Metastatic Disease Response and Patterns of Recurrence in Men with High-Risk Prostate Cancer after Neo-Adjuvant Chemohormonal Therapy and Radical Prostatectomy utilizing PSMA-Targeted ¹⁸F-DCFPyL PET/CT

Background: Although it is known that the overall risk of prostate cancer (PCa) recurrence after radical prostatectomy depends on the risk group and pathologic features, there is limited information on metastatic disease patterns of response and recurrence after neoadjuvant chemohormonal therapy followed by prostatectomy in patients with high-risk PCa. It was our aim to evaluate this utilizing the prostate-specific membrane antigen (PSMA)-based ¹⁸F-DCFPyL (PyL) PET imaging.

Methods: Patients with newly diagnosed high-risk PCa underwent a baseline PyL whole body PET/CT (PET1) followed by neoadjuvant docetaxel and androgen deprivation therapy. Repeat set of imaging was obtained prior to prostatectomy (PET2), and 1 yr after prostatectomy or earlier if PSA progression criteria were met (PET3). Scans were evaluated by a two independent-reader central review with third-reader adjudication. Sites of suspected PET-positive metastatic disease were evaluated by 5-point scale, anatomic region (pelvic nodal [LN], extrapelvic LN and bone), and maximum standardized update value (SUV_max). Interval SUV_max (iSUV) change between each time point was calculated as absolute and percent change for the highest SUV_max intra-patient metastasis (hottest lesion) and max of 5 lesions per region (tumor burden). PET findings were correlated to progression type based on PSA progression (no progression [NP], early progression ≤1 yr post-prostatectomy [EP], or late progression >1 yr post-prostatectomy [LP]), time to progression (TTP) and interval PSA change (iPSA).

Results: A total of 27 patients were enrolled. At the time of evaluation, 10 patients were disease free, 16 patients demonstrated early or late recurrence, and 1 patient was lost to follow up. Median follow-up time was 659 days (range 364-928). 12 of 16 patients with disease progression presented with metastatic disease on initial exam, 10 of whom exhibited EP. Patients with bone and extrapelvic LN metastases were associated with poor outcome and EP (4 of 5 and 7 of 7, respectively). Presence of >3 intrapelvic LN metastases was also associated with poor outcome and EP (8 of 8). No new sites of metastatic disease were seen on PET2 or PET3, and all patients progressed at the sites of initially identified metastases on PET1. Absence of metastatic disease at PET1 was correlated with durable PSA response to therapy (8 of 10). Significant correlation was found between tumor burden iSUV change and iPSA change (r =-0.58), but no significant correlation was found between tumor burden iSUV change and TTP (r=-0.25) or outcome. Median absolute iSUV change for NP was -0.20 (range -0.10 to -0.30), EP -3.60 (range 2.45 to -25.20) and LP -2.60 (range -0.70 to -4.50). Median percent iSUV change for NP was -7.70 % (range -3.85 to -11.54), EP -59.16 % (range 13.69 to -84.37) and LP -54.53 % (range -24.14 to 84.91). The initial hottest lesion SUV_max was significantly different for EP, LP, and NP, and inversely associated with time to progression (r =-0.48).

Conclusions: Initial staging DCFPyL PET detection of >3 intrapelvic LN, any extrapelvic LN or bone metastases in patients with high-risk PCa was associated with early progression. All patients with progressive disease progressed at the sites of metastatic disease identified at baseline, and no new sites of PET positive metastatic disease were found at time of progression. SUV_max of the hottest metastasis on initial exam was prognostic of time to progression and overall change in metastatic disease PET uptake on chemohormonal therapy was correlated to the iPSA change. However, no significant correlation was found between interval SUV_max change on neoadjuvant chemohormonal therapy and progression type or TTP. DCFPyL PET imaging can provide important prognostic information to patients with high-risk primary prostate cancer undergoing neoadjuvant chemohormonal therapy.