Cancer/Radiothrapie 18 (2014) 736739

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Original article

Fiducial marker implantation in prostate radiation therapy:

Complication rates and technique
Implantation de marqueurs duciels intraprostatiques avant radiothrapie :
taux de complications et technique
Z.S. Fawaz a,,b , M. Yassa a , D.H. Nguyen a , P. Vavassis a
a
b

Department of Radiation Oncology, Maisonneuve-Rosemont Hospital, University of Montreal, Montreal, Quebec, Canada
Department of Radiation Oncology, McGill University Health Center, Montreal, Canada

a r t i c l e

i n f o

Article history:
Received 22 April 2014
Accepted 2 July 2014
Keywords:
Complications
Fiducial markers
Gold seeds
Prostate cancer
Technique
Radiotherapy
Radiation therapy

a b s t r a c t
Purpose. This study aims to report the complication rate from the transrectal ultrasound-guided implantation of gold seed markers in prostate radiotherapy, as well as describing the technique used.
Materials and methods. Between May 2010 and December 2012, 169 patients with localized prostate
cancer had an intraprostatic ducial marker implantation under transrectal ultrasound guidance. The
procedure included prophylactic antibiotic therapy, eet enema, implantation performed by trained
radiation oncologists at our center prior to image-guided radiotherapy. Toxicity occurring between
implantation and subsequent radiotherapy start date was assessed. The following parameters were analyzed via medical chart review: antibiotic therapy, anticoagulant interruption, bleeding, pain, prostate
volume, number of markers implanted, post-implantation complications and delay before starting radiotherapy.
Results. Of the 169 men, 119 (70.4%) underwent insertion of 4 ducial markers and the other 50 (29.6%)
had 3. The procedure was well-tolerated. There was no interruption of the implantation with regards to
pain or hemorrhage. No grade 3 or 4 complications were observed. Seed migration rate was 0.32%, for the
migration of 2 markers on 626 implanted. Mean prostate volume was 38 cm3 (range: 10150 cm3 ). Two
patients (1.18%) developed a urinary tract infection following the procedure: prostate volume of 25 and
65 cm3 , four gold seed markers implanted, urinary tract infection resistant to prophylactic antibiotherapy,
and treated with antibiotics specic to their infection as determined on urine culture.
Conclusion. Transrectal ducial marker implantation for image-guided radiotherapy in prostate cancer
is a well-tolerated procedure without major associated complications.
2014 Socit franaise de radiothrapie oncologique (SFRO). Published by Elsevier Masson SAS. All
rights reserved.

r s u m
Mots cls :
Complications
Marqueurs duciaires
Grains dor
Cancer de la prostate
Technique
Radiothrapie

Objectif de ltude. Cette tude vise prsenter le taux de complication de limplantation transrectale
guide par chographie de grains dor pour une radiothrapie de la prostate, ainsi qu dcrire la technique
utilise.
Matriels et mthodes. Entre mai 2010 et dcembre 2012, 169 patients avec un cancer localis de la
prostate ont eu une implantation intraprostatique transrectale de marqueurs duciels sous contrle
chographique. La procdure comprenait un traitement antibiotique prophylactique, un lavement eet,
une implantation ralise dans notre centre par des oncologues-radiothrapeutes forms avant une radiothrapie guide par limage. La toxicit survenant entre limplantation et le dbut de la radiothrapie a t
value. Les paramtres suivants ont t valus par lanalyse des dossiers mdicaux : antibiothrapie,
interruption de lanticoagulation, saignements, douleur, volume de la prostate, nombre de marqueurs
implants, complications de limplantation et temps coul avant le dbut de la radiothrapie.

Corresponding author.
E-mail address: ziadsimon.fawaz@gmail.com (Z.S. Fawaz).
http://dx.doi.org/10.1016/j.canrad.2014.07.160
1278-3218/ 2014 Socit franaise de radiothrapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.

Z.S. Fawaz et al. / Cancer/Radiothrapie 18 (2014) 736739

737

Rsultats. Sur les 169 hommes, 119 (70,4 %) ont eu linsertion de quatre marqueurs duciels et les autres
50 (29,6 %) de trois. La procdure a bien t tolre. Il ny a pas eu dinterruption de limplantation pour
cause de douleur ou dhmorragie. Aucune complication de grade 3 ou 4 na t observe. Le taux de
migration des marqueurs a t de 0,32 %, pour un total de deux marqueurs sur 626 implants. Le volume
moyen de la prostate tait de 38 cm3 (10150). Deux hommes (1,18 %) ont souffert dune infection urinaire suite la procdure ; le volume de la prostate tait de 25 et 65 cm3 , quatre grains dor avaient t
implants ; il y avait une rsistance lantibiothrapie prophylactique, et il a t administr un traitement
avec des antibiotiques spciques leur infection urinaire tel que dtermin sur la culture durine.
Conclusion. Limplantation transrectale de marqueurs duciels pour la radiothrapie guide par image
du cancer de la prostate est une procdure bien tolre sans complications majeures associes.
2014 Socit franaise de radiothrapie oncologique (SFRO). Publi par Elsevier Masson SAS. Tous
droits rservs.

1. Introduction
Real-time imaging is used in image-guided radiation therapy
(IGRT) to deliver a more accurate beam targeting with respect
to tumors. In clinical practice, large uncertainties remain in target localization and volume delineation due to physiologic organ
movements. For prostate radiotherapy, relying on bony structures
can be risky considering prostate motion within the pelvis. Since
1993, multiple investigators assessed the prostate motion over the
course of routine radiotherapy [14], and recommended that conformal planning take this motion into consideration to address
displacements reaching up to 5 mm [5]. Thus, bony anatomy-based
correction for prostate radiotherapy precludes the use of standard
margins, and encompasses a considerable volume to account for
organ motion [69].
Implantation of gold seed markers represents a practical means
for daily prostate localization during IGRT [10]. The use of these
markers has become part of routine practice during external
beam radiation therapy (EBRT). The latter, delivered at high doses,
has been proven to achieve optimal tumor-control outcomes in
patients with localized prostate cancer [11].
In this context, intraprostatic radiopaque ducial markers have
shown value for daily assessment of set-up and physiological
motion errors and adjustment of external radiation beam targeting
for prostate cancer [12]. However, data on the toxicity of the procedure is sparse. This study aims to report the complication rate and
the morbidity from the transrectal ultrasound-guided implantation
of gold seed markers in prostate radiotherapy, and to describe the
technique used for the implantation of ducial markers.
2. Materials and methods
Between May 2010 and December 2012, 169 patients with localized or locally advanced prostate adenocarcinoma had ducial
markers placement in the prostate under transrectal ultrasound
guidance at the Maisonneuve-Rosemont Hospital (University of
Montreal) in Montreal, Canada. Following approval by the Institutional Review Board, all 169 patients were included in the current
study and retrospectively analyzed.
2.1. Fiducial markers implantation technique description
Following the diagnosis of the prostate cancer, the patients were
informed about the different available therapeutic options. In the
case of gold seeds implantation, thorough anamnesis and physical
examination were performed before the procedure. The insertion
was performed as soon as possible following the radiation oncology
consult. All the patients received a three-day course of prophylactic
antibiotic therapy. The prophylaxis was performed with 1000 mg
of ciprooxacin XL the evening before the procedure followed by
another dose of 1000 mg on the evening after the implantation,
and 1000 mg the morning following the intervention, for a total

of three tablets of one gram. If the patient was undergoing anticoagulation or antiplatelet treatment, the anticoagulants and the
antiplatetet drugs were stopped one week prior to implantation,
with the proper authorization of a cardiologist. The patients underwent eet enema three hours before the procedure. They were also
advised to take light meals the evening and the morning prior to
the procedure.
The procedure was performed by one of three trained radiation
oncologists at our center. A local intrarectal anaesthetic gel was
applied prior to insertion. The patients were placed in fetal position on their side, and an ultrasound transducer was introduced in
the rectum with a guide for the markers implantation. Each gold
seed is made of pure 24 carat gold and measures 4 mm in length
and 0.72 mm in diameter. The markers were inserted in a 18 Gauge
brachytherapy needle. Once the needle insertion had been veried
by ultrasound, the gold seed was implanted by pushing it with the
fastener. The markers, three or four, were implanted in an asymmetrical manner: one or two in the right lobe, one or two in the
left lobe. The rst one was inserted at the base of the prostate in
its posterior aspect. The second marker was located in the middle third of the prostate at a similar depth as the rst. The third
marker was inserted at the apex closer to the urethra, without
puncturing it to prevent hematuria and seed migration. The fourth
marker, if present, was deposited more anterior and caudally in
the prostate. The markers are hyperechogenic in comparison to
prostate tissue making them easy to distinguish with their typical shape. Total procedure time is around 10 minutes. One week
following the implantation, the planning CT was acquired.
Position of the markers was assessed at different times as seen in
Fig. 1. First, it was assessed immediately after the procedure on the
anteroposterior and lateral orthogonal lm. Second, it was veried
again on the planning scan. Third, it was evaluated on the cone
beam computed tomography (CBCT) during the treatment: at every
positioning by the technologists, and once a week by the radiation
oncologist. The presence of the markers was veried, and loss of
any markers was recorded.
2.2. Complications monitoring and analysis
Following the procedure, the patients were told to consult at
the emergency department of our center if the following symptoms appeared de novo: fever, chills, dysuria, burning micturition,
hematuria, rectal bleeding or moderate to severe pain. Furthermore, the complications observed by the patient were taken into
account at the following visits. Toxicity occurring between implantation and subsequent radiotherapy start date was assessed. The
following parameters were analyzed: antibiotic therapy, anticoagulant interruption, bleeding, pain, prostate volume, number of
markers implanted, post-implant complications and delay before
starting radiotherapy. All parameters were evaluated by reviewing
the medical charts.

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Z.S. Fawaz et al. / Cancer/Radiothrapie 18 (2014) 736739

3 or 4 complications were observed, according to the RTOG Radiation Morbidity Scoring Criteria. None of the patients presented with
hematuria, rectal bleeding or symptoms of septicemia. The average
for the delay before starting radiotherapy was 25.07 days (95% CI:
23,9926,15 days).
Two men developed a urinary tract infection following the procedure, accounting for 1.18% (95% condence interval: 0.334.21%).
Both had received the usual prophylactic antibiotic therapy, but
presented with a ciprooxacin-resistant germ. Both had stopped
the anticoagulants one week before the procedure. Both had 4
gold seed markers implanted. They had a prostate volume of
25 and 65 cm3 , respectively (mean: 38 cm3 , range: 10 150 cm3 ).
None of these patients presented seed migration. In both cases,
the patients developed UTI resistant to the prophylactic antibiotherapy. Thereafter, the patients were successfully treated with
antibiotics specic to their urinary tract infection according to the
antibiogram. There was no delay to start radiotherapy (19 and
23 days for these patients, compared to an average of 25.07 days
for the whole cohort).
4. Discussion
Fig. 1. Evaluation of the markers position on imaging.
valuation de la position des marqueurs en imagerie.

3. Results
The characteristics of the patients who underwent gold seeds
implantation in our study are shown in Table 1. Of the 169 men, 119
(70.4%) had an insertion of four ducial markers, and the other 50
(29.6%) had three. All the patients received the antibiotic prophylaxis (100%), and those on anticoagulants stopped their medication
one week prior to the procedure (100%).
Concerning post-implantation complications, the procedure
was well-tolerated and in no patient was it necessary to interrupt
the implant with regards to pain or bleeding. Pain assessment was
done using the verbal descriptor scale (VDS): none to minor discomfort for all the patients, and no pain medication was required.
Bleeding was assessed according to the physician: minor bleeding
during the insertion was observed in most of the patients, with
no active bleeding at the end of the procedure. Seed migration
occurred twice: one in the bladder, one in the soft tissues, with
three remaining intraprostatic markers in both cases. The seed loss
rate in our study was 0.32% (for the loss of these 2 markers on 626
implanted in total). There was no impact on treatment planning,
delivery or side effects with regards to these two patients. No grade

Intrafraction and interfraction motions are contributing factors to the radiotherapy toxicity for prostate cancer due to the
dose reaching adjacent normal tissues [13]. Other factors, such as
bladder lling, rectal repletion or respiratory movements, are also
implicated in the movement of the prostate in relation to bony
anatomy. Considering the importance of treatment precision, gold
seed markers have become a routine technique for localization of
the prostate during radiation therapy [1417]. This procedure has
also been studied previously, and the experience of some centers
has been described.
In 2007, Langenhuijsen et al. published a study where
209 patients with localized prostate cancer had four gold markers
implanted under ultrasound guidance [18]. The following toxicity
was reported: pain and fever that resolved with oral medication in
6.2%, hematuria lasting more than 3 days in 3.8%, hematospermia
in 18.5%, rectal bleeding in 9.1%.
In 2009, Igdem et al. published a study to evaluate patientreported morbidity for this procedure [19]. One hundred and
seventy-seven patients were retrospectively analyzed, and the following complications were reported: 15% had hematuria, 4% had
rectal bleeding, and 2% had fever, but none required an intervention.
In 2012, Gill et al. published an article to report the complications from the implantation of gold seed markers [20]. Two hundred
and thirty-four patients were assessed, and 32% had at least one

Table 1
Characteristics of patients who underwent ducial marker implantation for prostate radiation therapy.
Caractristiques des patients ayant eu une implantation de marqueurs duciels pour une radiothrapie de la prostate.
Antibiotic therapy

Not received
Received

0 patient
169 patients (100%)

Interruption of anticoagulation

Uninterrupted
Interrupted

0 patient
169 patients (100%)

Pain, bleeding

Minor discomfort, light bleeding. No interruption of the

implant needed (for pain or bleeding)
3 gold seeds
4 gold seeds

50 patients (29.6%)
119 patients (70.4%)

Number of markers implanted

Prostate volume

Average: 38 cm3 ; range: 10150 cm3

Post-implant complications

2 urinary tract infections: 1.18% (95% CI: 0.334.21%)

Unusual migration: 2 in total (1 in bladder, 1 in soft tissues
3 remaining markers in both cases)
No complications of grade 3 or 4
Average: 25,07 days (95% CI: 23,9926,15 days)

Delay before starting radiotherapy

CI: condence interval.

Z.S. Fawaz et al. / Cancer/Radiothrapie 18 (2014) 736739

post-procedure new symptom: hematuria, rectal bleeding, dysuria

and hematospermia in 9 to 13% of patients, and one case of sepsis. Among the patients, 0.5 to 1.5% had grade 3 rectal bleeding,
hematuria, fever and shivers, or change in urinary frequency.
In this review, 1.18% of the patients developed an urinary
tract infection. Both patients with urinary tract infection had
ciprooxacin-resistant germs. Seed loss rate was 0.32% (2 markers
on 626 implanted), comparable to the percentages reported in
other studies with a variation between less than 1 and 8% [21].
Regarding the variation between the implantation of three or
four gold seeds, patients at the beginning of the period analyzed
had four markers implanted. Thereafter, three seeds began to be
implanted when we noticed that there was no migration. The
decision to interrupt anticoagulants comes from a group decision considering the hemorrhage risk. In higher-risk individual, the
treating cardiologist was consulted prior to anticoagulant interruption. We are aware that antiplatelet drugs were not discontinued
in a few studies on prostate biopsy [2224], but we maintained
the withdrawal of anticoagulation therapy for a gesture that we
consider simple and safer.
This study supports the practice of ducial markers implantation, and describes the technique used. This procedure is easily
reproducible, which makes it simpler to accomplish and reproduce. Since it was conducted in an afliated teaching hospital with
a policy to send the patients to the belonging department and performed at a single care center, a consistency in the care and the
management of the procedure is noted.
5. Conclusions
Transrectal ducial marker implantation for IGRT in prostate
cancer allows the localization of the prostate during the treatment,
which enables us to perform IGRT. The latter adds greater precision
to the treatment, and reduces the toxicity to adjacent tissues.
This procedure is a technique of simple execution, and easily
reproducible. It is minimally invasive, well-tolerated, and almost
free of adverse effects. There are no major associated complications.
Disclosure of interest
The authors declare that they have no conicts of interest concerning this article.
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