PRIMARY OBJECTIVES:
I. To determine whether men with National Comprehensive Cancer Network (NCCN) high risk
prostate cancer who are in the lower 2/3 of Decipher genomic risk (=< 0.85) can be treated
with 12 months androgen deprivation therapy (ADT) plus radiation therapy (RT) instead of 24
months ADT+RT and experience non-inferior metastasis-free survival. (De-intensification
study) II. To determine whether men with NCCN high risk prostate cancer who are in the upper
1/3 of Decipher genomic risk (> 0.85) or have node-positive disease by conventional imaging
(magnetic resonance imaging [MRI] or computed tomography [CT] scan) will have a superior
metastasis-free survival (MFS) through treatment intensification with apalutamide added to
the standard of RT plus 24 month ADT. (Intensification study)
SECONDARY OBJECTIVES:
I. To compare overall survival (OS) between the standard of care (RT plus 24 months of ADT)
and either the de-intensification (RT plus 12 months of ADT) or intensification arm (RT plus
24 months of ADT plus apalutamide). (De-intensification and intensification studies) II. To
compare time to prostate specific antigen (PSA) failure or start of salvage treatment between
the standard of care (RT plus 24 months of ADT) and either the de-intensification arm (RT
plus 12 months of ADT) or intensification arm (RT plus 24 months of ADT plus apalutamide).
(De-intensification and intensification studies) III. To compare PSA failure-free survival
with non-castrate testosterone and no additional therapies between the standard of care (RT
plus 24 months of ADT) and either the de-intensification arm (RT plus 12 months of ADT) or
intensification arm (RT plus 24 months of ADT plus apalutamide). (De-intensification and
intensification studies) IV. To compare MFS judged based on either standard or molecular
imaging between the standard of care (RT plus 24 months of ADT) and either the
de-intensification arm (RT plus 12 months of ADT) or intensification arm (RT plus 24 months
of ADT plus apalutamide). (De-intensification and intensification studies) V. To compare
prostate cancer-specific mortality between the standard of care (RT plus 24 months of ADT)
and either the de-intensification arm (RT plus 12 months of ADT) or intensification arm (RT
plus 24 months of ADT plus apalutamide). (De-intensification and intensification studies) VI.
To compare testosterone levels at the time of PSA failure and metastases between the standard
of care (RT plus 24 months of ADT) and either the de-intensification arm (RT plus 12 months
of ADT) or intensification arm (RT plus 24 months of ADT plus apalutamide).
(De-intensification and intensification studies) VII. To compare time to testosterone
recovery (defined as a T > 200) between the standard of care (RT plus 24 months of ADT) and
either the de-intensification arm (RT plus 12 months of ADT) or intensification arm (RT plus
24 months of ADT plus apalutamide). (De-intensification and intensification studies) VIII. To
compare adverse events, both clinician-reported using Common Terminology Criteria for Adverse
Events (CTCAE) version (v) 5.0 and patient-reported using Patient Reported Outcome
(PRO)-CTCAE items, between the standard of care (RT plus 24 months of ADT) and either the
de-intensification arm (RT plus 12 months of ADT) or intensification arm (RT plus 24 months
of ADT plus apalutamide). (De-intensification and intensification studies)
EXPLORATORY OBJECTIVES:
I. To compare changes in cardio-metabolic markers, including body mass index, and waist
circumference, between the standard of care (RT plus 24 months of ADT) and either the
de-intensification arm (RT plus 12 months of ADT) or intensification arm (RT plus 24 months
of ADT plus apalutamide). (De-intensification and intensification studies) II. To determine a
machine learning/artificial intelligence algorithm for radiotherapy quality assurance.
(De-intensification and Intensification studies) III. To perform future translational
correlative studies using biological and imaging data. (De-intensification and
intensification studies) IV. Impact of PET use in high-risk prostate cancer
PATIENT-REPORTED OUTCOMES OBJECTIVES:
PRIMARY OBJECTIVES:
I. To compare sexual and hormonal function related quality of life, as measured by the
Expanded Prostate Cancer Index Composite-26 (EPIC), between the standard of care (RT plus 24
months of ADT) and the de-intensification arm (RT plus 12 months of ADT). (De-Intensification
Study) II. To compare fatigue, as measured by the Patient Reported Outcomes Measurement
Information System (PROMIS)-Fatigue instrument, between the standard of care (RT plus 24
months of ADT) and the intensification arm (RT plus 24 months of ADT plus apalutamide).
(Intensification Study)
SECONDARY OBJECTIVES:
I. To compare depression, as measured by the PROMIS-depression, between the standard of care
(RT plus 24 months of ADT) and the de-intensification arm (RT plus 12 months of ADT).
(De-Intensification Study) II. To compare depression, as measured by the PROMIS-depression,
between the standard of care (RT plus 24 months of ADT) and the intensification arm (RT plus
24 months of ADT plus apalutamide). (Intensification Study)
EXPLORATORY OBJECTIVES:
I. To compare cognition, as measured by the Functional Assessment of Chronic Illness
Therapy-Cognitive (FACT-Cog) perceived cognitive abilities subscale, between the standard of
care (RT plus 24 months of ADT) and the de-intensification arm (RT plus 12 months of ADT).
(De-Intensification Study) II. To compare bowel and urinary function related quality of life,
as measured by the Expanded Prostate Cancer Index Composite-26 (EPIC), between the standard
of care (RT plus 24 months of ADT) and the de-intensification arm (RT plus 12 months of ADT).
(De-Intensification Study) III. To compare fatigue, as measured by the PROMIS-Fatigue
instrument, between the standard of care (RT plus 24 months of ADT) and the
de-intensification arm (RT plus 12 months of ADT). (De-Intensification Study) IV. To compare
sexual and hormonal function related quality of life, as measured by the Expanded Prostate
Cancer Index Composite-26 (EPIC), between the standard of care (RT plus 24 months of ADT) and
the intensification arm (RT plus 24 months of ADT plus apalutamide). (Intensification Study)
V. To compare bowel and urinary function related quality of life, as measured by the Expanded
Prostate Cancer Index Composite-26 (EPIC), between the standard of care (RT plus 24 months of
ADT) and the intensification arm (RT plus 24 months of ADT plus apalutamide).
(Intensification Study) VI. To compare cognition, as measured by the Functional Assessment of
Chronic Illness Therapy-Cognitive (FACT-Cog) perceived cognitive abilities subscale, between
the standard of care (RT plus 24 months of ADT) and the intensification arm (RT plus 24
months of ADT plus apalutamide). (Intensification Study)
OUTLINE: Patients are randomized to 1 of 4 arms.
DE-INTENSIFICATION STUDY (DECIPHER SCORE =< 0.85):
ARM I: Patients undergo radiation therapy (RT) over 2-11 weeks and receive ADT (consisting of
either leuprolide, goserelin, triptorelin, degarelix, buserelin or histrelin and bicalutamide
or flutamide) for 24 months in the absence of disease progression or unacceptable toxicity.
ARM II: Patients undergo RT over 2-11 weeks and receive ADT (consisting of either leuprolide,
goserelin, triptorelin, degarelix, buserelin or histrelin and bicalutamide or flutamide) for
12 months in the absence of disease progression or unacceptable toxicity.
INTENSIFICATION STUDY (DECIPHER SCORE > 0.85 OR NODE POSITIVE):
ARM III: Patients undergo RT over 2-11 weeks and receive ADT (consisting of either
leuprolide, goserelin, triptorelin, degarelix, buserelin or histrelin and bicalutamide or
flutamide) for 24 months in the absence of disease progression or unacceptable toxicity.
ARM IV: Patients undergo RT over 2-11 weeks and receive ADT (consisting of either leuprolide,
goserelin, triptorelin, degarelix, buserelin or histrelin) for 24 months in the absence of
disease progression or unacceptable toxicity. Patients also receive apalutamide orally (PO)
once daily (QD). Treatment repeats every 90 days for up to 8 cycles (24 months) in the
absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up annually.