Randomized MRI-Guided Prostate Boosts Via Initial Lattice Stereotactic vs Daily Moderately Hypofractionated Radiotherapy

Radiotherapy (RT) is a commonly applied primary (initial definitive) treatment alternative to
prostatectomy that allows for preservation of anatomy and the potential for improved
functional outcome with better tumor targeting and normal tissue sparing. About 30-50% of men
ultimately develop biochemical failure (BF) after RT. Persistence of disease in the dominant
lesion is indicated to be a common mechanism responsible for progression. Prostate cancer has
a long natural history. BF typically precedes clinical progression to metastasis by many
years and local persistence has been implicated. While survival at 10 years is high overall,
quality of life is affected by failure of any kind. Pathologic complete response (PathCR) by
standard ultrasound guided systematic prostate biopsies at 2-3 years after RT is the
strongest post-treatment (post-Tx) predictor of patient outcome yet identified.
Multiparametric-MRI (MP-MRI) parameters identify dominant tumor areas in the prostate with a
fairly high sensitivity and specificity, and MP-MRI directed biopsies should, therefore,
further strengthen the association between prostate biopsy results and patient outcome.

The proposed research compares two previously explored methods (LEAD and HEIGHT) for
escalating dose to MP-MRI defined prostate regions directly and addresses the goals of 1)
improving local control via targeted radiotherapy (RT) dose escalation to the MP-MRI defined
high risk (dominant) tumor areas using PathCR based on MP-MRI-directed biopsies at 2-2.5yr
after treatment as the primary endpoint; 2) preserving quality of life by minimizing dose to
the nearby organs at risk around the prostate; and 3) establishing the relationship of pre-
and serial post-Tx MP-MRI parameters to PathCR.

Eligibility Criteria:

- A. Biopsy confirmed adenocarcinoma (including ductal) of the prostate.

- B. T1-T3 disease based on digital rectal exam.

- C. No evidence of metastasis by any clinical criteria or available radiographic tests
(N0M0 by clinical or imaging criteria).

- D. Gleason score 6-10.

- E. Androgen deprivation therapy (ADT) is at the discretion of the treating physician;
but, must be decided (none, short-term or long-term as counted from the luteinizing
hormone-releasing hormone (LHRH) agonist or antagonist injection) prior to enrollment.
An anti-androgen (e.g., bicalutamide at 50 mg per day po) is recommended to start
prior to LHRH agonist injection (not recommended for LHRH antagonist injection) and is
recommended to not be administered for more than 4 months. If ADT is planned, the
following restrictions apply:

- i. It may be initiated no more than 3 months prior to the signing of consent

- ii. It must be started prior to the start of radiotherapy and

- iii. The total length planned must be ≤ 30 months

- F. Prostate-specific Antigen (PSA) ≤ 100 ng/mL within (+/-) 4 months of signing of
consent. If PSA was above 100 and drops to ≤ 100 with antibiotics, this is acceptable
for enrollment.

- G. Subjects with T3 disease based on digital rectal exam (DRE), Gleason 8-10 or a PSA
of >15 ng/ml, should have a bone scan within (+/-) 4 months of signing of consent that
is without evidence of metastasis. A questionable bone scan is acceptable if
additional imaging studies (e.g., plain x-rays, CT, or MRI) do not confirm for
metastasis.

- H. Suspicious peripheral zone or central gland lesion on MP-MRI

- i. Peripheral zone: Distinct lesion on dynamic contrast-enhanced MRI (DCE-MRI)
with early enhancement and later washout (Note: contrast not required for
enrollment), and/or distinct lesion on the ADC map (Value <1000).

- ii. Central gland: A suspicious central gland lesion on MP-MRI must have a
distinct lesion on the apparent diffusion coefficient (ADC) map (Value <1000)

- I. No previous pelvic radiotherapy.

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

- K. 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.

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

- M. Zubrod performance status ≤ 2. (Karnofsky or Eastern Cooperative Oncology Group
(ECOG) performance status may be used to estimate Zubrod).

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

- O. Age ≥ 35 and ≤ 85 years at signing of consent.