Prostate Radiation Therapy or Short-Term Androgen Deprivation Therapy and Pelvic Lymph Node Radiation Therapy With or Without Prostate Radiation Therapy in Treating Patients With a Rising Prostate Specific Antigen (PSA) After Surgery for Prostate Cancer
Condition: Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: PBRT; PLNRT; AA; LHRH agonist
Intervention description: 1.8 Gy per fraction once daily, 5 days a week totaling 64.8-70.2 Gy. 3D-CRT or IMRT required.; 1.8 Gy per fraction once daily, 5 days a week, totaling 45 Gy. 3D-CRT or IMRT required.; Antiandrogen (AA) therapy can be either 250 mg flutamide by mouth three times a day or 50 mg bicalutamide by mouth once a day.; Luteinizing hormone-releasing hormone (LHRH) agonist can be any analog approved by the FDA (or by Health Canada for Canadian institutions) and may be given in any possible combination such that the total LHRH treatment time is 4-6 months. LHRH analogs are administered with a variety of techniques, including subcutaneous insertion of a solid plug in the abdominal wall, intramuscular injection, and subcutaneous injection.
Intervention MeSH terms: Leuprolide; Goserelin; Triptorelin Pamoate; Flutamide; Bicalutamide; Buserelin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 1792.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: stage IIB prostate cancer; stage IIA prostate cancer; stage III prostate cancer; adenocarcinoma of the prostate

Summary:

      RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Androgens can cause
      the growth of prostate cancer cells. Antihormone therapy, such as flutamide, bicalutamide,
      and luteinizing hormone-releasing hormone agonist, may lessen the amount of androgens made by
      the body. It is not yet known which regimen of radiation therapy with or without
      androgen-deprivation therapy is more effective for prostate cancer.

      PURPOSE: This randomized phase III trial is studying prostate radiation therapy to see how
      well it works compared with short-term androgen deprivation therapy given together with
      pelvic lymph node radiation therapy with or without prostate radiation therapy in treating
      patients with a rising PSA after surgery for prostate cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Adenocarcinoma of the prostate treated primarily with radical prostatectomy,
             pathologically proven to be lymph node negative by pelvic lymphadenectomy (N0) or
             lymph node status pathologically unknown (undissected pelvic lymph nodes [Nx]), i.e.
             lymph node dissection is not required;

             • Any type of radical prostatectomy will be permitted, including retropubic, perineal,
             laparoscopic or robotically assisted. There is no time limit for the date of radical
             prostatectomy.

          2. A post-radical prostatectomy entry prostate-specific antigen (PSA) of ≥ 0.1 and < 2.0
             ng/mL at least 6 weeks (45 days) after prostatectomy and within 30 days of
             registration;

          3. One of the following pathologic classifications:

               -  T3N0/Nx disease with or without a positive prostatectomy surgical margin; or

               -  T2N0/Nx disease with or without a positive prostatectomy surgical margin;

          4. Prostatectomy Gleason score of 9 or less;

          5. Zubrod Performance Status of 0-1;

          6. Age ≥ 18;

          7. No distant metastases, based upon the following minimum diagnostic workup:

               -  History/physical examination (including digital rectal exam) within 8 weeks (60
                  days) prior to registration;

               -  A computerized tomography (CT) scan of the pelvis (with contrast if renal
                  function is acceptable; a noncontrast CT is permitted if the patient is not a
                  candidate for contrast) or magnetic resonance imaging (MRI) of the pelvis within
                  120 days prior to registration;

               -  Bone scan within 120 days prior to registration; if the bone scan is suspicious,
                  a plain x-ray and/or MRI must be obtained to rule out metastasis.

          8. Adequate bone marrow function, within 90 days prior to registration, defined as
             follows:

               -  Platelets ≥ 100,000 cells/mm^3 based upon compete blood count (CBC);

               -  Hemoglobin ≥ 10.0 g/dl based upon CBC (Note: The use of transfusion or other
                  intervention to achieve Hgb ≥ 10.0 g/dl is recommended).

          9. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 2 x the upper
             limit of normal within 90 days prior to registration;

         10. Serum total testosterone must be ≥ 40% of the lower limit of normal (LLN) of the assay
             used (testosterone ÷ LLN must be ≥ 0.40) within 90 days prior to registration (Note:
             Patients who have had a unilateral orchiectomy are eligible as long as this
             requirement is met);

         11. Patients must sign a study-specific informed consent prior to study entry.

        Exclusion Criteria:

          1. A palpable prostatic fossa abnormality/mass suggestive of recurrence, unless shown by
             biopsy under ultrasound guidance not to contain cancer;

          2. N1 patients are ineligible, as are those with pelvic lymph node enlargement ≥ 1.5 cm
             in greatest dimension by CT scan or MRI of the pelvis, unless the enlarged lymph node
             is sampled and is negative;

          3. Androgen deprivation therapy started prior to prostatectomy for > 6 months (180 days)
             duration. Note: The use of finasteride or dutasteride (±tamsulosin) for longer periods
             prior to prostatectomy is acceptable;

          4. Androgen deprivation therapy started after prostatectomy and prior to registration
             (Note: The use of finasteride or dutasteride (±tamsulosin) after prostatectomy is not
             acceptable - must be stopped within 3 months after prostatectomy. Androgen deprivation
             therapy must be stopped within 3 months after prostatectomy);

          5. Neoadjuvant chemotherapy before or after prostatectomy;

          6. Prior chemotherapy for any other disease site if given within 5 years prior to
             registration;

          7. Prior cryosurgery or brachytherapy of the prostate; prostatectomy should be the
             primary treatment and not a salvage procedure;

          8. Prior pelvic radiotherapy;

          9. Prior invasive malignancy (except non-melanomatous skin cancer) or superficial bladder
             cancer unless disease free for a minimum of 5 years [for example, carcinoma in situ of
             the oral cavity is permissible];

         10. Severe, active co-morbidity, defined as follows:

               -  History of inflammatory bowel disease;

               -  History of hepatitis B or C; Blood tests are not required to determine if the
                  patient has had hepatitis B or C, unless the patient reports a history of
                  hepatitis.

               -  Unstable angina and/or congestive heart failure requiring hospitalization within
                  the last 6 months;

               -  Transmural myocardial infarction within the last 6 months;

               -  Acute bacterial or fungal infection requiring intravenous antibiotics at the time
                  of registration;

               -  Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness
                  requiring hospitalization or precluding study therapy at the time of
                  registration;

               -  Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects;
                  AST or ALT are required; note, however, that laboratory tests for coagulation
                  parameters are not required for entry into this protocol.

               -  Acquired Immune Deficiency Syndrome (AIDS) based upon current Centers for Disease
                  Control and Prevention (CDC) definition; Note, however, that human
                  immunodeficiency viruses (HIV) testing is not required for entry into this
                  protocol. The need to exclude patients with acquired immunodeficiency syndrome
                  (AIDS) from this protocol is necessary because the treatments involved in this
                  protocol may result in increased toxicity and immunosuppression.

         11. Prior allergic reaction to the study drug(s) involved in this protocol.