Prostate Cancer
Conditions
Keywords
Active Surveillance, MRI-Guided Biopsy, Multi-parametric MRI, MP-MRI
Brief summary
The main purpose of this study is to determine if Magnetic Resonance Imaging (MRI), along with MRI targeted biopsy of suspicious lesions, is of value in detecting patients who would be likely to require treatment earlier.
Interventions
DEVICEMulti-Parametric MRI
Multi-Parametric MRI
DEVICEMRI-Guided Biopsy
MRI-Guided Biopsy
Sponsors
National Institutes of Health (NIH)
National Cancer Institute (NCI)
University of Miami
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
35 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
1. Biopsy confirmed adenocarcinoma of the prostate within 18 months prior to enrollment; 2. Pre-enrollment prostate biopsy must consist of at least 8 cores; 3. Biopsy reviewed by a University of Miami Pathologist; 4. Serum Prostate-Specific Antigen (PSA) ≤ 20 ng/ml within 3 months of study enrollment; 5. Age ≥ 35 and ≤ 85 years; 6. Ability to understand and willingness to sign a written informed consent document; 7. Patients must agree to undergo serial multiparametric MRI and MRI-guided biopsy; 8. Patients must agree to fill out the longitudinal psychosocial questionnaires assessing health related quality of life.
Exclusion criteria
1. Greater than 4 cores positive, of any Gleason score, on the University of Miami (UM) review, 2. Greater than 2 cores positive for Gleason 3+4 cancer, 3. Gleason 4+3 or higher cancer in any single biopsy core. 4. Extracapsular extension suspected on digital rectal exam with confirmation on MRI. Suspicion of extracapsular extension on MRI alone is not an exclusion for study enrollment. 5. Subject is not a candidate for multiparametric MRI with contrast. Some reasons may include (but are not limited to): renal insufficiency, foreign body or pacemakers. 6. No prior pelvic radiotherapy. 7. No prior surgery to the prostate, other than transurethral procedures for benign prostatic hyperplasia (e.g., transurethral resection, green light laser treatment). 8. No concurrent, active malignancy, other than non-metastatic skin cancer of any type, superficial bladder cancer, or early stage chronic lymphocytic leukemia (well-differentiated small cell lymphocytic lymphoma) or \<stage IV follicular lymphoma. If a prior malignancy is in remission for ≥ 3 years then the patient is eligible. 9. Bilateral hip replacement.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Disease Progression Within the First Two Surveillance Biopsies | 24 months | The rate of disease progression among participants within the first two surveillance biopsies will be reported. Progression refers to a repeat surveillance biopsy indicating any one of the following: 1. More than 4 positive cores involving any grade of cancer, 2. At least two core with Gleason 3+4 cancer, 3. Any single core with Gleason 4+3 cancer or higher, 4. A Gleason 3+3 at diagnosis that is upgraded to Gleason 3+4, or 5. Undergoing treatment, regardless of histological progression. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time-to-Biochemical Recurrence (BCR) | Up to 36 months | Biochemical recurrence (BCR) is defined as prostate-specific antigen (PSA) of 0.2 or higher on two or more separate measures after surgery or an increase of nadir + 2ng/ml or more after radiation. Time-to-BCR is defined as duration in days between date of treatment and date of BCR, if BCR occurs. The investigators will follow participants who have progressed and gone on to treatment. |
| Health-Related Quality of Life Scores: EPIC SF-12 | Up to 36 months | Health-Related Quality of Life will be assessed using scores from validated questionnaires. The Expanded Prostate Cancer Index Composite and Medical Outcomes Study Short Form-12 (EPIC SF-12) will be used to evaluate patient function and satisfaction after prostate cancer treatment. Response options for each item form a Likert scale, and multi-item scale scores are transformed linearly to a 0-100 scale, with higher scores representing better HRQOL. |
| Health-Related Quality of Life Scores: MAX-PC | Up to 36 months | Health-Related Quality of Life will be assessed using scores from validated questionnaires. The Memorial Anxiety Scale for Prostate Cancer (MAX-PC) will be used to measure anxiety from pre-treatment to post-treatment. The scale consists of 18 items (e.g. I thought about prostate cancer even though I didn't mean to.) scored on a scale from 0 (not at all) to 3 (often). Total scores range from 0 to 54, with higher scores indicating higher levels of anxiety. |
| Discriminative Performance of NCCN Risk and Clinical Markers for Predicting Progression on Active Surveillance | Up to 36 months | The investigators will assess the incremental benefit of multiparametric MRI (mpMRI), genomic risk test, and molecular markers compared to baseline National Comprehensive Cancer Network (NCCN) risk classification for predicting progression on active surveillance. Area under the receiver operating characteristic Curve (ROC) curves produced from logistic regression modeling will be used to evaluate the performance of NCCN risk and other variables (MRI, genomic testing, and molecular markers) for predicting progression on surveillance. Participants will be categorized at baseline by NCCN risk class ranging from very low risk to intermediate risk; and into those who progressed while on the trial. Additionally, MRI results, PSA density, 4K score, and Decipher Score in combination with NCCN risk were analyzed to see their additive value on determining who will experience progression on active surveillance. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Active Surveillance Participants in this group will receive a Multi-Parametric Magnetic Resonance Imaging (MP-MRI) of the prostate/pelvis and MRI-guided prostate biopsy at baseline (0-3 months from enrollment) and at the 12th, 24th and 36th month follow up.
Multi-Parametric MRI: Multi-Parametric MRI
MRI-Guided Biopsy: MRI-Guided Biopsy | 208 |
| Total | 208 |
Baseline characteristics
| Characteristic | Active Surveillance |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 81 Participants |
| Age, Categorical Between 18 and 65 years | 127 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 84 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 119 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 5 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 21 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race (NIH/OMB) White | 182 Participants |
| Region of Enrollment United States | 208 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 208 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 208 |
| other Total, other adverse events | 8 / 208 |
| serious Total, serious adverse events | 5 / 208 |
Outcome results
Primary
Rate of Disease Progression Within the First Two Surveillance Biopsies
The rate of disease progression among participants within the first two surveillance biopsies will be reported. Progression refers to a repeat surveillance biopsy indicating any one of the following: 1. More than 4 positive cores involving any grade of cancer, 2. At least two core with Gleason 3+4 cancer, 3. Any single core with Gleason 4+3 cancer or higher, 4. A Gleason 3+3 at diagnosis that is upgraded to Gleason 3+4, or 5. Undergoing treatment, regardless of histological progression.
Time frame: 24 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Active Surveillance | Rate of Disease Progression Within the First Two Surveillance Biopsies | 36.1 percentage of participants |
Secondary
Discriminative Performance of NCCN Risk and Clinical Markers for Predicting Progression on Active Surveillance
The investigators will assess the incremental benefit of multiparametric MRI (mpMRI), genomic risk test, and molecular markers compared to baseline National Comprehensive Cancer Network (NCCN) risk classification for predicting progression on active surveillance. Area under the receiver operating characteristic Curve (ROC) curves produced from logistic regression modeling will be used to evaluate the performance of NCCN risk and other variables (MRI, genomic testing, and molecular markers) for predicting progression on surveillance. Participants will be categorized at baseline by NCCN risk class ranging from very low risk to intermediate risk; and into those who progressed while on the trial. Additionally, MRI results, PSA density, 4K score, and Decipher Score in combination with NCCN risk were analyzed to see their additive value on determining who will experience progression on active surveillance.
Time frame: Up to 36 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Active Surveillance | Discriminative Performance of NCCN Risk and Clinical Markers for Predicting Progression on Active Surveillance | NCCN Risk | 0.6717 probability |
| Active Surveillance | Discriminative Performance of NCCN Risk and Clinical Markers for Predicting Progression on Active Surveillance | NCCN + MRI | 0.7398 probability |
| Active Surveillance | Discriminative Performance of NCCN Risk and Clinical Markers for Predicting Progression on Active Surveillance | NCCN + PSA Density (PSAd) | 0.7168 probability |
| Active Surveillance | Discriminative Performance of NCCN Risk and Clinical Markers for Predicting Progression on Active Surveillance | NCCN + Decipher Score | 0.6858 probability |
| Active Surveillance | Discriminative Performance of NCCN Risk and Clinical Markers for Predicting Progression on Active Surveillance | NCCN + 4k Score | 0.7412 probability |
Secondary
Health-Related Quality of Life Scores: EPIC SF-12
Health-Related Quality of Life will be assessed using scores from validated questionnaires. The Expanded Prostate Cancer Index Composite and Medical Outcomes Study Short Form-12 (EPIC SF-12) will be used to evaluate patient function and satisfaction after prostate cancer treatment. Response options for each item form a Likert scale, and multi-item scale scores are transformed linearly to a 0-100 scale, with higher scores representing better HRQOL.
Time frame: Up to 36 months
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Active Surveillance | Health-Related Quality of Life Scores: EPIC SF-12 | Median score at Baseline | 31 score on a scale |
| Active Surveillance | Health-Related Quality of Life Scores: EPIC SF-12 | Median score at Last Follow-up | 31 score on a scale |
Secondary
Health-Related Quality of Life Scores: MAX-PC
Health-Related Quality of Life will be assessed using scores from validated questionnaires. The Memorial Anxiety Scale for Prostate Cancer (MAX-PC) will be used to measure anxiety from pre-treatment to post-treatment. The scale consists of 18 items (e.g. I thought about prostate cancer even though I didn't mean to.) scored on a scale from 0 (not at all) to 3 (often). Total scores range from 0 to 54, with higher scores indicating higher levels of anxiety.
Time frame: Up to 36 months
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Active Surveillance | Health-Related Quality of Life Scores: MAX-PC | Median Score at Baseline | 15 score on a scale |
| Active Surveillance | Health-Related Quality of Life Scores: MAX-PC | Median Score at Last Follow-up | 12 score on a scale |
Secondary
Time-to-Biochemical Recurrence (BCR)
Biochemical recurrence (BCR) is defined as prostate-specific antigen (PSA) of 0.2 or higher on two or more separate measures after surgery or an increase of nadir + 2ng/ml or more after radiation. Time-to-BCR is defined as duration in days between date of treatment and date of BCR, if BCR occurs. The investigators will follow participants who have progressed and gone on to treatment.
Time frame: Up to 36 months
Population: Participants who underwent primary therapy for prostate cancer.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Active Surveillance | Time-to-Biochemical Recurrence (BCR) | 169 days |