EAU 2024: High-Risk Biochemical Recurrence after Radical Prostatectomy and Negative PSMA PET: What to Do? The Guideline’s View

(UroToday.com) The 2024 European Association of Urology (EAU) annual meeting featured a plenary session on personalized approaches in high-risk and metastatic prostate cancer, and a presentation by Dr. Derya Tilki discussing the guideline’s view for patients with high-risk biochemical recurrence after radical prostatectomy and negative PSMA PET. Dr. Tilki started by highlighting the background notes from the EAU guidelines, specifically “between 27% and 53% of all patients undergoing radical prostatectomy or radiotherapy develop a rising PSA (PSA recurrence). While metastatic progression is universally preceded by rising PSA levels, physicians must inform the patient that the natural history of PSA-only recurrence may be prolonged and that a measurable PSA may not necessarily lead to clinically apparent metastatic disease.”

Of note, Dr. Tilki states that the PSA level that defines treatment failure depends on the primary treatment. Biochemical recurrence after radical prostatectomy, as Dr. Tilki highlighted from her institution’s experience, is not infrequent as 20.3% of men in a sample of 14,532 patients experienced biochemical recurrence at a median follow-up of 50.8 months.1 Moreover, the risk of biochemical recurrence increases with increasing CAPRA-S score:

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Dr. Tilki then presented unpublished data looking at long-term oncological outcomes of patients with biochemical recurrence. Among 3,416 patients with radical prostatectomy (1992-2017) who experienced biochemical recurrence (PSA >= 0.2 ng/mL), those with pT3 and Gleason score 8-10 disease had worse metastasis free survival versus those with pT3 and Gleason score 7 disease versus those with pT2 disease:

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Dr. Tilki highlighted that the EAU guidelines recommend stratifying biochemical recurrence patients into EAU low-risk and high-risk biochemical recurrence group. This recommendation is based on a 2019 systematic review from Van Den Broeck et al.2 showing that low risk patients are those with a PSA doubling time > 12 months and pathologic Gleason Group 1-3. High risk patients are those with PSA doubling time < 12 months or pathologic Gleason Group 4-5.

Regarding imaging, Dr. Tilki notes that the EAU guidelines state “in patients with biochemical recurrence, imaging can detect both local recurrences and distant metastases, however, the sensitivity of detection depends on the PSA level. After radical prostatectomy, PSMA PET/CT is the imaging modality with the highest sensitivity at low PSA levels (<0.5 ng/mL)”

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The EAU recommendations are for a “PSMA PET/CT if the PSA level is > 0.2 ng/mL and if the results will influence subsequent treatment decisions.”

Dr. Tilki concluded her presentation by discussing the treatment of biochemical recurrence, with the EAU guidelines stating that “a negative PET/CT scan should not delay salvage radiotherapy if otherwise indicated” (Strength rating: Strong). Additionally, “offer monitoring including PSA, to EAU low-risk biochemical recurrence patients” (Strength rating: Weak). The potential benefits and toxicities of salvage treatment should be discussed with each patient considering both the EAU biochemical risk stratification and life expectancy. For recommendations for systemic salvage treatment the EAU guidelines state “Offer enzalutamide with or without ADT to M0 patients with high-risk biochemical recurrence, defined as a PSA doubling time of <= 9 months and a PSA level >= 2 ng/mL above nadir after radiation therapy or >= 1 ng/mL after radical prostatectomy with or without post-operative radiation therapy” (Strength rating: Strong).

Presented by: Derya Tilki, MD, Martini-Klinik Prostate Cancer Center, University Hospital Hamburg Eppendorf, Hamburg, Germany

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the 2024 European Association of Urology (EAU) annual congress, Paris, France, April 5th - April 8th, 2024 

References:

  1. Tilki D, Mandel P, Schlomm T, et al. External validation of the CAPRA-S score to predict biochemical recurrence, metastasis and mortality after radical prostatectomy in a European cohort. J Urol 2015;193(6):1970-1975.
  2. Van Den Broeck T, van den Bergh RCN, Arfi N, et al. Prognostic Value of Biochemical Recurrence Following Treatment with Curative Intent for Prostate Cancer: A Systematic Review. Eur Urol 2019 Jun;75(6):967-987.
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