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analyses in a cohort that included men with incomplete biopsy data also.

Multiple imputation was used to compensate for missing information in

the variables of interest

[22]

.

3.

Results

3.1.

Baseline characteristics

Overall, 79 (12%) patients had LNI

( Table 1

). The median

(IQR) number of lymph nodes removed was 16 (8–22). The

sites for positive lymph nodes were the obturator fossa

(

n

= 42; 53%); external (

n

= 34; 43%), internal (

n

= 20; 25%),

and common (

n

= 9; 11%) iliac stations; and presacral area

(

n

= 8; 9%). Preoperative PSA, biopsy grade group, percent-

age of positive cores, percentage of cores with highest-grade

PCa, maximum percentage of single core involvement with

highest- and lower-grade PCa, tumor length, tumor length

of highest-grade PCa, and percentage of tumor in biopsy

cores overall and stratified according to the presence of

highest- and lower-grade PCa differed among patients with

pN0 and pN1 disease (all

p

0.02). No differences were

observed with regard to age, the number of cores taken, and

the number of nodes removed (all

p

0.1). Robot-assisted

surgery was not associated with

[6_TD$DIFF]

the risk of LNI after

adjusting for preoperative disease characteristics (

p

= 0.2).

3.2.

Uni- and multivariable models predicting LNI

At univariable analyses, preoperative PSA, clinical stage,

biopsy Gleason grade group, percentage of positive cores,

percentage of cores with highest- and lower-grade PCa,

maximum percentage of single core involvement with

highest- and lower-grade PCa, and percentage of tumor in

biopsy cores overall and stratified according to the presence

of highest- and lower-grade PCa represented predictors of

LNI

( Table 2 ;

all

p

0.04). At multivariable analyses,

preoperative PSA, clinical stage, biopsy grade group, and

percentage of cores with highest-grade PCa were indepen-

dent predictors of LNI. When these parameters were fitted

in four different multivariable models accounting for other

biopsy characteristics, model 1 achieved an AUC of 90.8%

and represented the basis for the novel nomogram

predicting LNI.

Fig. 1

graphically depicts the multivariable

effect of each variable on the risk of LNI in the form of a

nomogram (coefficients are shown in Supplementary

Table 1). The calibration plot of predicted probabilities

against observed LNI rates indicated excellent concordance

( Fig. 2 )

. The DCA demonstrated that the novel nomogram

improved clinical risk prediction against threshold proba-

bilities of LNI 20%

( Fig. 3

).

Table 3

depicts errors associated

with the use of the novel nomogram when predicting a low

risk of LNI. Using a 7% cutoff, 471 (69%) ePLNDs would be

spared and LNI would be missed only in seven (1.5%)

patients. Among patients with a risk of LNI

<

7% according

to the novel nomogram, positive lymph nodes were located

in the obturator (

n

= 3; 43%), external iliac (

n

= 2; 29%),

internal iliac (

n

= 1; 14%), and presacral (

n

= 1; 14%) regions.

3.3.

Comparison of the novel nomogram with currently

available models

The AUCs of the Briganti and MSKCC nomograms

[7_TD$DIFF]

in our

cohort were 89.5% and 89.5%, respectively. The calibration of

the Briganti and MSKCC nomograms tended to underesti-

mate the LNI risk across the entire range of predicted

probabilities (Supplementary Fig. 1 and 2). The use of the

novel nomogram resulted in the highest net benefit

compared with the Briganti and MSKCC models (Supple-

mentary Fig. 3). The use of a 7% cutoff of the novel nomogram

would allow for sparing a similar number of ePLNDs (69% vs

68%), with a lower number of LNIs missed (1.5% vs 2.2%) as

compared with the Briganti nomogram if the same 7%

[(Fig._1)TD$FIG]

Fig. 1 – Novel Briganti nomogram predicting the probability of lymph node invasion (LNI) in patients undergoing extended pelvic lymphadenectomy.

Instructions: Locate the patient’s Gleason grade group on the corresponding axis. Draw a line straight upward to the point axis to determine how

many points toward the probability of positive lymph nodes the patient receives for his Gleason grade group value. Repeat the process for each

additional variable. Sum the points for each of the predictors. Locate the final sum on the total point axis. Draw a line straight down to find the

patient’s probability of having LNI. PSA = prostate-specific antigen.

E U R O P E A N U R O L O G Y 7 2 ( 2 0 1 7 ) 6 3 2 – 6 4 0

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