A Phase III Trial of Hypofractionated External Beam Image-Guided Highly Targeted Radiotherapy: The HEIGHT Trial

Inclusion Criteria:

- Biopsy confirmed adenocarcinoma of the prostate.

- T1-T2 disease based on digital rectal exam.

- T1a is permitted if peripheral zone biopsies are positive.

- T3a disease based on MRI only is acceptable.

- No evidence of metastasis by any clinical criteria or available radiographic tests.

- Gleason score 6-8.

- Patients with Gleason score 8 must be offered long term androgen deprivation therapy
(ADT) and refuse such treatment because only 4-6 months (short term ADT) is permitted
on this protocol. Gleason score 8 patients should be recommended to receive short
term ADT in conjunction with RT. When given, the ADT should begin after fiducial
marker placement.

- Patients with Gleason score 8 disease must have <20% of the diagnostic tumor
tissue involved with tumor.

- Patients with Gleason score ≤7 may be treated with 4-6 months of ADT if ≥20% of
the biopsy tissue is, or ≥50% of the cores are, positive for tumor.

- PSA ≤20 ng/mL within 8 weeks of enrollment.

- Bone scan negative if PSA ≥10 ng/mL or Gleason 8 disease.

- If PSA is >10 ng/ml or there is Gleason 8 disease, a bone scan should be obtained ≤4
months before enrollment and should be without evidence of metastasis. A questionable
bone scan is acceptable if plain x-rays and/or MRI are negative for metastasis.

- No previous pelvic radiotherapy

- No previous history of radical/total prostatectomy (suprapubic prostatectomy is
acceptable)

- No concurrent, active malignancy, other than nonmetastatic skin cancer or early stage
chronic lymphocytic leukemia (well-differentiated small cell lymphocytic lymphoma).
If a prior malignancy is in remission for ≥ 5 years then the patient is eligible.

- Identifiable DCE-MRI tumor lesion or lesions, that total in volume <33% of the
prostate within 8 weeks prior to protocol entry.

- DCE-MRI of prostate and pelvis is required prior to protocol consideration

- Ability to understand and the willingness to sign a written informed consent document

- Zubrod performance status <2

- Willingness to fill out quality of life/psychosocial forms.

- Age ≥35 and ≤85 years.

- Serum testosterone is within 40% of normal assay limits, taken within 4 months of
enrollment.

- Serum LFTs are within 40% of normal assay limits, taken within 8 weeks of
enrollment.

- Complete blood counts are within 40% of normal assay limits, taken within 8 weeks of
enrollment.

- BUN and creatinine are within 40% of normal assay limits, taken within 8 weeks of
enrollment.

Exclusion Criteria:

- >T2 on digital rectal exam.

- >T3a (T3b/T4) disease identified by MRI.

- Gleason score <6 or >8.

- Gleason score 8 disease and ≥20% of the diagnostic tissue containing tumor. For
example: (tumor length/other biopsy tissue length)*100 = ≥20%.

- Patients are not eligible if they have been started on androgen deprivation therapy
prior to enrollment.

- Androgen deprivation therapy planned for longer than 6 months. Androgen deprivation
timing is for the Luteinizing hormone-releasing hormone (LHRH) agonist portion only
and not when anti-androgen is started beforehand.

- PSA >20 ng/mL within 8 weeks of enrollment.

- Unable to obtain a 3T MRI of the pelvis and prostate with contrast prior to
enrollment.

- Unidentifiable distinct DCE-MRI tumor lesion.

- Identifiable DCE-MRI tumor lesions, that total in volume ≥33% of the prostate.

- Previous pelvic radiotherapy.

- Previous history of radical prostatectomy.

- Concurrent, active malignancy, which is not nonmetastatic skin cancer or early stage
chronic lymphocytic leukemia (well-differentiated small cell lymphocytic lymphoma).
If a prior malignancy is in remission for < 5 years then the patient is not eligible

- Zubrod performance status ≥ 2.

- Not willing to fill out quality of life/psychosocial questionnaires.

- Age <35 and >85 years.

- Serum testosterone is < 40% of normal assay limits, taken within within 4 months of
enrollment.

- Serum LFTs are < 40% of normal assay limits, taken within within 8 weeks of
enrollment.

- Complete blood counts are < 40% of normal assay limits, taken within within 8 weeks
of enrollment.

- BUN and creatinine are <40% of normal assay limits, taken within 8 weeks of
enrollment.