HDR Brachytherapy vs. LDR Brachytherapy Monotherapy in Localized Prostate Cancer
HDR Brachytherapy vs. LDR Brachytherapy Monotherapy in Localized Prostate Cancer
High-dose rate brachytherapy (HDRB) used as monotherapy is emerging as an alternative to
 Low-Dose Rate brachytherapy (LDRB) with excellent PSA-progression free survival as high as
 90-100% for favorable prostate cancer at a median follow-up of 3-5 years.

 HDRB has many advantages over LDRB such as prospective dosimetry not impacted by setup
 errors, organ motion and prostate swelling during treatment delivery. In addition, HDRB
 causes less acute and late urinary toxicity compared with LDRB. Acute urinary retention can
 lead to prolonged catheterization, pericatheter urine leakage, urinary tract infection and
 Trans-Urethral Resection of the Prostate resulting in diminished quality of life (QOL) and
 increased psychological distress.

 The goal of the investigators' phase II randomized study is to evaluate the differences in
 QOL in the urinary domain between patients with favourable intermediate risk or extensive
 low-risk prostate cancer treated with LDRB and HDRB at 3 months using the Expanded Prostate
 Cancer Index Composite (EPIC) QOL scores. The 3 months cut-off endpoint has been chosen since
 HDRB-induced urinary toxicity subsides at 12 weeks compared to 12 months with LDRB. Secondary
 objectives include: bowel and sexual domain EPIC scores and International Prostate Symptom
 Score. The absolute PSA nadir and a prostate biopsy at 36 months will be reported to assess
 local control.
Primary Endpoint:

 • To evaluate the differences in QOL in the urinary domain between patients treated with
 Low-Dose Rate Brachytherapy (LDRB) and High-Dose Rate Brachytherapy (HDRB) at 3 months.

 Secondary Endpoints:

 -  To compare LDRB vs. HDR as related to the Expanded Prostate Cancer Index Composite
 (EPIC) score in the bowel and sexual domain at baseline, 1, 3, 6, 12, and 24 months.

 -  To evaluate differences in urinary function using the IPSS which, will be filled in by
 the patient at baseline, 1, 3, 6, 12 and 24 months after the procedure.

 -  To report acute and long-term urinary, sexual and gastro-intestinal toxicity using the
 Common Terminology Criteria for Adverse Events (CTCAE) version 4 at each patient's
 visit.

 -  To report the dose to the bladder neck defined as 5 mm around the Foley catheter from
 the bottom of the Foley balloon to the prostatic urethra with a volume of at least 2 cc.

 -  To assess local control by performing prostate rebiopsy after radiotherapy at 36 months
 to assess treatment outcome.

 -  The absolute Prostate Specific Antigen ( PSA) nadir value will be reported as a
 secondary objective by PSA measurements every 6 months after the procedure.
Inclusion Criteria:

 -Histologically confirmed adenocarcinoma of the prostate diagnosed within the last 9
 months.

 Patients on active surveillance with evidence of disease progression are eligible to the
 protocol as long as they meet the eligibility criteria and have a recent prostate biopsy
 (within 9 months).

 -  Low-risk disease defined as: Clinical stage T1-T2 and Gleason 6 and PSA≤20 ng/mL.

 -  Intermediate-risk disease defined as: Clinical stage T1-T2 and Gleason 7 (3+4) and PSA
 ≤ 20 ng/mL and ≤ 60% of positive cores.

 -  Lymph node evaluation by either CT or MRI is optional and is left at the discretion of
 the treating physician.

 -  No alpha reductase inhibitors use within 2 weeks of randomization. A washout period of
 2 weeks is required prior to randomization.

 -  Eastern Cooperative Oncology Group status 0-1

 -  No hormonal therapy is accepted.

 -  Prostate volume by Trans-rectal Ultrasound (TRUS) ≤ 60 cc.

 -  Internation Prostate Symptom Score (IPSS) ≤ 20 (alpha blockers allowed)

 Exclusion Criteria:

 -  Patients with a history of other malignancies, except: adequately treated non-melanoma
 skin cancer, or other solid tumours curatively treated with no evidence of disease for
 ≥ 5 years.

 -  Prior or current bleeding diathesis

 -  Previous androgen deprivation therapy within 6 months of the registration.

 -  Radical surgery for carcinoma of the prostate, prior pelvic radiation, prior
 chemotherapy for prostate cancer, prior Transurethral resection of the prostate
 (TURP), prior cryosurgery of the prostate.

 -  Evidence of metastatic disease (radiology investigations at the discretion of the
 treating physician).

 -  Any serious active or co-morbid medical conditions, laboratory abnormality,
 psychiatric illness, active or uncontrolled infections, or serious illnesses or
 medical conditions that would prevent the patient from participating or to be managed
 according to the protocol (according to investigator's decision).

 -  Gleason score 7 (4+3), clinical stage≥ T3a, PSA > 20 and > 60% of positive cores.