Randomized Trial of Conventional vs Conventional Plus Fluciclovine (18F) PET/CT-Guided Post-Prostatectomy Radiotherapy for Prostate Cancer: Volumetric and Patient-Reported Toxicity Analyses

PURPOSE/OBJECTIVE(S) In recurrent post-prostatectomy prostate cancer pts, radiotherapy (XRT) planning with fluciclovine (18F) PET/CT (PET) has demonstrated improved disease-free survival without increase in provider-reported toxicity over conventional-only [CT or MRI-based] treatment planning. We hypothesized that incorporating PET would result in larger clinical target volumes (CTV's) without increasing patient-reported toxicities. MATERIALS/METHODS From 2012-2019, 165 post-prostatectomy pts with detectable PSA were randomized (Arm 1 [no PET]: 82; Arm 2 [PET]: 83). Prostate bed target volumes with (CTV1 [45.0-50.4 Gy/1.8 Gy]) or without (CTV2/CTV [64.8-70.2 Gy/1.8 Gy]) pelvic nodal treatment, as well as organ-at-risk dose endpoints, were compared pre- v post-PET (Arm 2 only) using the paired t-test and between Arms using the t-test. V40 Gy & V65 Gy rectum, bladder(-CTV) & penile bulb constraints were identical in all cases. Patient-reported outcomes (PRO's) utilized International Prostate Symptom Score (IPSS) & Expanded Prostate Cancer Index Composite for Clinical Practice (EPIC-CP) metrics. Linear mixed-models (LMMs) incorporating PRO changes over time were fitted comparing the Arms. Univariate & multivariable analyses (MVA) were performed including demographic, disease, and treatment factors. RESULTS Median FU of the whole cohort was 3.52 years. Though all pts had baseline PRO's, 1 pt in Arm 1 & 3 pts in Arm 2 withdrew, & 4 Arm 2 pts had extra-pelvic uptake on PET with XRT aborted, leaving 81 [Arm 1] & 76 pts [Arm 2] for toxicity analysis {1 Arm 2 pt unable to receive PET was not included in volumetric analysis but was included in toxicity analysis}. Mean CTV1 (427.63cc v 452.21cc [P = 0.462], Arm 1 v Arm 2) and CTV2/CTV (137.18cc v 134.20cc [P = 0.669]) were similar prior to PET incorporation. CTV1 (454.57cc v 461.33cc; P = 0.003) and CTV2/CTV (134.14cc v 135.61cc; P < 0.001) were significantly larger following PET incorporation. While V40 Gy (P = 0.402 & P = 0.522 for rectum & bladder, respectively) & V65 Gy (P = 0.157 & P = 0.182 for rectum & bladder, respectively) were not significantly different pre- v post-PET, penile bulb dose did significantly increase post-PET (P < 0.001 for both V40 Gy & V65 Gy). There was no significant difference in IPSS or EPIC-CP scores at baseline or beyond 18 mo between Arms. On MVA, Arm was not significant for any of the EPIC-CP subdomain scores [incontinence (P = 0.630), irritative (P = 0.076), sexual (P = 0.166), bowel (P = 0.402), vitality (P = 0.403)]. With LMMs there was no significant difference between Arms in IPSS (P = 0.276) or EPIC-CP (P = 0.209) scores over time. CONCLUSION Despite larger clinical target volumes after incorporation of fluciclovine (18F) PET into post-prostatectomy XRT treatment planning, we found no significant difference in patient-reported toxicities with long-term follow-up.