Curative-Intent Metastasis-Directed Therapies for Molecularly Defined Oligorecurrent Prostate Cancer
abstract
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Access this abstract now Full Text Available for ClinicalKey SubscribersBACKGROUND
The hypothesis of a curable oligometastatic prostate cancer (PCa) state remains to be clinically-proven. Conventional imaging often fails to localize early recurrences, hampering the potential for radical approaches.
OBJECTIVE
We hypothesize that prostate-specific membrane antigen (PSMA)-targeted PET-MR/CT allows for earlier detection and localization of oligorecurrent-PCa, unveiling a molecularly-defined state amenable to curative-intent metastasis-directed treatment (MDT).
DESIGN/SETTING/PARTICIPANTS
Single-institution single-arm phase-two study. Patients with rising PSA (0.4-3.0 ng/mL) after maximal local therapy (radical prostatectomy and post-operative radiotherapy), negative conventional staging, and no prior salvage hormonal therapy (HT) were eligible.
INTERVENTIONS
All patients underwent [18F]DCFPyL PET-MR/CT. Patients with molecularly-defined oligorecurrent-PCa had MDT (stereotactic ablative body radiotherapy [SABR] or surgery) without HT.
OUTCOME MEASUREMENTS/STATISTICAL ANALYSIS
Primary endpoint was biochemical response (complete, i.e. biochemical 'no evidence of disease' [bNED], or partial response [100% or ≥50% PSA decline from baseline, respectively]) after MDT. Simon's two-stage design was employed (null and alternate hypotheses <5% and >20% response rate, respectively), with α and β of 0.1.
RESULTS
Seventy-two patients were enrolled (May/2017-July/2019). Thirty-eight (53%) had PSMA-detected oligorecurrent-PCa amenable for MDT. Thirty-seven (51%) agreed to MDT: 10 and 27 underwent surgery and SABR, respectively. Median follow-up was 15.9 months (IQR 9.8-19.1). Of patients receiving MDT, the overall response rate was 60%, including 22% rendered bNED. One (2.7%) grade 3 toxicity (intra-operative ureteric injury) was observed.
CONCLUSIONS
PSMA-defined oligorecurrent-PCa can be rendered bNED, a necessary step towards cure, in 1 of 5 patients receiving MDT alone. Randomized trials are justified to determine if MDT +/- systemic agents can expand the curative therapeutic armamentarium for PCa.
PATIENT SUMMARY
We studied men treated for prostate cancer with rising PSA. We found PSMA imaging detected recurrent cancer in three-quarters of patients, and targeted treatment to these areas significantly decreased PSA in half of patients.
Additional Info
Disclosure statements are available on the authors' profiles:
Curative-Intent Metastasis-Directed Therapies for Molecularly-Defined Oligorecurrent Prostate Cancer: A Prospective Phase II Trial Testing the Oligometastasis Hypothesis
Eur Urol 2021 Mar 05;[EPub Ahead of Print], RM Glicksman, U Metser, D Vines, J Valliant, Z Liu, PW Chung, RG Bristow, A Finelli, R Hamilton, NE Fleshner, N Perlis, AR Zlotta, D Green, A Bayley, J Helou, S Raman, G Kulkarni, C Catton, T Lam, R Chan, P Warde, M Gospodarowicz, DA Jaffray, A BerlinFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
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