using the wire as a guide, the DVC is divided between the second and third sutures (b). Care must be taken to avoid incision into the prostatic apex. This is facilitated by having the assistant use a sponge stick placed on the anterior surface of the prostate to retract it cephalad and using the tip of a sucker to further retract the apex away from the wire. Bleeding from the transected DVC is controlled by oversewing the cut edges of the lateral pelvic fascia with a continuous suture (c), the last pass of which is brought through the periosteum of the pubis to compress the superficial venous complex and to fix the fascia to the periosteum, simulating the puboprostatic ligaments. Adapted from reference 13.

Download figure to PowerPoint

image

Figure 3. Endorectal magnetic resonance imaging of the prostate, demonstrating a large-volume anterior prostate cancer.

Download figure to PowerPoint

image

Figure 4. Laparoscopic view of prostatic apex, noting the puboprostatic ligaments that can be used as a guide to selecting the site where the dorsal venous complex can be transected.

Download figure to PowerPoint

A lateral approach to the NVB (Fig. 5) allows wide exposure of the apex so that the apical tissue can be completely resected.12,13 The lateral prostatic fascia overlying the NVB can be incised more medially or laterally to the nerve, depending on the extent or location of the tumor and whether the nerves are to be preserved (Fig. 6).13 To minimize the risk of positive apical margins, we recommend wide dissection around the apex of the prostate, specifically around the distal extension of the apex posteriorly. Over-dissection of the urethra and periurethral muscles distally could hinder the recovery of postoperative urinary continence. Releasing the NVB off the lateral aspect of the gland at the apex and the initial few millimeters of the urethra will reduce the likelihood of an apical positive margin when the urethra is later transected, and will also decrease the chance of injuring the NVB. The nerves also lie close to the prostate near the base. Dissection too close to the prostate will result in a positive margin in this area. The lateral approach has enabled us to preserve most or all of both NVB in the majority of patients while still allowing a wider dissection around the apex and base of the prostate, especially posteriorly.

image

Figure 5. Steps to reduce the rate of positive margins while preserving the neurovascular bundles (NVB). (a) Complete preservation of the left NVB. After division of the dorsal venous complex, the prostate is rotated to the right. The lateral prostatic fascia is then incised with either scissors or a knife in the groove between the prostate and the NVB. For low-risk cancers, this incision can be made high on the prostate to preserve as much periprostatic tissue as possible. This initial incision is opened either sharply or bluntly. The authors prefer to separate the cut edges of the lateral prostatic fascia with a fine right-angled clamp and have the assistant divide the tissue with a knife. This is continued from the urethra to the level of the seminal vesicle. Once this initial mobilization is completed, the neurovascular tissue is bluntly reflected off the lateral aspect of the gland. Care should be taken to avoid undue traction/tension on the tissue. Small vascular branches from the NVB to the prostate can usually be identified and clipped, further reducing blood loss and improving intraoperative visualization. The NVB is completely reflected off the prostate inferiorly until the anterior rectum covered by Denonvilliers' fascia is seen. Denonvilliers' fascia is incised sharply in the angle between the prostate and NVB, releasing the NVB from the prostate and urethra. This incision is usually easiest to make toward the base rather than the apex of the prostate. Clear visualization of periprostatic fat protruding through the fascial incision identifies the correct plane of dissection. The initial incision in Denonvilliers' fascia is extended the entire length of the NVB, completely freeing the bundle from the prostate. Later, when the urethra has been transected, the cut edges of Denonvilliers' fascia on each side are connected. This allows for sharp dissection of the prostate together with this fascial layer off the anterior rectal wall. Blunt dissection of the prostate off the rectum should be avoided. While blunt dissection is quicker, it frequently results in leaving all or part of Denonvilliers' fascia on the rectum rather than the prostate, thus increasing the likelihood of a positive surgical margin. For high-risk cancers located posteriorly, this dissection beneath Denonvilliers' fascia can be further deepened to keep perirectal fat on the prostate as well. (b) Gentle upward traction on the catheter allows the lateral vascular pedicles of the prostate to be isolated and divided. (c) The seminal vesicles are typically approached laterally and the plane between the vesicle and bladder developed with scissors. The vessels to the tip of the seminal vesicle are clipped and divided. Adapted from reference 13.

Download figure to PowerPoint

image

Figure 6. Preservation of left neurovascular bundle (NVB). After the dorsal vein complex has been divided, the prostate is rotated to the right and the levator muscles are bluntly dissected away. The lateral pelvic fascia is then incised in the groove between the prostate and the NVB. The NVB is most easily dissected away from the apical third of the prostate (a,b). The small branches of the vascular pedicle to the apex must be divided. The posterior layer of Denonvilliers' fascia is then incised, releasing the NVB from the prostate and urethra (c–e) so that the nerves will not be tethered when the urethral anastomotic sutures are tied. Adapted from reference 13.

Download figure to PowerPoint

Once the mobilization of the NVB off the gland is completed, a deliberate incision must be made into Denonvilliers' fascia (Fig. 7).13 Deep dissection beneath Denonvilliers' fascia should be performed routinely, because few nerves are present in this area and deep dissection will likely reduce the incidence of posterolateral margins. While blunt dissection is quicker, it frequently leaves all or part of Denonvilliers' fascia on the rectum rather than the prostate, thus increasing the likelihood of positive posterior margins. For high-risk cancers located posteriorly, dissection beneath Denonvilliers' fascia can be further deepened to include perirectal fat on the prostate.

image

Figure 7. After the nerves have been dissected free, Denonvilliers' fascia is incised, releasing the neurovascular bundle from the prostate and urethra (a–c) so that the nerves will not be tethered when the urethral anastomotic sutures are tied. Adapted from reference 13.

Download figure to PowerPoint

Techniques to improve the recovery of potency after RP

  1. Top of page
  2. Abstract
  3. Introduction
  4. Laparoscopic versus open radical prostatectomy: Is there an advantage?
  5. The role of the surgeon and surgical experience
  6. Impact of the surgeon on oncological outcomes after RP
  7. Technique to improve oncological outcomes after radical prostatectomy
  8. Techniques to improve the recovery of potency after RP
  9. RP in men with high-risk prostate cancer
  10. Identifying patients with high-risk disease
  11. Oncological outcomes of radical prostatectomy for high-risk cancers
  12. Pelvic lymph node dissection
  13. Conclusion
  14. References

Before the 1980s, most patients permanently lost erectile function after RP. Walsh et al. developed a technique for retropubic RP based on identification of the anatomic structures surrounding the prostate, including the autonomic nerves that control blood flow to the penis.11,14 Current surgical techniques are based on a more precise understanding of the autonomic innervation of the corpora cavernosa, allowing preservation of sexual function in most men undergoing RP. Quinlan et al. demonstrated that recovery of potency was quantitatively related to the preservation of nerves.15 These investigators identified three factors associated with recovery of potency after RP: age, clinical and pathological stage, and preservation of the NVB. Rabbani et al. developed a nomogram to predict the recovery of potency after RP.16 Factors significantly associated with recovery of spontaneous erections that were satisfactory for intercourse included the age of the patient, the quality of erections before the operation, and the degree of preservation of the NVB. Time elapsed after surgery is also an important factor. The median time to recovery of an International Index of Erectile Function (IIEF) ≥17 was 24 months; achieving an IIEF ≥26 required 42 months.

Recent studies suggest that the NVB is diffusely spread around the capsule of the prostate, rather than just in the posterolateral aspect of the gland, as originally described.17–21 Heichelberg et al. examined the permanent sections of 31 patients who underwent non-nerve-sparing retropubic RP.17 The study focused on the outside of the prostatic capsule and the periprostatic soft tissue where the sum of each nerve and ganglion was determined. The vast majority of nerves were found in the area corresponding to the rectolateral sides of the prostate at the typical location for the NVB. In these two areas (left and right), a median sum of 46%, 62%, and 66% of counted nerves were found in apex, mid-part, and base specimens, respectively. Only 3% to 5% of identified nerves were found in the area neighboring the rectal Denonvilliers' fascia. However, a significant number of nerves were found above the line marked by the 3 o'clock position. The sum of the median percentage of nerves detected in this area was 22%, 21%, and 28% for apex, mid-part, and base, respectively. These results suggest that, for men at low risk of developing extraprostatic cancer, an incision should be made high in the lateral prostatic fascia in order to preserve as much of the periprostatic neurovascular tissues as possible. This technique has been clearly demonstrated to improve potency after RP.20,22,23

Approaching the dissection of the NVB is rarely an all-or-none decision. Even in men with a high risk of extraprostatic cancer, a portion of the NVB can often be preserved (partial nerve sparing), thus improving the likelihood of recovery of postoperative erectile function. This concept has been further defined by recent anatomical descriptions of the periprostatic anatomy that define the planes of dissection surrounding the NVB into intrafascial (directly adjacent to the prostatic capsule; complete nerve sparing), interfascial (within the neurovascular bundle; partial nerve sparing) and extrafascial (outside the neurovascular bundle; nerve resection) (Fig. 8).24,25 Appropriate selection of patients for NVB preservation will result in comparable oncological outcomes while improving the likelihood of postoperative recovery of erectile function.26,27

image

Figure 8. Endorectal magnetic resonance imaging of the prostate, defining the location of the various fascial planes surrounding the neurovascular bundles (NVB). Intrafascial: directly adjacent to the prostatic capsule; complete nerve sparing. Interfascial: within the NVB; partial nerve sparing. Extrafascial: outside the NVB; nerve resection.

Download figure to PowerPoint

Several investigators have demonstrated that if patients are appropriately selected, NVB preservation at the time of RP does not increase the likelihood of a positive surgical margin and/or biochemical recurrence.24–27 Unfortunately, there are no absolute guidelines determining when a portion or all of the neurovascular tissue should be resected. As early detection programs have become commonplace, the vast majority of patients (at least 80% in most patient populations undergoing RP) are candidates for complete NVB preservation. Conversely, less than 5% of men undergoing RP require bilateral NVB resection. These men typically have already had unsuccessful local therapy (salvage RP) or have palpable disease directly involving the posterolateral aspect of the gland in the area of the NVB. The main difficulty, therefore, is in identifying the small group of men at high risk for microscopic extension of cancer outside the prostate – specifically in the area of the NVB – such that complete nerve preservation would significantly increase the likelihood of a positive surgical margin.

A variety of prediction tools have been developed that estimate the probability of extraprostatic cancer being identified on histological examination of the RP specimen.28–30 Even side-specific models are available.30 These models, however, do not identify the location or the extent of extraprostatic cancer, information critical for planning the operation. For example, a patient with a high risk of extraprostatic cancer directly posteriorly (or anteriorly) should still be a candidate for complete NVB preservation, whereas a patient with similar preoperative clinical parameters with the same likelihood of extraprostatic extension might require partial or complete NVB resection if the cancer is located posterolaterally. In addition, these models do not define the extent of extraprostatic cancer. A patient with focal extraprostatic cancer should be treated differently to a man with more extensive but still microscopic extraprostatic cancer. In an attempt to identify men at high risk for extraprostatic cancer in the area of the NVB, Tsuzuki et al. examined 2660 cases of clinically localized prostate cancer treated at The Johns Hopkins Hospital.31 Through univariable and multivariable analyses, prostate-specific antigen level (≥10 vs <10), biopsy Gleason score (≥7 vs <6), digital rectal examination (abnormal vs normal), percent of side-specific cores with tumor (>33.3% vs ≤33.3%) and average percent involvement of each positive core (>20% vs ≤20%) were found to be significant predictors of NVB involvement. A model was generated that stratified these variables into high and low risk (Table 1).31 The probability of extraprostatic cancer in the NVB was <10% in cases with one or fewer of the high-risk variables and ≥10% in cases with more than one high-risk variable.

Table 1.  Variables that were statistically significant independent predictors of EPE in the neurovascular bundles in the multivariate model, namely prostate-specific antigen, biopsy Gleason score, digital rectal examination, average percent of biopsy core involved with tumor and percent of side specific positive cores with tumor. The model generated using the test set resulted in a good fit when applied to the validation set with an area under the receiver–operator curve of 0.78. The probability of extraprostatic extension in the NVB was less than 10% in cases with one or fewer of the higher risk variables
Predictor variableHigh risk
  1. P < 0.0001. *All pathological variables are side specific. PSA, prostate-specific antigen; DRE; digital rectal examination.

PSA (ng/mL)10 or Greater
Biopsy Gleason score*7 or Greater
Average % of biopsy core involved with tumor*Greater than 20
% Cores with tumor*Greater than 33.3
DREAbnormal

For men with a low risk of extraprostatic cancer, a high incision of the lateral prostatic fascia will improve the likelihood of preserving the majority of the NVB. This approach, using RALP, has been summarized in the report by Kaul et al. from Henry Ford Hospital.22 The authors reported 97% potency in their initial 35 patients 12 months after surgery. The investigators concluded that preservation of the prostatic fascia was safe and feasible, did not compromise the surgical margins, and allowed enhanced preservation of neural tissue with an improvement in potency. Their initial report was followed by an expanded series that documented improvement in potency with high incision of the lateral prostatic fascia compared to ‘standard’ nerve-sparing techniques.32 Similar results have been published on open surgery as well. Walsh et al. reported improvement in overall potency with high incision of the lateral prostatic fascia near the apex of the prostate.23

These investigators suggested that the improvement in potency with this technique was more likely related to decreased traction on the NVB during its mobilization off the prostate than to preservation of anterior nerve fibers; a similar conclusion was reached by Masterson et al. in their description of NVB preservation.33 Regardless of the exact explanation of why potency is improved, these reports emphasize several important concepts: that the decisions made by the surgeon are critical to determining outcomes; that surgical technique is more important than the tools used in that technique; and that experienced surgeons can improve their results with seemingly minor changes in surgical technique.

RP in men with high-risk prostate cancer

  1. Top of page
  2. Abstract
  3. Introduction
  4. Laparoscopic versus open radical prostatectomy: Is there an advantage?
  5. The role of the surgeon and surgical experience
  6. Impact of the surgeon on oncological outcomes after RP
  7. Technique to improve oncological outcomes after radical prostatectomy
  8. Techniques to improve the recovery of potency after RP
  9. RP in men with high-risk prostate cancer
  10. Identifying patients with high-risk disease
  11. Oncological outcomes of radical prostatectomy for high-risk cancers
  12. Pelvic lymph node dissection
  13. Conclusion
  14. References

For patients with high-risk but clinically localized prostate cancer, urologists traditionally recommended radiotherapy or androgen deprivation therapy over RP, not because the oncological outcomes were better with radiotherapy, but because rates of incontinence and impotence with RP were high and cure rates were discouraging. This practice of steering such patients away from RP warrants reevaluation, particularly given the contemporary changes and advancements in prostate cancer treatment. With the development of an anatomic approach to RP, both morbidity and functional outcomes after surgery have improved substantially. In addition, largely as a result of the widespread application of PSA screening, not only has the proportion of men diagnosed with high-risk features decreased, but also the characteristics of high-risk cancers have changed dramatically. Men are currently more likely to be designated as high risk by Gleason grade alone rather than by elevated PSA, grossly abnormal rectal examination (clinical stage T3 disease), or multiple high-risk factors.34,35

Despite these changes, and despite the lack of contemporary evidence favoring one treatment modality over the other, radiotherapy is still recommended to high-risk patients. Population-based data indicate that the proportion of men with clinical T3 cancer undergoing RP declined dramatically, from 18% to 9%, between 1995 and 2001, with a corresponding 20% absolute increase in the frequency of radiotherapy.36 More worrisome, a quarter of these men under the age of 70 received no definitive local therapy. Similarly, according to the cancer of the prostate strategic urological research endeavor (CaPSURE) data, many newly diagnosed patients with localized prostate cancer with high-risk features are presumed incurable, perhaps unjustifiably, and are offered androgen deprivation therapy as their sole treatment modality.37

Identifying patients with high-risk disease

  1. Top of page
  2. Abstract
  3. Introduction
  4. Laparoscopic versus open radical prostatectomy: Is there an advantage?
  5. The role of the surgeon and surgical experience
  6. Impact of the surgeon on oncological outcomes after RP
  7. Technique to improve oncological outcomes after radical prostatectomy
  8. Techniques to improve the recovery of potency after RP
  9. RP in men with high-risk prostate cancer
  10. Identifying patients with high-risk disease
  11. Oncological outcomes of radical prostatectomy for high-risk cancers
  12. Pelvic lymph node dissection
  13. Conclusion
  14. References

A uniform definition for high-risk prostate cancer is lacking. Ideally, such a definition would reliably distinguish men whose cancer is curable with local therapy alone from those who already harbor micrometastases at diagnosis and therefore are not amenable to localized treatment alone. Although terms such as ‘clinical T3’,38‘locally advanced’,39–41 and ‘poorly differentiated’42,43 are often used as synonyms for high-risk disease, no single criterion adequately identifies cancers with a high probability of progression after local treatment. While, taken individually, clinical stage, biopsy results, and pretreatment PSA provide some prognostic information, the combination of these variables provides a markedly enhanced ability to predict treatment outcome. D'Amico and colleagues have defined high-risk prostate cancer as that associated with any one of three risk factors: biopsy Gleason score ≥8, PSA ≥20 ng/mL, or clinical stage ≥ T2c.44 This classification was endorsed by the American Urological Association in 2007.45 Unfortunately, reliance on this simple risk stratification scheme has led many patients and physicians to inappropriately select androgen deprivation instead of curative therapy.37,46

More recently, D'Amico and colleagues refined their definition to incorporate the absolute number of high-risk features (stage ≥ T2b, biopsy Gleason score ≥7, and pretreatment PSA >10 ng/mL).47 Patients are classified into one of three high-risk groups, defined by having one, two, or all three features. Probability of death from prostate cancer was highest among men with three high-risk features. However, this model is limited by the equal weight assigned to each factor and by the arbitrary selection of cut-offs for each risk factor. By this model, a man diagnosed with clinical stage T2c with a PSA of 15 ng/mL (two risk factors) will receive the same outcome prediction as a patient with bulky T3a cancer and a PSA level of 75 ng/mL.

An alternative to grouping patients with similar, though not identical, risk features is use of multivariable models such as nomograms. These models incorporate data from all risk factors relevant to the probability of treatment failure and proportionately weigh their relative contribution. Nomograms may be more accurate than a risk-group approach and represent an alternative method for risk assessment. However, a limitation of most available risk stratification tools is that they are based largely on an increased likelihood of biochemical (PSA) recurrence after local definitive therapy, and not on the likelihood of progression to symptomatic disease or death from prostate cancer. PSA recurrence can have a highly variable clinical course, which does not always culminate in symptoms and death.48 Because it is difficult to translate the risk of PSA relapse into a risk of clinical progression and death from prostate cancer, a nomogram cut-off that accurately distinguishes high-risk patients from non-high-risk patients remains elusive.

Oncological outcomes of radical prostatectomy for high-risk cancers

  1. Top of page
  2. Abstract
  3. Introduction
  4. Laparoscopic versus open radical prostatectomy: Is there an advantage?
  5. The role of the surgeon and surgical experience
  6. Impact of the surgeon on oncological outcomes after RP
  7. Technique to improve oncological outcomes after radical prostatectomy
  8. Techniques to improve the recovery of potency after RP
  9. RP in men with high-risk prostate cancer
  10. Identifying patients with high-risk disease
  11. Oncological outcomes of radical prostatectomy for high-risk cancers
  12. Pelvic lymph node dissection
  13. Conclusion
  14. References

Although urologists nearly uniformly recognize RP as the most effective means of controlling low-risk and intermediate-risk prostate cancers, many are reluctant to offer RP to men with high-risk features, even though the high-risk patients are those most likely to benefit from effective local therapy.49 This counterintuitive phenomenon is not seen with most other solid malignancies. Given that surgical technique has been refined and functional outcomes have improved, it is time to revisit the traditional practice of not operating on high-risk patients simply because surgical monotherapy is more likely to fail.

The results of contemporary RP series in high-risk patients appear more encouraging than studies prior to the PSA era. Ward et al. reported the long-term treatment outcomes and complications of RP in 842 men with clinical stage T3 disease treated at the Mayo Clinic from 1987 to 1997. The median follow-up was more than 10 years, and 78% of the patients received adjuvant therapy.38 Biochemical recurrence-free survival (defined as PSA level ≥0.4 ng/mL), cancer-specific survival, and overall survival at 15 years were 38%, 79%, and 53%, respectively.

Berglund and associates studied 281 consecutive high-risk patients treated by RP between 1998 and 2004.50 High risk was defined as clinical stage ≥ T2b, PSA ≥ 15, and/or biopsy Gleason score ≥8. Pathological examination revealed organ-confined disease in 12%, extraprostatic extension in 57%, seminal vesicle invasion in 23%, and lymph node involvement in 9%. Despite these relatively unfavorable histological features, 70% of the patients were without any evidence of disease recurrence at a mean follow up of 34 months.

We have also found relatively favorable outcomes in a contemporary cohort – in a study comparing pathological and biochemical outcomes of patients defined as high risk by eight different definitions,51 and in a study examining metastasis and cancer-specific death.52 Regardless of definition, roughly half the patients remained progression-free 10 years after RP alone, with 35% to 76% of the high-risk patients alive and free of additional cancer therapy 10 years after RP. These results demonstrate that local therapy can be curative for many men with high-risk disease.

Pelvic lymph node dissection

  1. Top of page
  2. Abstract
  3. Introduction
  4. Laparoscopic versus open radical prostatectomy: Is there an advantage?
  5. The role of the surgeon and surgical experience
  6. Impact of the surgeon on oncological outcomes after RP
  7. Technique to improve oncological outcomes after radical prostatectomy
  8. Techniques to improve the recovery of potency after RP
  9. RP in men with high-risk prostate cancer
  10. Identifying patients with high-risk disease
  11. Oncological outcomes of radical prostatectomy for high-risk cancers
  12. Pelvic lymph node dissection
  13. Conclusion
  14. References

It is imperative that surgical extirpation in patients undergoing RP includes a meticulous lymph node dissection (Fig. 9).53 Evidence exists demonstrating that the more we extend the indications for and the anatomical limits of the pelvic lymph node dissection (PLND), the more positive lymph nodes we detect.53 Limiting the PLND template risks not only understaging the disease, but also depriving a number of patients with nodal micrometastases a chance for cure. Large series of patients undergoing RP with long-term follow up have demonstrated a therapeutic benefit from PLND, particularly in those with a low burden of cancer in the pelvic lymph nodes.53–56

image

Figure 9. Boundaries of extended lymph node dissection and subdivision into three different locations, including the external iliac vein, obturator fossa, and internal iliac artery. Adapted from reference 53.

Download figure to PowerPoint

A PLND that includes the external iliac, hypogastric, and obturator nodal packets has been shown in both open and minimally invasive RP series to yield a higher nodal count, and detect more positive lymph nodes, than the often performed PLND that is limited to the nodal tissue between the external iliac vein and top of the obturator nerve.53,57 PLND including the external iliac, hypogastric, and obturator nodal packets is the most accurate staging procedure today because currently available imaging techniques remain insufficient.

Conclusion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Laparoscopic versus open radical prostatectomy: Is there an advantage?
  5. The role of the surgeon and surgical experience
  6. Impact of the surgeon on oncological outcomes after RP
  7. Technique to improve oncological outcomes after radical prostatectomy
  8. Techniques to improve the recovery of potency after RP
  9. RP in men with high-risk prostate cancer
  10. Identifying patients with high-risk disease
  11. Oncological outcomes of radical prostatectomy for high-risk cancers
  12. Pelvic lymph node dissection
  13. Conclusion
  14. References

RP reliably eradicates the cancer in most men with clinically localized prostate cancer. Although technically complex, this operation can generally be performed with a low level of acute and long-term morbidity, but the results are highly sensitive to fine details in surgical technique. Rates of blood loss, positive surgical margins, incontinence, and erectile dysfunction vary widely from surgeon to surgeon. Each surgeon should know his/her rate of each of these outcomes after RP and identify areas where improvement might be achieved. With careful attention to surgical technique, cancer control rates should improve further, and adverse effects on quality of life after RP should continue to decrease.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Laparoscopic versus open radical prostatectomy: Is there an advantage?
  5. The role of the surgeon and surgical experience
  6. Impact of the surgeon on oncological outcomes after RP
  7. Technique to improve oncological outcomes after radical prostatectomy
  8. Techniques to improve the recovery of potency after RP
  9. RP in men with high-risk prostate cancer
  10. Identifying patients with high-risk disease
  11. Oncological outcomes of radical prostatectomy for high-risk cancers
  12. Pelvic lymph node dissection
  13. Conclusion
  14. References