(UroToday.com) The 2023 ESMO annual meeting included a session on prostate cancer, featuring a presentation by Dr. David Goode discussing molecular features of circulating tumor cells (CTCs) associated with response to 177LuPSMA + pembrolizumab for mCRPC. The phase I PRINCE trial is evaluating the efficacy of 177Lu-PSMA-617 + pembrolizumab for mCRPC:
Importantly, genomic and clinical features at baseline of patients who respond best to this combination are not yet known.
A total of 37 patients were enrolled and PSA levels were assessed three times weekly. CTCs (CK+, CD45-, and DAPI+) were enumerated from 3 mL of blood, immunoassayed for PSMA expression, and single CTCs profiled with low-pass whole-genome sequencing. Baseline PSMA-PET metabolic tumour volume and PSMA expression (SUV) were measured. Patients were split into response groups based on the best percentage change in PSA from baseline:
- Good: drop in PSA >90%, n=17
- Intermediate: drop in PSA <90%, n=16
- Poor: no decrease in PSA, n=4
Metabolic tumor volume was lower in the good (median: 218 mL) than in both intermediate (median: 328 mL) and poor (median: 538 mL) response groups, but pairwise comparison of good versus intermediate-poor responders combined was not significant (Wilcoxon p=0.286). The strongest image-based association was mean PSMA-PET SUV, which increased from poor (median: 7.8), to intermediate (median: 8.5) and good (median: 11) responders, achieving a Wilcoxon p-value of 0.079 for the good versus the intermediate-poor groups: 
In contrast, stronger associations with PSA response were based on features of baseline CTCs:
Baseline PSMA+ CTC counts were higher in good (mean: 23.7) than intermediate (mean: 4.3) and poor (mean: 6) responders (p = 0.022). A number of Large-scale State Transitions, a measure of genome instability, was lowest for CTCs in good (mean: 10.2), higher in intermediate (mean: 15.1), and highest in poor responders group (mean: 24.4), a highly significant trend (Kruskal-Wallis p = 0.0004):
One limitation of the study is the limited sample size (n = 37).
Dr. Goode concluded his presentation discussing molecular features of CTCs associated with response to 177LuPSMA + pembrolizumab for mCRPC with the following concluding statements:
- Patients with lower PSMA expressing PET tumor burden at baseline were more likely to have a deeper PSA drop
- Features of CTCs differ by PSA response group
- Fraction of PSMA positive CTCs and Large Scale Transition score were most informative of CTC metrics
Presented by: David Goode, MD, PhD, Peter MacCallum Cancer Centre, Melbourne, Australia
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the 2023 European Society of Medical Oncology (ESMO) Annual Meeting, Madrid, Spain, Fri, Oct 20 – Tues, Oct 24, 2023.