(UroToday.com) The 2023 American Society of Clinical Oncology (ASCO) annual meeting held in Chicago, IL between June 2nd and June 6th was host to a prostate, testicular, and penile cancers poster session. Nonna Shakhnazaryan presented the results of a single institution analysis evaluating sequential metastasis-directed therapy (MDT) for oligometastatic prostate cancer patients, detected via PET-based imaging.
Over the last decade, prostate-specific membrane antigen (PSMA) and F-18-Fluciclovine PET (Axumin ®) imaging have been shown to have improved test performance characteristics for the detection of recurrent disease in the biochemical relapse setting, compared to conventional imaging techniques.1-3 MDT, commonly in the form of stereotactic body radiation therapy (SBRT), to PET-detected lesions has been shown to improve progression-free survival (PFS) and delay time to ADT use, compared to observation. However, the utility of repeat or subsequent SBRT treatments for patients with evidence of oligo-recurrence after initial SBRT is not well-defined. The objective of this study was to evaluate the feasibility and clinical outcomes of serial PET-directed SBRT for patients with evidence of oligo-progressive prostate cancer following initial SBRT treatment.
This was a single center, retrospective analysis of patients with evidence of PSMA or Axumin PET-positive oligometastatic disease (1-5 non-visceral lesions), who received two or more consecutive serial SBRT treatments between January 2017 and February 2023. The outcomes of interest were:
- PSA50 response
- Progression-free survival (PFS)
- ADT initiation/intensification-free survival (ADTFS)
Patient-level variables of interest were:
- Patient demographics
- Clinical characteristics
- Concurrent systemic therapy
- Prior responses to SBRT
The associations between these variables and PFS following SBRT2 were evaluated using multivariable Cox proportional hazards modeling.
Baseline patient characteristics are summarized below:
Thirty-four patients underwent at least two courses of MDT (cohorts: SBRT 2 and SBRT3). Oligoprogressive disease in the SBRT2 cohort was detected via PSMA PET in 26 (77%) patients and via Axumin® in 8 cases (23%). At the time of SBRT2, over half of patients (53%) had a concurrent change in systemic therapy choice and 29% did not receive any systemic therapy. Of these 34 patients, 12 subsequently underwent a third round of SBRT (SBRT3). In the SBRT3 cohort, progression was detected via PSMA PET in 9/12 (75%) and Axumin in 3/12 (25%).
As summarized in the table below, castrate resistance at SBRT was present in 21%, 35%, and 42% of patients in the SBRT1, SBRT2, and SBRT3 cohorts, respectively. PSA50 response was 82% in SBRT1 and 65-57% in SBRT2-3. The median PFS was longest in the SBRT1 cohort (20 months), compared to 14.1 months in SBRT2 (not reached in SBRT3). The median ADTFS was almost 2 years in SBRT2 and 15 months in SBRT3.
The maximum percent PSA change, PFS outcomes, and response to treatments for cohorts SBRT1, SBRT2, and SBRT3 are summarized in the figures below:
On multivariable analysis, the following associations were observed:
- Predictors of PSA50 response at SBRT2 included a prior PSA50 response at SBRT1 and concurrent change in systemic therapy at SBRT2 (p for both = 0.001)
- Predictors of prolonged PFS after SBRT2 included PSA50 response at SBRT1 (p=0.001), concurrent change in systemic therapy at SBRT2 (p=0.045), and a castrate-sensitive state (p=0.033)
- No variables were significantly associated with ADTFS following SBRT2
The investigators concluded that serial PET-directed SBRT for oligo progressive disease following initial SBRT is feasible and is associated with significant PSA responses in most patients, even when systemic therapy was withheld or remained unchanged. These findings provide support for the role of repeat SBRT in patients with an initial SBRT response but subsequently develop novel oligometastasis following the initial treatment course. These findings will need to be validated in larger prospective studies.
Presented by: Nonna Shakhnazaryan, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA
Written by: Rashid Sayyid, MD, MSc – Society of Urologic Oncology (SUO) Clinical Fellow at The University of Toronto, @rksayyid on Twitter during the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago, IL, Fri, June 2 – Tues, June 6, 2023.
References:- Hofman MS, Lawrentschuk N, Francis, RJ, et al. Prostate-specific membrane antigen PET-CT in patients with high-risk prostate cancer before curative-intent surgery or radiotherapy (proPSMA): A prospective, randomized, multicentre study. Lancet 2020 Apr 11;395(10231):1208-1216.
- De Feria Cardet RE, Hofman MS, Segard T, et al. Is Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography Imaging Cost-effective in Prostate Cancer: An Analysis Informed by the proPSMA Trial. Eur Urol. 2020 Dec 16;S0302-2838(20)30946-5.
- 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. Lancet. 2021 May 22;397(10288):1895-1904.