Volume 30, Issue 1 , Pages 26-32, January 2012
Nerve-sparing robotic prostatectomy in preoperatively high-risk patients is safe and efficacious
Article Outline
- Abstract
- 1. Introduction
- 2. Materials and methods
- 3. Results
- 4. Discussion
- 5. Conclusions
- References
- Copyright
Abstract
Objective
Given the higher likelihood of extraprostatic extension in high-risk patients, many urologists will sacrifice the neurovascular bundles in such patients in an attempt to decrease the risk of positive surgical margins. In contrast, we frequently perform nerve-sparing in high-risk patients. We analyzed our outcomes in patients with preoperatively high-risk prostate cancer according to the D'Amico risk group classification, and stratified by nerve-sparing status.
Materials and methods
An institutional database of 1,503 robotic-assisted laparoscopic prostatectomies (RALP) was queried for patients presenting with PSA > 20 ng/ml, Gleason 8 or higher on biopsy, or clinical stage T2c or higher. Interfascial nerve-sparing was performed whenever oncologically feasible. Validated questionnaires were used to assess baseline and postoperative functional outcomes.
Results
Adequate follow-up was available in 123 high-risk patients. Mean serum PSA was 10.8. Bilateral, unilateral, and non-nerve-sparing was performed on 58%, 15%, and 27%, respectively. On final histopathology, 42% were organ confined; 55 patients had extraprostatic extension, and 35 had seminal vesicle invasion. Positive surgical margins occurred in 31%: 15% focal and 16% extensive. Favorable pathologic outcomes (organ-confined and negative surgical margins) were observed in 40%. Biochemical recurrence occurred in 20%. Nerve-sparing was associated with more favorable pathologic features, possibly due to selection bias. When controlling for adverse pathologic features, nerve-sparing was not associated with higher rates of positive surgical margins or biochemical recurrence. At a median follow-up of 13 months, 78% were continent and 56% were potent. The “trifecta” of continence, potency, and freedom from recurrence was achieved in 28 patients (23%).
Conclusions
Nerve-sparing robotic-assisted laparoscopic prostatectomy can be safely performed in patients with preoperatively high risk prostate cancer. Histopathologic and short-term oncologic outcomes at 13-month median follow-up are comparable to those in open surgical series from similar cohorts.
Keywords: Neoplasm , Prostate , Robotics , Prostatectomy
1. Introduction
Oncologic control is of paramount importance in all patients with prostate cancer, and especially in those with high risk disease. However, the 10-year biochemical-free progression rate is 40% in such patients [1], and the 15-year prostate-cancer specific mortality is 19% [2]. As such, even high-risk patients have a long life expectancy to live with the functional complications of prostatectomy. Given the associations between preservation of the neurovascular bundles and the recovery of erectile function [3] and urinary continence [4], nerve-sparing can significantly improve a man's quality of life following prostatectomy.
Questions have arisen regarding the safety of nerve-sparing in high risk patients, partly due to the lack of haptic feedback on the robotic console. However, there is no standardized approach to select patients for nerve-sparing. Some urologists will widely resect the neurovascular bundles of all high-risk patients in an attempt to reduce the risk of positive surgical margins. Others have developed various criteria to determine preoperatively which patients should undergo nerve-sparing, including preoperative potency, PSA, imaging, location and number of positive biopsy cores, and digital rectal exam findings. These have led to the development of side-specific nerve-preservation nomograms and partial nerve-sparing techniques [5], [6], [7], [8], [9], [10], [11].
In our experience, there are visual clues, enhanced by the improved lighting and magnification of the robotic system, which may be used in selecting patients robotically for nerve-sparing, as these may allow determination of the presence of extraprostatic extension. Poorly defined or sticky dissection planes, bulging of the prostatic capsule, or the appearance of prostate tissue on the preserved neurovascular bundle are all worrisome for the presence of a locally-advanced tumor. Intraoperative frozen section (IFS) can be used in such circumstances to complement the visual inspection. With some exceptions, we have not routinely sacrificed nerves based on preoperative characteristics alone. We have performed bilateral nerve-sparing on most patients, including many high risk patients.
To evaluate the oncologic safety of this approach, as well as to answer the broader question of whether the robot can be used safely to treat high-risk patients, we analyzed our RALP database to evaluate the short-term oncologic and functional outcomes of patients who were preoperatively considered high-risk according to the D'Amico risk group stratification [12]. We then stratified such patients by nerve-sparing status and compared their oncologic and functional outcomes.
2. Materials and methods
An internal institutional review board approved database was created for all patients undergoing RALP by a single surgeon (DBS). The database was queried for patients undergoing RALP with high-risk features according to the D'Amico risk group stratification until September 2009. All patients with either PSA > 20 ng/ml, biopsy Gleason scores of 8 to 10, or clinical stage T2c or higher were evaluated [12]. Patients with incomplete pathologic data or follow-up of less than 6 weeks after surgery were excluded. All studied patients had negative bone scans and pelvic imaging (CT or endorectal coil MRI). We attempted to obtain outside biopsy slides for institutional re-review in all cases.
All patients with biopsy-proven seminal vesicle invasion or clear extracapsular extension of tumor on endorectal coil MRI had wide excision of the neurovascular bundle on the affected side. Additional patients with high volume of high grade disease also had nerves sacrificed on the side(s) of the adverse features. In the remaining patients, the decision to perform nerve-sparing was based on the combination of preoperative characteristics and intraoperative observations. At times of suspicion of a positive margin, we utilized frozen section assessment of the neurovascular bundle or urethral margin at the site that was suspected. All patients underwent bilateral pelvic lymphadenectomy.
Functional outcomes were collected at baseline, 6 weeks, and then every 3 months for the first year after surgery, using International Prostate Symptom Scores (IPSS) and Sexual Health Inventory for Men (SHIM) scores. Follow-up PSA measurements were obtained at the same intervals. Continence was defined as the use of either no pads or one security pad daily. Potency was defined as a SHIM ≥ 16 in patients who were preoperatively potent (SHIM ≥ 16). A postoperative PSA > 0.2 ng/ml at least 6 weeks following surgery was considered a biochemical recurrence. As an indicator of systemic disease, patients were evaluated for a nadir PSA below the threshold of ultrasensitive detection (<0.01 ng/ml). Volume of cancer was estimated based on the percentage of slides containing tumor (the positive-block ratio) [13]. Tumor at the inked resection margin was considered a positive surgical margin. Positive margins were dichotomized into “focal” or “extensive” if the length of the margin was less than or greater than 2 mm, respectively [14].
Comparisons between nerve-sparing groups were performed using ANOVA and χ2 analysis for the trend for continuous and categorical variables, respectively. Multivariate logistic regression analysis was conducted of known prostate cancer risk factors in the prediction of surgical margin status and biochemical recurrence. Data were analyzed with SPSS version 17.0 (SPSS Inc., Chicago IL).
3. Results
A total of 1,503 RALPs were performed in the selected time period, 146 (9.7%) of which were in high-risk patients as per the D'Amico risk group stratification. Of these, 23 patients were excluded due to incomplete data or inadequate follow-up, leaving a cohort of 123 patients who constituted the studied population. Of the 123 men, 21 had PSA > 20, 99 had biopsy Gleason sums of 8 or higher, and 12 were clinical stage T2c or higher. Twelve patients had more than 1 high risk factor. Institutional re-review of biopsy slides was performed on 67% of the patients. All baseline characteristics are given in Table 1. The mean PSA was 10.8, and 42 patients had a palpable nodule on digital rectal exam. The majority of the patients (62%) were clinical stage T1c, and had a biopsy Gleason score of 8 or higher (81%).
Table 1. Preoperative characteristics stratified by nerve-sparing technique; n (%)
| Overall (n = 123) | Bilateral NS (n = 64) | Unilateral NS (n = 17) | Non-nerve-sparing (n = 29) | P value (trend) | |
|---|---|---|---|---|---|
| PSA, mean (ng/ml) | 10.8 | 10.6 | 13.3 | 11.1 | 0.618 |
| Clinical stage | |||||
 T1c | 69(62) | 46 | 6 | 12 | 0.04 |
| T2a–c | 37(33) | 14 | 7 | 11 | |
| T3 | 5(4.5) | 3 | 1 | 0 | |
| Biopsy Gleason sum | |||||
| 6 | 8(6.5) | 6(9.4) | 0(0) | 1(3.4) | 0.15 |
| 7 | 16(13) | 9(14) | 4(24) | 1(3.4) | |
| 8–10 | 99(81) | 49(77) | 13(76) | 27(93) | |
| No. of biopsies reviewed by institutional pathologist | 55(67) | 29(63) | 10(91) | 13(77) | 0.34 |
| % Positive cores, mean | 37% | 31% | 37% | 51% | 0.006 |
| No. of patients with erMRI | 35(28) | 18(28) | 9(53) | 8(28) | 0.07 |
| + ECE on erMRI | 15(43) | 7(39) | 3(33) | 5(63) | |
| + SVI on erMRI | 10(29) | 7(39) | 0(0) | 3(38) |
Pathologic features are shown in Table 2. The prostates were large, with a median size of 56 g (range: 19–187 g), and contained large amounts of tumor, as seen on a mean of 50% of the slides. Despite the high-risk preoperative features, 42% of the specimens were organ-confined on pathologic evaluation of the surgical specimen. Positive margins occurred in 31% overall, subdivided into 15% that were focal and 16% that were extensive. Favorable pathologic outcome, defined as organ-confined disease with negative margins, was observed in 40%.
Table 2. Pathologic characteristics stratified by nerve-sparing technique; n (%)
| Overall (n = 123) | Bilateral NS (n = 64) | Unilateral NS (n = 17) | Non-nerve-sparing (n = 29) | P value (trend) | |
|---|---|---|---|---|---|
| Prostate weight, mean (g) | 56 | 60 | 49 | 52 | 0.36 |
| Mean % slides involved with tumor | 50 | 45 | 53 | 58 | 0.23 |
| Pathologic stage | |||||
| T2a–c | 52(42) | 35(55) | 3(18) | 7(24) | 0.004 |
| T3a | 31(25) | 13(20) | 8(47) | 7(24) | |
| T3b | 35(28) | 15(23) | 6(35) | 12(41) | |
| T4 | 5(4.1) | 1(1.6) | 0(0) | 3(10) | |
| Pathologic Gleason sum | |||||
| 6 | 4(3.6) | 3(4.7) | 0(0) | 1(3.4) | <0.001 |
| 7 | 53(48) | 40(63) | 6(35) | 7(24) | |
| 8–10 | 53(48) | 21(33) | 11(65) | 21(72) | |
| Extraprostatic extension | 55(50) | 24(38) | 14(82) | 17(61) | 0.002 |
| Seminal vesicle invasion | 35(32) | 15(23) | 6(39) | 14(48) | 0.007 |
| Positive surgical margins | 0.007 | ||||
| Focal | 17(15) | 7(11) | 5(29) | 5(17) | 0.11 |
| Extensive | 18(16) | 6(9.4) | 2(12) | 10(34) | <0.001 |
| Negative margin, organ confined | 49(40) | 33(52) | 3(18) | 6(21) | 0.003 |
| No. node positive patients | 3 | 1 | 0 | 2 | 0.26 |
| Biochemical recurrence | 31(26) | 10(16) | 6(35) | 12(43) | 0.02 |
| Time to biochemical recurrence, mean (months) | 4.6 | 5.2 | 6.5 | 2.7 | 0.55 |
Compared with the biopsy Gleason sums, final histopathologic Gleason scores tended to regress toward a mean of 7. Of the patients with Gleason 6 on biopsy, 73% were upgraded to Gleason 7, but none to Gleason 8 or above. No biopsy Gleason 7 patients were downgraded, but 28% were upgraded to Gleason 8 or 9. The majority of patients with Gleason 8–10 on biopsy remained so; however, 35% were downgraded to Gleason 7 and 2% to Gleason 6.
Nerve-sparing was performed on the majority of patients: 58% underwent bilateral and 15% unilateral nerve-sparing procedures (Table 3). No information on nerve-sparing technique was available in 13 patients. Overall, patients who underwent bilateral nerve-sparing had better pathologic features: they were more likely to have organ-confined disease and less likely to have pathologic Gleason 8–10, extraprostatic extension, or seminal vesicle invasion than patients undergoing unilateral or non-nerve-sparing. Nerve-sparing status had a significant inverse association with surgical margins: 80% of patients who underwent bilateral nerve-sparing had negative margins compared with 59% and 49% of unilateral and non-nerve-sparing patients, respectively (P < 0.05). When stratified by pathologic stage, only 2 of 38 patients (5%) who underwent bilateral or unilateral nerve-sparing with organ-confined disease had positive margins (Fig. 1). On multivariate analysis, nerve-sparing status was not associated with increased risk of positive surgical margins or biochemical recurrence. Prostatic bed IFS was performed on 7 patients (7%), none of which were positive for carcinoma, although one IFS from the urethral margin contained benign prostatic glands.
Table 3. Intraoperative and functional outcomes
| Median follow-up, months (range) | 12.5 (2–75) |
|---|---|
| Nerve-sparing status (%) (n = 110) | |
| Bilateral nerve-sparing | 64(58) |
| Unilateral nerve-sparing | 17(15) |
| Non-nerve-sparing | 29(26) |
| Continence (%) (n = 102) | 88(78) |
| Potency (n = 95) | 40(56) |
| ED preop | 23 |
| Biochemical recurrence | 31(26) |
| Trifecta (% of total) | 28(23) |
| Estimated blood loss, mean | 84 ml |
| Length of stay, mean | 1.6 days |
| Operative time, mean | 147 minutes |
Fig. 1.
Surgical margin status by pathologic stage and nerve-sparing procedure. (Color version of figure is available online.)
Median follow-up was 12.5 months, ranging from 2 to 75 months. Biochemical failure occurred in 31 patients (26%). Twelve of these 31 had negative surgical margins. Only 7 of the 31 ever reached an undetectable PSA after surgery, the other 24 had biochemical persistence following prostatectomy.
Functional data is presented in Table 3. Information on continence was available on 102 patients (83% of total); 88 (78%) were continent. Information on erectile function was available in 95 patients, 23 of whom had severe erectile dysfunction preoperatively. Of the remaining 72 patients, 40 were potent (56%). The “trifecta” of continence, potency, and freedom from biochemical recurrence was observed in 28 patients (23% of the entire cohort).
4. Discussion
By definition, patients with high preoperative risk prostate cancer by the D'Amico classification are more likely to have non-organ-confined disease [12]. Patients with extraprostatic extension or seminal vesicle invasion are more likely to have tumor at the inked resection margin and are more likely to experience recurrence. As such, high risk patients are often treated more cautiously during prostatectomy than patients with lower risk disease. Various nomograms have been created to predict the presence and/or location of extraprostatic extension to guide urologists who would decide preoperatively to sacrifice one or both neurovascular bundles [5], [6], [7], [8], [9], [10], [11]. However, some urologists do not decide to sacrifice nerves based on preoperative information, but rather use intraoperative findings instead. The most common intraoperative finding at open radical prostatectomy that leads urologists to perform a wide excision of a neurovascular bundle is palpable tumor near the planned resection margin, so-called “haptic feedback” [15].
A possible shortcoming of current surgical robotic technology is the lack of such haptic feedback, obviating the ability to palpate a tumor intraoperatively. In our experience, however, the lack of haptic feedback has not been problematic, having been sufficiently compensated by the improved vision offered by the robotic system. Like many open surgeons, we base our nerve-sparing decisions on intraoperative findings, with the exception of previously characterized locally-advanced disease. Rather than using direct tactile information to identify areas at risk for a positive margin, we have found that visual clues can be used to suggest the presence of extensive tumor. With significant experience on the robotic console comes a recognition of the way tissue planes interact during dissection of the neurovascular bundles. The intraoperative finding of adherent dissection planes or a bulging prostatic capsule suggests aggressive disease and will prompt wide dissection of the neurovascular bundle on that side. If we are confronted with the appearance of prostatic tissue on the preserved neurovascular bundle (which is easier to identify given the improved magnification available during RALP), we excise the suspicious area and send it to pathology for frozen section. A positive frozen section will lead us to resect more tissue at that location.
In testing the safety of our technique, we examined 123 of our patients who were preoperatively high-risk according to the D'Amico classification, as these were the patients most likely to have aggressive disease [10]. We were able to spare both nerves in 58% of these patients and 1 nerve in an additional 15%. Doing so did not appear to compromise the oncologic efficacy of the procedure. In fact, PSM rates were lowest in those undergoing bilateral nerve-sparing (20%), likely due to more favorable tumor characteristics in this group.
This supports the 1 large case series of high grade cancer treated by RALP, which suggested that robotic outcomes were comparable to those in open series [16]. Reported PSM rates in high risk patients undergoing open RRP range from 24% to 47% (Table 4), [1], [17], [18], [19], [20]. Our overall PSM rate was 31%, well within the reported range and very similar to a high-risk cohort from Memorial Sloan-Kettering Cancer Center [16]. Additionally, a substantial proportion (49%) of the PSMs were focal, suggested by some to be oncologically equivalent to negative margins [14], [21]. Favorable pathologic outcomes were found in 40%, similar to the rate in open RRP from the SEARCH database (41%) [1].
Table 4. Results of radical prostatectomy in preoperatively high-risk cohorts
| Author | Institution | Definition | N | Open/robot | % path T3/T4 | % PSM | % OC, neg. surg. margin |
|---|---|---|---|---|---|---|---|
| Donohue 17 | MSKCC | Bx Gl 8–10 | 238 | Open | 66 | 32 | n/a |
| Bastian 1 | SEARCH JHU | Bx Gl 8–10 | 149 220 | Open | n/a | 47 29 | 21 41 |
| Manoharan 18 | Miami | Bx Gl 8–10 | 79 | Open | 70 | 41 | n/a |
| Brandli 19 | IU | PSA > 20 | 50 | Open | 63 | 46 | n/a |
| Nguyen 20 | Pitie-Salp. | PSA > 20 | 41 | Open 83% | 49 | 36 | 46 |
| Shikanov 16 | U Chicago | Bx Gl 8–10 | 70 | Robotic | 53 | 24 | 44 |
| Current study | Mt. Sinai | D'Amico | 123 | Robotic | 57 | 31 | 40 |
One-year median follow-up may be an inadequate length of time by which to judge biochemical relapse rates or create actuarial relapse rates projected to more distant time points. Taking this into consideration, our BCR rate of 26% was found to be similar to 1-year BCR rates extrapolated from Kaplan-Meier curves of high risk open RRP series with longer follow-up [1], [17], [22], [23]. The fact that 39% of our BCRs happened in patients with negative surgical margins, and only 6 of the remaining 19 (32%) ever reached undetectable PSA levels, suggests that the vast majority of our biochemical failures were systemic rather than local. However, longer follow-up is warranted before final conclusions can be drawn about the oncologic safety of this procedure in high-risk patients.
An important concern is the high rate of downgrading (37%) seen in our cohort. This is consistent with previous reports [1], [17], and can be partially explained by “regression toward the mean,” a common statistical phenomenon observed when a “variable that is extreme on its first measurement will tend to be closer to the center of the distribution at the time of later measurement” [24]. As our patients were selected on the basis of their having high-risk features, our population is skewed, and a natural downgrading might be expected because of statistical probability alone. Another possible explanation is that as a referral center, many preoperative biopsies are read by community pathologists, whereas our prostatectomy specimens were read by dedicated genitourinary pathologists. To minimize this discrepancy, we attempted to have our institutional pathologists re-review all outside biopsy slides; we were successful in obtaining them two-thirds of the time.
It is possible that the high rate of downgrading is responsible for our favorable outcomes, and that our population was not “truly” high risk as defined by final histopathologic findings. Although this may be true, treatment decisions are based on preoperative findings. A high rate of downgrading and downstaging reinforces the well-described limitations of accurate preoperative staging of prostate cancer patients. This is important, as this is a group of patients who, had they opted for radiation, would have likely received high-dose radiation therapy with at least 6 months of androgen deprivation [25]. Based on our histopathologic data, a large portion of such patients would have been overtreated, as 42% had organ-confined disease.
While oncologic control is of paramount importance in all patients with prostate cancer, many with high risk disease may have a long life expectancy to live with the functional complications of prostatectomy. The primary reason for performing nerve-sparing is to improve a patient's quality of life after prostatectomy. For this reason, we have reported our short-term functional outcomes. Despite short follow-up and incomplete data, our overall continence rate was 78% and our potency rate was 56%. A cohort of 23% of the studied population achieved the proverbial “trifecta.” Only 1 study has reported potency outcomes in a high risk population, with a potency rate of 29% [26]. Our outcomes improve upon this and are within reported ranges of large published series of patients with lower risk disease [23], [27]. Higher risk patients are less likely to undergo nerve-sparing, which in turn has been shown to worsen functional outcomes. As such, it would be expected that the functional outcomes in any high risk cohort would be worse than those in the more heterogeneous populations previously reported.
As the body of research grows in support of adjuvant radiation for patients with pathologic T3 disease [28], a potential criticism is raised regarding the futility of nerve-sparing in such patients. If patients are likely to receive ionizing radiation to their spared neurovascular bundles, is it worth the risk and time to nerve-spare? Our response would again point to the inaccuracies of preoperative clinical staging, as a large portion of even these high-risk patients (40%) had organ-confined disease with negative margins. Until we are better able to predict preoperatively those who will have advanced disease, we should attempt to maximize functional outcomes.
We understand the concerns regarding the performance of nerve-sparing in high-risk patients, and recognize the potential morbidity and mortality associated with a positive surgical margin. The ability to recognize visual clues and react to them is a skill developed with experience, much like modifying an open prostatectomy after palpating tumor. As such, we would not advocate this technique in novice surgeons, but we believe others can learn these techniques as their robotic experience grows.
5. Conclusions
Nerve-sparing robotic-assisted laparoscopic prostatectomy can be safely performed in patients with preoperatively high risk prostate cancer. Histopathologic and short-term oncologic outcomes are comparable to open surgical series from similar cohorts. The use of visual clues by an experienced robotic surgeon to determine the need for nerve-sparing is a safe and efficacious procedure.
References
- Clinical and pathologic outcome after radical prostatectomy for prostate cancer patients with a preoperative Gleason sum of 8 to 10 . Cancer . 2006;107:1265–1272
- Prostate cancer-specific mortality after radical prostatectomy for patients treated in the prostate-specific antigen era . J Clin Oncol. 2009;27:4300–4305
- Sexual function following radical prostatectomy: Influence of preservation of neurovascular bundles . J Urol . 1991;145:998–1002
- Risk factors for urinary incontinence after radical prostatectomy . J Urol . 1996;156:1707–1713
- Planned nerve preservation to reduce positive surgical margins during robot-assisted laparoscopic radical prostatectomy . J Endourol . 2008;22:1303–1309
- Preoperative and intraoperative risk factors for side-specific positive surgical margins in laparoscopic radical prostatectomy for prostate cancer . Eur Urol . 2007;51:764–771
- A validated strategy for side specific prediction of organ confined prostate cancer: A tool to select for nerve-sparing radical prostatectomy . J Urol . 2001;165:857–863
- Validation of a nomogram for prediction of side specific extracapsular extension at radical prostatectomy . J Urol . 2006;175:939–944 Discussion 44
- Predicting the presence and side of extracapsular extension: A nomogram for staging prostate cancer . J Urol . 2004;171:1844–1849 Discussion 9
- Site-specific positive margins at radical prostatectomy: Assessing cancer-control benefits of wide excision of the neurovascular bundle on a side with cancer on biopsy . BJU Int . 2003;91:219–222
- Prediction of extraprostatic extension in the neurovascular bundle based on prostate needle biopsy pathology, serum prostate specific antigen, and digital rectal examination . J Urol . 2005;173:450–453
- Pretreatment nomogram for prostate-specific antigen recurrence after radical prostatectomy or external-beam radiation therapy for clinically localized prostate cancer . J Clin Oncol . 1999;17:168–172
- Positive-block ratio in radical prostatectomy specimens is an independent predictor of prostate-specific antigen recurrence . Am J Surg Pathol . 2007;31:877–881
- Length of positive surgical margin after radical prostatectomy as a predictor of biochemical recurrence . J Urol . 2009;182:139–144
- Intraoperative prostate examination: Predictive value and effect on margin status . BJU Int . 2005;96:1005–1008
- Robotic laparoscopic radical prostatectomy for biopsy Gleason 8 to 10: Prediction of favorable pathologic outcome with preoperative parameters . J Endourol . 2008;22:1477–1481
- Poorly differentiated prostate cancer treated with radical prostatectomy: Long-term outcome and incidence of pathological downgrading . J Urol . 2006;176:991–995
- Outcome after radical prostatectomy with a pretreatment prostate biopsy Gleason score of ≥8 . BJU Int . 2003;92:539–544
- Biochemical disease-free survival in patients with a high prostate-specific antigen level (20–100 ng/ml) and clinically localized prostate cancer after radical prostatectomy . BJU Int . 2003;92:19–22 Discussion 23
- Oncologic outcome after radical prostatectomy in men with PSA values above 20 ng/ml: A monocentric experience . World J Urol. 2009;27:653–658
- Natural history of biochemical progression after radical prostatectomy based on length of a positive margin . Urology . 2008;71:308–312
- Secondary therapy, metastatic progression, and cancer-specific mortality in men with clinically high-risk prostate cancer treated with radical prostatectomy . Eur Urol . 2008;53:950–959
- Retropubic, laparoscopic, and robot-assisted radical prostatectomy: A systematic review and cumulative analysis of comparative studies . Eur Urol. 2009;55:1037–1063
- . A dictionary of statistics . 2nd ed.. Oxford (UK): Oxford University Press; 2008;
- Androgen suppression and radiation vs. radiation alone for prostate cancer: A randomized trial . JAMA . 2008;299:289–295
- Preoperative criteria to select patients for bilateral nerve-sparing robotic-assisted radical prostatectomy . J Sex Med. 2009; in press
- Urinary and sexual function after radical prostatectomy for clinically localized prostate cancer: The Prostate Cancer Outcomes Study . JAMA . 2000;283:354–360
- Adjuvant radiotherapy for pathologic T3N0M0 prostate cancer significantly reduces risk of metastases and improves survival: Long-term follow-up of a randomized clinical trial . J Urol . 2009;181:956–962
PII: S1078-1439(09)00376-7
doi:10.1016/j.urolonc.2009.11.023
© 2012 Elsevier Inc. All rights reserved.
Volume 30, Issue 1 , Pages 26-32, January 2012
