Randomized Trial of 18F-fluciclovine vs. 68Ga-PSMA PET/CT Guided Post-Prostatectomy Radiotherapy: Interim Volumetric and Toxicity Analyses

Abstract

<h3>Purpose/Objective(s)</h3> Post-prostatectomy XRT with ¹⁸F-fluciclovine (fluciclovine) has demonstrated improved event-free survival compared to conventional imaging (CT and/or MRI) based planning. Recently, ⁶⁸Ga-PSMA (PSMA) has been explored as an alternative radiotracer. We hypothesized that both fluciclovine and PSMA would result in a) significant changes in XRT volumes and b) similar acute toxicity. <h3>Materials/Methods</h3> We conducted an IRB-approved, prospective, randomized control trial in post-prostatectomy patients with biochemical relapse comparing fluciclovine (Arm A) and PSMA (Arm B) incorporation. Target volume changes before (<i>pre)</i> and after (<i>post)</i> PET incorporation were assessed including: prostate bed with (CTV_PLV/ PTV_PLV) or without (CTV_PB/PTV_PB) pelvic nodal treatment. PTV_PB received 66.6Gy +/- boost up to 76Gy and PTV_PLV received 45Gy +/- boost up to 56Gy. We evaluated organ-at-risk (OAR) V40Gy and V65Gy <i>pre</i> & <i>post</i> for: bladder (-CTV), rectum, penile bulb and V45Gy for small bowel. Acute provider reported (<30days) toxicity was assessed using CTCAE v5.0. Fisher's exact test & Wilcoxon signed-rank test were used. This analysis includes 100 of 140 intended patients. <h3>Results</h3> Of 100 patients accrued 23 patients were excluded for extra-pelvic uptake, consent withdrawal, pending XRT or were not yet randomized (11 Arm A & 12 Arm B) leaving 77 patients for analysis (38 Arm A & 39 Arm B). Arm A patients had significantly increased mean CTV_PB (115.99cc v 116.72cc; <i>pre</i> v <i>post,</i> respectively; p<0.01); mean PTV_PB (282.26cc v 286.02cc, <i>pre</i> v <i>post</i>, respectively; p<0.01), mean CTV_PLV (474.58cc v 477.72cc; <i>pre</i> v <i>post,</i> respectively; p<0.01) and mean PTV_PLV (1063.65cc v 1073.17cc, <i>pre</i> v <i>post,</i> respectively; p=0.01) volumes. Arm B patients had increased mean CTV_PB (142.53 v 146.32cc; <i>pre</i> v <i>post,</i> respectively; p<0.01), however, there was no significant difference in mean PTV_PB (p=0.18); mean CTV_PLV (p=0.63); or mean PTV_PLV (p=0.22) volumes. Rectal V65Gy (p<0.01) & penile bulb V40Gy & V65Gy (p<0.01) were increased in Arm A <i>post</i> v <i>pre</i> but were within trial constraints. No other OAR constraints were significantly different <i>pre</i> v <i>post</i> in either Arm. Grade 2 GU (24.32% v 11.11%, Arm A v Arm B, respectively) & GI (8.11% v 2.78%, Arm A v Arm B, respectively) toxicity was moderate; overall toxicity was not significantly different between Arms (p=0.22 v 0.74, GU & GI, respectively) with no G3+ events reported. <h3>Conclusion</h3> Both fluciclovine & PSMA guided XRT planning impacted bed target volume. Due potentially to prostate bed uptake differences (in an earlier report of the first 65 patients PET uptake was 84.4% v 39.4% for prostate bed in Arm A v B, respectively), Arm A patients had significantly increased PTV_PB & PTV_PLV volumes post-PET. There was no significant difference in acute toxicity between Arms. Further analyses of biochemical control and patient reported outcomes are forthcoming.