Using Multiparametric MRI to Evaluate Intraprostatic Tumor Responses and Androgen Resistance Patterns in Newly Diagnosed Prostate Cancer

The prostate lesion is contoured manually by an expert radiologist. Research software (mim-vista) calculates the volume. Greater tumor volumes may indicate higher prostate tumor growth.

Time frame: Baseline and 6 months

Population: 37 out of 39 patients completed treatment and underwent pre- and post- mpMRI. Two patients did not-one patient died on study from a recreational drug overdose. The other had progression of disease on study.

The Youden index was used as a measure for evaluating biomarker effectiveness and was calculated to determine the cutoffs that gave the optimal combination of sensitivity and specificity for patient response to treatment. The index is: J=sensitivity + specificity -1. Its value ranges from 0 through 1 (inclusive). A value of 1 indicates that there are no false positives or false negatives, i.e. the test is perfect. The index gives equal weight to false positive and false negative values, so all tests with the same value of the index give the same proportion of total misclassified results. Sensitivity and specificity are the probability of truly identifying relative tumor burden on multiparametric magnetic resonance imaging (mpMRI) respectively at a statistically established cut point.

Time frame: 6 months

Population: 37 out of 39 patients completed treatment and underwent pre- and post- mpMRI. Two patients did not-one patient died on study from a recreational drug overdose. The other had progression of disease on study.

The Youden index was used as a measure for evaluating biomarker effectiveness and was calculated to determine the cutoffs that gave the optimal combination of sensitivity and specificity for patient response to treatment. The index is: J=sensitivity + specificity -1. Its value ranges from 0 through 1 (inclusive). A value of 1 indicates that there are no false positives or false negatives, i.e. the test is perfect. The index gives equal weight to false positive and false negative values, so all tests with the same value of the index give the same proportion of total misclassified results. Sensitivity and specificity are the probability of truly identifying relative tumor burden on multiparametric magnetic resonance imaging (mpMRI) respectively at a statistically established cut point.

Time frame: 6 months

The effect of intense androgen suppression and inhibition was measured on tumors using anti-AR immunostains of biopsy and surgical specimens. Detection of tumor nuclear AR was quantified on a per-nucleus basis using computer-aided image analysis with Definiens Developer XD 64, grouping nuclei into high, medium, low, and absent bins, a histology score was assigned to each sample. Nucleus classification is low vs. med. at 0.7; med. vs. high at 0.95. Definiens reported the total # of positively stained nuclei or cells, along with the distribution of low-, med.-, and high-intensity stained nuclei/cells for ea. tumor focus. A %positive index score was calculated using a weighted avg. divided by the total # of objects, where index = \[ (1 × nuclei/cells stained low) + (2 × nuclei/cells stained med.) + (3 × nuclei/cells stained high) \](3 × total nuclei).

Time frame: 6 months

Population: 37 out of 39 patients completed treatment and underwent pre- and post- mpMRI. Two patients did not-one patient died on study from a recreational drug overdose. The other had progression of disease on study.

Prostate lesion volumes on baseline and post-treatment multiparametric magnetic resonance imaging (mpMRI) were calculated from T2W-MRI sequences using software embedded in the PACS after manual contouring by the same radiologist. Lesion volume scores were categorized as low (2 or fewer positive sequences), moderate (3 positive sequences) and high (4 positive sequences). Lesion volume values are in cubic centimeters (cc's).

Time frame: Baseline and 6 months

Population: 37 out of 39 patients completed treatment and underwent pre- and post- mpMRI. Two patients did not-one patient died on study from a recreational drug overdose. The other had progression of disease on study.

Complete response was evaluated after neoadjuvant treatment with androgen deprivation therapy (ADT) and enzalutamide and assessed by pathologic exam. Pathologic complete response: the absence of residual invasive cancer confirmed by immunohistochemistry (IHC).

Time frame: After neoadjuvant treatment with androgen deprivation therapy (ADT) and enzalutamide, approximately 6 months

Population: 37 out of 39 patients completed treatment and underwent pre- and post- mpMRI. Two patients did not-one patient died on study from a recreational drug overdose. The other had progression of disease on study.

ERG protein overexpression was evaluated using immunohistochemistry in post treatment specimens. A positive ETS-related ERG overexpression is a bad outcome.

Time frame: Approximately one month-3 months post-treatment

Population: 37 out of 39 patients completed treatment and underwent pre- and post- mpMRI. Two patients did not-one patient died on study from a recreational drug overdose. The other had progression of disease on study.

PTEN level reduction was evaluated using immunohistochemistry in post treatment specimens. For anti-PTEN immunohistochemistry, a case was considered PTEN-reduced (abnormal) if at least 5% of tumor cells demonstrated reduced PTEN intensity relative to PTEN in benign cells (lower than 5%, then abnormal).

Time frame: post treatment, approximately 1-3 months

Population: 37 out of 39 patients completed treatment and underwent pre- and post- mpMRI. Two patients did not-one patient died on study from a recreational drug overdose. The other had progression of disease on study.

Here is the number of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

Time frame: Date treatment consent signed to date off study, approximately 51 months and 2 days.

Prostate lesion volumes on baseline and post-treatment mpMRI were calculated from T2W-MRI sequences using software embedded in the PACS after manual contouring by the same radiologist.

Time frame: Baseline and 6 months

Population: 37 out of 39 patients completed treatment and underwent pre- and post- mpMRI. Two patients did not-one patient died on study from a recreational drug overdose. The other had progression of disease on study.

Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A non-serious adverse event (i.e., Grade 1) is any untoward medical occurrence. A serious adverse event (i.e., Grade 2-3) is an adverse event or suspected adverse reaction that results in an adverse drug experience, and/or disruption of the ability to conduct normal life functions attributable to the research.

Time frame: Date treatment consent signed to date off study, approximately 51 months and 2 days.