Feasibility of MRI guided focal high-dose-rate brachytherapy for localized prostate cancer

Favourable risk prostate cancer is common in men in developed countries. These
cancers are often biologically indolent and therefore not clinically
significant. However, no consensus has been reached with regard to the best
approach of these tumours. Nowadays, low-dose-rate brachytherapy is often
implemented for patients with favourable risk prostate cancer since it is a
minimally invasive procedure. Still, severe toxicity remains a concern. Studies
regarding high-dose-rate brachytherapy as monotherapeutic treatment of the
entire prostate, show promising results regarding toxicity of bladder and
rectum. Nevertheless grade 3 toxicity is still present. To reduce toxicity in
patients with localized prostate cancer, focal treatment is warranted. This can
be achieved with MRI guided high-dose-rate brachytherapy. In the past, focal
treatment has not been explored since determination of exact tumour location
was not precise. Our radiotherapy centre has a MRI high-dose-rate brachytherapy
facility. With this facility, catheter placement can be done far more
accurately, which makes focal treatment possible. By using focal treatment,
less toxicity is expected. In earlier studies, a dose of 19 Gy to the entire
prostate was shown to be feasible. Therefore we believe that focal treatment of
19 Gy to the tumour focus will be of benefit to the patient with localized
prostate cancer. In case of recurrent (biochemical) disease, retreatment will
be applied.

To assess toxicity of MRI guided high-dose-rate focal brachytherapy as
monotherapy for favourable risk prostate cancer. As secondary objectives,
technical feasibility, quality of life and biochemical free survival will be
determined.

Prospective development study using MRI guidance to apply a single high dose
rate brachytherapy as focal monotherapy for favourable risk prostate cancer.
All UMC Utrecht prostate cancer patients meeting the inclusion criteria (see 4.
Study population), will be considered for inclusion.
Before treatment, a diagnostic MRI with contrast will be made. During
treatment, a MRI without contrast will be performed to visualize the
brachytherapy catheters in relation to prostate anatomy. Six months after
treatment, a diagnostic MRI will be done to assess treatment response.
The time span for inclusion of patients in this study will be three years.
During the first 90 days, acute gastro-intestinal and/or genital-urinary
toxicity will be monitored. Hereafter, late gastro-intestinal and/or
genital-urinary toxicity will be assessed during a 10 year period. Toxicity
will be determined by using the Common Toxicity Criteria for Adverse Events
(CTCAE) version 4.0. Quality of life will also be measured during a 10 year
period. The RAND-36, EORTC QLQ-PR-25, EORTC QLQ-C30 and IEFF-5 questionnaires
will be used. For assessment of biochemical recurrence, Prostae Specific
Antigen (PSA) monitoring will be performed during each follow-up visit.
Follow-up consultations will be performed 4 weeks after treatment and
thereafter every three months for the first year, every 6 months the second
year and thereafter annually for up to ten years, according the Dutch prostate
guideline (18).
In case of recurrent disease, a MRI and PET scan will be performed. Depending
on MRI and PET findings, suitable re-treatment will be performed.

High-dose-rate brachytherapy will be performed for patients with low to
intermediate risk prostate carcinoma. The treatment will include a single
fraction of 19 Gy. High-dose-rate brachytherapy will be performed by insertion
of catheters under ultrasound guidance. Under MR guidance, cathether placement
will be adjusted, according to the exact tumour position. Image datasets will
be transferred into the treatment planning computer to create a simulation of
dose distribution to Gross Tumour Volume (GTV), prostate, urethra, rectum and
bladder. Deliniation of the GTV will be performed by using the diagnostic MRI.
The Clinical Target Volume (CTV) will be defined as GTV with wider margins, to
account for tumour extension. The Planning Target Volume (PTV) will have no
extra margins. The treatment will include one high-dose-rate treatment. After
treatment, the implants will be removed and the patient will be discharged from
the hospital

With stringent dose constraints to urethra, bladder and rectum, and state of
the art planning procedure before focal high-dose-rate brachytherapy
application, it is unlikely that this treatment modalitiy will induce severe
toxicity. Above all, we expect that focal treatment will further reduce
toxicity compared to current commonly used low-dose-rate brachytherapy. The
additional MRI scan during treatment of focal high-dose-rate brachytherapy will
induce no additional health risks. Focal high-dose-rate brachytherapy treatment
of prostate cancer has never been implemented before. Therefore, recurrence
rates of prostate cancer after this treatment modality are unknown. In case of
a (biochemical) relapse, a MRI and PET scan will be performed and retreatment
will be applied.