University of Duisburg-Essen and German Cancer Consortium (DKTK)–University Hospital Essen, Essen, Germany
Boris A. Hadaschik , Matthias Eiber , Manuel Weber , Aravind Ravi Kumar , Jeremie Calais , Johannes Czernin , Harun Ilhan , Fred Saad , Alexander Kretschmer , Sabine D. Brookman-May , Suneel Mundle , Eric Jay Small , Matthew Raymond Smith , Paola M. Perez Rivera , Thomas A. Hope , Ken Herrmann , Michael S Hofman , Wolfgang P. Fendler
Background: PSMA-PET was positive for distant metastases (39% distant nodes, 24% bone, 6% visceral organ) in >50% of nmCRPC pts who were nonmetastatic by conventional imaging (Fendler et al. CCR 2019). However, the prognostic impact of PSMA-PET disease extent and its association with oncologic outcomes is unknown. We assessed the prognostic utility of PSMA-PET disease extent in nmCRPC pts defined by conventional imaging for OS and new metastases-free survival (nMFS). Methods: 200 pts (6 centers) with nmCRPC by conventional imaging and prostate-specific antigen doubling time (PSADT) ≤10 mo and/or ISUP grade group ≥4 underwent PSMA-PET. Clinical course and treatment management after PSMA-PET imaging were recorded for 4-9 y. Pt characteristics and PSMA-PET disease extent were analyzed retrospectively. OS and PSMA-PET nMFS (time from primary PSMA-PET to appearance of new distant metastases by PSMA-PET or death) were analyzed for pt subgroups based on disease extent by univariate Cox regression. Results: Median OS was 74 mo, similar to the SPARTAN study of nmCRPC pts (74 mo; Smith et al. Eur Urol 2021). Polymetastatic disease (≥5 distant lesions by PSMA-PET) was associated with shorter OS (median 61 mo vs not reached [NR]) and shorter PSMA-PET nMFS (HR 1.8, 95% CI 1.1-2.9; median 38 vs 60 mo; p=0.021). Any metastatic disease by PSMA-PET and whole-body PSMA tumor volume were not prognostic for OS and PSMA-PET nMFS (all p>0.05). Initial pN1 status was associated with shorter OS (median 55 mo vs NR), but not with PSMA-PET nMFS (p>0.05). Baseline age, baseline Gleason grade ≥8, prior radiotherapy (RT), and PSA and PSADT at time of primary PSMA-PET were not associated with outcomes (all p>0.05). Management after PSMA-PET imaging was mostly local/targeted therapy in pts with no visible/locoregional disease (40/30%) and androgen receptor signaling inhibition therapy in pts with nodal/bone distant metastases (35/43%). Conclusions: Polymetastases (>5) by PSMA-PET and initial pN1 status were significantly associated with worse OS. PSMA-PET disease extent provides a potential novel additional risk stratification for pts with nmCRPC without distant metastasis based on conventional imaging. Further validation is needed to prove its independent prognostic value. Clinical trial information: NCT01946204.
Subgroup (N=200) | N (%) | OS | |
---|---|---|---|
HR (95% CI) | p | ||
Age <65 y | 49 (25) | 0.97 (0.52-1.81) | 0.92 |
Gleason grade ≥8 | 151 (76) | 1.41 (1.77-2.58) | 0.27 |
pN1 | 45 (23) | 2.01 (1.17-3.45) | 0.012* |
Prior definitive RT | 64 (32) | 1.58 (0.93-2.70) | 0.092 |
Prior salvage RT | 40 (20) | 0.64 (0.31-1.31) | 0.22 |
PSA ≥5.5 mg/dL | 97 (49) | 1.29 (0.76-2.19) | 0.34 |
PSADT ≤6 | 85a (64) | 0.87 (0.45-1.66) | 0.66 |
Extrapelvic disease, any | 109 (55) | 1.41 (0.83-2.40) | 0.21 |
Extrapelvic disease, ≥5 lesions | 37 (19) | 1.93 (1.08-3.46) | 0.027* |
an=132, *p<0.05.
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