Abstract
PurposeTo assess the outcome of prostate cancer (PCa) patients diagnosed with oligorecurrent disease and treated with a first and a second PSMA (prostate-specific membrane antigen ligand) PET(positron-emission tomography)-directed radiotherapy (RT).Patients and methodsThirty-two patients with oligorecurrent relapse after curative therapy received a first PSMA PET-directed RT of all metastases. After biochemical progression, all patients received a second PSMA PET-directed RT of all metastases. The main outcome parameters were biochemical progression-free survival (bPFS) and androgen deprivation therapy-free survival (ADT-FS). The intervals of BPFS were analyzed separately as follows: the interval from the last day of PSMA PET-directed RT to the first biochemical progression was defined as bPFS_1 and the interval from second PSMA PET-directed RT to further biochemical progression was defined as bPFS_2.ResultsThe median follow-up duration was 39.5 months (18–60). One out of 32 (3.1%) patients died after 47 months of progressive metastatic prostate cancer (mPCa). All patients showed biochemical responses after the first PSMA PET-directed RT and the median prostate-specific antigen (PSA) level before RT was 1.70 ng/mL (0.2–3.8), which decreased significantly to a median PSA nadir level of 0.39 ng/mL (range <0.07–3.8; p = 0.004). The median PSA level at biochemical progression after the first PSMA PET-directed RT was 2.9 ng/mL (range 0.12–12.80; p = 0.24). Furthermore, the PSA level after the second PSMA PET-directed RT at the last follow-up (0.52 ng/mL, range <0.07–154.0) was not significantly different (p = 0.36) from the median PSA level (1.70 ng/mL, range 0.2–3.8) before the first PSMA PET-directed RT. The median bPFS_1 was 16.0 months after the first PSMA PET-directed RT (95% CI 11.9–19.2) and the median bPFS_2 was significantly shorter at 8.0 months (95% CI 6.3–17.7) after the second PSMA PET-directed RT (p = 0.03; 95% CI 1.9–8.3). Multivariate analysis revealed no significant parameter for bPFS_1, whereas extrapelvic disease was the only significant parameter (p = 0.02, OR 2.3; 95% CI 0.81-4.19) in multivariate analysis for bPFS_2. The median ADT-FS was 31.0 months (95% CI 20.1–41.8) and multivariate analysis showed that patients with bone metastases, compared to patients with only lymph node metastases at first PSMA PET-directed RT, had a significantly higher chance (p = 0.007, OR 4.51; 95% CI 1.8–13.47) of needing ADT at the last follow-up visit.ConclusionIf patients are followed up closely, including PSMA PET scans, a second PSMA PET-directed RT represents a viable treatment option for well-informed and well-selected patients.
Highlights
The cornerstone of treatment for non-castrated metastatic prostate cancer is androgen deprivation therapy (ADT), which has remained unchanged over the past years [1]
There is increasing evidence that patients with a limited number of metastases have a better prognosis than patients with widespread metastatic disease, and data outside large prospective trials suggest that metastasis-directed therapies (MDTs) for metastatic prostate cancer (mPCa) patients with a so-called “oligometastatic status,” based on a generally accepted imaging-based cut-off of five metastases, improve the clinical outcome [2, 6]
The recent introduction of PSMA ligand PET has substantially improved the diagnostic accuracy of staging at low prostatespecific antigen (PSA) levels [7,8,9,10,11], allowing refined and well-monitored individualized radio-oncological treatment concepts that aim to improve PSA kinetics, prolong progression-free survival, defer the initiation of ADT, and potentially cure the patient [2,3,4,5, 12]
Summary
The cornerstone of treatment for non-castrated metastatic prostate cancer (mPCa) is androgen deprivation therapy (ADT), which has remained unchanged over the past years [1]. There is increasing evidence that patients with a limited number of metastases have a better prognosis than patients with widespread metastatic disease, and data outside large prospective trials suggest that metastasis-directed therapies (MDTs) for mPCa patients with a so-called “oligometastatic status,” based on a generally accepted imaging-based cut-off of five metastases, improve the clinical outcome [2, 6]. The recent introduction of PSMA ligand PET has substantially improved the diagnostic accuracy of staging at low prostatespecific antigen (PSA) levels [7,8,9,10,11], allowing refined and well-monitored individualized radio-oncological treatment concepts that aim to improve PSA kinetics, prolong progression-free survival, defer the initiation of ADT, and potentially cure the patient [2,3,4,5, 12]. Data on the feasibility and clinical outcome of a second MDT guided by PSMA PET imaging after previous PSMA PET-directed radiotherapy (RT) are very limited
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