Examining the Effects of Presurgical Treatment for Prostate Cancer
Name of the Trial
mpMRI in Detecting and Goserelin Acetate and Enzalutamide in Treating Patients with Newly Diagnosed Prostate Cancer (NCI-15-C-0124). See the protocol summary.
Dr. William Dahut, NCI Center for Cancer Research
Why This Trial Is Important
Prostate cancer is the most common malignancy diagnosed among men in the United States. In most cases, prostate cancer tends to grow slowly, and the majority of men with this disease are likely to die from some other cause. However, as many as 15% of men with newly diagnosed prostate cancer have aggressive disease, or cancer that is likely to grow and spread quickly and may become fatal. Researchers are trying to develop new strategies to slow the growth of aggressive prostate cancers and treat them more effectively.
One potential strategy is to give systemic therapy before surgery to remove the prostate (radical prostatectomy). The objectives of this neoadjuvant therapy are to shrink prostate tumors, reducing the amount of normal tissue that needs to be removed, and to provide earlier systemic treatment for cancer cells that may have escaped the prostate.
One form of neoadjuvant therapy that has been shown to shrink prostate tumors in clinical trials is androgen-deprivation therapy (ADT), which blocks the production of male sex hormones (androgens) that prostate cancer cells need for growth. However, neoadjuvant ADT has not been shown to delay prostate cancer recurrence or improve survival.
Researchers have also been interested in testing the antiandrogen drug enzalutamide (Xtandi®) as neoadjuvant therapy for prostate cancer, and several clinical trials are currently evaluating this approach. Enzalutamide inhibits the activity of proteins called androgen receptors inside prostate cancer cells, preventing androgens from stimulating cell growth. Enzalutamide has been shown to improve survival in men with metastatic prostate cancer, and it has been approved by the FDA for treating such patients.
One difficulty in developing effective neoadjuvant therapy for localized, high-risk prostate cancer is identifying patients who are most likely to benefit from this approach. Currently, several measures are used in classifying prostate cancer as low, intermediate, or high risk, including Gleason score, clinical stage of the tumor, and PSA level. A number of potential tumor markers other than PSA have been investigated in an effort to refine the definition of high-risk disease, but none has been shown to be clinically useful. Better methods of identifying patients with high-risk disease who may benefit from neoadjuvant therapy are needed.
In this regard, doctors at NCI’s Center for Cancer Research are interested in using an imaging technique called multiparametric magnetic resonance imaging (mpMRI), along with targeted biopsies, to examine specific lesions within the prostate both before and after neoadjuvant therapy to determine how the therapy affects the lesions. Multiparametric MRI combines a number of features of MRI in a single imaging exam, including anatomic imaging and various types of functional imaging. By combining anatomic and functional parameters, doctors can better assess not only the extent of cancer in the prostate but also how aggressively the cancer is behaving.
In this study, men diagnosed with androgen-sensitive prostate cancer with intermediate- or high-risk features will be examined with mpMRI, undergo targeted biopsies, and be treated with neoadjuvant ADT, using the drug goserelin actetate (Zoladex®), and enzalutamide for 6 months. Following the neoadjuvant therapy, the men will undergo a second mpMRI exam to determine whether therapy has shrunk the size of their prostate tumors. They will then undergo radical prostatectomy.
The initial mpMRI scans will be used to identify specific prostate lesions that the researchers want to sample. They will then perform targeted biopsies of the lesions prior to surgery and conduct molecular and genomic studies to characterize them. After 6 months of neoadjuvant therapy, they will perform another mpMRI scan to determine the effect of the neoadjuvant therapy on the targeted lesions, followed by prostatectomy. They will use the second mpMRI scans to create three-dimensional molds of the prostate into which they can place the surgically removed organs so they can sample specific areas detected on the MRI image.
“Our study is designed to determine the impact of intensive hormonal therapy on high-risk prostate tumors using changes on MRI and examination of targeted biopsies,” said William Dahut, M.D., the study’s principal investigator. “We will also compare the molecular and genomic characteristics of the targeted biopsy samples from our initial assessment of the patient to those of the prostatectomy specimens of the same lesions.
“This study offers a chance to have a much better understanding of how high-risk prostate cancer responds to intensive hormonal therapy with ADT and enzalutamide, and it may potentially allow patients who otherwise would not be ideal candidates to be treated surgically,” Dr. Dahut said.