Curative-intent Metastasis-directed Therapies for Molecularly-defined Oligorecurrent Prostate Cancer: A Prospective Phase II Trial Testing the Oligometastasis Hypothesis

Rachel M Glicksman, Ur Metser, Douglass Vines, John Valliant, Zhihui Liu, Peter W Chung, Robert G Bristow, Antonio Finelli, Robert Hamilton, Neil E Fleshner, Nathan Perlis, Alexandre R Zlotta, David Green, Andrew Bayley, Joelle Helou, Srinivas Raman, Girish Kulkarni, Charles Catton, Tony Lam, Rosanna ChanPadraig Warde, Mary Gospodarowicz, David A Jaffray, Alejandro Berlin

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND: 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.

Original languageEnglish
JournalEuropean Urology
Early online date5 Mar 2021
DOIs
Publication statusPublished - 2021

Keywords

  • Metastasis directed treatment
  • Oligometastasis
  • PSMA PET
  • Prostate cancer
  • SABR

Research Beacons, Institutes and Platforms

  • Manchester Cancer Research Centre

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