Patient case: 54-year-old female with lung adenocarcinoma; genetic feature: SND1-BRAF fusion

Clinical trial: The Miami MAST Trial

Summary: 1. Multiparametric MRI ultrasound (MRIus)-guided or direct MRI-guided biopsies will allow for more directed sampling of the tumors from compartments with distinct multiparametric-MRI (MP-MRI) characteristics, termed habitats, that will increase the rate of "progression" on early (first and second) surveillance biopsies and decrease the rate of "progression" on late (third and further) surveillance biopsies compared to historic transrectal ultrasound (TRUS)-guided biopsy rates.
  2. Identifying higher risk tumor early on will reduce the proportions of patients with poor response to delayed primary treatment.
  3. Radiomics signatures from MP-MRI will define patterns that are associated with progression.
  4. Genomic signatures based on RNA from tumor tissue will define patterns that are associated with habitats and radiomics signatures, as well as progression.

Detailed description: Single arm therapeutic trial investigating the impact of MRI and MRI-US fusion biopsy to identify higher grade or volume tumors early on for better selection of patients for active surveillance and improved outcomes for those undergoing delayed treatment after initial observation.. MRI-US fusion biopsy will include targeting of suspicious areas seen on MRI as well as segmented sampling of the remaining gland. Patients will undergo MRI and MRI-US fusion biopsy within 3 months of enrollment in the trial and have repeat MRI-US fusion biopsies every year to assess overall rates and the temporal distribution of progression. Serum, urine and prostate biopsy tissue will be serially collected to investigate the association between various molecular biomarkers and radiologic and histological progression.

Eligibility: 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.

Relevance to patient case: not relevant