HDR vs LDR Brachytherapy as Monotherapy in the Treatment of Localized Prostate Cancer.

Study Overview
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Brief Summary
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Investigators compare in a randomized clinical trial the results and side effects of high-dose- and low-dose-rate brachytherapy as monotherapy in the treatment of early, organ confined prostate cancer patients.

Detailed Description
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Permanent implant prostate brachytherapy (LDRPBT) is a well established and proved method in the treatment of patients with low or selected intermediate risk, organ confined prostate cancer. There are number of studies with high-dose rate brachytherapy (HDRPBT) as monotherapy with several fractionation schedule treating the same group of patients. One phase II trial showed its effectiveness given in one fraction of 19 Gy. In the trial investigators randomly select patients to treat with either LDR prostate brachytherapy (145Gy) or HDR prostate brachytherapy (1x19Gy) as monotherapy. Patients are stratified into two pretreatment group: 1. low risk, 2. selected intermediate risk group. Brachytherapy is given in spinal anaesthesia, using transrectal ultrasound based real time treatment planning. Dose constraints are defined for both methods.

Official Title
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Comparison of High-dose- Versus Low-dose-rate Brachytherapy as Monotherapy in the Treatment of Early, Organ Confined Prostate Cancer.

Conditions
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Adenocarcinoma of Prostate

Intervention / Treatment
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* Radiation: LDR Brachytherapy
* Radiation: HDR Brachytherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eastern Cooperative Oncology Group (ECOG) status <=1 40-75 years old expected life expectancy>10 years low risk prostate cancer (Prostate specific antigen (PSA)<=10ng/ml, gleason score <7, T status<=2a), less than 50 % positive biopsy cores selected intermediate prostate cancer (PSA)=10-<15ng/ml or gleason score =3+4(but not 4+3), or T2b-c, less than 50 % positive biopsy cores) International prostate symptom score (IPSS) <=15 Prostate volume<=50cm3 no pubic interference no prior prostate operation, except biopsy no prior radiation to pelvis patient signed the informed consent Exclusion Criteria: <40 years or >75 years old PSA>15 ng/ml gleason score 4+3 , score 8-10 ECOG>=2 T3-4 percent core positivity >50 % TUR operation within six months prior to the brachytherapy prostate volume<10 cm3 or >50 cm3 IPSS >15

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: LDRPBT<br>Patients with low and selected intermediate risk prostate cancer are treated with Prostate LDR brachytherapy as monotherapy. 145 Gy is prescribed to the prostate. I-125 radioactive sources are used. Transperineal approach, rectal ultrasound guidance, inverse treatment planning, real time dose optimization is applied. | Radiation: LDR Brachytherapy<br>* In spinal anaesthesia patients' prostate are treated with low-dose-rate or brachytherapy using transrectal ultrasound guidance. Radiation sources (iodine-125 isotopes) are implanted into the prostate through transperineal needle insertion. Real time dose planning is applied. The prescribed dose to the whole prostate is 145 Gy.<br>* Other names: Permanent implantation prostate brachytherapy;|
| Experimental: HDRPBT<br>Patients with low and selected intermediate risk prostate cancer are treated with prostate HDR brachytherapy as monotherapy. The prescribed dose is 1x19 Gy to the whole prostate. Ir-192 radioactive source is used. Transperineal approach, rectal ultrasound guidance, inverse treatment planning, real time dose optimization is applied. | Radiation: HDR Brachytherapy<br>* In spinal anaesthesia patients' prostate are treated with one fraction of HDR brachytherapy. The prescribed dose to the whole prostate is 1x19 Gy. Ir-192 radioactive stepping source is used for the treatment with after-loading technique. Transperineal approach, rectal ultrasound guidance, inverse treatment planning, real time intraoperative needle position update and dose optimization is applied.<br>* Other names: temporary implant;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute side effects | Acute gastrointestinal, urogenital and other side effects occuring within six months after the procedure, according to the Common Toxicity Criteria for Adverse Effects (CTCAE 4.0v) scale | 6 months | 
| Chronic side effects | Chronic gastrointestinal, urogenital and other side effects occuring within six months after the procedure, according to the CTCAE 4.0v scale | from 6 months to five year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| quality of life | Assessing patients' quality of life according to the a 25 question prostate module (PR-25) of the European Organization for Research and Treatment of Cancer quality of life questionnaire (EORTC QlQ-30). | 5 years | 
| quality of life | Assessing patients' quality of life according to the International Index for Erectile Function (IIEF) questionnaire | 5 years | 
| Biochemical relapse free survival (bRFS) | Censoring an event when biochemical relapse occurs using the American Society of Therapeutic Radiation and Oncology (ASTRO) Phoenix definition for PSA relapse (nadir + 2 ng/ml increase) | 5 years | 
| Locoregional tumor free survival | Censoring an event when either local or regional relapse occurs | 5 years | 
| Disease specific survival (DSS) | Censoring an event when patient dies due to prostate cancer | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prostate, Cancer, Brachytherapy, HDR, LDR, monotherapy