EAU 2021: Radiotherapy After Radical Prostatectomy in the PSMA-PET Era

(UroToday.com) At the controversies in Onco-Urology session of the European Association of Urology 2021 annual meeting, Dr. Alberto Bossi discussed radiotherapy after radical prostatectomy in the PSMA-PET era. Adjuvant radiotherapy is defined as immediate postoperative radiation in the case of extraprostatic extension, positive margins, seminal vesicle infiltration, high Gleason score, or pN+ disease. Salvage radiotherapy is defined as a wait-and-see policy in that radiation is only given in the case of a rising postoperative PSA.

The ARTISTIC meta-analysis was published in 2020, combining data from RADICALS, GETUG-AFU 17, and RAVES showing no difference in PSA-driven event-free survival with a hazard ratio of 1.12 (95% CI 0.88-1.42), and a potential absolute difference of 1% at 5-years in favor of early salvage radiotherapy1. As such, Dr. Bossi notes that these results essentially nullify the notion of adjuvant radiotherapy.

The EAU/ESUR/ESTRO/SIOG 2020 guidelines relating to PSMA PET scan suggest that men with a persistent PSA > 0.2 ng/mL after radical prostatectomy should be offered a PSMA PET/CT to exclude metastatic disease (weak recommendation). Additionally, PSMA PET/T should be offered to men after a radical prostatectomy if the PSA level is rising above >0.2 ng/mL and if the results will influence subsequent treatment decisions (2b; weak recommendation). Finally, PSMA PET/CT should be offered in patients fit for curative salvage treatment with PSA recurrence after radiotherapy (2b; strong recommendation). The reason for waiting for the PSA to reach >0.2 ng/mL is the poor detection rate of 33% for PSMA PET/CT positivity in patients with a PSA <0.2 ng/mL. As follows are additional governing body’s guideline recommendations for the utilization of PSMA PET/CT:

Bossi_EAU21_Figure1.png

Utilization of PSMA PET/CT for recurrent disease certainly may change management (upwards of 40-75%) based on the location of detected disease, summarized in the following figure:

Bossi_EAU21_Figure2.png

Dr. Bossi then discussed the recently published EMPIRE-1 trial2, which was a single-center, open-label, phase 2/3 randomized controlled trial of patients with prostate cancer with detectable PSA after prostatectomy and negative conventional imaging (no extrapelvic or bone findings). Patients were randomly assigned in a 1:1 ratio to radiotherapy directed by conventional imaging alone or to conventional imaging plus 18F-fluciclovine-PET/CT. The primary endpoint was 3-year event-free survival, with events defined as biochemical or clinical recurrence or progression, or the initiation of systemic therapy. There were 165 patients randomly assigned, with a median follow-up of 3.52 years (95% CI 2.98-3.95).  The 3 year event-free survival rate was 63.0% (95% CI 49.2-74.0) in the conventional imaging group versus 75.5% (95% CI 62.5-84.6) for 18F-fluciclovine-PET/CT (difference 12.5; 95% CI 4.3-20.8; p=0.0028):

Bossi_EAU21_Figure3.png

Dr. Bossi concluded his presentation of radiotherapy after radical prostatectomy in the PSMA PET/CT era with the following take-home messages:

  • PSMA PET/CT before salvage radiotherapy should be performed if the results will possibly change the subsequent management strategy
  • PSMA PET/CT should be considered for postop persistent elevated PSA or for post-op rising PSA of at least 0.2 ng/mL
  • Currently, there is no place for delaying early salvage radiotherapy until PSMA reveals the origin of the rising PSA: we may miss the window of curability of early salvage radiotherapy
  • For the time being, adopting changes in the management of patients based on a positive PSMA should be preferably done in the framework of a randomized controlled trial

Presented by: Alberto Bossi, MD, Goustave Roussy Institute, Villejuif, France

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2021 European Association of Urology, EAU 2021- Virtual Meeting, July 8-12, 2021.

References: 

  1. Vale CL, Fisher D, Kneebone A, et al. Adjuvant or early salvage radiotherapy for the treatment of localized and locally advanced prostate cancer: A prospectively planned systematic review and meta-analysis of aggregate data. Lancet 2020 Oct 31;396(10260):1422-1431.
  2. Jani AB, Schreibmann E, Goyal S, et al. 18F-fluciclovine-PET/CT imaging versus conventional imaging alone to guide postprostatectomy salvage radiotherapy for prostate cancer (EMPIRE-1): A single centre, open-label, phase 2/3 randomized controlled trial. 2021 May 22;397(10288):1895-1904.
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