Acta Med. Okayama, 2024
Vol. 78, No. 4, pp. 307‑312
CopyrightⒸ 2024 by Okayama University Medical School.

Original Article

http://escholarship.lib.okayama-u.ac.jp/amo/

Can Pelvic Lymph Node Dissection in Prostate Cancer Patients with a 5%
Briganti Nomogram Cut-off Value Provide an Oncological Benefit?
A Large Multi-Institutional Cohort Study in Japan
Naoya Sugiharaa＊, Katsuyoshi Hashineb, Natsumi Yamashitac, Miki Sakamotoa,
Masato Terashitaa, Keisuke Funakia, Kaori Saikia, Takatora Sawadaa,
Toshio Kakudaa, Kenichi Nishimuraa, Tetsuya Fukumotoa, Noriyosi Miuraa,
Yuki Miyauchia, Tadahiko Kikugawaa, and Takashi Saikaa
aDepartment of Urology, Ehime University, Toon-shi, Ehime 791-0204, Japan,
Department of Urology, and cDivision of Epidemiology, National Hospital Organization Shikoku Cancer Center,
Matsuyama 791-0245, Japanb

The Briganti nomogram (cut-off value 5%) is commonly used to determine the indications for pelvic lymph
node dissection (PLND) in patients with prostate cancer. We retrospectively analyzed the potential oncologicalbenefit of PLND based on the 5% cut-off value on the Briganti nomogram. We obtained the data from theMedical Investigation Cancer Network (MICAN) Study, which included 3,463 patients who underwent a radical
prostatectomy (RP) at nine institutions in Japan between 2010 and 2020. We included patients with Brigantiscores ≥ 5% and a follow-up period ≥ 6 months and excluded patients categorized in the very high-risk group(based on NCCN categories); a final total of the cases of 1,068 patients were analyzed. The biochemical recurrence (BCR)-free survival was significantly worse in the patients who underwent PLND compared to those who
did not (p = 0.019). A multivariate analysis showed that high prostate-specific antigen (PSA) levels (p < 0.001)
and an advanced T-stage (p = 0.018) were significant prognostic factors for BCR, whereas PLND had no effect on
BCR (p = 0.059). Thus, PLND in patients with prostate cancer whose Briganti score was 5% did not provide any
oncological benefit. Further research is necessary to determine the indication criteria for conducting PLND.
Key words: Briganti nomogram, pelvic lymph node dissection, prostate cancer, radical prostatectomyT

he European Association of Urology (EAU)
guidelines recommend pelvic lymph node dissection (PLND) combined with a radical prostatectomy(RP) for patients with prostate cancer if the probability
of lymph node involvement is ≥ 5% [1]. Many institutes
use a Briganti score (BS) cut-off of ≥ 5% to determine
the indication for PLND in conjunction with RP. The
diagnostic validity of the Briganti nomogram has beenverified in several studies [2]. However, although the
Received December 14, 2023 ; accepted April 5, 2024.
Corresponding author. Phone : +81-89-943-1151; Fax : +81-89-947-0026
E-mail : ns.fish708majt@gmail.com (N. Sugihara)＊diagnostic value of PLND for lymph node involvementin patients with prostate cancer is well-established, thetherapeutic evidence for performing PLND in patientswith a BS cut-off of ≥ 5% to improve patient outcomes is
unclear. We conducted the present study to evaluate theoncological benefit of PLND in patients with a BS cutoff value of ≥ 5%.

Conflict of Interest Disclosures: No potential conflict of interest relevantto this article was reported.

308

Sugihara et al.

Acta Med. Okayama Vol. 78, No. 4

Patients and Methods

Results

The study was approved by institutional review
board of Ehime University (approval no. 1703014). The
requirement for patients’ informed consent was waived
based on the study’s retrospective design and the anonymization of the patients’ data. All aspects of the study
protocol were performed in accord with relevant guidelines and regulations. We used the perioperative andpostoperative follow-up data from the Medical
Investigation Cancer Network (MICAN) Study, which
was conducted in all of the urology-related medical
facilities in Ehime Prefecture, Japan. We obtained thedata of the 3,463 patients who underwent a radical
prostatectomy between 2010 and 2020 at any of the ninefacilities, and we analyzed the cases of the patients witha BS ≥ 5% and a follow-up period ≥ 6 months. The 2012
version of the Briganti nomogram had been used to
calculate each patient’s BS [3].
We excluded all of the very high-risk cases (according to the U.S. National Comprehensive Cancer Network[NCCN] criteria) in order to accurately assess thepotential oncological benefit of PLND because theinclusion of these patients could have worsened thepatient prognoses [4]. The clinical stage for each patient
was determined based on the clinical TNM classification (8th edition) recommended by the Union forInternational Cancer Control (UICC). Prostate biopsy
samples were obtained from 10-14 sites under ultrasound guidance. All patients underwent preoperative
pelvic magnetic resonance imaging (MRI) for the determination of the T-stage.
The patients’ postoperative prostate-specific antigen(PSA) levels were measured at 1 month post-surgery,every 3 months for 2 years, and then every 3-6 months.
A postoperative PSA level > 0.2 ng/mL was diagnosed as
biochemical recurrence (BCR). Treatment failure withan initial postoperative PSA level > 0.2 ng/mL wasdefined as BCR at 0 month postoperatively. Several
experienced surgeons performed the open, laparoscopic, and robot-assisted RP procedures.
Statistical analyses. The data of the patients who
showed BCR and who did and did not undergo PLND
were compared using the Kaplan–Meier method. We
compared the risk factors for BCR by conducting a multivariate Cox regression analysis, including variables
such as the presence/absence of PLND.

Baseline characteristics and surgical outcomes.
Of the 3,463 patients enrolled in the MICAN study,
3,182 had an evaluable BS and were followed up for ≥ 6months. After the exclusion of the patients who werecategorized into the very high-risk group (based on the
NCCN criteria), the cases of the remaining 2,648
patients were included, of which 1,068 had a BS ≥ 5%.
Of these 1,068 patients, 757 underwent PLND with aradical prostatectomy, and the other 311 did not. The
patients’ characteristics are summarized in Table 1.
The extent of PLND dissection varied by institution
and surgeon. Of the 757 patients who underwent
PLND, 153 patients (20.2%) had a clearly identified
extended bilateral pelvic lymph node dissection(eBPLND) according to Briganti’s definition; the characteristics of the patients who underwent eBPLND arelisted in Table 2. The remaining 604 patients (79.8%)
underwent a dissection around obturator lymph nodes,
with no clear extent of dissection.
The patients who did and did not undergo PLND
had similar BS scores (p = 0.347). Significantly higher
PSA levels (p < 0.001), higher clinical T-stages (p = 0.002),
and higher secondary Gleason scores (p < 0.001) wereobserved in the group of patients who underwent
PLND compared to the patients who did not undergo
PLND.
The median follow-up period was 54 months (6-110
months). Overall, 25% (n = 268) of the patients experienced BCR. The incidence of BCR was significantly
higher in the PLND group versus the non-PLND group(29.2% [n = 221] vs. 15.1% [n = 47]; p < 0.001). Perio­
perative complications occurred in 6.3% (n = 67) of thepatients: 7.8% (n = 59) of the patients were in the
PLND group, and 2.6% (n = 8) were in the non-PLND
group (p < 0.001). Complications of grade III or higher(based on the Clavien–Dindo classification) occurred in
1.4% (n = 15) of the cases: 1.7% (n = 13) patients were in
the PLND group and 0.6% (n = 2) were in the nonPLND group (Table 3).
Biochemical recurrence-free survival. The BCRfree survival rate at 5 years post-surgery was 70.6%(95% confidence interval [CI]: 66.8-74.1%) in the
PLND group and 77.5% (95%CI: 69.0-84.0%) in the
non-PLND group. Figure 1 depicts the Kaplan–Meiercurves for each group. The BCR-free survival rate wassignificantly worse in the PLND group compared to theDoes PLND with BS≥ 5% Have Oncological Beneﬁt?

August 2024

309

Table 1
Characteristics of patients with prostate cancer who underwent a radical prostatectomy (RP) atnine institutions in Japan between 2010 and 2020
with LND (n = 757)

without LND (n = 311)

P-valueAge (median: IQR)

69 (65-73)

69 (65-73)

0.347＊PSA (median: IQR)

7.8 (5.7-12.0)

6.9 (5.1-10.8)< 0.001＊

Clinical stage, n (%)
T1
T2
≧ T3

225 (29.7)512 (67.6)
20 (2.6)

61 (19.6)
243 (78.1)
7 (2.3)

Biopsy primary Gleason score, n (%)≦3≧4

140 (18.5)
617 (81.5)

53 (17)258 (83)

0.002＊＊

0.239＊＊

Biopsy secondary Gleason score, n (%)≦3≧4< 0.001＊＊284 (37.5)473 (62.5)

194 (62.3)
117 (37.7)% of positive cores (median: IQR)

33 (20-42)

33 (21-43)

0.795＊

Briganti score (mean ± SD)

11.6 ± 7.8

11.1 ± 7.4

0.346＊＊＊NCCN classiﬁcation, n (%)
very low risk
low riskintermediate risk
high risk

1 (0.1)5 (0.7)331 (43.7)
420 (55.5)0 (0)6 (1.9)212 (68.2)
93 (29.9)

Adverse event (any Grade), n (%)
yesno59 (7.8)698 (92.2)

8 (2.6)303 (97.4)< 0.001＊＊< 0.001＊＊

Observation period: 54 month (median) (6-110 month)
Mann-Whitney U Test, ＊＊Fisherʼs Exact Test, ＊＊＊Studentʼs T-Test＊

non-PLND group (log rank test, p = 0.019), and theperformance of PLND in patients with a BS ≥ 5% did
not improve the prognosis.
Predictive factors for BCR.
The results of themultivariate Cox regression analysis of the risk factors
for BCR are presented in Table 4. High serum PSA levels (p < 0.001) and clinical stage T3 or higher (p = 0.018)
were significant risk factors for BCR. The use of PLND
was not a significant risk factor, but BCR tended tooccur frequently in the patients who underwent PLND
(p = 0.059).

Discussion
Several guidelines (e.g., those issued by the EAU and
NCCN) currently recommend PLND for patients withprostate cancer who are categorized into intermediate-

to very high-risk groups [1 , 5]. However, a recent
report suggested that although many patients with prostate cancer have undergone PLND, no therapeuticvalue may be provided by PLND [6].
PLND has a high diagnostic value in cases of lymph
node involvement among patients with prostate cancer.
The diagnostic validity of PLND according to theBriganti nomogram has been assessed in various studies[2], but the prognostic value of PLND, according to theBriganti nomogram, has been unclear. In our present
study, of the 153 patients in whom eBPLND was clearly
identified based on Briganti’s definition, 5.2% (n = 8)
were at the pN1 stage. This result is comparable to thosereported by other researchers [2 , 7]. The MICAN study
thus verified the diagnostic validity of the Brigantinomogram for lymph node involvement, and our use of
the Briganti nomogram in the present study was there-

Sugihara et al.

Acta Med. Okayama Vol. 78, No. 4

fore appropriate. Few studies have examined the diagnostic validity of the Briganti nomogram in Japanesepatients, and our present findings are novel.
However, an anatomical indicator that clearly defines
the extent of lymph node dissection is lacking. In thisTable 2
Characteristics of the patients who underwent an
extended bilateral pelvic lymph node dissection (eBPLND)

study, the extent of lymph node dissection could not be
determined in some patients, which is a limitation. The
standardization of anatomical indices for assessments ofthe dissection site and extent is an important issue thatshould be tackled in future investigations.
We observed that the BS values were comparable in
the PLND and non-PLND groups, but the performance
1.0

ProﬁlesAge (median: IQR)

69 (65-72)

PSA (median: IQR)

7.6 (5.7-11.2)

Clinical stage, n (%)
≦ T2
≧ T3

144 (94.1)
9 (5.9)Biopsy primary Gleason score, n (%)≦3≧4

24 (15.6)
129 (84.3)

Biopsy secondary Gleason score, n (%)≦3≧4

67 (43.7)
86 (56.3)% of positive cores (median: IQR)

37 (21-50)

Briganti score (mean ± SD)

12.9 ± 9.1

Biochemical Recurrence, n (%)
yesno25 (16.3)
128 (83.7)

Table 3

BCR free survival (propotion)

310

without LND
with LND

0.8

0.6

0.4

p = 0.0192

0.2

0.0
0

20

Number at risk
without LND 311
with LND
757

242
597

40

60

80

120

1
73

0
26

Time (month)
106
403

31
275

4
147

Fig. 1The biochemical recurrence (BCR)-free survival rate wassigniﬁcantly worse in the group of patients who had undergone
pelvic lymph node dissection (PLND) compared to the patients inthe non-PLND group (log rank test, p = 0.019).

Details of the complications
with LND (n = 757)

without LND (n = 311)

59 (7.8)8 (2.6)

Complications of grade I or II (%)
bleeding
paralytic ileus
inguinal hernia
infection
lymphatic leakage
anastomotic urinary leakage
respiratory failure
cardiac failure
others46 (6.1)
6
1
22
5
4
3
2
3
5

6 (2.0)
2
1
2
0
0
1
0
1
0

Complications of grade III or more (%)
conversion to laparotomy
intestinal injury
ureteral injury
bladder injury
urethrorectal ﬁstula

13 (1.7)2
52
1
3

2 (0.6)02000Perioperative complications (%)

100

Does PLND with BS≥ 5% Have Oncological Beneﬁt?

August 2024

of PLND in the patients with a BS ≥ 5% (the cut-off
value) did not improve the rate of BCR-free survival.
This suggests that performing PLND in patients with a
BS ≥ 5% has negligible oncological benefit. Notably, theuse of PLND significantly increased the incidence ofcomplications. Several research groups have indicatedthat long hospital stays [8] and high medical costs [9]are associated with PLND. The disadvantages of PLND
may outweigh its benefits. However, an advantage of
PLND is that it can contribute to the prediction of postoperative prognoses; for example, a good cancer-speTable 4
Multivariate analysis of risk factors for biochemicalrecurrence (BCR)
Variable

HR

95%CI

P-valueAge
PSA
cT3 (vs ≤ cT2)
Primary GS = 4 (vs 3)
Secondary GS ≥ 4 (vs 3)% of positive cores
LND yes (vs no)

0.987
1.024
1.373
1.211
1.198
0.996
1.372

0.967-1.007
1.015-1.033
1.056-1.785
0.839-1.748
0.910-1.578
0.9899-1.003
0.988-1.905

0.198< 0.001
0.018
0.307
0.198
0.275
0.059

Table 5cific survival rate was reported in patients in which only
one lymph node metastasis was present [10].
The results of our multivariate Cox regression analysis also demonstrated that the use of PLND in patientswith a BS ≥ 5% was not a significant factor for improving BCR-free survival; rather, the oncological prognosis tended to be worse in the PLND group than that in
the non-PLND group. This may be because the patients
who underwent PLND had an advanced clinical T-stage
and high Gleason score. We thus conducted propensity
score matching to eliminate the influence of these background factors (Table 5). After the propensity scorematching, a multivariate Cox regression analysis showedthat PLND had no significant impact on BCR (Table 6).
As mentioned earlier, the BS values in our groups ofpatients who did and did not undergo PLND were comparable, and the multivariate Cox regression analysis
also revealed that PLND for patients with a BS ≥ 5% was
not significant therapeutically.
Another hypothesis is that patients in the PLND
group may potentially have undetected positive cores,
because MRI-ultrasound fusion biopsies are not commonly conducted in Japan. Further studies should be

Characteristics of the patients after propensity score matching

After propensity score matchwith LND (n = 302)

without LND (n = 302)

P-valueAge (median: IQR)

68 (65-72)

69 (65-73)

0.172＊PSA (median: IQR)

7.54 (5.6-11.0)

7.0 (5.2-10.9)

0.138＊

Cclinical stage, n (%)
≦ T2
≧ T3

297 (98.3)
5 (1.7)295 (97.7)
7 (2.3)

Biopsy primary Gleason score, n (%)≦3≧4

62 (20.5)240 (79.5)

51 (16.9)
251 (83.1)

Biopsy secondary Gleason score, n (%)≦3≧4

181 (59.9)
121 (40.1)

185 (61.3)
117 (38.7)% of positive cores (median: IQR)

35 (22-50)

40 (25-50)

0.408＊

Briganti score (mean ± SD)

10.5 ± 6.5

11.2 ± 7.4

0.224＊＊＊

Biochemical Recurrence, n (%)
yesno

73 (24.2)
229 (75.8)

Mann-Whitney U Test, ＊＊Fisherʼs Exact Test, ＊＊＊Studentʼs T-Test＊

311

47 (15.6)
255 (84.4)

0.772＊＊

0.914＊＊

0.803＊＊

0.011＊＊

312

Sugihara et al.

Acta Med. Okayama Vol. 78, No. 4

Table 6
Multivariate analysis of risk factors for BCR after propensity score matching2.

After propensity score matching
Variable

HR

95%CI

P-valueAge
PSA
cT3 (vs ≤ cT2)
Primary GS = 4 (vs 3)
Secondary GS ≥ 4 (vs 3)% of positive cores
LND yes (vs no)

0.993
1.060
2.208
1.554
1.235
0.996
1.220

0.986-1.024
1.036-1.085
0.693-7.031
0.845-2.856
0.804-1.898
0.986-1.006
0.8366-1.778

0.652< 0.001
0.180
0.156
0.335
0.434
0.302

conducted as the use of MRI-ultrasound fusion biopsies
becomes more widespread in Japan.
The use of the Briganti nomogram in daily practice
is complicated, and because its therapeutic significanceremains unknown, a simple criterion is required. At
our institution, our protocol is to perform eBPLND
only in patients who are at very high risk according to
the NCCN definition. Based on our present findings,
we intend to continue using the conventional protocol.
Further research should be conducted to identify therapeutically meaningful indications for PLND.
The limitations of this study include the fact that the
selection criteria for PLND and the extent of lymph
node resection varied from institution to institution. In
conclusion, our analyses demonstrated no oncologicalbenefit of conduction PLND in patients with prostatecancer and a Briganti score ≥ 5% who have undergone aradical prostatectomy.

3.

4.

5.

6.

7.

8.

References
1.

Mottet N, van den Bergh RCN, Briers E, Van den Broeck T,
Cumberbatch MG, De Santis M, Fanti S, Fossati N, Gandaglia G,
Gillessen S, Grivas N, Grummet J, Henry AM, van der Kwast TH,
Lam TB, Lardas M, Liew M, Mason MD, Moris L, Oprea-LagerDE, van der Poel HG, Rouvière O, Schoots IG, Tilki D, Wiegel T,
Willemse PM and Cornford P: EAU-EANM-ESTRO-ESUR-SIOG
Guidelines on Prostate Cancer-2020 Update. Part 1: Screening,
Diagnosis, and Local Treatment with Curative Intent. Eur Urol
(2021) 79: 243-262.

9.

10.

Peilleron N, Seigneurin A, Herault C, Verry C, Bolla M, Rambeaud
JJ, Descotes JL, Long JA and Fiard G: External evaluation of theBriganti nomogram to predict lymph node metastases in intermediate-risk prostate cancer patients. World J Urol (2020) 39: 14891497.
Briganti A, Joniau S, Gontero P, Abdollah F, Passoni NM, Tombal
B, Marchioro G, Kneitz B, Walz J, Frohneberg D, Bangma CH,
Graefen M, Tizzani A, Frea B, Karnes RJ, Montorsi F, Van
Poppel H and Spahn M: Identifying the best candidate for radical
prostatectomy among patients with high-risk prostate cancer. Eur
Urol (2012) 61: 584-592.
Miura N, Hashine K, Watanabe R, Noda T, Nishimura K,Fukumoto T, Miyauchi Y, Kikugawa T, Tacho T, Yanagaki T,
Oka A, Takeda H, Watanabe Y, Ninomiya I, Shirato A and Saika T:
Oncological Outcomes with Wide Resection in Robot-Assisted
Radical Prostatectomy as Primary Treatment for Very High-Risk
Prostate Cancer. Journal of Clinical Oncology (2023) 41: 357.
Mohler JL, Antonarakis ES, Armstrong AJ, DʼAmico AV, Davis
BJ, Dorﬀ T, Eastham JA, Enke CA, Farrington TA, Higano CS,
Horwitz EM, Hurwitz M, Ippolito JE, Kane CJ, Kuettel MR, Lang
JM, McKenney J, Netto G, Penson DF, Plimack ER, Pow-Sang
JM, Pugh TJ, Richey S, Roach M, Rosenfeld S, Schaeﬀer E,
Shabsigh A, Small EJ, Spratt DE, Srinivas S, Tward J, Shead
DA and Freedman-Cass DA: Prostate Cancer, Version 2. 2019,
NCCN Clinical Practice Guidelines in Oncology. J Natl Compr
Canc Network (2019) 17: 479-505.
Fujimoto N, Shiota M, Tomisaki I, Minato A and Yahara K:
Reconsideration on Clinical Beneﬁt of Pelvic Lymph Node
Dissection during Radical Prostatectomy for Clinically Localized
Prostate Cancer. Urol Int (2019) 103: 125-136.
Schiavina R, Manferrari F, Garofalo M, Bertaccini A, Vagnoni V,
Guidi M, Borghesi M, Baccos A, Morselli-Labate AM, Concetti S
and Martorana G: The extent of pelvic lymph node dissection correlates with the biochemical recurrence rate in patients with intermediate- and high-risk prostate cancer. BJU Int (2011) 108: 12621268.
Fossati N, Willemse PM, Van den Broeck T, van den Bergh RCN,
Yuan CY, Briers E, Bellmunt J, Bolla M, Cornford P, De Santis M,
MacPepple E, Henry AM, Mason MD, Matveev VB, van der Poel
HG, van der Kwast TH, Rouvière O, Schoots IG, Wiegel T, Lam
TB, Mottet N and Joniau S: The Beneﬁts and Harms of Diﬀerent
Extents of Lymph Node Dissection During Radical Prostatectomy
for Prostate Cancer: A Systematic Review. Eur Urol (2017) 72:
84-109.
Fujimoto N, Shiota M, Tomisaki I, Tomisaki I, Minato A andYahara K: Reconsideration on Clinical Beneﬁt of Pelvic Lymph
Node Dissection during Radical Prostatectomy for Clinically
Localized Prostate Cancer. Urol Int (2019) 103: 125-136.
Seiler R, Studer UE, Tschan K, Bader P and Burkhard FC:
Removal of limited nodal disease in patients undergoing radical
prostatectomy: long-term results conﬁrm a chance for cure. J Urol(2014) 191: 1280-1285.