(UroToday.com) The 2023 European Association of Urology (EAU) annual congress held in Milan, Italy between March 10th and 13th, 2023 was host to an abstract session of studies addressing long-term prostate cancer control outcomes. Dr. Matteo Droghetti presented the results of a study evaluating the utility and timing of PSMA-PET/CT for guidance of salvage treatments in patients with recurrent prostate cancer.
Dr. Droghetti began by noting that PSMA-PET/CT has emerged as the “tool of choice” for the restaging of patients with biochemical failure and may help guide subsequent salvage treatments. As has been demonstrated in previous studies, the detection of PSMA-positive lesions increases as the PSA at which the test is performed increases, with a detection rate varying between 38% with PSA <0.5 ng/ml and 97% with a PSA ≥5.0 ng/ml.1 As such, patients undergoing metastasis-directed therapy (MDT) for PET-positive lesions may be at risk for inherently worse outcomes given that performance of MDT is dependent upon the detection of PET-positive lesions which are increasingly detected at higher PSA levels. As such, the objective of this study was to evaluate the oncologic outcomes of patients with recurrent PCa according to PSMA-PET/CT results.
To this end, the authors included 134 patients with castrative-sensitive prostate cancer with biochemical relapse following a radical prostatectomy and who subsequently underwent a PSMA-PET/CT at one of three high-volume European Centers. Patients with oligometastatic disease (three or less PSMA-positive lesions) underwent whole pelvis salvage radiotherapy plus PSMA-guided MDT, including SBRT. Patients with poly-recurrent (i.e. more than three lesions) disease underwent a combination of systemic therapies. Conversely, patients with negative PSMA-PET/CT scans were treated with whole pelvis salvage radiotherapy and/or systemic therapies according to treating physician preference.
The outcome of progression-free survival, defined as freedom from PSA progression or new PSMA-PET/CT lesions, was evaluated using Kaplan Meier curves, stratified by PSMA-PET/CT results, with between-group comparisons performed using the log-rank test. The association between PSMA-PET/CT positivity and progression-free survival was evaluated using multivariable cox regression analyses, adjusted for pathologic stage, ISUP grade, and serum PSA level at the time of the PET scan.
This study included 134 patients, of whom 69 (52%) had PET-positive lesions. Compared to patients with negative PSMA-PET scans, patients with positive PSMA-PET/CT scans had:
- More advanced disease (pT3a-b: 83% versus 52%, p<0.01)
- More frequent lymph node involvement (38% versus 19%, p<0.01)
- Worse ISUP grade scores (ISUP 4-5: 65% versus 31%, p<0.01)
- Higher median PSA at time of the PET/CT (0.8 versus 0.33 ng/ml, p<0.01)
Among the 69 patients with PET-positive disease, 6 (9%) had “poly-metastatic” disease at first recurrence, whereas the remaining 63 (91%) had oligometastatic disease with a median of 2 positive lesions.
The binary outcome of 24-months progression-free survival demonstrated no significant differences between patients with and without PSMA-PET/CT-positive lesions (76% for PET negative versus 65% for PET positive, p=0.2). On multivariable regression analysis, PSMA positivity (versus negativity) was not significantly associated with the hazard of disease progression (HR: 1.23, 95% CI: 0.54 to 2.83, p=0.6).
The authors concluded that the presence of PSMA-PET/CT-positive lesions at the time of first recurrence post-radical prostatectomy was not a significant predictor of adverse oncologic outcomes, even after adjusting for pathologic stage, ISUP grade, and serum PSA levels at recurrence. It is important to note however that these findings might be secondary to limited power given the study sample size and lack of stratification by volume of metastatic disease (oligo versus poly). The authors surmised that these findings suggest that MDT may play an important oncologic role, even in the first recurrence setting, when compared to early “blind” salvage treatments.
Presented by: Dr. Matteo Droghetti, MD, Department of Urology, IRCCS Azienda Ospedaliero-universitaria di Bologna, Bologna, Italy
Written by: Rashid K. Sayyid, MD, MSc – Society of Urologic Oncology (SUO) Clinical Fellow at The University of Toronto, @rksayyid on Twitter during the 2023 European Association of Urology (EAU) Annual Meeting, Milan, IT, Fri, Mar 10 – Mon, Mar 13, 2023.
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