Curative-Intent Metastasis-Directed Therapies for Molecularly Defined Oligorecurrent Prostate Cancer

[Balsam01]

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In this study, men who had recurrent prostate cancer in an isolated, treatable site following definitive therapy underwent targeted surgery or radiation therapy of their oligometastatic disease. All men had negative conventional imaging and positive molecular PET-MRI/CT. Of 72 enrolled patients, 37 had identifiable oligorecurrent disease and agreed to metastasis-directed therapy (10 surgical resection, 27 radiation). Of these men, 22% achieve a complete biochemical disease–free response at a median of 15.9 months. Although most did not have a complete PSA response, median time to PSA progression was 17.7 months.

These findings suggest that oligometastasis-directed therapy may benefit selected men with recurrent prostate cancer after curative-intent prostate surgery or radiation.

– Joshua A. Cohn, MD

Abstract

This abstract is available on the publisher's site.

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.

Article citation:

European Urology

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 Berlin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

[Dban]

thanks Balsam. Really timely as I had SBRT+ 4 months ADT a year ago for a single met and am now waiting, with a rising PSA for PSMA PET scan to see where I am. May well be another hit of SBRT plus ADT Plus Chemo. We shall see.

[RGD115 in reply to Dban]

Balsam all l can say is shortly l was diagnosed in dec 2015 with prostate cancer 6.1 promptly rose to 13.1 went to prague had proton treatment in may 2017 put on Zoladex for 3 yrs after treatment had my last injection in nov 2019 after treatment my PSA was 0.01 4years on my last PSA last week was 0.02 well pleased at the moment don’t regret going to prague against all the advice from my consultant in uk