Feasibility of MRI-guided focal salvage high-dose-rate brachytherapy for locally recurrent prostate cancer

Prostate cancer recurrence after primary treatment is common, despite
improvements in primary curative treatment modalities. Various salvage
treatment modalities, like radical prostatectomy, low-dose-rate brachytherapy,
external beam radiotherapy, HIFU (high intensity focused ultrasound) and
cryosurgery have been investigated. However, because of high failure and high
toxicity rates, these treatment modalities remain unpopular. High failure rates
can be reduced by excluding patients with a high risk for early distant
metastasis. In these patients, salvage treatment will not be of benefit. High
toxicity rates can be explained by the fact that salvage therapy is often
performed on the entire prostate, which induces accumulation of a high
irradiation dose on healthy tissues. To reduce the burden of a high radiation
dose on healthy tissues, focal therapy is warranted. This can be achieved with
MRI-guided focal salvage high-dose-rate brachytherapy. In the past, focal
salvage treatment has not frequently been explored, since determination of
exact tumour location was not precise. Currently, our radiotherapy centre has a
MRI high-dose-rate brachytherapy facility, allowing MRI guided catheter
placement and treatment. With this facility, catheter placement can be done far
more accurately, which makes focal treatment possible. Due to the steep dose
fall-off, low radiation doses will be expected in the surrounding healthy
tissues. Therefore, less toxicity to the organs at risk is expected. In earlier
studies, salvage high-dose-rate brachytherpay has been shown to be feasible.
Moreover, results regarding toxicity are promising. Therefore, we expect that
MRI guided salvage treatment by using high-dose-rate brachytherapy will be of
benefit in patients with recurrent prostate cancer.

To assess toxicity of MRI guided focal salvage high-dose-rate brachytherapy as
monotherapy in patients with locally recurrent prostate cancer. As secondary
objectives, technical feasibility, quality of life and biochemical free
survival (Phoenix criteria) will be determined.

Prospective development study, using MRI guidance to apply a single fraction of
high dose rate brachytherapy as focal salvage monotherapy for treatment of
locally recurrent prostate cancer. All patients with recurrent prostate cancer
meeting the inclusion criteria, will be considered for inclusion.
Before treatment, a diagnostic MRI with contrast and a PSMA-PET scan 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 third MRI will be performed to assess treatment response.
The time span for inclusion of patients in this study will be two years. Before
treatment, toxicity of the primary treatment will be assessed. During the first
90 days after treatment, acute gastro-intestinal and genital-urinary toxicity
will be monitored. Hereafter, late gastro-intestinal and genital-urinary
toxicity will be assessed during a 10 year period. Toxicity and scoring of
symptoms before and after treatment will be determined by using the Common
Terminology Criteria for Adverse Events (CTCAE) version 4.0 criteria and
International Prostate Symptom Score (IPSS)questionnaire. Quality of life will
also be measured before high-dose-rate brachytherapy treatment and during a 10
year period after treatment. The RAND-36, EORTC QLQ-PR-25, EORTC QLQ-C30 and
IIEF-5 questionnaires will be used. For assessment of biochemical recurrence
(Phoenix criteria), Prostate 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.

High-dose-rate brachytherapy will be performed for patients with recurrent
prostate carcinoma. The treatment will include a single fraction of 19 Gy.
Salvage high-dose-rate brachytherapy will be performed by insertion of
catheters under ultrasound guidance. Before placement of the catheters,
ultrasound images will be fused with the diagnostic MR. Delineation of the
Gross Tumour Volume (GTV) will be performed by using the diagnostic MRI and the
PSMA-PET scan. With the help of T2, Dynamic Contrast Enhanced (DCE) and
Diffusion Weighted Imaging (DWI) sequences it is possible to make an accurate
delineation of the GTV. The Clinical Target Volume) (CTV) will be defined as
GTV with broader margins, to account for tumour extension. The Planning Target
Volume (PTV) will have no extra margins. Based on these merged images, the
catheters will be placed in the GTV. Consequently, the patient will be placed
in the MRI and under MR guidance catheter displacement in the tumour will be
adjusted for. Image datasets will be transferred to the treatment planning
computer to create a simulation of dose distribution to GTV, CTV, prostate,
urethra, rectum and bladder. The treatment will include a single fraction
high-dose-rate treatment. After treatment, the catheters will be removed and
the patient will be discharged from the hospital.

In order to keep toxicity to a minimum, strict dose constraints to the organs
at risk will be applied. With state of the art planning procedures prior to
focal salvage HDR-BT, a safe radiation dose to the CTV (clinical target volume)
can be determined. If the dose to the organs at risk is exceeded, the dosage to
the PTV will be decreased. To investigate quality of life, questionnaires will
be used. The additional MRI scan during treatment of focal HDR brachytherapy
will induce no additional health risks.
Because of the focal treatment, less toxicity of healthy tissues (bladder and
rectum) is expected in comparison with current salvage treatment modalities.
Furthermore, hormonal treatment in the future may be prevented or delayed by
the use of MRI guided focal salvage HDR-BT. This will prevent hormone induced
toxicity for the patient.
Focal salvage high-dose-rate brachytherapy treatment of prostate cancer has not
frequently been implemented before. Therefore, long term effects after this
treatment modality are unknown.