Quantitative results from PSMAtrack: A prospective study evaluating changes in PSMA-PET during initial systemic therapy for metastatic hormone-sensitive prostate cancer (mHSPC).

5102 Background: PSA <0.2 ng/mL after 6 months (m) of therapy with androgen deprivation therapy (ADT) and an androgen receptor pathway inhibitor (ARPI), ± docetaxel is strongly prognostic in patients (pts) with mHSPC. This prospective, single-institution pilot study aimed to investigate PSMA-PET for assessing early dynamic changes in PSMA expression and tumor volume in response to treatment for mHSPC and to determine if changes in quantitative PSMA-PET parameters are associated with 6m PSA response. Methods: Key eligibility was mHSPC by conventional imaging with plan to start ADT and ARPI ± docetaxel. Primary or metastasis-directed radiotherapy was not permitted during the first 6m. F18-flotufolastat PSMA-PET was performed at baseline within 21 days of ADT start and after 6m of ADT+ARPI±docetaxel. PSMA-PET scans were qualitatively reviewed for PSMA-avid prostate cancer, (i.e., PSMA uptake > background blood pool in a pattern consistent with prostate cancer). Quantitative PSMA-PET parameters were collected including PSMA-avid total tumor volume (TTV, voxel SUV>3), TTV SUVmean and TTV SUVmax (aPromise, EXINI Diagnostics; LesionID MIM software, GE Healthcare). PSA values at baseline and after 6m of therapy were collected. Descriptive statistical analyses, Wilcoxon test, and Pearson correlations were used. Results: 20/21 enrolled pts (median age 70 years [range 60-95]) had evaluable baseline and 6m PSMA-PET scans. 12 (60%) received ADT+ARPI, 8 (40%) received ADT+ARPI+docetaxel, and median baseline PSA was 55ng/mL (range 2-3,696); 13 (65%) had high-volume mHSPC by CHAARTED criteria. At 6m, median PSA was 0.29 ng/mL (range <0.02-177), and 9 pts (45%) had a PSA ≤0.2 ng/mL. All 20 pts had residual PSMA-avid disease at 6m by qualitative review, with most (n=17, 85%) having residual disease outside the prostate; 2 pts (10%) had new lesions seen on 6m PSMA-PET. At 6m, median TTV and SUVmax, but not SUVmean, were significantly lower for those with PSA ≤0.2 than PSA >0.2 ng/mL (Table); baseline TTV was strongly correlated with 6m PSA (r=0.74, p<0.01). PSA and TTV were well correlated at baseline (r=0.68, p=0.001) and at 6m (r=0.81, p<0.01), as were changes in PSA and TTV from baseline to 6 m (r=0.67, p=0.001). Conclusions: Persistent PSMA-avid disease was seen in all pts with mHSPC after 6m of ADT+ARPI±docetaxel, regardless of PSA at 6m. Pts with 6m PSA >0.2ng/mL had significantly higher TTV and SUVmax at 6m PSMA-PET, and TTV best correlated with PSA levels at baseline and 6 m. Using 6m PSMA-PET could identify mHSPC pts with suboptimal initial response to standard therapy for consolidative therapeutic strategies. Clinical trial information: NCT06479187 . 6m PSA≤0.2 ng/mL, median (range) 6m PSA>0.2 ng/mL, median (range) P TTV (mL) 7.7 (0.4-79.9) 147 (5.9-3440) <0.01 SUVmax 8.7 (4.8-39.2) 47.4 (11.7-162) <0.01 SUVmean 5.3 (4.0-8.8) 6.4 (4.2-16.8) 0.14