TY - JOUR
T1 - Curative-intent Metastasis-directed Therapies for Molecularly-defined Oligorecurrent Prostate Cancer
T2 - A Prospective Phase II Trial Testing the Oligometastasis Hypothesis[Formula presented]
AU - Glicksman, Rachel M.
AU - Metser, Ur
AU - Vines, Douglass
AU - Valliant, John
AU - Liu, Zhihui
AU - Chung, Peter W.
AU - Bristow, Robert G.
AU - Finelli, Antonio
AU - Hamilton, Robert
AU - Fleshner, Neil E.
AU - Perlis, Nathan
AU - Zlotta, Alexandre R.
AU - Green, David
AU - Bayley, Andrew
AU - Helou, Joelle
AU - Raman, Srinivas
AU - Kulkarni, Girish
AU - Catton, Charles
AU - Lam, Tony
AU - Chan, Rosanna
AU - Warde, Padraig
AU - Gospodarowicz, Mary
AU - Jaffray, David A.
AU - Berlin, Alejandro
N1 - Publisher Copyright:
© 2021 European Association of Urology
PY - 2021/9
Y1 - 2021/9
N2 - 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.
AB - 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.
KW - Metastasis directed treatment
KW - Oligometastasis
KW - PSMA PET
KW - Prostate cancer
KW - SABR
UR - http://www.scopus.com/inward/record.url?scp=85102073950&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85102073950&partnerID=8YFLogxK
U2 - 10.1016/j.eururo.2021.02.031
DO - 10.1016/j.eururo.2021.02.031
M3 - Article
C2 - 33685838
AN - SCOPUS:85102073950
SN - 0302-2838
VL - 80
SP - 374
EP - 382
JO - European urology
JF - European urology
IS - 3
ER -