Radiation Therapy in Treating Patients With Stage II Prostate Cancer

Radiation Therapy Oncology Group

Status and phase: Completed; Phase 3

Conditions: Prostate Cancer

Treatments: Radiation: Hypofractionated 3D-CRT or IMRT; Radiation: Conventional 3D-CRT or IMRT

Study type: Interventional

Funder types: Other; NETWORK; NIH

Identifiers

NCT00331773

RTOG-0415

CDR0000481119

NCI-2009-00721 (Registry Identifier)

Details and patient eligibility

About

RATIONALE: Giving radiation therapy that uses a 3-dimensional (3-D) image of the tumor to help focus thin beams of radiation directly on the tumor, and giving hypofractionated radiation therapy (higher doses over a shorter period of time), may be less costly with fewer side effects and just as effective in treating prostate cancer.

PURPOSE: This randomized phase III trial is studying several different radiation therapy regimens to compare how well they work in treating patients with stage II prostate cancer.

Full description

OBJECTIVES:

Primary

• Compare the disease-free survival (DFS) of patients with favorable-risk stage II prostate cancer treated with hypofractionated vs conventionally fractionated three-dimensional conformal radiotherapy (3D-CRT) or intensity-modulated radiotherapy (IMRT).

Secondary

• Compare time to local progression, freedom from biochemical recurrence, and disease-specific and overall survival of patients treated with these regimens.
• Determine the incidence of gastrointestinal and genitourinary toxic effects in patients treated with these regimens.
• Compare the degree, duration, and significant differences in disease-specific health-related quality of life (HRQOL) decrements, using the Expanded Prostate Cancer Index Composite (EPIC), in patients treated with these regimens.
• Determine whether anxiety and/or depression, as measured by the Hopkins Symptom Checklist-25 (HSCL-25), are decreased with therapy that improves DFS of these patients .
• Determine whether the incremental gain in DFS outweighs decrements in the generic domains of HRQOL (i.e., mobility, self care, usual activities, pain/discomfort, and anxiety/depression) in patients treated with these regimens.
• Conduct a cost-utility analysis of hypofractionated 3D-CRT or IMRT as a prostate cancer therapy if this regimen is shown to be as effective as conventionally fractionated 3D-CRT or IMRT in improving DFS.

OUTLINE: This is a randomized, controlled, multicenter study. Patients are stratified according to Gleason score (2-4 vs 5-6), prostate-specific antigen (PSA) level (< 4 ng/mL vs 4-<9 ng/mL), and planned radiotherapy modality (three-dimensional conformal radiotherapy [3D-CRT] vs intensity-modulated radiotherapy [IMRT]). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients undergo conventionally fractionated 3D-CRT or IMRT once daily 5 days a week for 8.2 weeks (total of 41 treatments).
• Arm II: Patients undergo hypofractionated 3D-CRT or IMRT once daily 5 days a week for 5.6 weeks (total of 28 treatments).

Quality of life, anxiety, and depression are assessed at baseline and then at 6 months and 1, 2, and 5 years after the start of radiotherapy.

After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 1,067 patients will be accrued to this study.

Enrollment: 1,116 patients

Sex: Male

Ages: 18 to 120 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the prostate within the past 6 months

  • Clinical stage T1-2c

• Combined Gleason score 2-6

• Prostate-specific antigen (PSA) < 10 ng/mL within the past 6 months

  • PSA evaluated at least 10 days after prostate biopsy
  • For patients who received finasteride, PSA evaluated at least 30 after completion of finasteride
  • For patients who received dutasteride, PSA evaluated at least 90 after completion of dutasteride

• No regional lymph node involvement

• No distant metastases

PATIENT CHARACTERISTICS:

• Zubrod performance status 0-1
• No unstable angina and/or congestive heart failure requiring hospitalization within the past 6 months
• No transmural myocardial infarction within the past 6 months
• No acute bacterial or fungal infection requiring IV antibiotics
• No chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study treatment
• No hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
• No known AIDS
• No prior or concurrent lymphomatous/hematogenous malignancy or other invasive malignancy except nonmelanomatous skin cancer or any other cancer for which the patient has been continually disease-free for ≥ 5 years (e.g., carcinoma in situ of the bladder or oral cavity)
• No other severe, active comorbidity

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• No prior radical prostatectomy or cryosurgery for prostate cancer

• No prior hormonal therapy, including any of the following:

  • Luteinizing hormone-releasing hormone agonists (e.g., goserelin or leuprolide)
  • Antiandrogens (e.g., flutamide or bicalutamide)
  • Estrogens [e.g., diethylstilbestrol (DES)]
  • Surgical castration (bilateral orchiectomy)

• No prior pelvic radiotherapy or prostate brachytherapy

• No prior or concurrent cytotoxic chemotherapy for prostate cancer

• At least 30 days since prior finasteride

• At least 90 days since prior dutasteride

• No concurrent neoadjuvant or adjuvant hormonal therapy

• Concurrent warfarin or other blood-thinning agents allowed

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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1,116 participants in 2 patient groups

Conventional 3D-CRT

Active Comparator group

Description:

Conventional 3D-CRT or IMRT to 73.8 Gy in 41 fractions

Treatment:

Radiation: Conventional 3D-CRT or IMRT

Hypofractionated 3D-CRT

Experimental group

Description:

Hypofractionated 3D-CRT or IMRT to 70 Gy in 28 fractions

Treatment:

Radiation: Hypofractionated 3D-CRT or IMRT