Treatment interruption guided by on-treatment prostate-specific membrane antigen (PSMA) PET/CT imaging in metastatic hormone-sensitive prostate cancer (mHSPC).

Abstract

22 Background: PSMA PET/CT (PET) imaging is approved for staging high-risk prostate cancer (PCa) and for suspected PCa recurrence based on elevated PSA levels, but is not validated for clinical decision making in patients (pts) responding to treatment. We investigated clinical management and outcomes of pts with mHSPC who underwent on-treatment PET at our institution. Methods: The Dana-Farber/Harvard Cancer Center (DF/HCC) Oncology Data Retrieval System (OncDRS) was queried for pts with mHSPC (by PET or conventional imaging) who underwent PET 3-24 months after starting androgen deprivation therapy (ADT) plus an AR pathway inhibitor (ARPI). Pts with castration-resistant PCa (CRPC), non-metastatic PCa, without a PET in this window, and those treated with ADT alone were excluded. Pts were categorized as having no active disease on PET (group 1), uptake only in sites previously treated with radiation therapy (RT) (group 2) or uptake in sites not previously treated with RT (group 3) based on the 1st on-treatment PET. RT to local or distant site(s) post-PET, and treatment interruption / resumption were descriptively tabulated. Time to development of CRPC was analyzed by group using landmark analysis. Results: The OncDRS query returned 596 pts, 68 meeting eligibility criteria. 19 were categorized into group 1, 13 in group 2 and 36 in group 3. 14 pts underwent RT after PET. 28 of 32 pts in groups 1+2 eventually interrupted systemic therapy (of whom 2 of 28 had received post-PET RT) compared to 18 of 36 in group 3 (of whom 8 of 18 had received post-PET RT). At median follow up of 35.3 months from ADT start, 11 of 68 pts developed CRPC and 3 of 68 pts died; 30 of 46 pts who interrupted treatment remained off hormonal therapy (Table). Conclusions: A majority of pts with mHSPC at our institution who underwent on-treatment PSMA PET 3-24 months after starting ADT+ARPI (without evidence of CRPC) eventually interrupted systemic therapy, a subset of whom underwent post-PET RT prior to interruption. Given the favorable clinical outcomes observed in these responding pts, the utility of on-treatment PSMA PET in mHSPC warrants prospective investigation in larger cohorts. DF/HCC protocol 24-620. Clinical outcomes by PET response. PET response Group 1 (N=19) Group 2 (N=13) Group 3 (N=36) PSA detectable at 1 st on treatment PET, N (%) (min-max) 1 (5.3%)(<0.02, 0.04) 6 (46.2%)(<0.02, 1.10) 18 (50.0%)(<0.02, 4.45) Median (range) time from treatment start to PET, mo 12.0 (5.6, 24.3) 9.2 (6.5, 25.1) 9.0 (3.8, 23.8) Median (range) follow-up post PET, mo 16.7 (2.9, 35.5) 27.6 (8.8, 44.3) 25.7 (14,4, 45.3) Post-PET RT 1 1 12 Treatment interruption / resumption 16 / 3 12 / 7 18 / 6 Treatment resumption rate at 12 mo after interruption 27.0%(9.1%, 64.7%) 39.4%(16.6%, 74.9%) 15.4%(4.1%, 48.8%) CRPC events 3 1 7 CRPC-free rate at 2-years from PET (landmark) 78.8% (38.1%, 94.3%) 100% 81.0% (62.0%, 91.1%) Deaths 0 1 2