Impact of Adjuvant Radiation Therapy on Urinary Continence Recovery After Radical Prostatectomy

EUROPEAN UROLOGY 65 (2014) 546–551

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Impact of Adjuvant Radiation Therapy on Urinary Continence Recovery After Radical Prostatectomy Nazareno Suardi *, Andrea Gallina, Giuliana Lista, Giorgio Gandaglia, Firas Abdollah, Umberto Capitanio, Paolo Dell’Oglio, Alessandro Nini, Andrea Salonia, Francesco Montorsi, Alberto Briganti Department of Urology, Urological Research Institute, University Vita-Salute San Raffaele, Milan, Italy

Article info

Abstract

Article history: Accepted January 24, 2013 Published online ahead of print on February 4, 2013

Background: Little is known about the impact of adjuvant radiation therapy (aRT) after radical prostatectomy (RP) on urinary continence (UC). Objective: To evaluate the impact of aRT on UC recovery in patients with unfavourable pathologic characteristics. Design, setting, and participants: The study included 361 patients with either pT2 with positive surgical margin(s) or pT3a/pT3b node-negative disease treated with RP at a tertiary care referral centre. Intervention: Patients were stratified according to the administration of aRT into two groups: group 1 (no aRT; n = 208; 57.8%) and group 2 (aRT; n = 153; 42.2%). Outcome measurements and statistical analysis: Continence was defined as no use of protective pads. Log-rank test was used to compare the rate of UC recovery according to aRT status. The association between aRT and UC was also tested in Cox regression models after accounting for age, Cancer of the Prostate Risk Assessment (CAPRA) score, nerve-sparing (NS) status, Charlson Comorbidity Index, body mass index, and year of surgery. Results and limitations: At a mean follow-up of 30 mo, 254 patients (70.4%) recovered complete UC. The 1- and 3-yr UC recovery was 51% and 59% for patients submitted to aRT versus 81% and 87% for patients not receiving aRT, respectively ( p < 0.001). At univariable analysis, older age ( p < 0.001), presence of non–organ-confined disease ( p < 0.001), non-NS procedure ( p < 0.001), and delivery of aRT ( p < 0.001) were significantly associated with lower UC. At multivariable analysis, the delivery of aRT remained an independent predictor of worse UC recovery (hazard ratio: 0.57; p = 0.001). Patients treated with aRT had a 1.6-fold higher risk of incontinence. Younger age ( p = 0.02), lower CAPRA score ( p = 0.03), and NS approach ( p < 0.001) also represented independent predictors of UC recovery. The main limitations of the study are related to the lack of validated questionnaires in the evaluation of UC and in the lack of information regarding UC status at aRT. Conclusions: The delivery of aRT has a detrimental effect on UC. The oncologic benefits must be balanced with an impaired UC recovery. Patients should be informed of such impairment before adjuvant treatments are planned. # 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Keywords: Prostate cancer Radical prostatectomy Adjuvant radiation therapy Urinary continence

* Corresponding author. Department of Urology, Urological Research Institute, University Vita-Salute San Raffaele, Via Olgettina 60, 20132 Milan, Italy. Tel. +39 02 26435663; Fax: +39 02 26437298. E-mail address: [email protected] (N. Suardi).

0302-2838/$ – see back matter # 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.eururo.2013.01.027

EUROPEAN UROLOGY 65 (2014) 546–551

1.

Introduction

547

patient in the non-aRT group received salvage RT within the study period. Patients previously submitted to surgery for benign prostatic

Radical prostatectomy (RP) represents an effective treatment for patients with organ-confined prostate cancer (PCa), associated with excellent long-term cancer control and acceptable morbidity [1]. However, up to 30% of patients undergoing RP are diagnosed with locally advanced disease (pT3a) with or without positive surgical margins at final pathology [2]. The presence of positive surgical margins, extracapsular extension, and/or seminal vesicle invasion is associated with higher rates of biochemical recurrence as well as of metastatic progression after RP [3,4]. Three prospective randomised trials reported improved cancer recurrence–free rates in patients affected by PCa with poor pathologic characteristics receiving adjuvant radiotherapy (aRT), although in those studies salvage radiation therapy (RT) was delivered at high prostatespecific antigen (PSA) levels in most of the patients not receiving immediate aRT. However, little is known concerning the potential urologic side effects of aRT, namely erectile dysfunction (ED) and the recovery of urinary continence (UC). Although the effect of aRT on ED might be of relative interest for patients with locally advanced disease, the potential detrimental effect of aRT on UC recovery represents a major issue. Nevertheless, only a few studies addressed the association between aRT and UC recovery, reporting controversial results [5–7]. All these studies originated from small series, mainly based on noncontemporary patients. None of these studies extensively accounted for all parameters associated with postoperative UC recovery, such as cancer stage and grade, patient comorbidity [8], and surgical technique (namely, nerve sparing [NS] vs non-NS) [9]. This is key because UC recovery after RP represents a multifactorial time-dependent phenomenon. To address this issue, we evaluated the impact of aRT on UC recovery in a series of contemporary patients with unfavourable PCa characteristics treated with RP.

enlargement were excluded from the analyses, as well as patients reporting the use of any pad before surgery [12]. UC recovery was defined as the use of no pads [13]. Patients were followed up at 1, 3, 6, and 12 mo postoperatively and every 6 mo thereafter. At each visit postoperative UC recovery was assessed. Patients were stratified according to the administration of aRT into two groups: group 1 (no aRT; n = 208; 57.8%) and group 2 (aRT; n = 153; 42.2%). Administration of aRT was based on the indication given by each treating physician and followed extensive discussion with patients about treatment options and expectations. In patients treated with aRT, it was delivered within a period of 1–6 mo after surgery. The details of the RT techniques used in the treatment of these patients were previously published [14]. In this context, it should only be emphasised that all patients received a three-dimensional conformal approach: the clinical target volume (CTV) was drawn on computed tomography (CT) images by the physicians and included the prostatic fossa and periprostatic tissue: clinical findings, presurgery CT scan, and surgical clips guided the clinicians in defining the CTV. The planned target volume (PTV) was defined as the CTV plus a 1-cm margin (to account for organ motion and set-up error). A small margin around the PTV (ie, 0.8–1 cm) was retained only for the posterior orientation (ie, at the interface between PTV and rectum), resulting in a more rectumsparing technique when compared with our conventional treatment. All patients received irradiation of the prostatic bed only to a median dose of 70.2 Gy (interquartile range [IQR]: 65.8–72.0). With respect to the volumes irradiated, the seminal vesicles bed was always irradiated regardless of the pathologic stage (pT2, pT3a, or pT3b) with a median dose delivered to the seminal vesicles bed of 60–61 Gy. All treatments were delivered at conventional fractionation (1.8 Gy per fraction).

2.1.

Statistical analyses

Descriptive statistics were performed with the independent t test for continuous variables and with the Pearson chi-square test for categorical variables, respectively. Kaplan-Meier univariable analyses targeted time to UC recovery after surgery according to the delivery of aRT in the overall population as well as in the population of patients treated with a bilateral NS approach. The log-rank test was used to compare the rate of UC recovery over time according to aRT status. Second, the association between aRT and UC recovery was tested in univariable and multivariable Cox regression models. Covariates consisted of patient age at

2.

Materials and methods

surgery, Cancer of the Prostate Risk Assessment (CAPRA) score (used as a proxy for disease severity) [15], NS technique, categorised CCI, and

Since September 2002, data from patients treated with RP at our centre

preoperative BMI. Multivariable analyses were also adjusted for the year

were collected in a prospective institutional review board database. All

of surgery to minimise the impact of different RT schedules and of

patients were asked to provide informed consent to be included

surgical skills over time. Finally, univariable and multivariable Cox

anonymously in the database. Among all patients treated with RP at our

regression analyses were performed in patients submitted to aRT only to

institution, we analysed data from 361 men diagnosed with either pT2

identify predictors of delayed continence recovery including as

disease and positive surgical margin(s) or pT3a/pT3b node-negative

covariates time from RP to aRT delivery and total radiation dose.

disease between January 2006 and October 2011 treated with open RP.

Statistical analyses were performed using SPSS v.17 (IBM Corp., Armonk,

The pathologic inclusion criteria had been previously adopted by a

NY, USA), with a two-sided significance level set at p < 0.05.

prospective randomised trial testing the role of aRT after RP. All patients had complete preoperative clinical data including age at

3.

Results

surgery, PSA at diagnosis, clinical stage, biopsy Gleason sum, percentage of positive cores at biopsy, comorbidity profile assessed by the Charlson Comorbidity Index (CCI; stratified into 1 and 2) [10], and body mass index (BMI). All patients were treated with RP performed by seven highvolume surgeons. An NS approach, when indicated, was performed with a previously described technique [11]. NS status at surgery was defined by each operating surgeon at the end of the procedure and reported in our prospectively collected database. No patient received neoadjuvant, adjuvant, or salvage hormonal therapy during the study period. No

Table 1 shows the preoperative clinical characteristics of the 361 patients included in the study. Several statistically significant differences were noted between the two groups of patients (namely aRT vs no aRT; Table 1). Men treated with aRT were older ( p = 0.01), had a higher clinical and pathologic stage ( p = 0.01 and p < 0.001, respectively) distribution as well as Gleason score ( p < 0.001) as

548

EUROPEAN UROLOGY 65 (2014) 546–551

Table 1 – Patient characteristics and descriptive statistics in the overall population and according to adjuvant radiation therapy status n No. of patients (%) Age at surgery, yr Mean (median) IQR PSA, ng/ml Mean (median) IQR Body mass index Mean (median) IQR Charlson Comorbidity Index (%) 0 1 2 Clinical stage distribution (%) T1c T2 T3 RP Gleason sum (%) 2–6 7 8–10 Pathologic stage (%) pT2 pT3a pT3b Positive surgical margins Yes No CAPRA score Mean (median) IQR Nerve-sparing status (%) Yes No Radiation dose, Gy Mean (median) IQR Time to aRT, mo Mean (median) IQR

361

aRT 153 (42.4)

No aRT 208 (57.6)

p value –

63.9 (64.2) 58.9–68.6

65.0 (65.1) 60.8–69.2

63.2 (63.6) 57.5–68.3

0.01

11.5 (6.8) 5.0–8.3

13.7 (8.0) 5.5–12.2

9.9 (6.2) 4.6–8.6

0.12

26.2 (25.9) 24.1–27.9

26.4 (26.2) 24.1–28.7

26.0 (25.9) 24.1–27.4

0.22

277 (76.7) 69 (19.1) 15 (4.2)

115 (75.2) 29 (19.0) 9 (5.8)

162 (77.9) 40 (19.2) 6 (2.9)

0.37

191 (52.9) 124 (34.3) 46 (12.8)

66 (42.9) 63 (41.4) 24 (15.8)

124 (59.7) 62 (29.6) 22 (10.7)

0.01

61 (17.0) 234 (64.8) 66 (18.2)

12 (7.7) 94 (61.5) 47 (30.8)

47 (22.6) 133 (63.9) 18 (8.7)

<0.001

134 (37.1) 141 (39.1) 86 (23.8)

21 (13.8) 66 (43.1) 66 (43.1)

113 (54.3) 75 (36.1) 20 (9.6)

<0.001

122 (33.7) 239 (66.3)

59 (38.7) 94 (61.3)

63 (30.1) 145 (69.9)

0.1

2.9 (3) 2–5

3.4 (3) 2–5

2.4 (2) 1–3

<0.001

232 (64.3) 129 (35.7)

82 (53.6) 71 (46.4)

150 (72.1) 58 (27.9)

<0.001

– –

68.9 (70.2) 65.8–72

– –

–

– –

4.5 (4.3) 3.4–5.1

– –

–

aRT = adjuvant radiation therapy; CAPRA = Cancer of the Prostate Risk Assessment; IQR = interquartile range; NS = nerve sparing; PSA = prostate-specific antigen; RP = radical prostatectomy.

compared with their counterparts treated by RP alone. A significantly lower proportion of patients submitted to aRT received a bilateral NS procedure (53.6% vs 72.1%, respectively; p < 0.001). At a mean follow-up of 30 mo after surgery (median: 23, range: 11–44), 254 patients (70.4%) recovered complete UC. Overall, UC recovery rate at 1 and 3 yr was 68% and 75%, respectively. The 1- and 3-yr UC recovery was 51% and 59% for patients submitted to aRT versus 81% and 87% for patients who did not receive aRT, respectively ( p < 0.001; Fig. 1A). When the Kaplan-Meier analysis was repeated separately in patients submitted to NS surgery only (Fig. 1B), UC at 1 and 3 yr was recovered in 67% and 73% versus 85% and 91% of patients who received aRT versus patients who were treated by RP alone, respectively ( p < 0.001). Table 2 shows univariable and multivariable Cox regression analyses predicting UC recovery after surgery. At univariable analysis, older age at surgery ( p < 0.001),

higher CAPRA score ( p < 0.001), a non-NS procedure ( p < 0.001), higher CCI ( p = 0.03), and the delivery of aRT ( p < 0.001) were significantly associated with lower UC recovery rates after RP. In contrast, BMI was not significantly associated with UC recovery. The results were confirmed at multivariable analysis, where the delivery of aRT remained an independent predictor of delayed UC recovery (hazard ratio [HR]: 0.57; p = 0.001), even after accounting for all other predictors and after adjusting for the year of treatment. Patients treated with RP alone had a 1.6-fold higher probability of recovering UC compared with those receiving aRT after accounting for all covariates. Younger age at surgery ( p = 0.02), lower CAPRA score ( p = 0.03), and a bilateral NS approach ( p < 0.001) also represented independent predictors of UC recovery after RP. The results of the multivariable analysis were confirmed in a propensity score matched analysis, after 1:1 matching of patients submitted to aRT (n = 147) with patients not submitted to aRT (n = 147). At the multivariable analysis

549

EUROPEAN UROLOGY 65 (2014) 546–551

Table 2 – Univariable and multivariable Cox regression analyses addressing urinary continence recovery after radical prostatectomy (n = 361) Univariable analysis

Age at surgery Year of treatment CAPRA score Bilateral NS vs nonbilateral NS Adjuvant RT vs no RT Charlson Comorbidity Index 1 vs 0 2 vs 0 BMI, kg/m2

Multivariable analysis

HR (95% CI)

p value

0.96 (0.95–0.98) 1.2 (1.12–1.28) 0.83 (0.77–0.9) 2.43 (1.82–3.25) 0.49 (0.37–0.63)

<0.001 <0.001 <0.001 <0.001 <0.001

0.68 (0.49–0.96) 1.1 (0.6–2.02) 0.99 (0.95–1.03)

0.03 0.8 0.85

HR (95% CI) 0.98 1.18 0.91 1.88 0.57

(0.96–0.99) (1.1–1.27) (0.84–0.99) (1.34–2.64) (0.43–0.76)

0.79 (0.56–1.14) 1.28 (0.69–2.39) 1.03 (0.99–1.08)

p value 0.02 <0.001 0.03 <0.001 <0.001 0.2 0.4 0.2

BMI = body mass index; CAPRA = Cancer of the Prostate Risk Assessment; CI = confidence interval; HR = hazard ratio; NS = nerve sparing; RT = radiation therapy.

(matched patients only), after adjusting for age, CAPRA score, NS status, BMI, categorised CCI, and year of treatment, the delivery of aRT was associated with worse UC recovery (HR: 0.62; p = 0.002). When the multivariable Cox regression analyses were performed in patients treated with aRT only (Table 3), neither total radiation dose nor time to aRT initiation represented independent predictors of delayed UC recovery. Conversely, the adoption of a bilateral NS approach (HR: 2.33; p = 0.03) represented an independent predictor of improved UC.

[(Fig._1)TD$IG] (A)

1.0 No adjuvant RT

% connence

0.8

0.6

Adjuvant RT

0.4

4.

p<0.001 0.2 % connence

0.0 0

12 months

24 months

36 months

Adjuvant RT

51

57

59

No adjuvant RT

81

86

87

12

24

36

Time to connence recovery

(B) 1.0

No adjuvant RT

0.8

% connence

Adjuvant RT 0.6

0.4

p<0.001

0.2

12 months

24 months

36 months

Adjuvant RT

67

70

73

No adjuvant RT

85

90

91

% connence

0.0 0

12

24

Time to connence recovery

36

Fig. 1 – Kaplan-Meier curve depicting time to urinary continence recovery (A) in 361 patients treated with radical prostatectomy and (B) in 232 patients treated with bilateral nerve-sparing radical prostatectomy, stratified according to the delivery of adjuvant radiation therapy.

Discussion

Our study, based on a population of men with positive surgical margins and/or pT3 disease (n = 361), demonstrates that the delivery of aRT has a detrimental effect on UC recovery after RP. Such an effect was noted even after accounting for several confounders including patient age and comorbidity profile, PCa characteristics, and NS status. In contrast to previous studies, we also accounted for the time to UC recovery by using Kaplan-Meier and Cox regression analyses. Such multivariable assessment represents the major strength of our study because UC recovery represents a multifactorial, time-dependent phenomenon. We believe that these results are important due to the ongoing debate about the optimal treatment of locally advanced and positive surgical margins patients. Indeed, although previous level 1 evidence studies have shown that aRT improves cancer control in these patients, most patients with pT3 disease and/or positive surgical margins are not currently receiving aRT [16]. The reasons might reside in possible aRT-related toxicity and the lack of a clear benefit of aRT on patient survival. However, to date only a few studies have addressed the effect of aRT on UC recovery, which represents the major determinant of quality of life of surgically treated patients. Interestingly, these studies showed controversial results [6,7,17–19]. Van Cangh et al. reported on a randomised controlled trial investigating UC recovery on 100 patients treated with RP alone or with RP and aRT. The authors did not find significant differences in UC recovery between the two

550

EUROPEAN UROLOGY 65 (2014) 546–551

Table 3 – Univariable and multivariable Cox regression analyses predicting urinary continence recovery in patients submitted to adjuvant radiation therapy (n = 153) Univariable analysis

Age at surgery Year of treatment CAPRA score Bilateral NS vs nonbilateral NS RT dose, Gy Time to aRT initiation

Multivariable analysis

HR (95% CI)

p value

0.96 (0.95–0.98) 1.2 (1.12–1.28) 0.83 (0.77–0.9) 2.43 (1.82–3.25) 0.96 (0.89–1.04) 0.98 (0.81–1.19)

<0.001 <0.001 <0.001 <0.001 0.35 0.88

HR (95% CI) 0.98 1.25 0.99 2.33 1.01 1.03

(094–1.08) (1.02–1.54) (0.83–1.25) (0.92–5.26) (0.91–1.11) (0.82–1.29)

p value 0.54 0.02 0.94 0.03 0.92 0.79

aRT = adjuvant radiation therapy; CAPRA = Cancer of the Prostate Risk Assessment; CI = confidence interval; HR = hazard ratio; NS = nerve sparing; RT = radiation therapy.

groups of patients. Despite the excellent study design, it needs to be acknowledged that their study was based on a small number of patients submitted to RT (n = 48) and that the RT dose (60 Gy) was lower than that used in our series [7]. In 1996 Formenti et al. reported the results of a study investigating the effects of aRT on UC recovery after RP [5]. In that study, as well as in the update published with a 3-yr follow-up [17], the authors did not find significant differences in terms of UC recovery between patients who did and who did not undergo aRT. However, some points need to be addressed. First, patients were only evaluated 1 yr after treatment, whereas the most critical period for UC recovery is within the first year [20]. Second, the delivered doses of RT were extremely low (45–55 Gy) as compared with those that are currently recommended [21]. It has to be acknowledged that in our study neither radiotherapy dose not time to aRT delivery were significantly associated with the rate of UC recovery. However, these results must be interpreted with care because our patients were submitted to aRT with very homogeneous doses (mean: 68.9; IQR: 65.8–72 Gy) and timing of aRT delivery (mean: 4.5; IQR: 3.4–5.1 mo). In contrast, our findings corroborate the results of some previous studies where the delivery of aRT was associated with higher rates of incontinence. First, Hofmann et al. demonstrated that patients submitted to aRT had worse rates of UC recovery at 4- and 8-mo follow-up, whereas at 12 mo such differences were not significant [22]. Again, some limitations need to be considered because only 30 patients received RT and a median dose of 54 Gy was used in this series; therefore the results must be interpreted with caution. Second, also in the randomised trial by Thompson et al., men receiving aRT had significantly higher rates of total UC as compared with controls (6.5 vs 2.8 respectively) [18], whereas in the randomised study reported by Bolla et al., UC was not considered among the side effects of RT [23]. The relation between irradiation and impaired UC recovery needs to be found in animal studies, although the pathophysiology of radiation-induced bladder injury is not fully understood. Irradiation may cause injury in the urothelium, in the vasculature as well as in bladder muscle [24]. All these mechanisms when associated with the injuries related to a recent surgical intervention might explain the results observed in our study.

In our analyses, BMI was not independently associated with a delayed return to UC. However, it must be recognised that the IQR of BMI in our patient population was narrow, and only 8% of the population included had a BMI >30 kg/m2. This might partially explain the lack of significance of BMI in predicting UC recovery in our study. Interestingly, increasing year of treatment was a significant predictor of faster UC outcome. This might be due to refinements in either surgical or radiation technique over the study period. In our study, a strong correlation between NS technique and UC recovery was observed. There are several possible explanations for this association, such as the preservation of membranous urethral blood flow that may in turn lead to maintained vascular blood supply to the external urinary sphincter. However, this association might simply represent the consequence of a more careful apical dissection during the NS approach [9]. These hypotheses need to be tested in future studies. Despite several strengths, our study has some limitation. First, we do not have information regarding the continence status at the delivery of aRT. However, all patients were continent before surgery, and our data can be safely used to analyse the results of the combination therapy with RP and aRT. Second, we used pad usage as a definition of UC; other studies used different parameters. UC assessment should be performed with validated instruments such as the Expanded Prostate Cancer Index Composite questionnaire [25], clinical evaluation, and instrumental diagnostic tools. The use of more than one parameter would be more accurate as compared with pad usage only. However, it has been demonstrated that pad testing provides an inexpensive and simple form of objective assessment in patients with bothersome incontinence and that patients made lifestyle changes proportional to the level of incontinence [13,26]. Finally, aRT could also induce an impairment in urinary function related to storage symptoms, strictures, and urge incontinence. Unfortunately, data addressing these issues are not available in our cohort of patients. All these limitations might be solved only by the consideration of the results of randomised trials comparing adjuvant and salvage RT after RP. 5.

Conclusions

The delivery of aRT has a detrimental effect on UC recovery itself as well as on time to UC recovery in patients treated

EUROPEAN UROLOGY 65 (2014) 546–551

with RP. Therefore, the oncologic benefits of aRT must be balanced with an impaired UC recovery, and patients should be informed of such impairment before adjuvant treatments are planned.

551

[9] Suardi N, Moschini M, Gallina A, et al. Nerve-sparing approach during radical prostatectomy is strongly associated with the rate of postoperative urinary continence recovery. BJU Int 2013;111: 717–22. [10] Charlson ME, Pompei P, Ales KL, et al. A new method of classifying prognostic comorbidity in longitudinal studies: development and

Author contributions: Nazareno Suardi had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

validation. J Chronic Dis 1987;40:373–83. [11] Montorsi F, Salonia A, Suardi N, et al. Improving the preservation of the urethral sphincter and neurovascular bundles during open radical retropubic prostatectomy. Eur Urol 2005;48:938–45.

Study concept and design: Suardi, Gallina, Lista, Montorsi, Briganti. Acquisition of data: Suardi, Gandaglia, Capitanio, Dell’Oglio, Nini, Briganti. Analysis and interpretation of data: Suardi, Gallina, Abdollah, Briganti.

[12] Colombo R, Naspro R, Salonia A, et al. Radical prostatectomy after previous prostate surgery: clinical and functional outcomes. J Urol 2006;176:2459–63. [13] Liss MA, Osann K, Canvasser N, et al. Continence definition after

Drafting of the manuscript: Suardi, Lista, Montorsi, Briganti.

radical prostatectomy using urinary quality of life: evaluation

Critical revision of the manuscript for important intellectual content:

of patient reported validated questionnaires. J Urol 2010;183:

Suardi, Gallina, Lista, Abdollah, Gandaglia, Capitanio, Dell’Oglio, Salonia, Nini, Montorsi, Briganti.

1464–8. [14] Cozzarini C, Montorsi F, Fiorino C, et al. Need for high radiation dose

Statistical analysis: Suardi, Gallina, Briganti.

(>or = 70 gy) in early postoperative irradiation after radical pros-

Obtaining funding: Montorsi.

tatectomy: a single-institution analysis of 334 high-risk, node-

Administrative, technical, or material support: Montorsi. Supervision: Montorsi, Briganti. Other (specify): None. Financial disclosures: Nazareno Suardi certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: None. Funding/Support and role of the sponsor: None.

negative patients. Int J Radiat Oncol Biol Phys 2009;75:966–74. [15] Cooperberg MR, Pasta DJ, Elkin EP, et al. The University of California, San Francisco Cancer of the Prostate Risk Assessment score: a straightforward and reliable preoperative predictor of disease recurrence after radical prostatectomy. J Urol 2005;173:1938–42. [16] Ghia AJ, Shrieve DC, Tward JD. Adjuvant radiotherapy use and patterns of care analysis for margin-positive prostate adenocarcinoma with extracapsular extension: postprostatectomy adjuvant radiotherapy: a SEER analysis. Urology 2010;76:1169–74. [17] Formenti SC, Lieskovsky G, Skinner D, et al. Update on impact of moderate dose of adjuvant radiation on urinary continence and sexual potency in prostate cancer patients treated with nervesparing prostatectomy. Urology 2000;56:453–8.

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