Hypofractionated Radiation Therapy or Conventional Radiation Therapy After Surgery in Treating Patients With Prostate Cancer

PRIMARY OBJECTIVES:

I. To demonstrate that hypofractionated post-prostatectomy radiotherapy (HYPORT) does not
increase patient-reported gastrointestinal (GI) or genitourinary (GU) symptoms over
conventionally fractionated post-prostatectomy (COPORT) at the 2-year time point.

SECONDARY OBJECTIVES:

I. To compare patient-reported GI symptoms using the Expanded Prostate Cancer Index Composite
(EPIC)-26 at end of radiation therapy (RT) and 6, 12, 24, and 60 months from end of
treatment.

II. To compare patient-reported GU symptoms using the EPIC-26 at end of RT and 6, 12, 24, and
60 months from end of treatment.

III. To compare the cost effectiveness based on the cost of radiotherapy and measured
utilities for health outcomes using the EuroQol five dimensions questionnaire (EQ-5D).

IV. To compare time to progression (TTP) where progression is defined as the first occurrence
of biochemical failure (BF), local failure, regional failure, distant metastasis (DM),
institution of new unplanned anticancer treatment, or death from prostate cancer (prostate
cancer specific mortality [PCSM]).

V. To compare freedom from biochemical failure (FFBF) and TTP rates with an alternate
prostate specific antigen (PSA) >= PSA nadir + 2 ng/mL definition of BF.

VI. To compare local failure, regional failure, salvage therapy (i.e. institution of new
unplanned anticancer treatment), DM, PCSM, and overall survival (OS) rates.

VII. Assessment of adverse events. VIII. Paraffin-embedded tissue block, serum, plasma, whole
blood, and urine for future translational research analyses for predictors of toxicity
following hypofractionated or conventionally fractionated post-prostatectomy radiotherapy.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients undergo conventional radiation therapy for 37 fractions over 7 weeks in the
absence of disease progression or unacceptable toxicity. Patients may also receive androgen
deprivation therapy for up to 6 months as per doctor recommendation.

ARM II: Patients undergo hypofractionated radiation therapy for 25 fractions over 5 weeks in
the absence of disease progression or unacceptable toxicity. Patients may also receive
androgen deprivation therapy for up to 6 months as per doctor recommendation.

After completion of study treatment, patients are followed up every 6 months for 2 years and
every year for 3 years and thereafter.

Inclusion Criteria:

- PRIOR TO STEP 1 REGISTRATION

- Adenocarcinoma of the prostate treated primarily with radical prostatectomy

- 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

- One of the following pathologic T-classifications: pT2 or pT3

- Patients with positive surgical margins are eligible

- One of the following pathologic N-classifications: pN0, pNX

- If a lymph node dissection is performed, the number of lymph nodes removed per
side of the pelvis and the extent of the pelvic lymph node dissection (obturator
versus (vs.) extended lymph node dissection) should be noted whenever possible

- No clinical evidence of regional lymph node metastasis

- Computed tomography (CT) (with contrast if renal function is acceptable; a
noncontrast CT is permitted if the patient is not a candidate for contrast),
magnetic resonance imaging (MRI), nodal sampling, or dissection of the pelvis
within 120 days prior to step 1 registration

- Patients with pelvic lymph nodes equivocal or questionable by imaging are
eligible if the nodes are =< 1 cm in the short axis

- A post-radical prostatectomy study entry PSA >= 45 days after prostatectomy and within
30 days prior to step 1, < 2.0 ng/mL

- No evidence of a local recurrence in the prostate fossa based on a digital rectal
examination (DRE) within 60 days prior to step 1 registration

- Patients with equivocal or questionable DRE findings should have an MRI of the
pelvis to exclude the presence of a prostate fossa mass

- Patients with equivocal or questionable exam findings by DRE or MRI are eligible
if a biopsy of the lesion is negative for tumor

- No evidence of bone metastases (M0) on bone scan (Na F positron emission tomography
(PET)/CT is an acceptable substitute) within 120 days prior to step 1 registration

- Equivocal bone scan findings are allowed if plain films and/or MRI are negative
for metastasis

- Zubrod performance status 0-1 within 60 days prior to step 1 registration

- The patient or a legally authorized representative must provide study-specific
informed consent prior to step 1 registration

- Willingness and ability to complete the Expanded Prostate Cancer Index Composite
(EPIC-26) questionnaire

- Only English and French-speaking patients are eligible to participate

- PRIOR TO STEP 2 REGISTRATION

- The EPIC-26 must be completed in full and entered within 10 business days after step 1
registration; NRG Oncology Statistical and Data Management Center has 3 business days
to score the results and send a notification to the site to proceed to step 2
randomization

Exclusion Criteria:

- A post-prostatectomy PSA nadir >= 0.2 ng/mL AND Gleason >= 7

- pT2 with a negative surgical margin and PSA < 0.1 ng/mL

- 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

- Androgen deprivation therapy started after prostatectomy and prior to step 1
registration for > 6 weeks (42 days)

- Neoadjuvant chemotherapy before or after prostatectomy

- Prior invasive (except non-melanoma skin cancer) malignancy unless disease-free for a
minimum of 3 years and not in the pelvis; (for example, carcinoma in situ of the oral
cavity is permissible if disease free for a minimum of 3 years; however, patients with
prior history of bladder cancer are not allowed no matter the disease free duration);
prior hematological (e.g., leukemia, lymphoma, myeloma) malignancy is not allowed

- Previous chemotherapy for any other disease site if given within 3 years prior to step
1

- Prior radiotherapy, including brachytherapy, to the region of the study cancer that
would result in overlap of radiation therapy treatment volumes

- Severe, active co-morbidity, defined as follows:

- 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 step 1 registration

- Chronic obstructive pulmonary disease exacerbation or other respiratory illness
requiring hospitalization or precluding study therapy at the time of step 1
registration

- Severe hepatic disease, defined as a diagnosis of Child-Pugh class B or C hepatic
disease

- Human immunodeficiency virus (HIV) positive with cluster of differentiation (CD)4
count < 200 cells/microliter; note that patients who are HIV positive are
eligible, provided they are under treatment with highly active antiretroviral
therapy (HAART) and have a CD4 count >= 200 cells/microliter within 30 days prior
to registration; note also that HIV testing is not required for eligibility for
this protocol

- End-stage renal disease (ie, on dialysis or dialysis has been recommended)

- Prior allergic reaction to the study drugs involved in this protocol

- History of inflammatory bowel disease, prior bowel surgeries (or colostomy) for any
reason, or prior partial/radical cystectomy for any reason