Internal Radiation Therapy With or Without External-Beam Radiation Therapy in Treating Patients With Localized Prostate Cancer

Study Overview
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Brief Summary
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RATIONALE: Internal radiation uses radioactive material placed directly into or near a tumor to kill tumor cells. Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. PURPOSE: This phase II trial is studying the side effects of internal radiation therapy when given with or without external-beam radiation therapy and to see how well it works in treating patients with localized prostate cancer.

Detailed Description
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OBJECTIVES: Primary Evaluate the tolerability of 2 radiotherapeutic regimens (high dose-rate brachytherapy [HDR] with or without image-guided intensity-modulated hypofractionated external beam radiotherapy [EBRT]), as measured by the Common Terminology Criteria for Adverse Events (CTCAE v3.0), in patients with localized prostate cancer. Secondary Identify any associations between dose-volume parameters for organs at risk and the rate and severity of genitourinary or gastrointestinal adverse events. Evaluate patient preference with regard to selection of a second treatment (a second HDR brachytherapy session or an EBRT session). Evaluate patient-reported health-related quality of life (HRQOL) as measured by validated HRQOL instruments for 5 years. Describe the probability of freedom from biochemical and clinical failure. Describe the probability of freedom from salvage androgen suppression. OUTLINE: Patients undergo high dose-rate (HDR) brachytherapy (2 fractions ≥ 5 hours apart). Beginning 2-4 weeks after completion of the first HDR brachytherapy session, patients undergo either a second session of HDR brachytherapy (2 fractions ≥ 5 hours apart) OR image-guided intensity-modulated hypofractionated external beam radiotherapy once daily 5 days a week for 3 weeks. Quality of life is assessed at baseline, prior to the second treatment session, at 1 and 6 months after completion of treatment, every 6 months for 3 years, and then annually for 2 years. After completion of study treatment, patients are followed at 1 and 6 months, every 6 months for 3 years, and then annually for 2 years.

Official Title
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Pilot Evaluation of High Dose-Rate Brachytherapy ± Image-Guided Intensity Modulated Hypofractionated External Radiotherapy for Localized Prostate Cancer

Conditions
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Prostate Cancer

Intervention / Treatment
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* Radiation: brachytherapy
* Radiation: hypofractionated radiation therapy
* Radiation: image-guided radiation therapy
* Radiation: intensity-modulated radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed adenocarcinoma of the prostate, meeting one of the following criteria: Low-risk disease (T1-T2a, Gleason score ≤ 6, and PSA < 10 ng/mL) Low intermediate-risk disease (T1-T2c, Gleason score ≤ 6, and PSA < 20 ng/mL OR T1-T2a, Gleason score 7, and PSA < 10 ng/mL) No known nodal (N0 or NX) or distant (M0 or MX) metastases No pubic arch interference, as defined by either of the following: Maximum transrectal ultrasound-determined anterior-posterior (z-axis) dimension < 4.3 cm No more than 25% prostate volume blocked (by pubic arch) on CT scan simulation at A10°I beam's eye view Prostate planimetry volume ≤ 60 cc as determined by step-section transrectal ultrasound American Urological Association voiding symptom index ≤ 12 Peak uroflow rate (Q_max) ≥ 12 cc/second Post-void ultrasound bladder residual volume ≤ 100 cc PATIENT CHARACTERISTICS: Zubrod performance status 0-1 Life expectancy ≥ 5 years WBC > 2,000/μL Platelet count > 100,000/μL PT < 1.5 times upper limit of normal No diabetes mellitus associated with vascular ulcers or wound-healing problems No blood dyscrasias No inflammatory bowel disease No connective tissue disorder No other prior or concurrent invasive malignancy (except nonmelanoma skin cancer) or lymphomatous or hematological malignancy (except chronic lymphocytic leukemia/lymphoma) unless patient has been continually disease-free for ≥ 5 years No medical or psychiatric condition that would preclude giving informed consent or complying with study treatment Able to undergo anesthesia PRIOR CONCURRENT THERAPY: No prior transurethral resection of the prostate No prior prostatic cryoablation or high-intensity focused ultrasound No prior prostatectomy No prior prostatic enucleation No prior pelvic external beam radiotherapy No prior radionuclide prostate brachytherapy No prior hemi- or total hip arthroplasty Neoadjuvant androgen suppression therapy allowed provided it was initiated 2-6 months prior to study entry and its total duration is ≤ 6 months No concurrent anticoagulation therapy, including heparin or coumadin

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention Group<br>Protocol treatment consists of either two high dose-rate (HDR) brachytherapy implantation sessions or one HDR brachytherapy session followed by external beam radiotherapy (EBRT). Each HDR session consists of two 9.5Gy fractions. After the first HDR session of two fractions, patients express a preference for: (1) a second HDR brachytherapy implantation session, or (2) EBRT. The second HDR session or EBRT will begin 2-4 weeks after the first HDR brachytherapy session. | Radiation: brachytherapy<br> <br> Radiation: hypofractionated radiation therapy<br> <br> Radiation: image-guided radiation therapy<br> <br> Radiation: intensity-modulated radiation therapy<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment Tolerance (Genitourinary [GU] or Gastrointestinal [GI] Adverse Events) | Separately evaluate the tolerance of 2 radiotherapeutic regimens (HDR alone and HDR followed by hypofractionated EBRT) using the Common Terminology Criteria for Adverse Events (CTCAE v3.0). The specific adverse events (AEs) are early (i.e., within 270 days of treatment completion) grade >3 genitourinary (GU) and/or gastrointestinal (GI) AEs, late grade 2 GU and GI AEs, and late grade ≥3 GU and GI AEs. | From baseline to 3 years after registration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Association Between Dose-volume Limitations for Organs at Risk and Rate and Severity of GU or GI Adverse Events | Dose-volume limitations for organs at risk will be analyzed byassociating GU or GI AEs (both rate and severity) with dosimetric parameters using simple correlational methods. These parameters will include (1) bladder V80, V60, V50, and Dmax; (2) penile bulb median dose; (3) rectum V80, V60, V50 and Dmax; and (4) urethra V120, V110, V100, and Dmax. | From baseline to 5 years after registration | 
| Patient Preference for a Second Treatment (a Second High Dose-rate Brachytherapy Session or an External Beam Radiotherapy Session) | Patient preference for second treatment (group 1 or group 2) will be assessed using a Treatment Preference Questionnaire (Appendix IX) developed specifically for this study. Qualitative and quantitative analyses will be performed on patient responses to the questions posed after choosing their second treatment in an exploratory fashion. | From baseline until the end of the first treatment | 
| Changes in Health-related Quality of Life Scores | A pretest-posttest design will be employed to detect changes in HRQOL scores over time. The HRQOL scores will be calculated per assessment, as appropriate. Each construct will be standardized to a range of 0-100 so that comparison across constructs is facilitated. Sets of difference scores will be computed: 1) differences between baseline and treatment completion (at 1 month post treatment follow up), and 2) differences between treatment completion and all post-treatment follow-up examinations for up to five years after finishing the protocol treatment (see Section 4.1 for specific HRQOL instruments to be completed at follow-up visits). The first analysis will allow for determination of the short-term impact of treatment on HRQOL, while the second will investigate the long-term treatment effect. Student's t-test methodology will be applied to the differences at end of treatment (1 month post treatment follow up) and at each follow-up. | From baseline to 5 years after registration | 
| Freedom From Biochemical and Clinical Failure | Freedom from biochemical and clinical failure, will be analyzed using Kaplan-Meier procedures. Estimates will be drawn from the Kaplan-Meier curves for the probability of freedom from biochemical and clinical failure. | From baseline to 5 years after registration | 
| Freedom From Salvage Androgen Suppression Treatment | Estimates will be drawn from the Kaplan-Meier curves for the probability of freedom from salvage androgen suppression therapy. | From baseline to 5 years after registration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage II prostate cancer, stage I prostate cancer, adenocarcinoma of the prostate