This study aimed to investigate the association between the 68Ga- or 18F-radiolabeled prostate-specific membrane antigen (PSMA) tracer expression, represented by the maximum standardised uptake value (SUVmax) of the dominant intraprostatic lesion, and biochemical recurrence (BCR) in primary prostate cancer (PCa) patients prior to robot-assisted radical prostatectomy (RARP). This was a retrospective, multi-centre cohort study of 446 patients who underwent [68Ga]Ga-PSMA-11 (n = 238) or [18F]DCFPyL (n = 206) Positron Emission Tomography/Computed Tomography (PET/CT) imaging prior to RARP. SUVmax was measured in the dominant intraprostatic PCa lesions. [18F]DCFPyL patients were scanned 60 ([18F]DCFPyL-60; n = 106) or 120 ([18F]DCFPyL-120; n = 120) minutes post-injection of a radiotracer and were analysed separately. To normalise the data, SUVmax was log transformed for further analyses. During a median follow-up of 24 months, 141 (30.4%) patients experienced BCR. Log2SUVmax was a significant predictor for BCR (p < 0.001). In the multivariable analysis accounting for these preoperative variables: initial prostate-specific antigen (PSA), radiologic tumour stage (mT), the biopsy International Society of Urological Pathology grade group (bISUP) and the prostate imaging and reporting data system (PI-RADS), Log2SUVmax was found to be an independent predictor for BCR in [68Ga]Ga-PSMA-11 (HR 1.32, p = 0.04) and [18F]DCFPyL-120 PET/CT scans (HR 1.55, p = 0.04), but not in [18F]DCFPyL-60 ones (HR 0.92, p = 0.72). The PSMA expression of the dominant intraprostatic lesion proved to be an independent predictor for BCR in patients with primary PCa who underwent [68Ga]Ga-PSMA-11 or [18F]DCFPyL-120 PET/CT scans, but not in those who underwent [18F]DCFPyL-60 PET/CT scans.
Background: Focal laser ablation (FLA) serves as a targeted therapy for prostate cancer (PCa). Clinical studies have demonstrated significant variations in ablation volumes with consistent fiber configurations. Consequently, a prediction model is needed for the safe application of FLA in treating PCa.Objective: This study aimed to evaluate the reproducibility of FLA–induced temperature profiles in controlled ex vivo experiments using clinical laser treatment protocols. Additionally, it sought to examine the effectiveness of the CEM43 model in predicting the zone of irreversible damage (ZID) and to compare these findings with outcomes derived from the Arrhenius model.Methods: Freshly excised postmortem human prostate and porcine liver specimens were used for controlled ex vivo ablation. Tissues were secured in a Perspex sample holder for precise placement of the laser fiber and thermocouples. FLA was conducted with a 1064‐nm Nd:YAG laser at 3 W in continuous‐wave mode for 10 min. Pre– and post–FLA 3D T1‐weighted 7 T MRI scans were obtained to assess the treatment area. Whole‐mount hematoxylin and eosin histological slides were prepared and digitized. On histology, the ZID was defined as the total of vaporized, carbonized, and coagulated tissue. A 2D thermal development map was created from temperature data, using bi‐cubic interpolation. The cumulative equivalent thermal isoeffect dose at 43°C in minutes (CEM43) model was applied to predict the ZID, with 240 equivalent minutes (240‐CEM43) used as the damage threshold. Additionally, the Arrhenius thermal model was used for comparison of CEM43 results. Predicted ZIDs were compared to MRI and histology.Results: FLA treatment was performed on ex vivo human prostate samples (n = 2) and porcine liver specimens (n = 5). For human prostate tissue, FLA did not result in an identifiable ZID upon histological macroscopic examination or a lesion on MRI. Ex vivo porcine liver samples showed a clearly demarcated oval‐shaped hyperintense lesion surrounding the laser fiber tip on post–FLA MRI. The MRI lesion (range 1.6–2.1 cm2) corresponded with the shape and location of the ZID on histology, but was smaller (median 1.7 vs. 3.2, p = 0.02). Histological examination of porcine liver samples revealed ZIDs ranging from 2.1 to 4.1 cm2, whereas 240‐CEM43–predicted ZIDs ranged from 3.3 to 3.8 cm2. Although the median 240‐CEM43–predicted ZID was not significantly larger than the histology ZID (3.8 vs. 3.2 cm2, p = 0.22), it tended to overpredict the histological results in most experiments. The median Arrhenius‐predicted ZID was similar to the histological ZID (3.2 vs. 3.2 cm2, p = 0.56), but varied in size when comparing individual experiments (range 2.5–3.2 cm2).Conclusion: FLA on ex vivo human prostate showed no thermal damage on histopathology or MRI. Ex vivo porcine liver FLA resulted in identifiable ZID on histology and lesions on MRI. 240‐CEM43 generally overestimated the ZID and had less variability compared to histology. Results from the Arrhenius model were in better agreement with the histology findings, but still did not predict the individual FLA–induced histological thermal damage. Inter‐experiment ZID variability underlines the need for developing a more comprehensive predictive dosimetry model for FLA in PCa treatment.
Multifiber micro-US–guided focal laser ablation in participants with localized prostate cancer was safe and feasible, with 18% recurrence at 1-year follow-up.
In patients with biochemical recurrence (BCR), prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) can detect oligometastatic prostate cancer (PCa). However, the optimal treatment approach for oligometastatic disease remains unclear. This study aims to assess the oncological outcomes of metachronous oligometastatic PCa patients treated with metastasis-directed radiotherapy (MDRT). We retrospectively evaluated patients with hormone-sensitive, metachronous oligometastatic PCa who underwent MDRT for BCR (from July 2012 to September 2022). Patients had one to four lymph nodes and/or bone metastases on PSMA PET/CT and were irradiated with 5 × 7 or 3 × 10 Gy. The biochemical response to MDRT was assessed as undetectable prostate-specific antigen (PSA) at follow-up, PSA response (PSA ≤ pretreatment level), or biochemical progression (PSA > pretreatment level). Biochemical progression-free survival (bPFS) and local remission of disease (absence of disease at the MDRT site on follow-up PSMA PET/CT or undetectable PSA) were evaluated. Eighty patients underwent MDRT for 105 PSMA PET/CT-confirmed lesions. The median time from curative treatment to MDRT was 55 mo (interquartile range [IQR] 31-103). At a median follow-up of 32 mo after MDRT (IQR 21-64), 10% of the patients were PSA free, 10% had a PSA response, and 80% experienced biochemical progression. The bPFS rates at 1 and 2 yr were 54% and 38%, respectively. A total of 87% of patients had local control of disease after MDRT, whereas 72% had new metastatic lesions on repeated PSMA PET/CT. Limitations include the retrospective design and a small cohort. MDRT for oligometastatic disease shows high local efficacy. However, disease progression is observed in a substantial proportion of patients.
Background/Objectives: In men with biochemical recurrence (BCR) after a radical prostatectomy (RP), salvage radiotherapy (SRT) is commonly recommended when imaging shows no metastases. The optimal management for patients with negative prostate-specific membrane antigen (PSMA) PET/CT findings at BCR remains uncertain. This study evaluated outcomes of patients with BCR and negative PSMA PET/CT to identify who may be safely observed and who may benefit from early SRT. Methods: This retrospective multicentre cohort study included 89 patients with BCR and negative PSMA PET/CT findings after a RP (2015–2022) who were managed with observation. The exclusion criteria were PSA levels ≥ 0.8 ng/mL at baseline, prior SRT, or prior or ongoing hormonal therapy. Minimum follow-up was 3 years. Biochemical progression (PSA rise > 0.2 ng/mL above baseline or initiation of additional treatment) and radiological progression (local or metastatic disease on follow-up PSMA PET/CT) were assessed. Patients were stratified by EAU BCR-risk classification. Multivariable Cox regression included age, biochemical persistence (BCP) after a RP, pathological tumour stage (pT), pathological ISUP grade group (pISUP), node status (pN), margin status (R), and PSA doubling time (PSAdt). Results: The median age was 66 years (IQR 60–69) and the median PSA measurement at BCR was 0.2 ng/mL (IQR 0.2–0.3). A total of 27/89 (30%) patients were EAU BCR low-risk and 62/89 (70%) were high-risk. At three years, biochemical progression occurred in 14/27 (52%) low-risk vs. 51/62 (83%) high-risk patients, with time to progression being 21 vs. 12 months (p = 0.01). A pISUP grade group ≥ 4 (HR 2.04 [95%-CI 1.11–3.74]; p = 0.022) and a PSAdt < 20 months (HR 5.72 [95%-CI 2.41–13,56]; p < 0.01) independently predicted biochemical progression. Radiological progression occurred in 43/68 (66%) rescanned patients, with 32/43 (74%) showing disease outside the prostatic fossa. Conclusions: Nearly half of patients with BCR and negative PSMA PET/CT findings who were classified as EAU BCR low-risk remained progression-free at three years. These results support a risk-adapted approach, indicating that SRT may be deferred in selected low-risk patients.