Preliminary Analysis of PSMA-Targeted 18F-DCFPyL PET/MRI for Assessment of Response to Neo-Adjuvant Chemohormonal Therapy in Men with High-Risk Primary Prostate Cancer

1264 Background: There is a clinical unmet need to develop and properly assess multimodal therapeutic regimens for men with newly diagnosed high risk and oligometastatic prostate cancer (PCa) given the lethal nature of this disease. Results from prior studies support a combined multimodality treatment approach with neoadjuvant chemohormonal therapy followed by cytoreductive radical prostatectomy in patients with newly diagnosed high-risk primary PCa with oligometastatic disease. We evaluated the utility of prostate-specific membrane antigen (PSMA)-based 18F-DCFPyL (DCFPyL) PET imaging for treatment response assessment to neoadjuvant chemohormonal therapy in men with high risk PCa. Methods: An IRB-approved open-label, single-arm prospective Phase II trial is enrolling patients with newly diagnosed PCa at UW-Madison (ClinicalTrials.gov Identifier: NCT03358563). Patient eligibility included men with high risk PCa (extracapsular extension (cT3a) or seminal vesicle involvement (cT3b) or invasion of adjacent structures (cT4), serum PSA >20 ng/mL or Gleason score of 8 to 10 and/or regional lymph node) or oligometastatic disease (metastases beyond regional lymph nodes defined as less than four bone metastases by conventional imaging (CT, bone scan) but no visceral metastases). Patients underwent a baseline DCFPyL pelvic PET/magnetic resonance imaging (PET/MRI) (PET1) followed by neoadjuvant chemohormonal therapy with androgen deprivation therapy and docetaxel for three cycles (3 months). This was followed by a repeat pelvis PSMA PET/MRI (PET2) prior to prostatectomy. Patients were clinically followed for 1 year after prostatectomy or/unless until they meet criteria for prostate specific antigen (PSA) failure criteria. Results: Patient characteristics: A total of 27 patients have been enrolled on this study to date, with 8 patients demonstrating PSA recurrence within the first year, 9 completing their 1 year follow-up, and 10 patients still in their one year follow-up period. Baseline biopsy Gleason score ranged from 7 to 9 (2 - Gl 7, 1 - Gl 8, 24 - Gl 9) with Gleason pattern ranging from 3-5. PSA at baseline ranged from 2.7 to 336 ng/mL (median 22.3, mean 35.3). Percent PSA level decreased on chemohormonal therapy ranged from 91.64% to 100% (median 98.6% and mean 98.1%) and absolute decrease in PSA level ranged from 317.30 to 4.38 ng/mL (median -20.5, mean -38.8). PET standardized uptake value (SUV) change: Primary PCa DCFPyL PET SUVmax at baseline PET1 ranged from 7.4 to 86.6 (median 25.5, mean 28.2) and post-chemohormonal PET2 ranged from 3.5 to 51.9 (median 8.2, mean 14.1). Percent change in SUVmax from PET1 to PET2 ranged from -83.12% to +72.97% (median -61.0%, mean -49.1%), and absolute SUVmax change from PET1 to PET2 ranged from -34.7 to +5.4 (median -12.2, mean -14.1). PET SUV change correlated with PSA: Baseline PET1 and PET2 SUVmax was moderately correlated with baseline and post-chemohormonal PSA levels, respectively (correlation coefficient of 0.58 and 0.59, respectively). Absolute SUVmax change was only weakly correlated with absolute PSA change (correlation coefficient 0.23), and percent SUVmax change was not correlated with PSA percent change. PET SUV change and PSA recurrence: Two of 27 patients showed an increased PSMA SUVmax on PET2, and both subsequently developed early PSA recurrence within 1 year (126 and 286 days post prostatectomy). Ten patients had less than 50% decrease in PSMA SUVmax on PET2, of whom 6 (60%) developed early PSA recurrence within one year of follow-up. Conclusions: Preliminary analysis demonstrates DCFPyL PSMA PET/MR can assess response to neoadjuvant chemohormal therapy in men with high-risk primary PCa. PET SUVmax was correlated with PSA and early PSA recurrence. Further analyses to explore correlation of PSMA PET with histopathological response, clinical outcomes and tumor microenvironment studies are ongoing.