Dose-Escalated Proton Radiation Therapy for High-Risk Prostate Cancer

Prostate cancer is the most common noncutaneous cancer among men in the United States. The
purpose of this research study is to determine if dose-escalated proton radiation therapy is
a good way to treat high-risk prostate cancer.

Proton therapy (PT) is a type of ionizing radiation therapy that reduces the dose of excess
radiation delivered to normal tissues. By escalating the radiation dose just to the area of
the known tumor within the prostate, one could potentially reduce the amount of excess
radiation delivered to surrounding organs.This reduction in dose would improve the
therapeutic ratio by improving disease control while minimizing the risk for additional
toxicity.

In an effort to take advantage of dose escalation's potential for improving disease control
but also to limit toxicity, the use of advanced imaging to identify prostate cancer and
provide a focal radiation boost to the area have proven to be useful. Recent advances in MRI
have made it the most promising technique in identifying and targeting IPTs, improving both
cancer control rates and decreasing toxicity.

The study features hypofractionation and a simultaneous integrated boost to the MRI
identified intraprostatic tumor (IPT) as a method of dose-escalating radiation therapy. The
study will include patients with high-risk prostate cancer who are at the highest risk for
recurrence. Radiation therapy will be delivered over the course of 8-9 weeks. Additionally,
androgen deprivation therapy (ADT) will be started 8-10 weeks prior to starting radiation and
continued for a total of 18 months.

Inclusion Criteria:

- Patient must give study-specific informed consent on an IRB-approved consent prior to
any research related procedures or study treatment.

- Patient must be at least 18 years at the time of consent.

- Adenocarcinoma of the prostate with AJCC Clinical Stage T1to T3b disease with
histological evaluation via biopsy or repeat biopsy within 12 months prior to
registration.

- Patients must undergo a pretreatment diagnostic MRI of the prostate on a 1.5T to 3T
Tesla machine within 6 months prior to study registration.

- A focal IPT must be visible on MRI within the prostate and/or seminal vesicles and
this MRI must be obtained within 6 months of planning CT scan.

- A biopsy of the dominant lesion is recommended but not required. If an ultrasound
guided sextant biopsy was positive for prostatic adenocarcinoma in the area of the MRI
identified intraprostatic lesion, this will be acceptable and another guided biopsy
targeting the MRI identified disease will not be necessary.

- Patients with at least one of the following high-risk factors: cT3a-T3b OR Gleason
9-10 OR PSA > 30 OR more than 1 high-risk factors must be present: clinical stage of
T3, Gleason score 8-10, or PSA 20 ng/ml or greater.

- Hemoglobin must be ≥ 10 g/ml within 4 months prior to registration.

- Zubrod performance status must be 0-1 within 4 months prior to registration.

- If patient has child-producing potential, they must be willing to use medically
acceptable contraception during treatment and must be advised to use it for at least 1
year thereafter. This is not applicable if the patient is not sexually active or has
had a vasectomy.

- Patients must be able to start treatment within 16 weeks of registration.

Exclusion Criteria:

- T4 prostate disease on CT, MRI, or physical exam.

- Patients unable to undergo MRI of the prostate.

- Patients with a greater than 25% change in prostate volume from the pretreatment MRI
of the prostate demonstrating the IPT and the treatment planning MRI. Patients in this
case must undergo a repeat diagnostic MRI on a 1.5T to 3.0T Tesla machine and an IPT
must still be visible.

- Patients with posterior or posterolateral extracapsular extension of prostate cancer.
If this is present, it must resolve on diagnostic MRI after 2 to 3 months of
neoadjuvant androgen deprivation therapy prior to enrollment.

- IPT that is more than 75% of the prostate volume when measured on the CT simulation
scan.

- Evidence of distant metastasis (M1).

- Patients with positive nodes on cross-sectional imaging.

- Previous prostate cancer local treatment including prostatectomy, hyperthermia, high
intensity focused ultrasound, brachytherapy, external-beam radiation therapy, and/or
cryotherapy.

- Prior pelvic radiation therapy.

- No prior myocardial infarction within the last 6 months, congestive heart failure, or
end stage renal disease.

- Active inflammatory bowel disease (diverticulitis, Crohn's disease, ulcerative
colitis) affecting the rectum.

- Bilateral hip replacement

- Prior intrapelvic surgery. This includes the following:

- Bladder surgery

- Transrectal or rectal surgery other than prostate biopsy

- Polypectomy or hemorrhoid removal or banding

- Prior transurethral resection of the prostate (TURP) or laser ablation for benign
prostatic hyperplasia (BPH).

- Patients receiving continuous and current anticoagulation with warfarin sodium
(Coumadin), heparin sodium, clopidogrel bisulfate (Plavix), dabigatran etexilate
mesylate (Pradaxa), rivaroxaban (Xarelto), apixaban (Eliquis), edoxaban (Savaysa),
enoxaparin sodium (Lovenox), prasugrel (Effient), ticagrelor (Brilinta), aspirin/er
dipyridamole (Aggrenox), or fondaparinux sodium (Arixtra).