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(n = 2191) compared with men included in our cohort. No
differences were observed in age, preoperative PSA, clinical
stage, biopsy grade group, number of cores taken, number of
lymph nodes removed, proportion of patients with positive
lymph nodes, and number of positive lymph nodes (all
p 0.07). After multiple imputation, the use of a 7% cutoff of
the novel nomogram was associated with 75% ePLND
spared and 3.2% LNIs missed.
4. Discussion
Nodal staging is crucial to identify patients with localized
PCa at a higher risk of adverse oncologic outcomes and plan
their optimal management . Available imaging mo-
dalities are associated with suboptimal performance
characteristics . Therefore, an anatomically defined
ePLND still represents the gold standard for the detection
of nodal metastases Given the potential morbidity
associated with this procedure an ePLND should be
considered only in men with an increased risk of LNI
. The EAU–ESTRO–SIOG and the NCCN guidelines
recommend the use of the Briganti and MSKCC nomograms,
respectively, to identify individuals at a higher risk of LNI
who should be considered for an ePLND Al-
though these models are associated with very good
performance characteristics, they are missing potential
important information such as the extent of cancer
involvement within the cores. Moreover, they do not take
into account for grading heterogeneity among different
cores. For example, a patient with two cores of Gleason
grade group 3 and four cores of grade group 1 PCa out of
12 cores is assigned a 50% positive cores of grade group
3 disease (highest grade within the biopsy), which is not the
case. This may lead to an overestimation of the risk of LNI
. We hypothesized that the availability of detailed
biopsy reports that also account for PCa heterogeneity
might improve our ability to identify patients at a higher
risk of LNI who should be considered for an ePLND. To test
our hypothesis, we developed a novel tool predicting LNI in
contemporary patients treated with RP and ePLND, with
detailed biopsy information available after centralized
biopsy specimens’ review.
Distinct facets of our results deserve attention. First, our
results show that detailed biopsy characteristics such as the
maximumpercentage of single core involvement and tumor
length in cores with the highest- and lower-grade diseases
represent predictors of LNI at univariable analyses. These
observations confirm the association between variables
that can be considered as a proxy of pathologic tumor
volume and the risk of adverse pathologic findings
. Nonetheless, inclusion of these covariates into
multivariable models predicting LNI did not improve their
accuracy compared with a base model including PSA,
clinical stage, biopsy grade group, percentage of cores with
highest-grade PCa, and percentage of cores with lower-
grade PCa. Therefore, in the absence of detailed biopsy data,
the use of a prediction tool based on these covariates is not
warranted, where the base model depicted excellent
calibration characteristics and was associated with an
improvement in clinical risk prediction against threshold
probabilities 20%.
Second, we demonstrated that the adoption of a 7% cutoff
would result into sparing approximately 70% of ePLNDs at
the cost of missing only 1.5% of LNIs. The use of an arbitrary
cutoff to select patients who should receive nodal staging
implies the acceptance of the possibility of missing LNI in a
certain proportion of individuals below that cutoff. For
example, the threshold recommended by the EAU–ESTRO–
SIOG guidelines is 5% according to the previous Briganti
nomogram. The adoption of this cutoff in the original cohort
was associated with 65% of ePLNDs spared and 1.5% of
patients with LNIs missed With the novel nomogram,
the use of a 7% cutoff would increase the number of patients
in whom an ePLND (and its morbidity) could be avoided,
missing exactly the same proportion of LNIs. Therefore, a
cutoff of 7% can be considered to reduce the number of
ePLNDs performed without missing additional node-posi-
tive patients as compared with the previous Briganti
nomogram .
Third, we compared the performance characteristics of
the novel model with the Briganti and MSKCC nomograms.
Our tool achieved higher predictive accuracy and net
benefit at DCA Moreover, the adoption of a 7%
cutoff calculated with our novel nomogram was associated
with a lower proportion of LNIs missed and a similar
percentage of ePLNDs spared as compared with the Briganti
nomogram, which is currently recommended by the EAU–
ESTRO–SIOG guidelines The use of a 7% cutoff with our
novel nomogram was associated with a higher number of
ePLNDs spared without an increase in the percentage of
LNIs missed when compared with the MSKCC nomogram,
which is recommended by the NCCN guidelines . The
better performance characteristics associated with the use
of our novel nomogram might be related to the inclusion of
detailed data on PCa grading. In particular, while the
previous nomograms include information on the percent-
age of positive cores regardless of the presence of cores with
different grading, we were able to demonstrate that the
percentage of cores with the highest- and lower-grade
diseases has different prognostic implications. Availability
of detailed biopsy information would result into improved
predictive accuracy and reduce overestimation of the risk of
LNI associated with the adoption of previous models. For
example, the calculated risk of LNI in a patient with
preoperative PSA 4 ng/ml, T1c, Gleason grade group
3 disease in one core, and grade group 1 PCa in five out
of 16 cores would be higher than 5% according to the
Briganti nomogram, and this patient should be considered
for an ePLND according to the EAU–ESTRO–SIOG guidelines.
However, using the novel nomogram, this patient would
have a risk of LNI lower than 5% and an ePLND could be
spared.
From a clinical standpoint, our model improves our
ability to identify patients at a higher risk of LNI, and its
implementation in the clinical practice would reduce the
number of ePLNDs performed without compromising the
identification of LNI. While an ePLND should be considered
in virtually all patients with high-risk characteristics ,
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