Scandinavian Journal of Urology. 2014; 48: 356–366

ORIGINAL ARTICLE

Early biochemical recurrence, urinary continence and potency outcomes following robot-assisted radical prostatectomy

KASPER DRIMER BERG1, FREDERIK BIRKEBÆK THOMSEN1, HELLE HVARNESS2, IB JARLE CHRISTENSEN3 & PETER IVERSEN1,2 1

Copenhagen Prostate Cancer Center, Department of Urology, Rigshospitalet, University of Copenhagen, Denmark, Department of Urology, Rigshospitalet, University of Copenhagen, Denmark, and 3The Finsen Laboratory, Copenhagen Biocenter and Biotech Research and Innovation Centre (BRIC), Rigshospitalet, University of Copenhagen, Denmark

2

Abstract Objective. The aim of this study was to describe recovery of urinary continence and potency and report oncological and functional outcomes using the survival, continence and potency (SCP) system for patients undergoing robot-assisted radical prostatectomy (RARP). Material and methods. From 2009 to 2012, 232 patients underwent RARP. Self-reported continence, erection sufficient for intercourse (ESI) and scores on the five-item version of the International Index of Erectile Function-5 (IIEF-5) were registered by questionnaire and physician’s interview preoperatively and at 3, 6 and 12 month follow-up, and subsequently on a yearly basis. Continence was defined as 0 pads, and potency as ESI or IIEF-5 greater than 17 with or without the aid of phosphodiesterase type 5 inhibitors. Oncological success was defined as absence of biochemical failure (BF) [prostate-specific antigen (PSA) ‡0.2 ng/ml]. The SCP system was used to evaluate combined oncological and functional outcomes. Results. In total, 184 patients were followed for more than 1 year. The 12 month BF-free survival rate was 97.7%. Median time to regain continence was 6.2 months; 12 months postoperatively 79.9% used 0 pads/day. Of patients with preoperative ESI, 77.6% (67.9–86.1) and 34.4% (24.1–47.5) maintained ESI 12 months postoperatively after bilateral and unilateral nerve-sparing surgery (NS), respectively. NS (p < 0.0001), increasing prostate volume (p = 0.014) and lower age (p < 0.0001) were positively associated with recovery of potency. Using the SCP system and defining potency as ESI, functional and oncological success 12 months after surgery was achieved in 69 out of 135 (51.1%) preoperative continent and potent patients who underwent unilateral or bilateral NS, and did not require adjuvant treatment; when defining potency as IIEF greater than 17, this figure was 45 out of 108 (41.7%). As expected, the proportions were significantly higher for bilateral than for unilateral NS (p £ 0.0014). Conclusion. RARP provides good early BF-free survival, continence and potency recovery rates for patients eligible for NS.

Key Words: biochemical recurrence, erectile function, robot-assisted radical prostatectomy, SCP outcome, urinary continence

Introduction Increased awareness and use of prostate-specific antigen (PSA)-based detection have resulted in a sharp rise in the detection of prostate cancer [1]. Recent Danish figures from the cancer register demonstrate that the number of newly diagnosed patients younger than 60 years of age has increased by 40% since 2005 [2]. Parallel to this development, the use of curative

treatment, especially radical prostatectomy (RP), has increased significantly. However, post-RP urinary incontinence and erectile dysfunction have a profound impact on patients’ quality of life [3]. The aim of curative treatment is therefore to achieve cancer control with the lowest impact on quality of life. An attempt to combine cancer control with functional endpoints is the well-known “trifecta” outcome [4]. In 2012, Ficarra et al. proposed a novel biochemical

Correspondence: K. D. Berg, Copenhagen Prostate Cancer Center, Unit 7521, Rigshospitalet, Tagensvej 20, Copenhagen N, DK-2200, Denmark. Tel: +45 35 45 71 25. Fax: +45 35 45 27 26. E-mail: [email protected]

(Received 5 November 2013; revised 9 January 2014; accepted 6 February 2014) ISSN 2168-1805 print/ISSN 2168-1813 online  2014 Informa Healthcare DOI: 10.3109/21681805.2014.893534

Biochemical and functional outcomes after RARP failure-free survival, continence and potency (SCP) system to classify patients undergoing RP [5]. The system allows classification of operated patients into four groups: patients with (1) oncological and functional success; (2) oncological success and functional failure; (3) oncological failure and functional success; and (4) oncological and functional failure. It has been hypothesized that robot-assisted radical prostatectomy (RARP), allowing tridimensional magnification and seven degrees of freedom, could facilitate surgical accuracy and improve the results of the nerve-sparing procedure by better preserving the key anatomical structures. As a result, better functional outcome may be achieved without compromising cancer control [6,7]. However, this has not been proven in a randomized study. The objective of this study was to describe urinary continence and potency recovery rates, and to present SCP outcomes [5] for the first 232 consecutive patients who underwent RARP at the authors’ institution [8]. To their knowledge, this is the first report on early SCP outcomes in patients undergoing RARP. Material and methods Between January 2009 and August 2012, a consecutive series of 232 patients underwent RARP at the Department of Urology, Rigshospitalet, Copenhagen, Denmark. The eligibility criteria and preoperative work-up for the cohort have previously been described [8]. Patient data were prospectively collected in a database approved by the Danish Data Protection Agency (file no. 2006-41-6256). Preoperative variables were retrieved from patient charts and included lower urinary tract symptoms (LUTS), body mass index (BMI), clinical tumour category (cT), biopsy Gleason score (bGS), PSA, percentage of biopsies with cancer (PPB), determination of prostate volume by transrectal ultrasound (TRUS) and type of nerve-sparing surgery (NS). Patients were staged according to the Union for International Cancer Control’s tumour, node, metastasis (TNM) classification 2002. Surgical technique RARP was performed with a DaVinci version A5.0 robot (Intuitive Surgical, Sunnyvale, CA, USA) as described by Glickman Urological Institute [9]. Two surgeons performed all procedures. Unilateral NS was initially carried out in selected patients with preoperative erection sufficient for intercourse (ESI), grade cT2b tumour or below, no tumour at the apex, PSA less than 10 mg/ml and bGS less than or equal to 6. As the surgeons’ experience with the

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procedure increased, patients with bGS 3 + 4 were also considered candidates [8,10]. Bilateral NS was performed only in patients with non-palpable disease (cT1). The NS dissection was performed with clips and without the use of cautery. Both intrafascial and interfascial techniques were used, according to perioperative findings. Definitions of biochemical recurrence, urinary continence and potency Patients were routinely followed in the outpatient clinic 3, 6 and 12 months after surgery, and subsequently on a yearly basis (Figure 1). Oncological success designated the absence of biochemical failure (BF), defined as a PSA level of at least 0.2 ng/ml. Two self-reported definitions of urinary continence were used: no need for pads (0 pads/day), and the use of at most one pad per day (£1 pad/day). Self-reported continence was reported preoperatively and at followup. Patients were asked to rate their subjective continence, ranging from completely dry to severely incontinent, and the number of daily pads/diapers used. Preoperative potency status and potency recovery were recorded using the abridged five-item version of the International Index of Erectile Function (IIEF-5) as a diagnostic tool [11]. The possible scores for the IIEF-5 range from 5 to 25. Erectile dysfunction was classified into five categories based on IIEF-5 scores: severe (5–7), moderate (8–11), mild to moderate (12– 17), mild (18–21) and no erectile dysfunction (22–25) [11]. Self-reported ESI was recorded preoperatively and at postoperative controls using the physician’s interview. In January 2013, all patients were asked to fill in a questionnaire addressing ESI, IIEF-5 score and continence status using a five-point continence scale ranging from completely dry to severely incontinent. Two patients did not receive the questionnaire; this was due to non-prostate cancer-related death before the sending date (one patient) and emigration (one patient). Results from the questionnaires were included in the analyses regarding continence and potency follow-up of the patients. A slight modification of the recently developed SCP system was used to evaluate the combined oncological and functional outcome [5]. Patients were classified in categories according to their BFfree survival (S0: no BF; S1: BF; Sx: treated with adjuvant treatment) and continence status (C0: 0 pads/day; C1: 1 pad/day; C2: >1 pad/day). Two separate definitions for potency were used [P0: either ESI or IIEF >17 without aid; P1: ESI or IIEF >17 with the use of oral phosphodiesterase type 5 inhibitors (PDE5-I); P2: no ESI or IIEF £17; Px: did not undergo NS or were not potent/no information

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Patients who underwent RARP (n = 232)

Pre-operative work-up including: • Physicians interview regarding ESI, available for n = 220 • Physicians interview regarding continence, available for n = 232 • Completion of IIEF-5 questionnaire, available for n = 151

No nerve sparing (n = 75)

Unilateral nerve sparing (n = 72)

Bilateral nerve sparing (n = 85)

Follow-up

3, 6, and 12 months post-operative follow-up and here after annual follow-up; including: • Physicians interview regarding ESI • Physicians interview regarding continence • Completion of IIEF-5 questionnaire • PSA measurements

Questionnaire

No nerve sparing (n = 75) In january 2013 a questionnaire was mailed regarding: • Self-reported ESI • Self-reported continence • IIEF-5 score Respondents n = 67 Non-respondents n = 6 Death prior to questionnaire: n = 1 Emigration prior to questionnaire: n = 1

Unilateral nerve sparing (n = 72)

Bilateral nerve sparing (n = 85)

In january 2013 a questionnaire was mailed regarding:

In january 2013 a questionnaire was mailed regarding:

• Self-reported ESI • Self-reported continence • IIEF-5 score Respondents n = 61 Non-respondents n = 11

• Self-reported ESI • Self-reported continence • IIEF-5 score Respondents n = 77 Non-respondents n = 8

Figure 1. Flowchart of preoperative work-up and postoperative follow-up for 232 patients undergoing robot-assisted radical prostatectomy. ESI = erection sufficient for intercourse; IIEF-5 = Five-item version of the International Index of Erectile Function.

regarding potency status preoperatively]. Patients who needed either penile injections or transurethral alprostadil for intercourse were classified as P2. In cases of missing data regarding functional outcome, patients were characterized as having functional failure. Statistics The chi-squared test for trend (Cochran–Armitage trend test) was used for tests of independence and the

Kruskal–Wallis test to compare continuous data. Univariate and multivariate analyses for potency and continence recovery were conducted using Cox proportional hazard models, and actuarial life tables were plotted. Continence and potency recovery was reported at the date of control in the outpatient clinic, beginning on the date of surgery and ending on 15 March 2013 or the date of death, whichever came first. To allow for deferment of outpatient follow-up and left-censoring of data, cut-off values

Biochemical and functional outcomes after RARP for recovery were expanded by 1 month for the 3 month follow-up, and subsequently by 2 months for the subsequent follow-up data. The 12 and 24 month SCP outcomes (12-SCP, 24-SCP) were estimated for patients followed for at least 10 and 22 months, respectively, and time to functional recovery and BF were expanded to 14 and 26 months, respectively, to account for deferment of follow-up and left-censoring of data. All tests were two-sided, with p less than 0.05 considered statistically significant. Statistical analyses were performed using SAS, version 9.2 (SAS institute, Cary, NC, USA). Results Of the 232 patients who underwent RARP, 72 patients (31.0%) and 85 (36.6%) underwent unilateral and bilateral NS, respectively. Baseline characteristics are shown in Table I. Patients undergoing NS had significantly better prognostic parameters preoperatively, compared with non-NS patients. Preoperatively, all patients reported themselves as being urinary continent and 190 out of 220 (86.4%) claimed to have ESI. A preoperative IIEF-5 score was available in 151 patients, with a median score of 23 (range 5–25); of these, 142 (94.0%) reported an IIEF-5 greater than 17. Biochemical recurrence-free survival The median time of follow-up was 1.7 years (range 0.54–4.17 years), and 184 out of 232 patients (79.3%) were followed for more than 12 months. In total, eight out of 232 (3.5%) experienced BF, resulting in 12 and 24 month BF-free survival rates of 97.7% and 96.3%, respectively. Four patients underwent adjuvant radiation therapy plus androgen deprivation therapy and were characterized as Sx. Urinary continence outcomes The response rate to the mailed questionnaire was 89.1% (205 out of 230). Median times to regain continence were 6.2 and 3.2 months for 0 pads/day and maximum 1 pad/day, respectively. After 3, 6, 12 and 24 months of follow-up, 28.9%, 61.9%, 79.9% and 83.2%, respectively, used 0 pads/day, whereas 56.9%, 79.4%, 91.3% and 92.4% used maximum 1 pad/day (Figure 2A and Table II). Patients who underwent NS had a significantly higher recovery rate than non-NS patients in univariate analysis (p = 0.002) (Figure 2B). Moreover, for every increase of 5 in BMI, the recovery rate decreased by 25.6% [hazard ratio 0.74, 95% confidence interval (CI) 0.56–0.99, p = 0.044]. However, no parameters

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were found to be independently associated with continence recovery in multivariate modelling (Table III). In a multivariate Cox proportional hazard analysis with backwards selection, only nerve-sparing surgery was found to be associated with recovery of urinary continence. Therefore, the hazard ratio and confidence limits are the same as in the univariate model. Potency outcomes The 12 month cumulative incidence of ESI with or without the aid of PDE5-I for patients undergoing bilateral or unilateral NS was 77.6% (95% CI 67.9– 86.1) and 34.4% (95% CI 24.1–47.5), respectively (Figure 2C). The cumulative incidence increased to 84.3% (95% CI 74.9–91.6) for bilateral NS and 45.5% (95% CI 33.5–59.5) for unilateral NS 24 months postoperatively (Table II). In univariate analyses increasing age (p < 0.0001), increasing cT stage (p < 0.0001), biopsy Gleason score of 3 + 4 or higher (p < 0.0001), increasing PPB (p = 0.010) and higher PSA (p = 0.040) were associated with a lower chance of regaining ESI, while NS (p < 0.0001) was associated with an increased chance (Table III). In a multivariate analysis NS (p < 0.0001) and increasing TRUS volume (p = 0.014) were independently positively associated with increased chance of regaining ESI, whereas increasing age (p < 0.0001) was negatively associated with the likelihood of maintained ESI. Survival, continence and potency outcomes Preoperatively, 146 patients (62.9%) had an ESI without aid and underwent NS, and six patients (2.6%) had ESI with PDE5-I and underwent NS. Eighty patients were excluded from postoperative potency analyses because of preoperative impotency, missing information about preoperative potency and/or no NS because of preoperative tumour characteristics. It was possible to evaluate the SCP-12 in 135 out of 149 patients (90.6%) and the SCP-24 in 68 out of 149 patients (45.6%), who were continent and potent preoperatively, underwent NS and had no adjuvant treatment. The SCP-12 outcome for these patients demonstrated that 69 out of 135 (51.1%) had oncological and functional success, whereas 65 out of 135 (48.2%) had oncological success but functional failure (Figure 3). As expected, the proportion achieving oncological and functional success was significantly higher for patients undergoing bilateral NS [50 out of 74 (67.6%)] than for those undergoing unilateral NS [19 out of 61 (31.1%)] (p < 0.0001). For SCP-24 outcomes, 32 out of 68 (47.1%) had

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Table I. Baseline characteristics. Study population (n = 232)

No NS (n = 75) Median

Unilateral NS (n = 72)

Min–max

Median

Min–max

Bilateral NS (n = 85) Median

pa

Median

Min–max

Min–max

Age (years)

63

40–73

66

48–73

63

52–71

60

40–72

< 0.0001

BMI (kg/m2)

25.9

19.2–32.3

26.5

19.9–30.6

25.7

19.9–31.2

25.8

19.2–32.3

0.29

PSA (ng/ml)

6.9

1.7–54.0

7.8

3.1–54

6.6

2.5–21

6.5

1.7–28

0.026

TRUS prostate volume (ml)

39.0

14.0–86.5

39

16–75

39

16–64

40

14–86.5

0.63

IIEF-5 score (n = 151)

23

5–25

21

5–25

23

16–25

24

19–25

< 0.0001

n

%

n

%

n

%

n

%

£3 + 3

118

50.9

21

28.0

36

50.0

61

71.8

‡3 + 4

114

49.1

54

72.0

36

50.0

24

28.2

cT1c

143

61.6

34

45.3

38

52.8

71

83.5

cT2a/b

59

25.4

24

32.0

24

33.3

11

12.9

cT2c

30

12.9

17

22.7

10

13.9

3

3.5

£25

88

37.9

24

32.0

28

38.9

36

42.4

>25

144

62.1

51

68.0

44

61.1

49

57.6

< 0.0001

Biopsy Gleason score

< 0.0001

Clinical stage (cT)

2

BMI (kg/m )

0.18

LUTSc

0.028

Yes

94

40.5

24

32.0

27

37.5

43

No

124

53.4

45

60.0

40

55.6

39

45.9

Not assigned

14

6.0

6

8.0

5

6.9

3

3.5

50.6

–

Continence 0 pads/day

pb

232

100

75

100

72

100

85

100

Self-reported ESI

190

81.9

38

50.7

68f

94.4

84g

98.8

No ESI

30

12.9

26

34.7

4

5.6

0

0

Not assigned

12

5.2

11

14.6

0

0

1

1.2

22–25

110

47.4

10

13.3

36

50.0

64

75.3

Due to PDE5-I

7

6.4

1

10.0

3

8.3

3

4.7

18–21

31

13.8

7

9.3

12

16.7

12

14.1

12–17

7

2.6

5

6.7

2

2.8

0

0

8–11

2

0.9

2

2.7

0

0

0

0

5–7

1

0.4

1

1.3

0

0

0

0

Not assigned

81

34.9

50

66.7

22

30.5

9

10.6

< 0.0001

Potencyd

< 0.0001

IIEF-5 scoree

NS = nerve-sparing surgery; BMI = body mass index; PSA = prostate-specific antigen; TRUS = transrectal ultrasound; IIEF-5 = Five-item version of the International Index of Erectile Function; LUTS = lower urinary tract symptoms; ESI = erection sufficient for intercourse; PDE5-I = phosphodiesterase type 5 inhibitor. a Kruskal–Wallis test for independent samples; bchi-squared test for trend. Patients for whom cLUTS, dpotency and eIIEF-5 score were not assigned were excluded from the chi-squared test for trend. For fthree and gthree patients, ESI was due to PDE5-I.

oncological and functional success, whereas 35 out of 68 (51.5%) had oncological success but functional failure. When using IIEF greater than 17 as the definition for potency, the SCP-12 and SCP-24 functional and oncological success rates were 45 out of 108 (41.7%) and 21 out of 50 (42.0%), respectively, and again

significantly higher among bilateral NS [36 out of 66 (54.5%)] than unilateral NS patients [nine out of 42 (21.4%)] (p = 0.0014). For patients characterized as Px, functional and oncological success was seen in 45 out of 66 (68.2%) for SC-12 and 26 out of 40 (65.0%) for SC-24.

Biochemical and functional outcomes after RARP A

B 100 Cumulative incidence, %

Cumulative incidence, %

100

80

60 40 20

0

80

60 40 20

0 1

0

2 Time from surgery, years

Definition of continence

0 pads/day

3

4

0

≤ 1 pad/day

1

2 Time from surgery, years

Nerve sparing procedure

C

None

Unilateral

3

4

Bilateral

D 100 Cumulative incidence, %

100 Cumulative incidence, %

361

80

60 40 20

0

80

60 40 20

0 1

0

2 Time from surgery, years

Nerve sparing procedure

None

Unilateral

3 Bilateral

4

0

1

2 Time from surgery, years

Nerve sparing procedure

None

Unilateral

3

4

Bilateral

Figure 2. (A,B) Time to self-reported continence and (C,D) erection sufficient for intercourse (ESI) after surgery, plotted as actuarial life tables: (A) 0 vs £1 pad/day; (B) 0 pads/day stratified by type of nerve-sparing surgery (NS); (C) ESI without pharmaceutical aid stratified by type of NS; (D) ESI with or without the use of phosphodiesterase type 5 inhibitors stratified by type of NS. For (C) and (D) only patients reporting ESI preoperatively are included in the analyses.

Discussion Postoperative urinary incontinence and erectile dysfunction have obvious implications for quality of life in patients undergoing RP [3]. The introduction of RARP raised expectations that this new and refined technology would lead to a reduction in the incidence of these side-effects [6,7]. Median time to pad-free (or one liner for security) urinary continence following RARP has been reported to be between 1.5 and 3.7 months [12,13], and published 12 month pad free continence rates are between 78% and 97% [14,15]. In a recent review, mostly based on patients from high-volume centres and with the use of 0 pads/day as the definition of continence, the 12 month urinary incontinence rate ranged from 4% to 31% with a mean value of 16% [16]. The 12 month cumulative incidence of 79.9% for using 0 pads/day in the present study thus compares favourably to international figures. Nonetheless,

a learning curve for achieving optimal continence outcome seems to exist, with reported improvements after 500 [17] and even 760 cases [18]. Most of the published data suggest a correlation between age at surgery and risk of postoperative incontinence [16,19,20]. It is known that a higher proportion of older men have urinary leakage compared with younger men, regardless of prostate cancer diagnosis [21]. This may in part be explained by a larger prostate volume [19] and/or a weaker pelvic floor/sphincter in older men [22]. In the present study, the correlation between age at surgery and risk of postoperative urinary incontinence could not be confirmed. Obesity has previously been reported as a predictor for postoperative urinary incontinence, with a statistically significant lower pad-free continence rate for obese patients (BMI > 30) than for patients of normal weight or overweight (BMI £ 30) [23]. Furthermore, it has been reported that large prostate volumes

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Table II. Recovery of (a) urinary continence and (b) potency. 3 months

6 months

12 months

24 months

0 pads/day

67/232 [28.9 (23.5–35.2)]

142/232 [61.9 (55.7–68.2)]

179/202 [79.9 (74.4–85.0)]

184/107 [83.2 (77.7–88.9)]

£1 pad/day

132/232 [56.9 (50.6–63.3)]

184/232 [79.4 (74.0–84.4)]

210/202 [91.3 (87.2–94.5)]

212/107 [92.4 (88.4–95.4)]

(a) Urinary continence

0 pads/day by NS Bilateral NS

34/85 [40.0 (30.5–51.2)]

63/85 [74.8 (65.2–83.5)]

73/75 [88.4 (80.2–94.3)]

73/33 [88.4 (80.2–94.3)]

Unilateral NS

17/72 [23.6 (15.4–35.2)]

42/72 [58.7 (47.6–70.1)]

55/67 [77.8 (67.5–86.7)]

58/38 [82.9 (73.0–90.8)]

No NS

16/75 [21.3 (13.7–32.4)]

37/75 [50.3 (39.5–62.2)]

51/60 [72.4 (61.4–82.5)]

53/36 [76.5 (65.4–86.1)]

18/85 [21.4 (14.1–31.8)]

28/85 [33.8 (24.7–45.1)]

42/75 [54.2 (43.3–65.8)]

48/33 [66.9 (55.0–78.4)]

Unilateral NS

2/72 [2.9 (0.8–11.3)]

7/72 [10.5 (5.2–20.8)]

12/67 [19.2 (11.4–31.4)]

16/38 [28.6 (18.3–42.9)]

No NS

0/75 [0.0]

1/75 [2.8 (0.4–18.4)]

2/60 [6.4 (1.6–23.6)]

3/36 [12.3 (4.9–35.2)]

25/85 [29.8 (21.2–40.8)]

45/85 [54.0 (43.7–64.9)]

63/75 [77.6 (67.9–86.1)]

67/33 [84.3 (74.9–91.6)]

5/72 [7.4 (4.1–16.8)]

14/72 [20.9 (13.0–32.7)]

22/67 [34.4 (24.1–47.5)]

27/38 [45.5 (33.5–59.5)]

2/75 [5.6 (1.4–20.7)]

5/60 [16.5 (7.2–35.5)]

5/36 [16.5 (7.2–35.5)]

(b) Potency ESI without aid Bilateral NS

ESI with/without PDE5-I Bilateral NS Unilateral NS No NS

0/75 [0.0]

Data are shown as n/N [% (95% confidence interval)]. Urinary continence and potency recovery at/before the specified time-points; results are shown as cumulated number of events (n) in the group, number of patients followed until the specified time-point (N) and the percentage achieving the event according to the actuarial life tables [% (95% CI)]. The number of events divided by the number of patients in the group does not equal the results from actuarial life tables owing to censoring of data. NS = nerve-sparing surgery; ESI = erection sufficient for intercourse; PDE5-I = phosphodiesterase type 5 inhibitor.

(‡70 g), at least in univariate analyses, are negatively associated with the time to return to maximum 1 pad/ day and 12 month continence rates compared with smaller prostate volumes [24]. In the present study an independent association between BMI and postoperative urinary continence recovery could not be confirmed; however, the results show a tendency for deferred recovery with increasing BMI. An explanation for the differences may be the selection of patients for RARP or interactions not accounted for in the model. A recent meta-analysis found a modest risk reduction for 12 month incontinence rates in favour of RARP over RP [16]. However, no randomized trials were included and differences in surgical skills were not accounted for; thus, the apparent advantage of RARP may be dwarfed by the 30–40% betweensurgeon difference in continence rates [25]. The aetiology of erectile dysfunction following surgery is multifactorial, including vascular factors, but impairment of cavernous nerves plays a major role [26], as the most important prognostic factors for regaining potency are preservation of the nervous bundles in combination with patient age and preoperative sexual function [27]. For patients undergoing unilateral or bilateral RARP-NS, 12 month mean potency recovery rates have been reported to be around 70% (54–90%) [27], and median time to

return of intercourse has been found to be 340 days [13]. The wide variability is probably due to differences in patient age, preoperative potency status, comorbidity, extension of NS and definition of potency: most authors considered patients with an ESI as being potent regardless of the use of PDE5-I, but for studies using validated questionnaires cut-off values for potency vary widely, which strongly influences the comparison of potency rates [27]. Shikanov et al. reported potency recovery rates at 3, 6, 12 and 24 months as 44%, 50%, 62% and 69%, respectively, using the validated University of California Los Angeles Prostate Cancer Index questionnaire, and 57%, 63%, 82% and 93%, respectively, using the physician’s interview [28]. In the present study, 34.4–77.6% had regained ESI 12 months after surgery and 45.5–84.3% had regained ESI 24 months after surgery, which is in line with international series. Furthermore, the negative association between age and recovery of erectile function was confirmed. Wiltz et al. reported significantly lower 12 month ESI rates in obese men (BMI > 30) than in patients of normal weight (20 < BMI £ 25) or overweight (25 < BMI £ 30) [23]. In the present study BMI was analysed as a continuous variable and no association with recovery of potency was found. This probably reflects the limited number of overweight and obese patients in the present series owing to patient selection.

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Biochemical and functional outcomes after RARP

Table III. Time to (a) postoperative continence (0 pads/day) and (b) postoperative potency (erection sufficient for intercourse with or without phosphodiesterase type 5 inhibitors)a. Univariate analysis Variable

Reference

HR

95% CI

Multivariate analysis p

HR

95% CI

p

(a) Time to postoperative continence Age

For 10 years change

0.85

(0.67–1.09)

0.20

0.98

(0.72–1.33)

0.89

BMI

For 5 kg/m2 change

0.74

(0.56–0.99)

0.044

0.79

(0.58–1.07)

0.13

LUTS

No LUTS

1.01

(0.75–1.37)

0.94

0.88

(0.63–1.22)

0.43

Preoperative ESI

No ESI

1.59

(0.99–2.53)

0.053

1.18

(0.65–2.12)

0.59

cT stage

cT1c 0.90

(0.64–1.26)

0.95

(0.64–1.41)

cT2a/b cT2c

0.66

0.52

1.13

(0.72–1.75)

1.29

(0.78–2.13)

Biopsy GS

£3 + 3

0.82

(0.62–1.10)

0.18

0.96

(0.68–1.35)

0.79

PPB

For 10 percentage point change

0.94

(0.86–1.04)

0.23

0.99

(0.89–1.11)

0.91

TRUS volume

For 10 ml change

1.08

(0.97–1.20)

0.19

1.06

(0.94–1.19)

0.35

PSA

For two-fold change

0.99

(0.80–1.21)

0.89

0.98

(0.77–1.24)

Surgery

No NS

0.002

0.86 0.16

Unilateral NS

1.20

(0.83–1.74)

1.06

(0.67–1.67)

Bilateral NS

1.82

(1.28–2.59)

1.51

(0.91–2.50)

(b) Time to postoperative potency Age

For 10 years change

0.37

(0.26–0.53)

< 0.0001

0.43

(0.28–0.65)

< 0.0001

BMI

For 5 kg/m2 change

0.95

(0.64–1.40)

0.78

0.98

(0.65–1.47)

0.91

(0.90–1.97)

0.15

0.89

(0.58–1.36)

0.58

LUTS

No LUTS

1.33

Preoperative ESI

No ESI

–

cT stage

cT1c

–

–

–

< 0.0001

0.063

cT2a/b

0.43

(0.26–0.73)

0.69

(0.38–1.25)

cT2c

0.28

(0.12–0.64)

0.35

(0.14–0.88)

Biopsy GS

£3 + 3

0.45

(0.30–0.68)

< 0.0001

0.74

(0.45–1.19)

0.21

PPB

For 10 percentage point change

0.83

(0.72–0.96)

0.010

1.03

(0.87–1.21)

0.73

TRUS volume

For 10 ml change

1.11

(0.97–1.28)

0.13

1.21

(1.04–1.40)

0.014

PSA

For two-fold change

0.73

(0.54–0.99)

0.040

0.85

(0.63–1.14)

0.28

Surgery

No NS 3.84

(1.49–9.88)

2.82

(1.08–7.39)

12.28

(4.92–30.63)

6.84

(2.60–18.00)

Unilateral NS Bilateral NS

< 0.0001

< 0.0001

a

Only patients with preoperative erection sufficient for intercourse (ESI) were included. HR = hazard ratio; CI = confidence interval; BMI = body mass index; LUTS = lower urinary tract symptoms; GS = Gleason score; PPB = percentage of positive biopsies; TRUS = transrectal ultrasound; PSA = prostate-specific antigen; NS = nerve-sparing surgery.

A recent meta-analysis compared open surgery with RARP for 12 month prevalence of erectile dysfunction, and found a modest risk reduction in favour of RARP [27]. Adding the aforementioned concerns regarding study design and differences in collecting data, these promising results may reflect intersurgeon differences rather than differences between techniques [25]. The combined trifecta state (oncological and functional outcomes) has been used to assess surgical success following RARP. Available studies show that functional and biochemical success is achieved in 44–91% of patients [28,29]; however, these recovery rates are logically affected by the definition of

continence, potency and BF, as well as time of follow-up. Most often, the limiting factor in reaching the trifecta outcome is erectile function [5]. It is well known that trifecta outcomes are only reported in the best subpopulation of patients and outcomes for the majority of patients are not considered [5,30]. Ficarra et al. recently proposed the use of the SCP system to provide a more comprehensive overview of the heterogeneous population not reaching the trifecta state and to evaluate not only the often limited subpopulation of preoperatively potent and continent patients who undergo NS [5]. In the present study, using the SCP system and focusing on patients who

364 A

K. D. Berg et al. Potency defined as ESI 24 Months (n = 68)

12 Months (n = 135)

S0

S0 Patients with oncological and functional success 69/135 cases (51.1%)

Patients with oncological and functional success 32/68 cases (47.1%)

Patients with oncological success and functional failure 65/135 cases (48.2%)

C0, P0-1

C1-2/P2 Patients with oncological failure and functional success 0/135 cases (0%)

C0, P0-1

C1-2/P2 Patients with oncological failure and functional success 1/68 cases (1.4%)

Patients with oncological and functional failure 1/135 cases (0.7%)

Patients with oncological and functional failure 0/68 cases (0%)

S1

S1

B

Patients with oncological success and functional failure 35/68 cases (51.5%)

Potency defined as IIEF >17 24 Months (n = 50)**

12 Months (n = 108)*

S0

S0 Patients with oncological and functional success

Patients with oncological success and functional failure

45/108 cases (41.7%)

65/135 cases (57.4%)

C0, P0-1

C1-2/P2 Patients with oncological failure and functional success 0/108 cases (0%)

21/50 cases (42.0%)

29/50 cases (58.0%)

Patients with oncological failure and functional success 0/50 cases (0%)

Patients with oncological and functional failure 0/50 cases (0%)

C0, P0-1

Patients with oncological and functional failure 1/108 cases (0.9%)

C1-2/P2

S1

S1

C

Patients with oncological success and functional failure

Patients with oncological and functional success

SC-outcomes for Px-patients

12 Months (n = 66)

24 Months (n = 40)

S0 Patients with oncological success and functional failure 18/66 cases (27.3%)

Patients with oncological and functional success 45/66 cases (68.2%) C0

Patients with oncological and functional success 26/40 cases (65.0%) C1-2

Patients with oncological failure and functional success 2/66 cases (3.0%)

S0 Patients with oncological success and functional failure 11/40 cases (27.5%)

C0

C1-2

Patients with oncological and functional failure

Patients with oncological failure and functional success

Patients with oncological and functional failure

1/66 cases (1.5%)

2/40 cases (5.0%)

1/40 cases (2.5%)

S1

S1

Figure 3. Survival, continence and potency outcome: preoperatively potent men according to (A) erection sufficient for intercourse (ESI) or (B) International Index of Erectile Function (IIEF) > 17 who underwent unilateral or bilateral nerve-sparing robot-assisted radical prostatectomy are included, whereas patients characterized as Sx and/or Px are excluded. (C) Survival and continence outcomes for men who preoperatively were characterized as Px. C0 = not using pads; C1 = 1 pad/day; C2: >1 pad/day; P0 = ESI/IIEF > 17 without aid; P1 = ESI/ IIEF > 17 with use of phosphodiesterase type 5 inhibitors; P2 = no ESI or requirement of alprostadil for intercourse; Px = did not undergo nerve-sparing surgery or were not potent/no information regarding potency status preoperatively; S0 = no biochemical failure; S1 = biochemical failure; Sx = patient received adjuvant therapy. For *24 and **13 patients no IIEF-5 score was recorded during the first 12 and 24 months after surgery, respectively, resulting in patients being characterized as having functional failure.

were potent and continent preoperatively and underwent NS, 41.7–51.1% achieved 12 month functional and oncological success, whereas the rates were 42.0– 47.1% 24 months after surgery. These rates are somewhat lower than reported in most RARP series using the traditional trifecta outcome (44–91%) [5].

The initial series of two surgeons were presented here, and the data could be influenced by the learning curve. Thus, functional outcomes, which are rate limiting, may improve with more experience [17,18]. The oncological results remain the main outcome of curatively intended RARP and must be considered

Biochemical and functional outcomes after RARP the main priority, with functional outcomes as secondary important endpoints. Evaluation of biochemical recurrence-free survival in this series is immature and longer follow-up will logically affect the SCP outcome. The present study has several limitations. First, the sample size is limited compared with other RARP series; however, it represents the complete cohort of patients who have undergone RARP at this tertiary referral institution. Secondly, the initial series of two robotic surgeons are presented; therefore, the results may be influenced by the learning curve and the time of follow-up is still limited. Thirdly, not all patients had completed the IIEF-5 questionnaire, resulting in missing data, and most analyses were performed using results from the physician’s interview. Preoperative self-reported sexual activity shortly after the psychological impact of the diagnosis of cancer has inherent flaws which call for cautious interpretation. Finally, even though patient data were collected prospectively, the study design is retrospective, with unmeasured confounders as a limitation. In conclusion, RARP provides good early BF-free survival and recovery of continence and potency for patients eligible for NS. When the recently proposed SCP system was applied, 40–50% of patients achieved oncological and functional success within the first 12 months following RARP; for patients who did not undergo NS or were not potent preoperatively, the success rate was roughly 70%. Declaration of interest: This study was performed without any financial support. None of the authors has anything to disclose.

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NOTICE OF CORRECTION The Early Online version of this article published online ahead of print on 3 Mar 2014 contained errors in figure 3. The correct version is shown here.

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