Current conventional prostate cancer (PCa) imaging modalities (computed tomography, bone
      scan, magnetic resonance imaging, ultrasound) have limited accuracy in the initial staging
      and for determining prognosis of PCa. Prostate-specific membrane antigen (PSMA) is a cell
      surface antigen which is highly expressed in PCa and correlates with prognostic factors such
      as Gleason score. High PSMA expression in prostate tumor has been significantly associated
      with lethality of disease, allowing specific identification of tumors most in need of
      treatment. Combined PET and computed tomography (PET-CT) imaging using small molecules
      targeting PSMA-expressing cells have been developed and tested clinically, and have shown
      superiority when compared with conventional imaging.

      An added advantage of PET compared to MRI is the ability to identify both distant metastatic
      disease as well as intraprostatic disease with one imaging modality. PSMA-radiotracers have
      continued to evolve since their initial development, with successive improvements in imaging
      and diagnostic characteristics. One such second-generation PSMA-binding compound, 18F-DCFPyl,
      has been developed and characterized at our institution, and offers superior imaging
      qualities compared to prior PSMA-based radiotracers.

      In realization of the toxicity of current therapies, there is substantial interest throughout
      the urologic oncology community in utilizing focal therapy to mitigate such toxicities. The
      rationale for focal therapy is based upon the recognition that whole gland treatment is
      associated with unacceptable toxicity rates, while concurrently it is also realized that
      patient morbidity and mortality is due to the progression of major foci of high-grade
      disease, i.e. the index lesion.

      Planning studies have shown that focal brachytherapy is feasible and results in significant
      reductions of dose to critical structures. In a historic cohort of patients treated at Johns
      Hopkins, the investigators have demonstrated that a modest reduction in dose results in
      clinically meaningful reductions in urinary toxicity. Al-Qaiseh et al. found that focal plans
      resulted in >50% reductions in dose to urethra and rectum. However, focal plans were highly
      sensitive to seed positioning errors, and focal targeting made seed positioning more
      critical. This highlights the key utility and importance of the investigators' iRUF system
      (integrated Registered Fluoroscopy and Ultrasound) in delivering focal therapy.

      The investigators have developed a system of true dynamic intraoperative dosimetry which
      utilizes fluoroscopy for seed cloud reconstruction and fusion to transrectal ultrasound
      imaging. The investigators previously confirmed this method in a pilot trial of 6 patients
      with encouraging results. Further refinement of the system was followed by a Phase II
      clinical trial of this integrated platform on a larger group of patients. The investigators
      confirmed the primary endpoint to compare intraoperative dosimetric predicted values using
      iRUF method vs standard ultrasound-based seed tracking. The iRUF Phase II cohort had
      statistically significant improvements in prostate coverage parameters, as well as lower
      rates of rectal doses exceeding prescribed tolerance limits when compared to a historical
      group of patients. Importantly, there was no trend toward higher prostate V200 doses,
      indicating that excellent coverage did not come at the expense of excessive dose within
      prostate.

      This study will test the combination of PSMA-imaging with iRUF dynamic dosimetry to treat
      prostate cancer with a focal approach.