UAMS - Translational Research Institute

Condition

• Prostate Cancer

Eligibility

Eligible Ages

Over 18 Years

Eligible Sex

Male

Accepts Healthy Volunteers

No

Criteria

DISEASE CHARACTERISTICS:

Pathologically (histologically or cytologically) proven diagnosis of prostatic
adenocarcinoma within 180 days of registration at moderate to high risk for recurrence as
determined by one of the following combinations:

- Gleason score 7-10 + T1c-T2b (palpation) + PSA < 50 ng/ml (includes intermediate and
high risk patients);

- Gleason score 6 + T2c-T4 (palpation) + PSA < 50 ng/ml

-ORGleason score 6 + ≥ 50% (positive) biopsies + PSA < 50 ng/ml;

- Gleason score 6 + T1c-T2b (palpation) + PSA > 20 ng/ml. Patients previously
diagnosed with low risk prostate cancer undergoing active surveillance who are
re-biopsied and found to have unfavorable intermediate risk disease or favorable
high risk disease according to the protocol criteria are eligible for enrollment
within 180 days of the repeat biopsy procedure.

- History/physical examination (to include at a minimum digital rectal
examination of the prostate and examination of the skeletal system and abdomen)
within 90 days prior to registration.

- Clinically negative lymph nodes as established by imaging (pelvic ± abdominal
CT or MR), (but not by nodal sampling, or dissection) within 90 days prior to
registration.

- Patients with lymph nodes equivocal or questionable by imaging are eligible if the
nodes are ≤ 1.5 cm.

*No evidence of bone metastases (M0) on bone scan within 120 days prior to
registration (Na F PET/CT is an acceptable substitute).

- Equivocal bone scan findings are allowed if plain films (or CT or MRI) are negative
for metastasis.

*Baseline serum PSA value performed with an FDA-approved assay (e.g., Abbott,
Hybritech) within 120 days prior to registration.

- Study entry PSA should not be obtained during the following time frames: (1) 10- day
period following prostate biopsy; (2) following initiation of hormonal therapy; (3)
within 30 days after discontinuation of finasteride; (4) within 90 days after
discontinuation of dutasteride.

- Zubrod Performance Status 0-1(unless otherwise specified);

- Age ≥ 18;

- CBC/differential obtained within 60 days prior to registration on study, with
adequate bone marrow function defined as follows:

- Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3;

- Platelets ≥ 100,000 cells/mm3;

- Hemoglobin ≥ 8.0 g/dl (Note: The use of transfusion or other intervention to achieve
Hgb ≥ 8.0 g/dl is acceptable.);

- Patient must be able to provide study specific informed consent prior to study
entry.

Detailed Description

OBJECTIVES: Primary - Demonstrate that prophylactic, neoadjuvant androgen-deprivation therapy (NADT) combined with whole-pelvic radiation therapy (WPRT) improves overall survival (OS) compared with NADT combined with prostate and seminal vesicle radiation therapy (RT), with both arms receiving a high-dose prostate boost delivered by intensity-modulated RT (IMRT), external-beam RT (EBRT), high-dose-rate (HDR) brachytherapy, or permanent prostate implant (PPI). Secondary - Demonstrate that prophylactic WPRT improves biochemical control. - Determine the distant metastasis (DM)-free survival. - Determine the cause-specific survival (CSS). - Compare acute and late treatment-adverse events between patients receiving NADT and WPRT versus NADT, P, and SV RT. - Determine whether health-related quality of life (HRQOL), as measured by the Expanded Prostate Cancer Index Composite (EPIC), significantly worsens with increasing aggressiveness of treatment (i.e., Arm 2, NADT + WPRT). - Determine whether more aggressive treatment (Arm 2, NADT + WPRT) is associated with a greater increase in fatigue (PROMIS Fatigue Short Form) from baseline to last week of treatment, and a greater increase in circulating inflammatory markers (IL-1, IL-1ra, IL-6, tumor necrosis factor (TNF)-alpha, and C-reactive protein). - Demonstrate an incremental gain in OS and CSS with more aggressive therapy that outweighs any detriments in the primary generic domains of HRQOL (i.e., mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). - Determine whether changes in fatigue from baseline to the next three time points (week prior to RT, last week of treatment, and 3 months after treatment) are associated with changes in circulating cytokines, mood, sleep, and daily activities across the same time points. - Collect paraffin-embedded tissue blocks, plasma, whole blood, and urine for planned and future translational research analyses. OUTLINE: This is a multicenter study. Patients are stratified according to moderate- to high-risk groups as listed in the Disease Characteristics of this abstract, type of radiotherapy boost (IMRT vs brachytherapy [Low-dose rate (LDR) using PPI or HDR]), and duration of androgen-deprivation therapy (short-term [4-6 months] vs long-term [32 months]). Patients are randomized to 1 of 2 treatment arms. All patients receive neoadjuvant androgen-deprivation therapy comprising bicalutamide orally (PO) once daily or flutamide PO thrice daily for 4-6 months, and luteinizing hormone-releasing hormone (LHRH) agonist/antagonist therapy comprising leuprolide acetate, goserelin acetate, buserelin, triptorelin, or degarelix subcutaneously (SC) or intramuscularly (IM) every 1 to 3 months beginning 2 months prior to radiotherapy and continuing for 4-6 or 32 months. Radiotherapy begins within 8 weeks after beginning LHRH agonist/antagonist injection. Patients may undergo blood and urine sample collection for correlative studies. Primary tumor tissue samples may also be collected. Patients may complete the Expanded Prostate Cancer Index Composite (EPIC), the PROMIS-Fatigue Short Form, and the EuroQol (EQ-5D) quality-of-life (QOL) questionnaires at baseline and periodically during treatment. Patients who participate in the QOL portion of the study must also agree to periodic blood collection. After completion of study therapy, patients are followed up every 3 months for 1 year, every 6 months for 3 years, and then yearly thereafter.