Interstitial Brachytherapy With or Without External-Beam Radiation Therapy in Treating Patients With Prostate Cancer

• Biochemical (i.e., prostate-specific antigen) failure for at least 5 years [ Designated as safety issue: No ]
• Biochemical failure by the Phoenix definition [ Designated as safety issue: No ]
• Disease-specific survival [ Designated as safety issue: No ]
• Local progression [ Designated as safety issue: No ]
• Distant metastases [ Designated as safety issue: No ]
• Overall survival [ Designated as safety issue: No ]
• Incidence of "acute" toxicities [ Designated as safety issue: Yes ]
• Time to "late" 3+ toxicities [ Designated as safety issue: Yes ]
• Health-related quality of life as measured by EPIC, EQ5D, and AUA-SI from baseline to 4 months (early) and then at 2 years (late) after initiation of therapy [ Designated as safety issue: No ]
• Feasibility of collecting Medicare data in a large RTOG prostate cancer clinical trial for cost effectiveness and cost utility analysis of combined treatment with interstitial brachytherapy and external beam radiotherapy [ Designated as safety issue: No ]

RATIONALE: Radiation therapy uses high-energy x-rays and other sources to damage tumor cells. Interstitial brachytherapy uses radioactive material placed directly into or near a tumor to kill tumor cells. Combining interstitial brachytherapy with external-beam radiation therapy may kill more tumor cells. It is not yet known whether interstitial brachytherapy is more effective with or without external-beam radiation therapy in treating prostate cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of interstitial brachytherapy with or without external-beam radiation therapy in treating patients who have prostate cancer.

OBJECTIVES:

• Compare the 5-year freedom from progression in patients with intermediate-risk prostate cancer treated with interstitial brachytherapy with or without external beam radiotherapy (EBRT).
• Compare biochemical (i.e., prostate-specific antigen) failure, biochemical failure by the Phoenix definition, disease-specific survival, local progression, and distant metastases in patients treated with these regimens.
• Compare morbidity and quality of life of patients treated with these regimens.
• Determine the feasibility of collecting Medicare data in a large RTOG prostate cancer clinical trial for cost effectiveness and cost utility analysis of combined treatment with interstitial brachytherapy and EBRT.
• Prospectively collect diagnostic biopsy samples from these patients for future biomarker analyses.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to disease stage (T1c vs T2a or T2b), Gleason score (≤ 6 vs 7), prostate-specific antigen (< 10 ng/mL vs 10-20 ng/mL), and prior neoadjuvant hormonal therapy (yes vs no). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients undergo external beam radiotherapy 5 days a week for 5 weeks. Within 2-4 weeks of radiotherapy, patients undergo interstitial brachytherapy with iodine I 125 or palladium Pd 103 seeds.
• Arm II: Patients undergo interstitial brachytherapy only, as in arm I. Quality of life is assessed at baseline, at 4, 12, and 24 months, and then annually for 3 years.

After completion of study treatment, patients are followed at 3-5 weeks, at 4, 6, 9, and 12 months, every 6 months for 4 years, and then annually thereafter.

• Radiation: iodine I 125
  Given as interstitial seeds
• Radiation: palladium Pd 103
  Given as interstitial seeds
• Radiation: radiation therapy
  Given as external beam radiation therapy over 5 weeks

• Experimental: Arm I
  Patients undergo external beam radiotherapy 5 days a week for 5 weeks. Within 2-4 weeks of radiotherapy, patients undergo interstitial brachytherapy with iodine I 125 or palladium Pd 103 seeds.
  Interventions:

  • Radiation: iodine I 125
  • Radiation: palladium Pd 103
  • Radiation: radiation therapy
• Active Comparator: Arm II
  Patients undergo interstitial brachytherapy only, as in arm I.
  Interventions:

  • Radiation: iodine I 125
  • Radiation: palladium Pd 103

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the prostate

  • T1c-T2b, N0, M0

• Intermediate-risk disease, as defined by 1 of the following:

  • Gleason score < 7 AND prostate-specific antigen (PSA) 10-20 ng/mL
  • Gleason score 7 AND PSA < 10 ng/mL
• No evidence of distant metastases
• Prostate volume ≤ 60 cc by transrectal ultrasonography
• American Urological Association voiding symptom score no greater than 15 (alpha blockers allowed)

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Zubrod 0-1

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

• Not specified

Renal

• Not specified

Other

• Patients must use effective contraception
• No other malignancy within the past 5 years except basal cell or squamous cell skin cancer or carcinoma in situ at any other site
• No major medical or psychiatric illness that would preclude study therapy
• No hip prosthesis

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• No prior chemotherapy

Endocrine therapy

• Prior neoadjuvant hormonal therapy allowed provided the following are true:

  • Therapy was initiated within 2-6 months of study enrollment
  • Therapy was no more than 6 months in duration
  • Use of 5-alpha reductase inhibitors (e.g., finasteride) is discontinued before registration
• No concurrent hormonal therapy

Radiotherapy

• No prior pelvic radiotherapy

Surgery

• No prior radical surgery for prostate cancer
• No prior transurethral resection of the prostate
• No prior cryosurgery

Other

• No prior transurethral needle ablation of the prostate
• No prior transurethral microwave thermotherapy of the prostate