Original Article

Yonago Acta medica 2016;59:288–295

Biochemical Recurrence Prediction in High-Risk Prostate Cancer Patients,
Following Robot-Assisted Radical Prostatectomy
Noriya Yamaguchi,* Tetsuya Yumioka,* Hideto Iwamoto,* Toshihiko Masago,* Shuichi Morizane,* Masashi
Honda,* Takehiro Sejima† and Atsushi Takenaka**Division of Urology, Department of Surgery, School of Medicine, Tottori University Faculty of Medicine, Yonago 683-8503, Japan and†Department of Urology, Matsue City Hospital, Matsue 690-8509, Japan

ABSTRACT

Conclusion

High-risk prostate cancer patients with 1
NCCN high-risk factor can be considered for robot-assisted radical prostatectomy treatment only.

Background

High-risk prostate cancer treatment
has been controversial. Some high-risk prostate cancer
patients fail to respond to radical prostatectomy only.
Thus, we aimed to investigate the predictive factors forbiochemical recurrence (BCR) and identify patients who
could achieve sufficient therapeutic effect by radical
prostatectomy only.
Methods Of 264 medical records reviewed, 141
low-intermediate-risk and 100 high-risk prostate cancer
patients, excluding those who had received neoadjuvant
hormone therapy, were analyzed. BCR was defined as
the first increase in prostate-specific antigen levels (≥0.2 ng/mL), with levels not decreasing to undetectable
limits, after radical prostatectomy. Log-rank test andCox proportional hazards regression analyses were performed to determine the prognostic factors. We investigated the perioperative predictive factors for BCR andBCR-free survival rates, with the number of National
Comprehensive Cancer Network (NCCN) high-risk factors for high-risk prostate cancer patients who underwent
robot-assisted radical prostatectomy.
Results Multivariate analyses showed that clinical T3
was significantly associated with BCR [hazard ratio (HR)= 4.052; 95% confidence interval (CI), 1.26–12.99; P =0.019]. Of the 100 patients, 77 had 1 high-risk factor and23 had ≥ 2 high-risk factors; the 1-year BCR-free survival rate of patients with 1 high-risk factor and those with
≥ 2 high-risk factors was 94.8% and 69.6%, respectively.
Patients with ≥ 2 high-risk factors were significantly
associated with BCR (P = 0.002). No difference in BCR
rate between patients with 1 high-risk factor and thosewith low- and intermediate-risk was found.

Key words

biochemical recurrence; high-risk prostatecancer; robot-assisted radical prostatectomy

High-risk prostate cancer treatment has been controversial. Surgical treatment results in high biochemicalrecurrence (BCR) rates; thus, some studies have reported that a combination of hormone therapy and radiation
therapy (RT; external beam radiation or brachytherapy)1
or radical prostatectomy and adjuvant RT after preoperative hormone therapy is effective in high-risk prostatecancer.2 The decision on whether to elect surgery as the
local therapy should be based on the best available clinical evidence in the European Association of Urology(EAU) guidelines.3 Although a combination of hormone
therapy and RT is one of the recommended treatments,
adverse events due to RT and long-term hormone therapy, such as radiation cystitis, rectal breeding, liver dysfunction, hot flush, and glucose intolerance, pose a problem for prostate cancer patients. Such adverse effects
are addressed by robot-assisted radical prostatectomy(RARP) as the first-line therapy for prostate cancer patients.4 Although we might perform radical prostatectomy as local therapy for high-risk prostate cancer patients
who caused a BCR after long-term androgen deprivation
therapy (ADT) and/or RT, it might be associated withincreasing high complications by the adhesion of theorganization. On the other hand, it is easier to add hormone therapy and RT for patients who underwent radical prostatectomy.5 Thus, identifying the patients who
could achieve the sufficient therapeutic effect by radical
prostatectomy only is essential.
We hypothesized that high-risk prostate cancer patients with only 1 National Comprehensive Cancer Network (NCCN) high-risk factor can benefit from surgicaltreatment only.6 We investigated the predictive factors
for BCR and BCR-free survival rates with the numberof NCCN high-risk factors for high-risk prostate cancer
patients who underwent RARP.

Corresponding author: Noriya Yamaguchi, MD
nyamaguchi@med.tottori-u.ac.jp
Received 2016 September 21
Accepted 2016 November 14
Abbreviations: ADT, androgen deprivation therapy; BCR, biochemical recurrence; BMI, body mass index; CI, confidence interval; cT3, clinical T3; EPE, extra-prostatic extension; GS, Gleason
score; HR, hazard ratio; NCCN, National Comprehensive Cancer
Network; PSA, prostate-specific antigen; PSM, positive surgicalmargin; RARP, robot-assisted radical prostatectomy; RT, radiation
therapy

288

BCR prediction in high-risk prostate cancer patients

MATERIALS AND METHODS

to compare the BCR risk and BCR-free survival rate
difference among the low-intermediate-risk, 1 high-riskfactor, and ≥ 2 high-risk factors groups. Cox proportional
hazards regression analysis was performed to define theprognostic factors. All statistical analyses were performed
using Easy R (EZR; Saitama Medical Center, Jichi Medical University, Saitama, Japan).7 Significance was considered at P < 0.05. The association between BCR-freesurvival and perioperative factors was evaluated.

Patients and data collection

We reviewed the medical records of 264 patients who
underwent RARP between October 2010 and September
2015. The study protocol was approved by the Institutional Review Board of the Tottori University Faculty of
Medicine (Approval No. 2008). We excluded 23 patients
who had undergone neoadjuvant hormone therapy and,
consequently, analyzed 141 low-intermediate-risk and100 high-risk prostate cancer patients. The NCCN risk
classification of the 241 patients was as follows: low risk,
32 (13.3%); intermediate risk, 109 (45.2%); and high risk,
100 (41.5%). Patients in the high-risk prostate cancergroup had at least one of the following high-risk factors:
prostate-specific antigen (PSA) ≥ 20 ng/mL, clinical T3(cT3), and Gleason score (GS) ≥ 8 and were subsequently divided into two groups, according to the number of
NCCN high-risk factors, i.e., 1 high-risk factor and ≥ 2high-risk factor groups.

RESULTS
Patient characteristics

The characteristics of low-intermediate-risk and highrisk prostate cancer patients are shown in Table 1. No
difference with regard to age, body mass index, andprostate volume between the low-intermediate-risk andhigh-risk prostate cancer patients was found. Of the 100
high-risk prostate cancer patients, 24 had ≥ cT3, 87 had
GS ≥ 8, and 14 had PSA ≥ 20 ng/mL.
The pathological characteristics of the 241 patients
who underwent RARP are shown in Table 2. A positive
surgical margin (PSM) was identified in 44 patients(27 low-intermediate-risk and 17 high-risk patients).
Extra-prostatic extension (EPE) was identified in 33
patients, but was not evaluated in 30 patients because
either the prostrate was cut or EPE in the prostate apex
could not be detected. Seminal vesicle invasion andlymph node metastasis occurred in 7 and 6 high-risk
prostate cancer patients, respectively. The median follow-up period was 27 months, and BCR occurred in 19(7.9%) patients. The 1- and 3-year BCR-free survival
rates for high-risk prostate cancer patients were 89.0%
and 85.5%, respectively, while those for low-intermediate-risk prostate cancer patients were similar at 95.7%.

Surgical technique

The operation was performed using a standard 6-port,
trans-peritoneal technique, employing the da Vinci S
and da Vinci Si surgical robotic system (Intuitive Surgery, Sunnyvale, CA). Of the 100 high-risk prostatecancer patients, 66 (66.0%) patients underwent extended lymph node dissection, which includes the external
iliac, obturator, and internal iliac lymph nodes, and 34(34.0%) patients underwent limited node dissection, i.e.,
including the obturator lymph nodes only. Althoughextended lymph node dissection for high-risk prostatecancer patients has been recommended in the EAU
guidelines,3 limited node dissection was performed inthe 34 patients because of initial RARP case and patientcomplications. Of the 141 low-intermediate-risk prostatecancer patients, 101 (71.6%) patients underwent limited
node dissection; the rest have not undergone lymph nodedissection.
In this study, the nerve preservation group composedof both the unilateral and bilateral nerve preservation.
The clinical stage of the 241 patients was evaluated using computed tomography, magnetic resonance imaging,and bone radionuclide scintigraphy. BCR was defined as
the first increase in PSA levels (≥ 0.2 ng/mL), with levels
not decreasing to undetectable limits, after radical prostatectomy.

Clinicopathological characteristics of the high-risk
prostate cancer patients

Table 3 shows that of the 100 high-risk prostate cancer patients, 77 had 1 high-risk factor (median age at surgery, 66
years; median follow-up period, 24 months) and 23 had ≥ 2high-risk factors (median age at surgery, 63 years; medianfollow-up period, 12 months). The median PSA levels andthe ratio of ≥ cT3 were significantly higher in the ≥ 2 highrisk factors group than in the 1 high-risk factor group. BCR
occurred in 6 (7.8%) patients who had 1 high-risk factor
and in 7 (30.4%) patients who had ≥ 2 high-risk factors. The
ratio of lymph node metastasis and seminal vesicle invasion
was higher in patients who had ≥ 2 high-risk factors than inthose who had 1 high-risk factor. The median time to progression of the two groups was 3 months. Of the 6 high-risk
prostate cancer patients with lymph node metastasis, 5 had
a BCR and received adjuvant or salvage hormone therapy.

Statistical analyses

Student t-test and χ2 test were used to compare the significance of the difference in means and proportionsof the clinical characteristics and perioperative patientcharacteristics, respectively. The log-rank test was used289

N. Yamaguchi et al.
Table 1. Clinical characteristics of the low-intermediate and high risk prostate cancer patients
NCCN risk group
Low and intermediate risk(n = 141)Median age (year, range)
65 (50–76)
23.4 (18.6–30.6)
Median body mass index (kg/m2, range)
Median prostate volume (mL, range)
29.6 (11.1–130.9)
Median preoperative PSA (ng/mL, range)
Total
7.69 (1.17–19.4)
Preoperative PSA (n, %)≤ 20
141 (100.0)> 20–
Biopsy Gleason score (n, %)2–6
48 (34.0)
7
93 (66.0)
8–10–
Clinical T stage (n, %)T1a–c
40 (28.4)
T2a–c
101 (71.6)
T3a–
NCCN, National Comprehensive Cancer Network; PSA, prostate-specific antigen.

High risk(n = 100)

P-value

66 (48–76)
24.0 (18.0–29.8)
27.0 (10.0–68.3)

0.738
0.708
0.012

8.64 (3.8–50.5)< 0.001< 0.00186 (86.0)
14 (14.0)< 0.001
2 (2.0)11 (11.0)
87 (87.0)< 0.00111 (11.0)
65 (65.0)
24 (24.0）

Table 2. Pathological characteristics of the low-intermediate and high risk prostate cancer patients
NCCN risk group
Low and Intermediate risk(n = 141)

High risk(n = 100)

P-value

Pathological T Stage (n, %)0.01
pT2a–c127 (90.1)
80 (80.0)
pT3a–b14 (9.9)20 (20.0)
Gleason score (n, %)< 0.01
623 (16.3)
3 (3.0)7104 (73.8)
62 (62.0)
8–10
14 (9.9)35 (35.0)
Nerve sparing (n, %)94/141 (66.7)
19 (19.0)< 0.01
Lymph node dissection (n, %)101 (71.6)
100 (100.0)
Limited / Extended (n)
101/0
34/66
Median Nodes removed (range)
8.1 (2–23)
15.9 (3–40)< 0.01
EPE
Total (n, %)0.04
Positive
15 (10.6)
18 (18.0)
Negative
105 (74.5)
73 (73.0)
Unknown
21 (14.9)9 (9.0)PSM
Total (n, %)27 (19.1)
17 (17.0)
0.62
Lymph node metastasis (n, %)1 (0.7)6 (6.0)0.04
Seminal vesicle invasion (n, %)0 (0)7 (7.0)0.02
Follow-up time, months, median (range)
30 (3–60)
24 (0–60)
BCR free survival rates
1-year (%)
95.7
89.0
0.01
3-year (%)
95.7
85.5
0.01
BCR, biochemical recurrence; EPE, extra-prostatic extension; NCCN, National Comprehensive Cancer Network; PSM, positive surgicalmargin.

290

BCR prediction in high-risk prostate cancer patients
Table 3. Clinicopathological characteristics of the high risk prostate cancer patients
The Number of NCCN high risk factor
Two or more factors
One factor(n = 77)(n = 23)

P-valueMedian age (year, range)
66 (49–75)
63 (55–73)
0.187
Median prostate volume (mL, range)
28.6 (14.5–68.3)
26.0 (10–60)
0.58Median Preoperative PSA (ng/mL, range)
8.14 (4.1–34.6)
14.98 (6.9–39.2)
0.001
Clinical T stage [≥ cT3 (n, %)]7 (9.1)17 (73.9)
0.001
Biopsy GS [≥ 8 (n, %)]65 (84.4)
22 (95.7)
0.288
Extended lymph node dissection {n, %}45 (58.4)
21 (91.3)
0.003
Pathological T stage [≥ pT3 ( n, %)]13 (16.9)
7 (30.4)
0.232
Pathological GS [≥ 8 ( n, %)]24 (31.2)
11 (47.8)
0.212Median nodes removed (median, range)
11 (3–39)
20 (4–31)
0.837
EPE positive (n, %)13 (16.9)
6 (26.1)
0.36
PSM (n, %)10 (13.0)
7 (30.4)
0.063
Lymph node metastasis (n, %)2 (2.6)4 (17.4)
0.024
Seminal vesicle invasion (n, %)1 (1.3)5 (21.7)
0.002
Follow-up time, months, median (range)
24 (0–60)
12 (0–45)
0.001
EPE, extra-prostatic extension; GS, Gleason score; NCCN, National Comprehensive Cancer Network; PSA, prostate-specific antigen;
PSM, positive surgical margin.

Table 4. Univariate and multivariate logistic regression analyses for BCR prediction in high-risk prostate cancer
patients

Univariate
Preoperative predictors

P-value

Multivariate
HR

95% CI

P-valueAge (year)≥ 65 vs < 65
0.104
0.230
≥ 25 vs < 25
0.773
BMI （kg/m2）
Prostate volume (mL)
≥ 40 vs < 40
0.320
PSA （ng/mL）≥ 20 vs < 20
0.774
0.568
PSA density (ng/mL/mL)≥ 0.3 vs < 0.3
0.423
Biopsy GS≥ 8 vs < 8
0.156
0.998
Clinical T stage≥ T3 vs ≤ T2c
0.036
4.052
1.26–12.99
0.019
Nerve sparing(+) vs (–)
0.664
Lymph node dissection
Limited vs extended
0.959
postoperative predictors
Pathological T stage≥ pT3 vs ≤ pT2c
0.077
0.573
Pathological Gleason score≥ 8 vs < 8
0.339
EPE
(+) vs (–)
0.001
0.634
PSM
(+) vs (–)< 0.001
17.21
2.65–111.8
0.003
Lymph node metastasis(+) vs (–)< 0.001
18.3
1.35–248.7
0.029
Seminal vesicle invasion(+) vs (–)
0.003
0.242
BCR, biochemical recurrence; BMI, body mass index; CI, confidence interval; EPE, eextra-prostatic extension; GS, Gleason score; HR,hazard ratio; PSA, prostate-specific antigen; PSM, positive surgical margin.

PSA ≥ 20, P = 1). Performing nerve-sparing surgery andextended lymph node dissection showed no effects on
the BCR-free rates. Additionally, multivariate analysis
showed that PSM (HR = 17.21; 95% CI, 2.65–111.8; P =0.003) and lymph node metastasis (HR = 18.3; 95% CI,
1.35–248.7; P = 0.029), as postoperative factors, weresignificantly associated with BCR (Table 4).

Identification of perioperative predictors of BCRfree survival in high-risk prostate cancer patients

Univariate and multivariate analyses showed that cT3
was significantly associated with BCR [hazard ratio(HR) = 4.052; 95% confidence interval (CI), 1.26–12.99;
P = 0.019]. However, no difference in BCR rates in the
1 high-risk factor group was observed (≥ cT3 vs. GS ≥8, P = 0.429; PSA ≥ 20 vs. GS ≥ 8, P = 0.523; ≥ cT3 vs.
291

N. Yamaguchi et al.

Low and intermediate risk

Proportion of BCR-free survival

1 high-risk factor≥2 high-risk factors

Time (months)
Fig. 1. BCR-free survival rate after RARP for low-intermediate-risk and high-risk prostate cancer patients, according to the number of
NCCN risk factors. Low and intermediate risk versus 1 high-risk factor, log-rank P = 0.251; low and intermediate risk versus ≥ 2 highrisk factors, log-rank P = 0.001; 1 high-risk factor versus ≥ 2 high-risk factors, log-rank P = 0.002. BCR, biochemical recurrence; NCCN,
National Comprehensive Cancer Network; RARP, robot-assisted radical prostatectomy.
Table 5. Univariate and multivariate logistic regression analyses for preoperative BCR prediction in high-risk
prostate cancer patients including a number of high-risk factors
Preoperative predictors
Age (year)
BMI （kg/m2）
Prostate volume (mL)
PSA （ng/mL）
PSA density (ng/mL/mL)
Biopsy GS
Clinical T stage
NCCN high-risk factors
Nerve sparing
Lymph node dissection≥ 65 vs < 65
≥ 25 vs < 25
≥ 40 vs < 40
≥ 20 vs < 20
≥ 0.3 vs < 0.3≥ 8 vs < 8≥ T3 vs ≤ T2c≥ 2 vs 1(+) vs (–)
Limited vs extended

Univariate
P-value
0.104
0.773
0.320
0.774
0.423
0.156
0.036
0.002
0.664
0.959

Multivariate
HR

95% CI

P-value
0.320

4.624

1.54–13.89

0.998
0.792
0.006

BCR, biochemical recurrence; BMI, body mass index; CI, confidence interval; GS, Gleason score; HR, hazard ratio; NCCN, National
Comprehensive Cancer Network; PSA, prostate-specific antigen.

BCR-free survival according to the number of
NCCN risk factors

risk factors were significantly associated with BCR (P= 0.002). However, no difference in BCR rates between
patients with 1 high-risk factor and low-intermediate-risk patients was found (P = 0.251) (Fig. 1). In themultivariate analysis for preoperative BCR prediction,

The 1-year BCR-free survival rate of patients with 1
high-risk factor and those with > 2 high-risk factors was
94.8% and 69.6%, respectively. Patients with ≥ 2 high292

BCR prediction in high-risk prostate cancer patients≥ 2 high-risk factors were significantly associated with
BCR (P = 0.006) (Table 5).

the efficacy of radical prostatectomy in achieving complete primary tumor excision while preserving erectile
function in high-risk prostate cancer patients. Of 584
patients, 515 (88%) had some degree of bilateral neurovascular bundle preservation, of which 125 (24%) had
a PSM. Of 160 patients with preoperatively functional
erections and available erectile function follow-up, 75(47%) had recovered erectile function within 2 years.
Moreover, they reported that high-risk prostate cancer
should not be considered an indication for complete
bilateral neurovascular bundle resection.20 In our study,
performing nerve-sparing surgery or not showed no effects on the BCR-free rates (graph not shown P = 0.664).
Although cT3 was significantly associated with
BCR, no difference in BCR rates in the 1 high-risk factor group was observed. However, a significant difference in BCR-free survival rates between patients with
1 high-risk factor and those with ≥ 2 high-risk factors
was found (P = 0.002). The 1-year BCR-free survival
rate of patients with 1 high-risk factor and those with ≥2 high-risk factors was 94.8% and 69.6%, respectively.
No significant difference in BCR-free survival rates between patients with 1 high-risk factor and low-intermediate-risk patients was observed.
Several studies have attempted to elucidate whether
a difference in postoperative outcomes according to thenumber and combination of high-risk factors exists.4,
21, 22
Jung Ki et al. analyzed 546 patients, classified as
high-risk according to the NCCN risk classification andwho underwent radical prostatectomy between 2006 and2013, and reported significant differences in BCR-freesurvival rates between patients with 1 high-risk factor
and those with ≥ 2 high-risk factors. They divided the546 high-risk prostate cancer patients into two groups:
unfavorable group (biopsy GS primary pattern 5 and/or the presence of ≥ 2 high-risk factors) and favorable
group (all others). Significant differences in 5-year BCRfree survival rates between the favorable (56.35%) andunfavorable (18.75%) groups were noted.21 In addition,
Huai et al. analyzed 85 patients, classified as high-riskbased on the D`Amico risk classification and who underwent laparoscopic radical prostatectomy between
2002 and 2009, and reported significant differences in
BCR-free survival rates between patients with 1 highrisk factor and those with ≥ 2 high-risk factors.4 Joniau
et al. analyzed 1,360 high-risk prostate cancer patients
who underwent radical prostatectomy between 1987 and2009 at 8 European high-volume centers and divided thepatients into three groups: good prognosis (1 high-riskfactor), intermediate prognosis (PSA levels > 20 ng/mL
and stage cT3–4), and poor prognosis (GS 8–10 in combination with at least 1 other high-risk factor). They re-

DISCUSSION
Radical prostatectomy, hormone therapy, and RT are thetreatments available for prostate cancer. However, obtaining a sufficient therapeutic effect using one therapy
only for high-risk prostate cancer is difficult.8, 9 Longterm hormone therapy plus RT was considered the standard treatment for localized high-risk prostate cancer.10
Hanks GE et al. reported that long-term ADT (2 years)
plus RT for patients with a GS 8–10 locally advanced
prostate cancer is associated with a 5-year biochemical
failure rate of 33.4%, which means that one-third ofpatients with high-risk prostate cancer under long-term
ADT plus RT have a BCR within 5 years.1 Wirth et al.
reported that adjuvant hormone therapy following radical prostatectomy improves progression-free survival insome patients with advanced prostate cancer.11 Bolla etal. reported that adjuvant RT after radical prostatectomy in patients with high-risk prostate cancer improves
10-year BCR-free survival rates.12 Moreover, with therecent spread of awareness regarding PSA screening
and RARP, a trend has been demonstrated toward an
improved pathologic stage in carefully selected patientswith a high clinical stage. Such difference may suggest
an expanded role of RARP in prostate cancer.13, 14 Nevertheless, not all high-risk prostate cancer patients benefit from radical prostatectomy only. Thus, we investigated the predictive factors for BCR and BCR-free survival
rates with the number of NCCN high-risk factors forhigh-risk prostate cancer patients who underwent RARP.
In this study, the preoperative and postoperative
factors of BCR are ≥ cT3, PSM, and lymph node metastasis (Table 4). In previous reports, PSM, seminal vesicle
invasion, pathologic GS (GS ≥ 8), pathologic T stage(≥ pT3a), and lymph node metastasis were identified as
the postoperative factors predicting BCR.15, 16 On theother hand, Steuber et al. assessed the prognostic role ofradical prostatectomy in lymph-node-positive prostatecancer patients and reported that radical prostatectomy
improves progression-free and cancer-specific survival.17
Jaunarena et al. reported that radical prostatectomy has
been superior in getting better local control of prostatecancer, making radiation therapy and hormone therapy
as secondary therapies.18 In our study, we consider that
RARP, as a local therapy, contributed to good prognosis
in high-risk prostate cancer patients.
In relation to nerve sparing, Lavery et al. reported
that of 123 patients who underwent RARP at their institution, 42% underwent nerve-sparing surgery, withsafe and effective outcomes.19 Recabal et al. analyzed
293

N. Yamaguchi et al.

ported a significant difference in cancer-specific survival
rates among the groups. The good prognosis subgroup
had exceptionally good 10-year prostate cancer-specificsurvival (95.4%). The poor prognosis subgroup neededmuch more multimodal treatment, and their 10-year
prostate cancer-specific survival was significantly worse(79.7%).22 These findings and our study results show thatprostate cancer patients with only 1 high-risk factor may
be considered for RARP only.
This study has certain limitations. First, our study
was retrospective. Second, not all patients underwent extended lymph node dissection. Pierro et al. and the EAU
guidelines have recommended high-risk prostate cancer
patients to undergo extended lymph node dissection.23
This may have influenced the BCR rates in our study.
Third, the number of patients was small and the observation period was short. Of 77 patients who had 1 highrisk factor, 7, 5, and 65 patients had ≥ cT3, PSA ≥ 20,
and GS ≥ 8, respectively. Although cT3 was significantly
associated with BCR in patients with 1 high-risk factor,
6 patients with BCR had GS ≥ 8. The verification of the
combination of cT3 and other factors were not sufficientbecause of the small number of concerned patients.
Thus, further continued observation with a larger number of patients is warranted.
In conclusion, high-risk prostate cancer patientswith only 1 NCCN high-risk factor can be considered
for RARP only. The patients with ≥ 2 high-risk factors
should be considered for a multimodal treatment strategy.

5 Stephenson AJ, Scardino PT, Bianco FJ Jr, DiBlasio CJ,
Fearn PA, Eastham JA. Morbidity and functional outcomesof salvage radical prostatectomy for locally recurrent prostate cancer after radiation therapy. J Urol. 2004;172:2239-43.
PMID: 15538239.
6 National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guideline®).
Prostate cancer. Version 1.2014 [Internet]. Washington (PA):National Comprehensive Cancer Network; 2013 [cited 2016
Sep 1]. Available from: http://www.cus.cz/wp-content/uploads/2012/10/NCCN-C61-2014.pdf
7 Kanda Y. Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transplant.
2013;48:452-8. PMID: 23208313.
8 Pilepich MV, Winter K, Lawton CA, Krisch RE, Wolkov HB,
Movsas B, et al. Androgen suppression adjuvant to definitive
radiotherapy in prostate carcinoma--long-term results of phase
III RTOG 85-31. Int J Radiat Oncol Biol Phys. 2005;61:128590. PMID: 15817329.
9 Bolla M, Collette L, Blank L, Warde P, Dubois JB,
Mirimanoff RO, et al. Long-term results with immediate androgen suppression and external irradiation in patients with locally advanced prostate cancer (an EORTC study): a phase III
randomised trial. Lancet. 2002;360:103-6. PMID: 12126818.
10 Milecki T, Antczak A, Kwias Z, Milecki P. Hormone therapy
in combination with radiotherapy in the treatment of prostatecancer: why and in which group of patients? Contemp Oncol(Pozn). 2015;19:1-5. PMID: 26199563.
11 Wirth M, Tyrrell C, Delaere K, Sánchez-Chapado M,
Ramon J, Wallace DM, et al. Bicalutamide (Casodex) 150 mg
plus standard care in early non-metastatic prostate cancer:
results from Early Prostate Cancer Trial 24 at a median 7
years’ follow-up. Prostate Cancer Prostatic Dis. 2007;10:8793. PMID: 17102802.
12 Bolla M, van Poppel H, Tombal B, Vekemans K, Da Pozzo L,
de Reijke TM, et al. Postoperative radiotherapy after radical
prostatectomy for high-risk prostate cancer: long-term resultsof a randomised controlled trial (EORTC trial 22911). Lancet.
2012;380:2018-27. PMID: 23084481.
13 Suardi N, Dell’Oglio P, Gallina A, Gandaglia G, Buffi N,
Moschini M, et al. Evaluation of positive surgical margins inpatients undergoing robot-assisted and open radical prostatectomy according to preoperative risk groups. Urol Oncol.
2016;34:57. PMID: 26427694.
14 Seo HJ, Lee NR, Son SK, Kim DK, Rha KH, Lee SH. Comparison of robot-assisted radical prostatectomy and open
radical prostatectomy outcomes: a systematic review and meta-analysis. Yonsei Med J. 2016;57:1165-77. PMID: 27401648.
15 Menon M, Bhandari M, Gupta N, Lane Z, Peabody JO, Rogers
CG, et al. Biochemical recurrence following robot-assisted
radical prostatectomy: analysis of 1384 patients with a median
5-year follow-up. Eur Urol. 2010;58:838-46. PMID: 20869162.
16 Liss MA, Lusch A, Morales B, Beheshti N, Skarecky D,
Narula N, et al. Robot-assisted radical prostatectomy: 5-year
oncological and biochemical outcomes. J Urol. 2012;188:220510. PMID: 23083657.
17 Steuber T, Budäus L, Walz J, Zorn KC, Schlomm T, Chun F,
et al. Radical prostatectomy improves progression-free andcancer-specific survival in men with lymph node positive
prostate cancer in the prostate-specific antigen era: a confirmatory study. BJU Int. 2011;107:1755-61. PMID: 20942833.
18 Jaunarena JH, Villamil W, Martínez PF, Gueglio G, Giudice
CR. The role of radical prostatectomy as an initial approach

The authors declare no conflict of interest.

REFERENCES
1 Hanks GE, Pajak TF, Porter A, Grignon D, Brereton H,
Venkatesan V, et al. Phase III trial of long-term adjuvant androgen deprivation after neoadjuvant hormonal cytoreduction
and radiotherapy in locally advanced carcinoma of the prostate: the Radiation Therapy Oncology Group Protocol 92-02.
J Clin Oncol. 2003;21:3972-8. PMID: 14581419.
2 Connolly SS, Cathcart PJ, Gilmore P, Kerger M, Crowe H,
Peters JS, et al. Robotic radical prostatectomy as the initial
step in multimodal therapy for men with high-risk localised
prostate cancer: initial experience of 160 men. BJU Int.
2012;109:752-9. PMID: 21992472.
3 Heidenreich A, Bastian PJ, Bellmunt J, Bolla M, Joniau S,
van der Kwast T, et al. EAU guidelines on prostate cancer.
Part II: Treatment of advanced, relapsing, and castration-resistant prostate cancer. Eur Urol. 2014;65:467-79. PMID:
24321502.
4 Tai HC, Lai MK, Huang CY, Wang SM, Huang KH, Chen CH,
et al. Laparoscopic radical prostatectomy monotherapy, amore aggressive yet less invasive option, is oncologically effective in selected men with high-risk prostate cancer having
only 1 D’Amico risk factor: experience from an Asian tertiaryreferral center. J Endourol. 2014;28:165-71. PMID: 23987245.

294

BCR prediction in high-risk prostate cancer patientsfor the treatment of high-risk prostate cancer. Actas Urol Esp.
2016;40:353-60. PMID: 26794623.
19 Lavery HJ, Nabizada-Pace F, Carlucci JR, Brajtbord JS,
Samadi DB. Nerve-sparing robotic prostatectomy in preoperatively high-risk patients is safe and efficacious. Urol Oncol.
2012;30:26-32. PMID: 20189844.
20 Recabal P, Assel M, Musser JE, Caras RJ, Sjoberg DD,
Coleman JA, et al. Erectile function recovery after radical prostatectomy in men with high risk features. J Urol.
2016;196:507-13. PMID: 26905018.
21 Jo JK, Kook HR, Byun SS, Lee SE, Hong SK. Stratificationof contemporary patients undergoing radical prostatectomy

for high-risk prostate cancer. Ann Surg Oncol. 2015;22:208893. PMID: 25398277.
22 Joniau S, Briganti A, Gontero P, Gandaglia G, Tosco L,
Fieuws S. Stratification of high-risk prostate cancer into prognostic categories: a European multi-institutional study. Eur
Urol. 2015;67:157-64. PMID: 24486307.
23 Di Pierro GB, Grande P, Wirth JG, Danuser H, Mattei A.
Extended pelvic lymph node dissection at the time of robot-assisted radical prostatectomy: impact of surgical volume
on efficacy and complications in a single-surgeon series. Can
Urol Assoc J. 2015;9:107-13. PMID: 26085867.

295