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\begin{document}

\title{Evaluation of four pre-operative models for prediction of biochemical
recurrence after radical prostatectomy in localized prostate cancer}



\author[1]{Musab Kutluhan}%
\author[1]{Selman Ünal}%
\author[2]{Emrah Özsoy}%
\author[3]{Aytaç Şahin}%
\author[1]{Asim  Ozayar}%
\author[1]{Emrah Okulu}%
\author[1]{önder kayıgil}%
\affil[1]{Yildirim Beyazit University}%
\affil[2]{Ünye State Hospital}%
\affil[3]{Health Sciences University, Fatih Sultan Mehmet Training and Research Hospital}%


\vspace{-1em}



  
  \date{June 10, 2024}


\begingroup
\let\center\flushleft
\let\endcenter\endflushleft
\maketitle
\endgroup





\selectlanguage{english}
\begin{abstract}
Background: Biochemical recurrence (BCR) can be seen in the early or
late period after radical prostatectomy (RP). Various models have been
developed to predict BCR. Objective: In our study we evaluated accuracy
of four pre-operative models (GP score, PRIX, D'Amico risk
classification, CAPRA) in predicting BCR after RP in Turkish patients.
Methods: Age, preoperative total prostate specific antigen (PSA) values,
clinical stages, total number of cores taken in biopsy, number of
positive cores, preoperative biopsy Gleason score (GS), follow-up time
and presence of BCR after RP were recorded. BCR was defined as a total
PSA value \textgreater{} 0.2 ng / dl twice consecutively after RP.
Classifications or scoring was performed according to pre-operative
models. The 1, 3 and 5 year (yr) BCR-free rates of the patients were
determined for each model. Also the accuracy of four predictive models
for predicting 1, 3 and 5-yr BCR was evaluated. Results: For all
pre-operative models there was statistically significant difference
between risk groups in BCR free rates at 1, 3 and 5-yr after RP
(p\textless{}0.001). The Harrell's concordance index for 1-yr BCR
predictions was 0,802, 0,831, 0,773 and 0,745 for the GP score, PRIX,
CAPRA and D'Amico and respectively. For 3-yr BCR predictions it was
0,798, 0,791, 0,723 and 0,714 for the GP score, PRIX, CAPRA and D'Amico
and respectively. Finally, The Harrell's concordance index for 5-yr BCR
predictions was 0,778, 0,771, 0,702 and 0,693 for the GP score, PRIX,
CAPRA and D'Amico and respectively. Conclusion: In prediction of BCR,
accuracy of GP scoring and PRIX seems slightly higher than CAPRA and
D'Amico risk classification. Surely our results should be supported by
head to head comparisons with in other larger cohorts%
\end{abstract}%



\sloppy


\textbf{Title: Evaluation of four pre-operative models for prediction of
biochemical recurrence after radical prostatectomy in localized prostate
cancer}

\textbf{Abstract}

\textbf{Background:} Biochemical recurrence (BCR) can be seen in the
early or late period after radical prostatectomy (RP). Various models
have been developed to predict BCR.

\textbf{Objective:} In our study we evaluated accuracy of four
pre-operative models (GP score, PRIX, D'Amico risk classification,
CAPRA) in predicting BCR after RP in Turkish patients.

\textbf{Methods:} Age, preoperative total prostate specific antigen
(PSA) values, clinical stages, total number of cores taken in biopsy,
number of positive cores, preoperative biopsy Gleason score (GS),
follow-up time and presence of BCR after RP were recorded. BCR was
defined as a total PSA value \textgreater{} 0.2 ng / dl twice
consecutively after RP. Classifications or scoring was performed
according to pre-operative models. The 1, 3 and 5 year (yr) BCR-free
rates of the patients were determined for each model. Also the accuracy
of four predictive models for predicting 1, 3 and 5-yr BCR was
evaluated.

\textbf{Results:} For all pre-operative models there was statistically
significant difference between risk groups in BCR free rates at 1, 3 and
5-yr after RP (p\textless{}0.001). The Harrell's concordance index for
1-yr BCR predictions was 0,802, 0,831, 0,773 and 0,745 for the GP score,
PRIX, CAPRA and D'Amico and respectively. For 3-yr BCR predictions it
was 0,798, 0,791, 0,723 and 0,714 for the GP score, PRIX, CAPRA and
D'Amico and respectively. Finally, The Harrell's concordance index for
5-yr BCR predictions was 0,778, 0,771, 0,702 and 0,693 for the GP score,
PRIX, CAPRA and D'Amico and respectively.

\textbf{Conclusion:} In prediction of BCR, accuracy of GP scoring and
PRIX seems slightly higher than CAPRA and D'Amico risk classification.
Surely our results should be supported by head to head comparisons with
in other larger cohorts

\textbf{Keywords:} Prostate cancer, preoperative predictive models,
radical prostatectomy, biochemical recurrence

\textbf{What's known}

\begin{itemize}
\tightlist
\item
  Biochemical recurrence can be seen in the early or late period after
  radical prostatectomy.
\item
  Pre-operative models are used in prediction of biochemical recurrence
\item
  D'Amico risk classification and CAPRA scoring are widely used well
  performed predictive models.
\end{itemize}

\textbf{What's new}

\begin{itemize}
\tightlist
\item
  GP score and PRIX are relatively new models
\item
  There is not so much study that indicates performance of these models
  especially for GP score.
\item
  There is no study in literature that compares them with other
  well-known models.
\item
  Accuracy of GP score and PRIX in prediction of biochemical recurrence
  is comparable with other well-known models.
\end{itemize}

\textbf{INTRODUCTION}

Prostate cancer (PCa) is the second most common cancer in
men\textsuperscript{1}. Today, the gold standard treatment for localized
prostate cancer is radical prostatectomy. Biochemical recurrence (BCR)
can be seen in the early or late period after RP. BCR is an important
condition in patients who have undergone radical prostatectomy as it
indicates that clinical recurrence may also occur. Characteristics of
patients such as prostate biopsy Gleason score (GS), clinical stage,
preoperative total prostate specific antigen (PSA) value may differ.
Various models have been developed using these pre-operative
characteristics to predict BCR \textsuperscript{2}.

In clinical practice, the D'Amico risk classification and the Cancer of
prostate risk assessment (CAPRA) are frequently used models to predict
BCR. In D'Amico risk classification, pre-operative total PSA, clinical
stage and prostate biopsy GS score are used \textsuperscript{3}. In
addition to these parameters, in CAPRA scoring, patient age and positive
core ratio are also used \textsuperscript{4}. On the other hand, in
addition to frequently used models, models that are relatively less used
in clinical practice have been defined. Yoshida et al. defined The
prostate cancer risk index (PRIX) \textsuperscript{5}. In addition, the
external validation of the PRIX scoring has been
performed\textsuperscript{6}. Soga et al. defined The GP Score, a
Simplified Formula (Bioptic Gleason Score Times Prostate Specific
Antigen) and demonstrated that it could predict BCR after RP
\textsuperscript{7}.

The models used to predict BCR after RP have been compared. D'Amico risk
classification, CAPRA scoring and Stephenson nomogram, which are
frequently used in clinical practice, were compared in the same patient
group \textsuperscript{8}. Although there is studies that indicate
predictive values of GP and PRIX score in BCR, to best our knowledge
there is no head to head comparison of GP score and PRIX score with
other well-known models in predicting BCR. These models are relatively
new and use of GP score is easier than other prediction models. It was
known that predictions of BCR can be varied between pre-operative
models. So in our study we evaluated accuracy of four pre-operative
models (GP score, PRIX, D'Amico risk classification, CAPRA) in
predicting BCR after RP in Turkish patients.

\textbf{MATERIAL AND METHOD}

\textbf{Patient selection and study design}

After local ethic committee approval (26379996/49), 259 patients from 3
different hospitals who were diagnosed with localized prostate cancer
and underwent radical prostatectomy were included in our study. Age,
preoperative total PSA values, clinical stages, total number of cores
taken in biopsy, number of positive cores, preoperative biopsy GS,
follow-up time and presence of BCR after RP were recorded. PCa diagnosis
was made by trans rectal-ultrasonography-guided prostate biopsy.
Patients with a total PSA value\textgreater{} 2.5 in two consecutive
measurements and / or with suspicious nodules on digital rectal
examination (DRE) had prostate biopsy. Pathology results were evaluated
by 3 different dedicated uropathologists. American Joint Committee on
Cancer Tumor (T) node (N) metastasis (M) classification was used for
assignment of clinical stage \textsuperscript{9}. Multiparametric MRI
(mpMRI) was not used in clinical staging. Post-operative nadir PSA was
evaluated in 4-6 week. Afterwards, the total PSA was evaluated every 3
months for the first two years and then every 6 months for up to 5
years. BCR was defined as a total PSA value \textgreater{} 0.2 ng / dl
twice consecutively after RP.

\textbf{Inclusion and exclusion criteria}

Patients who were diagnosed with localized (cT1-T2) PCa, had RP
operation and were followed up regularly for BCR were included in our
study. Patients diagnosed with metastatic or locally advanced PCa,
patients with positive surgical margins, patients with pathological
lymph node metastasis, patients receiving neo-adjuvant hormonotherapy or
radio-chemotherapy, patients receiving adjuvant therapy after RP,
patients who had nadir PSA above 0.2 ng/dl after RP, patients without
regular follow-up were not included in the study.

\textbf{D'Amico risk classification}

D'Amico risk classification was performed according to the preoperative
total PSA value, prostate biopsy GS and clinical T stages. According to
this classification, patients were divided into 3 groups as low risk,
intermediate risk and high risk. Patients with preoperative total PSA
\textless{}10 ng / dl, GS \textless{}7 and clinical stage cT1-2a were
considered low-risk group. Patients with total PSA 10-20 ng / dl or GS 7
or clinical stage cT2b were defined as intermediate-risk group. Lastly,
patients with total PSA value\textgreater{} 20 ng / dl or
GS\textgreater{} 7 or clinical stage cT2c were identified as the
high-risk group \textsuperscript{3}.

\textbf{CAPRA scoring}

According to the CAPRA scoring, patients were divided into 3 groups as
low, intermediate and high risk. Scoring was done according to
preoperative total PSA value, GS pattern, clinical T stage, percentage
of positive biopsy cores and age \textsuperscript{10}. Accordingly, the
total PSA value between 2.1-6 ng / dl was given 0 point, 6.1-10 ng / dl
1 point, 10.1-20 ng / dl 2 points, 20.1-30 ng / dl 3 points and above 30
ng / dl. 4 points. A score of 0 was given to the patient with no GS
pattern, 1 point to the patient with a seconder GS pattern of 4 or 5,
and 2 points to the patient with a primary GS pattern of 4 or 5. The
patient with clinical T stage 1-2 was given a score of 0 and to the
patient with 3a 1 point. A score of 0 was given to the patient whose
positive core percentage was below 34, and 1 point to the patient with a
higher core percentage. Lastly, a score of 0 was given to patients under
the age of 50 and 1 point to patients over the age of 50. 0-2 points
were defined as low risk, 3-5 points as intermediate risk, and 6 and
above points as high risk.

\textbf{PRIX Scoring}

PRIX scoring was performed according to preoperative total PSA level,
prostate biopsy GS and clinical stage according to the definition of
Yoshida T et al \textsuperscript{6}. Accordingly, patients with a total
PSA value of less than 10 ng / dl were given 0 points, patients between
10-20 ng / dl 1 point, and patients with 20 mg / dl above 2 points. A
score of 0 was given to patients with GS 6, 1 point to patients with 7,
and 2 points to patients with a score of 8 and above. Patients with
clinical stage T1-T2a were given 0 points, patients with T2b-T2c 1
point, and patients with T3-4 2 points. A total of 3 scores was defined
as the PRIX score. The patients were divided into 4 groups according to
their PRIX scores: with a score of 0, a score of 1, a score of 2, and a
score of 3 or more.

\textbf{GP Scoring}

GP score was obtained by multiplying the preoperative total PSA value
with the prostate biopsy GS according to the definition of Soga N et
al\textsuperscript{7}. According to the distribution of scores, patients
were divided into 3 groups as low, intermediate and high risk
(\textless{}50, 50-100, \textgreater{}100).

After the patients were divided into risk groups with each predictive
model, the 1, 3 and 5 year (yr) BCR-free rates of the patients were
determined for each model. Also the accuracy of four predictive models
for predicting 1, 3 and 5-yr BCR was evaluated.

\textbf{Statistical evaluation}

Statistical analyses were performed via S-PLUS Professional and R
statistics v.1 (MathSoft, Seattle, WA, USA). The descriptive
characteristics of the variables are summarized by mean, median,
frequency and percentage. Kaplan-Meier survival analyses and log rank
test were done to estimate BCR-free rates of all classifications and
compare them. The accuracy of the four prognostic models for prediction
of BCR was quantified according to Harrell's concordance
index\textsuperscript{11,12}. Harrell's concordance index provides the
probability that, in a randomly selected pair of patients in which one
patient experiences the event (BCR) before the other, the patient who
experiences the event had the worse predicted outcome according to the
predictive model. In accuracy analyses, a value of 100\% indicates
perfect prediction versus 50\% being equivalent to a toss of a coin. In
our study, the accuracy value of four prognostic models were calculated
according to Harrell's concordance index. 0.05 was considered as the
significance threshold for p-value.

\textbf{RESULTS}

All patients were Turkish. The mean age of the patients included in our
study was 63.89 \selectlanguage{ngerman}± 6.08. The median follow-up period of the patients was
60.0 (6.0-148.0) months. Median BCR time was 12.0 (3.0-48.0) months. The
clinical characteristics of the patients are summarized in table 1.
Patient distribution according to risk groups of predictive models was
indicated in table 2.

Overall BCR free rates at 1, 3 and 5-yr after RP was 89\%, 77,9\% and
75,8\% respectively (Figure 1). According to D'Amico risk classification
there was statistically significant difference between risk groups in
BCR free rates at 1, 3 and 5-yr after RP (p\textless{}0.001). According
to CAPRA score categories BCR free rates at 3-yr after RP was 93.9\%,
64.5\% and 37.5\% for low, intermediate and high risk groups
respectively. There was statistically significant difference between
risk groups in BCR free rates at 1, 3 and 5-yr after RP
(p\textless{}0.001). In addition, there was statistically significant
difference between risk groups of GP score in BCR free rates at 1, 3 and
5-yr after RP (p\textless{}0.001). For PRIX we combined patients with a
score of 3, 4 and 5 because there were few patients with these scores.
There was statistically significant difference between score groups of
PRIX score in BCR free rates at 1, 3 and 5-yr after RP
(p\textless{}0.001) (Figure 2).

In our study, the accuracy of four prognostic models were calculated
according to Harrell's concordance index. The Harrell's concordance
index for 1-yr BCR predictions was 0,802, 0,831, 0,773 and 0,745 for the
GP score, PRIX, CAPRA and D'Amico and respectively. For 3-yr BCR
predictions it was 0,798, 0,791, 0,723 and 0,714 for the GP score, PRIX,
CAPRA and D'Amico and respectively. Finally, The Harrell's concordance
index for 5-yr BCR predictions was 0,778, 0,771, 0,702 and 0,693 for the
GP score, PRIX, CAPRA and D'Amico and respectively.

\textbf{DISCUSSION}

Post-RP BCR is a condition that can be encountered in clinical practice
due to heterogeneity in prostate cancer. Although RP is the gold
standard treatment option for localized PCa, radiotherapy and local
ablative treatments are also available, and BCR prediction is important
for optimal treatment in patients diagnosed with localized PCa.
Occurrence of BCR depends on clinical stage, pre-operative total PSA
value and pre-operative prostate biopsy GS \textsuperscript{13}.
Predictive models for BCR after RP have been developed to date. D'Amico
risk classification and CAPRA scoring are frequently used
models\textsuperscript{3,4}. To best of our knowledge, there is no study
in the literature that compares GP scoring and PRIX scoring which are
relatively newly developed and are not frequently used in clinical
practice with D'Amico risk classification and CAPRA scoring. In our
study, we evaluated these four predictive models in terms of their
predictive value of BCR for the first time in Turkish patients.

According to our results Harrell's concordance index results of all
predictive models were range from 0,693 to 0,831. It means that all
predictive models performed well both in short-term and long-term
prediction of BCR. In the study conducted by Lughezzani et al. the
Harrell's concordance index for 3-yr BCR predictions was 70.4\%, 74.3\%,
and 75.2\% for the D'Amico, CAPRA, and Stephenson models, respectively.
Similarly, 5 yr after RP, the Harrell's concordance index of the three
BCR predictive models was 67.4\%, 72.9\%, and 73.5\%,
respectively\textsuperscript{8}. In an another study conducted by
Tamblyn et al. the Harrell's concordance index was 0.791 and 0.787 for
the Stephenson and CAPRA models respectively \textsuperscript{14}. Also,
in a study conducted by Yoshida et al indicated that the concordance
index of the PRIX score and the D'Amico classification to predict BCR
was 0.719 and 0.730, respectively \textsuperscript{6}. To best of our
knowledge there is no study evaluating concordance index for GP score in
literature. In our study the Harrell's concordance index for 3 year BCR
predictions was 79,8\%, 79,1\%, 72,3\% and 71,4\% for the GP score,
PRIX, CAPRA and D'Amico respectively. In addition, the Harrell's
concordance index for 5 year BCR predictions was 77,8\%, 77,1\%, 70,2\%
and 69,3\% for the GP score, PRIX, CAPRA and D'Amico respectively. Our
results for D'Amico, CAPRA and PRIX was similar with literature in
respect of the Harrell's concordance index for 3-yr and 5-yr BCR
predictions. This can indicate us that the Harrell's concordance index
for 3-yr and 5-yr BCR predictions of GP score was reliable. In addition,
Harrell's concordance index for 3-yr and 5-yr of GP score was slightly
higher than D'Amico and CAPRA.

Pre-operative total PSA and GS score which are parameters of GP score
are important predictive factors for BCR. In a study conducted by Mithal
et al. shown that the greatest improvement in accuracy over the BCR was
GS. Specifically, for the outcomes of BCR, c-indices for Gleason score
were 0.66 \textsuperscript{15}. In addition, Acimovic et al stated that
increasing level of preoperative Gleason score, higher level of
preoperative PSA and higher percent of positive biopsies were
independently associated with occurrence of BCR but clinical stage of
disease, number of biopsies and Free/Total PSA ratio did not affect the
occurrence of BCR \textsuperscript{16}. Literature indicates that for
BCR pre-operative total PSA level and GS score are more important
factors than others like clinical stage. In our study all predictive
models other than GP score use clinical stage in scoring or
classification of patient. Although multiparametric MRI (mpMRI) has been
increasingly used in clinical practice, digital rectal examination (DRE)
is still mostly used tool for clinical staging. In our study we also
used DRE in clinical staging of patients. We think that more accurate
clinical staging can be performed with mpMRI but its contribution to
prediction of BCR is not certain. In a study conducted by Capogrosso et
al indicated that the accuracy of the Kattan nomogram (c-index, 0.724)
and the D'Amico risk classification (c-index, 0.651) was not
significantly improved by adding the mpMRI score (Model 1: c-index,
0.725; Model 2: c-index, 0.674) \textsuperscript{17}. On the other hand,
Manceau et al defined mpMRI Imaging-Based Risk Classification for
recurrence. They concluded that this classification was significantly
correlated with the risk of BCR (p \textless{} 0.001) and the area under
curve (AUC) for predicting BCR was 0.714 for the imaging-based
classification compared with 0.710 for the D'Amico
classification\textsuperscript{18}. It is still controversial that
routinely available mpMRI information is a potential marker to add to
preoperative prediction models to stratify patients'risk and inform
treatment planning.

Nonetheless, there are some limitations to this study. Firstly, our
study population was not large. Secondly, we couldn't perform
decision-curve analyses. Thirdly, our study has short median follow-up.
Certainly, longer median follow-up could affect our results. All
prostate biopsy pathology reports were not evaluated by same one
pathologist. This could result in differences in GS assignment and
thought affect score or classifications of predictive models. Lastly,
BCR prediction was performed according to pre-operative models. Surely
after RP, more precise BCR predictions can be acquired using models that
depend on pathologic RP \textsuperscript{19}.

\textbf{CONCLUSION}

In clinical practice pre-operative models are routinely used before RP
for prediction of BCR. Our results demonstrate that all four models
performed well. In prediction of BCR, accuracy of GP scoring and PRIX
seems slightly higher than CAPRA and D'Amico risk classification. Surely
our results should be supported by head to head comparisons with in
other larger cohorts.

\textbf{ACKNOWLEDGEMENTS}

None

\textbf{CONFLICT OF INTEREST}

The authors declare that they have no conflict of interest.

\textbf{FUNDING}

This research did not receive any specific grant from funding agencies
in the public, commercial, or not-for-profit sectors.

\textbf{ETHICAL APPROVAL}

All procedures performed in studies involving human participants were in
accordance with the ethical standards of the institutional and/or
national research committee and with the 1964 Helsinki declaration and
its later amendments or comparable ethical standards.

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\textbf{Table 1: The clinical characteristics of the patients}\selectlanguage{english}
\begin{longtable}[]{@{}ll@{}}
\toprule
Patient number n & 259\tabularnewline
\midrule
\endhead
Mean age Mean\selectlanguage{ngerman}±SD & 63.89\selectlanguage{ngerman}±6.08\tabularnewline
Pre-operative Total PSA (ng/dl) n (\%) &\tabularnewline
0-10 & 188 (72.6\%)\tabularnewline
11-20 & 56 (21.6\%)\tabularnewline
\textgreater{}20 & 15 (5.8\%)\tabularnewline
Clinical stage n (\%) &\tabularnewline
T1c- T2a & 219 (84.6\%)\tabularnewline
T2b & 27 (10.4\%)\tabularnewline
T2c & 13 (5.0\%)\tabularnewline
Total core number Median (min-max) & 12 (6-30)\tabularnewline
Positive core percentage Mean & 33,77\%\tabularnewline
Pre-operative biopsy score n (\%) &\tabularnewline
GS 3+3 & 186 (71.8\%)\tabularnewline
GS 3+4 & 45 (17.3\%)\tabularnewline
GS 4+3 & 16 (6.2\%)\tabularnewline
GS 4+4 & 8 (3.1\%)\tabularnewline
GS 3+5 & 3 (1.2\%)\tabularnewline
GS 4+5 & 1 (0.4\%)\tabularnewline
Biochemical recurrence n(\%) &\tabularnewline
Yes & 52 (20.1\%)\tabularnewline
No & 207 (79.9\%)\tabularnewline
Follow-up time (month) Median (min-max) & 60.0
(6.0-148.0)\tabularnewline
BCR time (month) Median (min-max) & 12.0 (3.0-48.0)\tabularnewline
\bottomrule
\end{longtable}

\emph{SD: Standard deviation, PSA: Prostate specific antigen, T: Tumor,
GS: Gleason score, BCR: Biochemical recurrence}

\textbf{Table 2: Patient distribution according to risk groups of
predictive models}\selectlanguage{english}
\begin{longtable}[]{@{}lll@{}}
\toprule
& n & \%\tabularnewline
\midrule
\endhead
\textbf{D'Amico risk classification} & &\tabularnewline
Low & 142 & 54.8\tabularnewline
Intermediate & 95 & 36.7\tabularnewline
High & 22 & 8.5\tabularnewline
\textbf{CAPRA score categories} & &\tabularnewline
Low & 134 & 51.7\tabularnewline
Intermediate & 109 & 42.1\tabularnewline
High & 16 & 6.2\tabularnewline
\textbf{GP score categories} & &\tabularnewline
Low & 145 & 56.4\tabularnewline
Intermediate & 82 & 31.9\tabularnewline
High & 30 & 11.7\tabularnewline
\textbf{PRIX score categories} & &\tabularnewline
0 & 133 & 51.4\tabularnewline
1 & 79 & 30.5\tabularnewline
2 & 27 & 10.4\tabularnewline
3 & 11 & 4.2\tabularnewline
4 & 7 & 2.7\tabularnewline
5 & 2 & 0.8\tabularnewline
\bottomrule
\end{longtable}

\emph{CAPRA: Cancer of prostate risk assessment, GP:} \emph{Bioptic
Gleason Score Times Prostate Specific Antigen, PRIX: The prostate cancer
risk index}

\textbf{FIGURE LEGENDS}

\textbf{Figure} \textbf{1:} Overall non-biochemical failure rate

\textbf{Figure 2: A:} BCR free rates according to D'Amico risk
classification, \textbf{B:} BCR free rates according to CAPRA score
categories, \textbf{C:} BCR free rates according to GP score
categories,\textbf{D:} BCR free rates according to PRIX score categories

\textbf{Hosted file}

\verb`Figure 1.docx`  available at \url{https://authorea.com/users/422893/articles/528503-evaluation-of-four-pre-operative-models-for-prediction-of-biochemical-recurrence-after-radical-prostatectomy-in-localized-prostate-cancer}

\textbf{Hosted file}

\verb`Figure 2.docx`  available at \url{https://authorea.com/users/422893/articles/528503-evaluation-of-four-pre-operative-models-for-prediction-of-biochemical-recurrence-after-radical-prostatectomy-in-localized-prostate-cancer}

\selectlanguage{english}
\FloatBarrier
\end{document}

