PET/CT-Guided Salvage Radiotherapy Improves Event-Free Survival After Prostatectomy

Author: By Lynda Williams, Senior medwireNews Reporter 

medwireNews: The EMPIRE-1 trial findings support the use of 18F-fluciclovine-positron emission tomography/computed tomography (PET/CT) during the planning of salvage radiotherapy for men with detectable prostate-specific antigen (PSA) after prostatectomy. 

“[O]ur study provides highest-level available evidence that incorporating advanced molecular imaging with PET into therapy planning improves cancer control without increasing toxicity”, say Ashesh Jani, from Winship Cancer Institute of Emory University in Atlanta, Georgia, USA, and co-investigators. 

The phase II/III trial included 76 patients who underwent radiotherapy guided by 18F-fluciclovine-PET/CT alongside conventional imaging – consisting of whole-body bone scanning plus abdominopelvic CT and magnetic resonance imaging – and 81 patients assessed by conventional imaging alone. 

The investigators explain that patients assessed using PET/CT had their radiotherapy regimen “rigidly determined” by radiotracer uptake in the extrapelvic areas or skeleton (no radiotherapy), pelvic nodes (45.0–50.4 Gy) and prostate bed (64.8–70.2 Gy). 

By contrast, the control arm received radiotherapy to the prostate bed (64.8–70.2 Gy) based on presurgical disease and prostatectomy pathological findings and PSA trajectory, with pelvic radiotherapy (45.0–50.4 Gy) given at the discretion of the treating physician. 

The participants were followed up for a median 3.52 years after the end of radiotherapy for prostate cancer events, defined as: a PSA level 0.2 ng/mL above postradiotherapy nadir followed by a subsequent PSA increase; a persistent PSA increase; a positive imaging or rectal examination; or a need for systemic therapy. 

As reported in The Lancet, median survival was not reached in either the PET or control groups, with events occurring in 20% and 33% of patients, respectively. 

The 3-year modified intention-to-treat rates of event-free survival were 75.5% and 63.0%, respectively, and after adjusting for age, race, PSA, prostate cancer features and treatment, patients treated after conventional imaging were a significant 2.04 times more likely to have had events than those who had PET/CT imaging. 

Multivariable analyses also showed a significantly increased risk of events in patients with a PSA of 1.0 ng/mL or greater (hazard ratio [HR]=3.49) and those who received only prostate bed radiation (HR=2.09 vs prostate bed and pelvis), whereas patients without extracapsular extension had a significantly reduced risk of events than those with (HR=0.45). 

In addition, the 4-year rate of failure-free survival was significantly higher in the PET/CT arm than the conventional imaging only arm at 75.5% versus 51.2%. 

Ashesh Jani and co-authors cite “similar” toxicity in the PET/CT and conventional imaging groups, most commonly late urinary frequency or urgency (41 vs 46%) and acute diarrhoea (21 vs 14%). Grade 3 toxic effects were “infrequent” and there were no grade 4 or 5 events, they say. 

“Although much recent progress has been made in understanding the role of timing of radiotherapy (RAVES, RADICALS-RT, and GETUG-AFU 17 trials, and associated meta-analyses), as well as the role of androgen deprivation therapy and pelvic lymph node radiation (GETUG-AFU 16, RTOG 9601, and RTOG 0534 trials), molecular imaging with PET also seems have value in guiding final radiotherapy treatment decisions as well as radiotherapy target design to improve outcomes”, the investigators conclude. 

Reference  

Jani AB, Schreibmann E, Goyal S, et al. 18F-fluciclovine-PET/CT imaging versus conventional imaging alone to guide postprostactectomy salvage radiotherapy for prostate cancer (EMPIRE-1): a single centre, open-label, phase 2/3 randomised controlled trial. Lancet; Advance online publication 7 May 2021. DOI: 10.1016/ S0140-6736(21)00581-X