The aim of the study was to examine the detection rate of PCa recurrences in patients with low PSA levels, before reaching the Phoenix criteria for a BCR. The study hypothesized that recurrences in these patients could potentially be detected in a more limited stage of disease, enabling options for e.g. local salvage therapies or metastasis-directed therapy (MDT). These therapies could potentially halt further disease progression.

Biochemical recurrence (BCR) of prostate cancer (PCa) after curative radiotherapy is in 2005 defined with the ‘Phoenix criteria’: a prostate-specific antigen (PSA) rise of ≥2 ng/ml above the nadir. Since BCR precedes clinical failure, imaging for (re)staging potential PCa recurrences is warranted in patients meeting the Phoenix criteria. In 2005 at the time these criteria were drawn up, detection of PCa recurrenceswas based on conventional imaging (CT, bone scan), however offering poor diagnostic accuracy for BCR.

Since the introduction of the prostate-specific membrane antigen positron emission tomography (PSMA-PET/CT) the ability to localize PCa recurrences has increased markedly, especially in patients with low PSA levels.

We conducted a retrospective analysis of the Prostate Cancer Network Amsterdam (2015–2023) cohort of 568 patients who received curative-intent RT for PCa. Patients were categorized into two cohorts, based on their PSA level at the time of PSMA-PET/CT:

  • Group 1 (n=222): patients with a PSA rise <2 ng/mL above the nadir (not meeting the Phoenix criteria for a BCR)
  • Group 2 (n=346): patients who did officially meet the criteria for a BCR.

Data on PSMA PET/CT outcomes, therapeutic management, and clinical follow-up were collected, including (re)initiation of androgen deprivation therapy (ADT), progression to castration resistant prostate cancer (CRPC) and overall-survival. Results were compared between both cohorts with logistic regression and survival analyses.

Baseline characteristics were in general similar between both cohorts. PSMA-PET/CT was performed 9 months (median difference) earlier in group 1 compared to group 2.

  1. PSMA-PET/CT detected PCa recurrences in 77% of the patients before reaching the criteria for BCR (group 1). According to the Phoenix criteria, there is no indication for imaging for (re)staging purposes in these patients as they are still considered as patients without PCa recurrence from a biochemical perspective.
  2. PCa recurrences in this group were indeed detected at a significant less advanced stage of disease compared to group 2. For example, group 1 had PCa lesions that were four times more often still eligible for local salvage therapy, did have a 3.5 lower odds of having distant metastastes and showed a significant lower median number of metastases (2 . 5 metastases). Early detection of limited recurrences enables therapeutical options that could halt disease progression (e.g. a salvage prostatectomy). This could ideally postpone the need for ADT and other systemic treatment, which significantly impacts quality of life.
  3. Moreover, we found promising long-term clinical outcomes in group 1 after PSMA-PET/CT, with a delay of starting ADT, CRPC onset and overall-survival. However, since the retrospective design, these last clinical outcomes should be regarded as associations instead of causality by early performance of PSMA-PET/CT.

Prostate cancer recurrences are much earlier present and detectable with PSMA-PET/CT than the current criteria for BCR after curative radiotherapy postulate. Recurrences were detected in the majority (77%) of patients with PSA rises below these Phoenix criteria. Early detection of these significant more limited stages of disease improves therapeutical options and could potentially delay disease progression.

Link to publication
Prostate-specific Membrane Antigen Positron Emission Tomography Before Reaching the Phoenix Criteria for Biochemical Recurrence of Prostate Cancer After Radiotherapy: Earlier Detection of Recurrences - ScienceDirect

Authors

  • Evelien J.E. van Altena a,b
  • Bernard H.E. Jansen a,b
  • Marieke L. Korbee a,b
  • Jakko A. Nieuwenhuijzen a,b
  • Wietske I. Luining a,b
  • André N. Vis a,b
  • Daniela E. Oprea-Lager c
  • Stéphanie L. van der Pas d
  • Pim J. van Leeuwen e
  • Maurits Wondergem f
  • Remco J.J. Knol f
  • Friso M. van der Zant f
  • Jochem R.N. van der Voort van Zyp g

a) Department of Urology, Amsterdam University Medical Centers, Amsterdam, The Netherlands
b) Prostate Cancer Network Amsterdam, Amsterdam, The Netherlands
c) Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers, Amsterdam, The Netherlands
d) Department of Epidemiology and Data Science, Amsterdam University Medical Centers, Amsterdam, The Netherlands
e) Department of Urology, Netherlands Cancer Institute, Amsterdam, The Netherlands
f) Department of Nuclear Medicine, Northwest Clinics, Alkmaar, The Netherlands
g) Department of Radiotherapy, University Medical Center Utrecht, Utrecht, The Netherlands

No funders involved.

Grants
EMUC 2024: prize for Best Abstract in category Prostate Cancer

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