Phase III IGRT and SBRT vs IGRT and Hypofractionated IMRT for Localized Intermediate Risk Prostate Cancer
Brief SummaryThis randomized phase III trial studies how well stereotactic body radiation therapy works compared to intensity-modulated radiation therapy in treating patients with stage IIA-B prostate cancer. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Stereotactic body radiation therapy is a specialized radiation therapy that sends x-rays directly to the tumor using smaller doses over several days and may cause less damage to normal tissue. Stereotactic body radiation therapy may work better in treating patients with prostate cancer.
Detailed DescriptionI. To determine whether stereotactic body radiation therapy (SBRT) can be shown to be superior to hypofractionated intensity-modulated radiation therapy (IMRT) in terms of genitourinary (GU) and gastrointestinal (GI) toxicity by having fewer patients that experience a minimal important decline (MID) in urinary irritation/obstructive and bowel Health Related Quality of Life (HRQOL) as measured by Expanded Prostate Cancer Index Composite (EPIC)-26 at 24 months post completion of therapy. SECONDARY OBJECTIVES: I. To determine if SBRT (5 fractions of 7.25 Gy) is superior to hypofractionated IMRT (28 fractions of 2.5 Gy) as measured by disease free survival (DFS). II. To determine whether SBRT can be shown to be superior to hypofractionated IMRT at 12 and 24 months post completion of therapy in terms of HRQOL by having fewer patients that experience a minimal important decline (MID) bowel (12 months only) sexual, hormonal, urinary irritation/obstructive (12 months only) and in urinary incontinence HRQOL as measured by EPIC-26. III. To determine if SBRT (5 fractions of 7.25 Gy) is superior to hypofractionated IMRT (28 fractions of 2.5 Gy) as measured by biochemical failure, overall survival, local failure, prostate cancer specific survival, and distant metastases. IV. To determine if prostate imaging-reporting and data system (PIRADS)version (v)2 = 4/5 disease is predictive for biochemical failure. TERTIARY OBJECTIVES: I. To determine whether a potentially more expensive therapy, SBRT, would be cost-effective than standard hypofractionated IMRT as measured by the European Quality of Life Five Dimension Five Level Scale Questionnaire (EQ-5D-5L). II. To determine if disease characteristics captured on MRI can be used to predict which patients will respond to SBRT versus hypofractionated IMRT. III. Collect specimens for future translational research analyses. OUTLINE: Patients are randomized into 1 of 2 arms. ARM I: Patients undergo IMRT once daily for 5 fractions per week for 28 fractions over less than 32 business days. ARM II: Patients undergo SBRT at least every other day for 2-3 fractions per week for 5 fractions over less than 12 business days. After completion of study treatment, patients are followed up every 6-12 months until death or study termination.
Inclusion and Exclusion Criteria
- Previously untreated (no local therapy such as surgery, radiation cryotherapy, HIFU, etc.) localized adenocarcinoma of the prostate with the following clinical findings:
- Clinical stage by digital rectal exam of either T1c or T2a/b (limited to one side of the gland); (American Joint Committee on Cancer [AJCC], version 7) or cT1a-c or 2a or 2b,
- Stages T1a-T1b are eligible if patient underwent transurethral prostatic resection (TURP), the patient must meet one of the following 3 criteria: 1) Gleason score must be Gleason 7(3+4) with a PSA < 20 ng/mL, or 2) Gleason 6(3+3) with a PSA > 10 ng/mL and < 20 ng/mL; (AJCC, version 7) or 3) Group Grade 1 or 2
- If patient is receiving a 5-alpha reductase inhibitor at the time of enrollment the baseline PSA value may be double the initial value and the medication should be discontinued but a washout period is not required to eligible, a PSA drawn while still on the medicine must be:
- < 10 ng/mL if Gleason 7(3+4) (Note: This patient would be on stratification level 1 if PSA < 5 ng/mL and stratification level 2 if less than 10 ng/mL).
- > 5 ng/mL and less than 10 ng/mL for Gleason 6(3+3) (Note: This patients would be on stratification level 3).
- Percent of submitted positive core biopsies must be < 50% of all sextants (Sextant refers to the bilateral base, mid and apex of the gland and the left and right, resulting in six sections or sextants. Biopsies may take 2 from each sextant. If more than 12 are sampled, some may be from a targeted region possibly with multiple cores to ensure adequate tissue.)
- NOTE: all cores from a targeted lesion will be counted as an N of 1 core for calculating percent positive cores in total
- The prostate volume must be < 60 cc as reported at time of biopsy or by separate measure with ultrasound or other imaging modalities including magnetic resonance imaging (MRI) or computed tomography (CT) scan
- Patients in active surveillance who elect to be treated are eligible if they meet protocol requirements
- History and physical including a digital rectal exam 60 days prior to registration
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1 60 days prior to registration
- MRI of pelvis (compliant with PIRADSv2 guidelines) within 90 days prior to registration
- Bone scan or sodium fluoride positron emission tomography (PET) scan within 90 days prior to registration
- Charlson modified co-morbidity score =< 3 for patients under 60 and =< 4 for patients 60 and over 21 days prior to registration
- International prostate symptom score (IPSS) of < 15 21 days prior to registration
- The patient must provide study-specific informed consent prior to study entry
- Willingness and ability to complete the Expanded Prostate Cancer Index Composite (EPIC-26) questionnaire
- Completion of all items of the EPIC-26 which will be data entered at registration 60 days prior to registration
- Only English, Spanish, and French-speaking patients are eligible to participate
- Definitive clinical or radiologic evidence of metastatic disease; no nodal involvement or evidence of metastatic disease allowed as defined by screening of the pelvis and a bone scan or sodium fluoride PET scan
- Definitive T3 disease on MRI
- Prior or current invasive malignancy with current evidence of active disease within the past 3 years
- Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different cancer is allowable; must be off treatment for at least 3 years; [applicable only to studies that incorporate systemic therapy]
- Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
- The use of hormonal therapy is not allowed; if the patient in on a 5-alpha reductase inhibitor, then they should be stopped prior to treatment once enrolled onto the study; no washout period is required for this study to participate
- Severe, active co-morbidity defined as follows:
- Human immunodeficiency virus (HIV) positive with CD4 count < 200 cells/microliter; Note that patients who are HIV positive are eligible, provided they are under treatment with highly active antiretroviral therapy (HAART) and have a CD4 count >= 200 cells/microliter within 30 days prior to registration; Note also that HIV testing is not required for eligibility for this protocol
- Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for liver function and coagulation parameters are not required for entry into this protocol; (patients on Coumadin or other blood thinning agents are eligible for this study)
- Contraindication to MRI
- Cardiac pacemaker or defibrillator
- Surgically implanted electrical devices such as spinal stimulation devices or intracranial stimulation devices, cochlear implants, the presence of metallic foreign bodies in the orbits, and incompatible old mechanical heart valves and aneurysm clips
Please contact the trial administrator to learn more about where you can participate in this trial. Please use the contact form on the right side.