Active Surveillance Exercise Clinical Trial

This is a PI initiated, randomized clinical trial of exercise vs. usual care among men opting
for active surveillance for prostate cancer. The AS RCT study is a randomized controlled
trial of 16-weeks aerobic exercise (e.g., brisk walking) vs. usual care among 150 men with
prostate cancer on active surveillance. After obtaining written informed consent, enrolled
subjects will be scheduled for the baseline assessments. The men randomized to the
Intervention Arm will engage in an individually tailored aerobic exercise program (home-based
walking) following the principles of aerobic exercise training guidelines for adults as
recommended by the American College of Sports Medicine (ACSM). The men in the Control Arm
will be asked to continue their typical exercise practices for 16 weeks. Men in both arms
will be asked to complete questionnaires at baseline and at week 16, months 12 & 24.
Specimens from biopsy will be reviewed by the investigators' collaborator, GenomeDx, for RNA
characterization and assessment of the genomic risk scores.

There is also a non-randomized observational component to the study where we will collect
biospecimens, survey, data, and administer one CPET. Individuals who will be enrolled to this
group include those who do not meet all eligibility criteria for the RCT, or those who do not
wish to be in a RCT, but are interested to participate in some lifestyle research. This group
also provides us with a larger more heterogeneous population to follow long term to examine
associations between exercise, biomarkers, fitness metrics, and clinical and psychosocial
outcomes.

Inclusion Criteria:

- Histologically-documented localized (stage
- Patient has selected active surveillance as their management strategy for low- or
lowintermediate risk prostate cancer as defined below;

- ≥10 core prostate biopsy completed prior to randomization with at least 2mm of tumor
and Gleason sum ≤6 with no pattern 4, or Gleason 3+4 in <34% of all cores;

- Diagnostic or most recent PSA ≤15 ng/ml, or PSA density (PSAD) <0.15;

- Low to Moderate fitness level at baseline (to be assessed via interview with the
exercise Protocol Protocol staff and through CPET);

- Medical clearance based on medical chart review and normal ECG (administered by a
trained health professional) to undergo a symptom-limited cardiopulmonary exercise
test and aerobic training intervention

- Able to achieve and complete an acceptable cardiopulmonary exercise test defined as
follows: achieving peak or plateau in oxygen consumption concurrent with increased
power output; a respiratory exchange ratio ≥ 1.1 or volitional exhaustion- rating of
perceived exertion >19

- English-speaking

A priori, we will allow men with concurrent benign prostatic hyperplasia (prostate volume
>50g) to have a PSA between 10-15 ng/ml; and include men with low volume Gleason 3+4
disease. Also a priori, we will allow men with < than a 10 core biopsy at the discretion of
the urologist if s/he classifies the patient as "low-risk" and a good candidate for active
surveillance based on other favorable features (e.g., tumor molecular tests, prostate
imaging, etc.). Sufficient tumor will be determined based on review of pathology notes and
if needed, consultation with study pathologist. Current criteria for "sufficient" includes:
>=1mm tumor and >=25% of available sample is tumor.

Non-Randomized Observational Component Eligibility: Eligibility for the non-randomized
observational component are:

- Histologically-documented localized (stage
- Undergoing or initiating active surveillance;

- Medical clearance based on medical chart review and normal ECG (administered by a
trained health professional) to undergo a symptom-limited cardiopulmonary exercise
test and aerobic training intervention

- English-speaking

Exclusion Criteria:

- Any prior or concurrent treatment for prostate cancer;

- Use of finasteride or dutasteride within 3 weeks or 6 months, respectively, of study
entry;57

- Uncontrolled illness, physical disability, or other contraindication to aerobic
exercise training including, but not limited to:

- Acute myocardial Infarction (within 5 days of any planned study procedure);

- Unstable angina;

- Uncontrolled arrhythmia causing symptoms or hemodynamic compromise;

- Recurrent syncope;

- Active endocarditis;

- Acute myocarditis or pericarditis;

- Symptomatic severe aortic stenosis;

- Uncontrolled heart failure;

- Acute (within 3 months) pulmonary embolus or pulmonary infarction;

- Thrombosis of lower extremities;

- Suspected dissecting aneurysm;

- Uncontrolled asthma;

- Pulmonary edema;

- Room air desaturation at rest ≤85%;

- Respiratory failure;

- Acute non-cardiopulmonary disorders that may affect exercise performance or be
aggravated by exercise (ie infection, renal failure, thyrotoxicosis); and

- Mental impairment leading to inability to cooperate.

Non-Randomized Observational Component:

- The same exclusion criteria apply as above.