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Background and Objective: Radiographic progression in prostate cancer (PCa) can occur even when prostate-specific antigen (PSA) levels are undetectable. We aimed to determine the frequency and characteristics of radiographic disease progression (rDP) on PSMA PET/CT in patients with undetectable PSA, referred to as PSA zero rDP. Methods: We analyzed the Mayo Clinic PSMA PET Prostate Cancer Registry to identify patients with rDP on PSMA PET/CT despite undetectable PSA levels. Disease progression was confirmed via biopsy or treatment response. The cohort included patients with non-metastatic and metastatic hormone-sensitive disease, as well as those with castration-resistant prostate cancer at the time of imaging. Overall survival (OS) was estimated using the Kaplan–Meier method. Group comparisons were performed with the log-rank test. Univariate Cox regression was used to identify factors associated with poor OS. Key findings and Limitations: Among 2141 patients imaged between 2021 and 2023, 257 (12%) had PSA zero rDP. Sixty-one percent had initially localized disease; 39% had de novo metastatic disease. Median (IQR) time from diagnosis to PSA zero rDP was 51.9 (18.4–115.5) months. A total of 184 patients (72%) progressed to castration-resistant PCa. Sites of rDP included bone (57%), visceral (15%), lymph node (18%), and local recurrence (10%). During median follow-up of 8.1 (3.5–11.9) months, 5% of patients died. Only visceral metastases were significantly associated with poorer OS (p < 0.0001). Conclusions and Clinical Implications: Prostate cancer patients frequently develop metastatic disease with undetectable PSA values. Our findings suggest the use of periodic advanced imaging techniques, irrespective of PSA value, for more prompt detection and early management of disease progress.

e17081 Background: Prostate cancer is the most common cancer in men. In early localized disease, surgery represents the mainstay treatment. However, management of metastatic and advanced stages requires multidisciplinary approach. The prognosis in metastatic prostate cancer has improved recently due to advanced pharmaceutical and interventional methods of treatment with modern diagnostic methods. In our study, we aim to investigate the impact of concomitant treatment with 2nd generation hormonal therapy and 177Lut PSMA on PSA response in patients with metastatic CRPC Methods: In a retrospective observation study including 91male patients with metastatic CRPC treated with 177Lut PSMA, we divided our cohort into 2 groups depending on whether they had 2nd generation hormonal therapy alongside their treatment with 177Lut PSMA. 43 patients received 177Lut PSMA (group A). While the other 48 patients (group B) had 2 nd generation hormone therapy with 177Lut PSMA. Primary endpoint was PSA response after they complete their therapy. Favorable PSA response was defined by PSA reduction more than 50% from baseline PSA before treatment Results: Statistical analysis identified 91 male patients, median (IQR) age of 61.5 years (56,67.75). Median (IQR) Gleason score 8 (7 - 9). Pre-177Lut PSMA PSA had a median of 2 (0.255 - 99), post-177Lut PSMA had a median of 0.15 (0.1 - 2.7). Median (IQR) 177Lut PSMA 6 (5 - 6). There was no significant change in PSA response in patients who received 177Lut PSMA alone versus 177Lut PSMA with concomitant 2 nd generation hormonal therapy. Of that, 54.17% of group B had favorable PSA response compared to 48.84% of group A (P value 0.6115). In multivariable analysis, concomitant treatment with 2nd generation hormone therapy and 177Lut PSMA has no impact on PSA response rates. Conclusions: This data suggests that concomitant treatment with 2nd generation therapy and 177Lut PSMA did not demonstrate superior PSA response than treatment with 177Lut PSMA alone. This data contributes to the current literature and serve in patients counseling. Further studies are warranted.

175 Background: 177 Lu-PSMA-617, a PSMA-directed radionuclide therapy, is an emerging treatment for metastatic castration-resistant prostate cancer (mCRPC). This retrospective study evaluates clinical outcomes of 177 Lu-PSMA-617 in low volume (LV) and high volume (HV) mCRPC, classified using the CHAARTED criteria. Methods: We conducted a retrospective review of the Mayo Clinic Prostate Cancer Registry, including mCRPC patients treated with 177 Lu-PSMA-617 at Mayo Clinic Rochester, MN, from August 2017 to August 2024. Patients were categorized based on CHAARTED criteria, which define high-volume disease by the presence of visceral metastases and/or four or more bone metastases, with at least one outside the vertebral column and pelvis. PSA-response rate (PSA-RR), overall survival (OS), PSA-progression-free survival (PSA-PFS), and radiographic progression-free survival (rPFS) were analyzed using Kaplan-Meier curves with log-rank tests, as well as uni- and multivariate Cox regression. Results: Of the 264 patients treated with 177 Lu-PSMA-617, 83 were classified as LV (median follow-up: 17.1 months) and 177 as HV (median follow-up: 13.7 months). LV patients had lower serum PSA levels (P < 0.0001), higher hemoglobin levels (P < 0.0001), and a longer time from diagnosis to treatment initiation (10.3 years vs. 7.2 years, P = 0.04). In the HV group, 92% had bone metastases, 60% had lymph node involvement, 54% had both, and 35% had visceral metastases. In the LV group, 64% had bone metastases, 84% had lymph node involvement, 25% had both, and none had visceral metastases. Median OS was 14.4 months for HV patients and 17.6 months for LV patients (P < 0.0001). Median PSA-PFS was 11.4 months for HV patients and 13 months for LV patients. Median rPFS was 9.1 months for HV patients and 10.6 months for LV patients. PSA-RR significantly differed between groups (P < 0.0001). In the HV group, 20% achieved CR (PSA < 0.2 ng/mL), 29% had PR (PSA decreased by ≥50%), 16% experienced SD, and 35% had PD (PSA increased ≥25% from nadir). In contrast, the LV group had 51% achieving CR, 10% achieving PR, 18% with SD, and 11% with PD. Conclusions: Lower disease volume in mCRPC is strongly associated with improved outcomes following 177 Lu-PSMA-617 therapy. These findings suggest that tumor burden is a key predictor of response to PSMA radioligand therapy.

Prostate cancer lung metastasis represents a clinical conundrum due to its implications for advanced disease progression and the complexities it introduces in treatment planning. As the disease progresses to distant sites such as the lung, the clinical management becomes increasingly intricate, requiring tailored therapeutic strategies to address the unique characteristics of metastatic lesions. This review seeks to synthesize the current state of knowledge surrounding prostate cancer metastasis to the lung, shedding light on the diverse array of clinical presentations encountered, ranging from subtle radiological findings to overt symptomatic manifestations. By examining the diagnostic modalities utilized in identifying this metastasis, including advanced imaging techniques and histopathological analyses, this review aims to provide insights into the diagnostic landscape and the challenges associated with accurately characterizing lung metastatic lesions in prostate cancer patients. Moreover, this review delves into the nuances of therapeutic interventions employed in managing prostate cancer lung metastasis, encompassing systemic treatments such as hormonal therapies and chemotherapy, as well as metastasis-directed therapies including surgery and radiotherapy.

Abstract Background The objective of this study was to evaluate the prognostic value of early PSA decline following initiation of second-generation hormone therapy (2nd HT), namely abiraterone acetate or enzalutamide, in patients with taxane-refractory metastatic castrate-resistant prostate cancer (mCRPC) and evaluate utility of this metric in informing intensified surveillance/imaging protocols. Methods We retrospectively identified 75 mCRPC patients treated with 2nd HT following docetaxel failure (defined as PSA rise and radiographic progression). Patients were categorized patients into two cohorts based on the first PSA within 3 months after initiation of therapy: PSA reduction ≥ 50% (Group A) and PSA reduction < 50% (Group B). The primary endpoint was cancer-specific mortality (CSM). The secondary endpoint was radiographic disease progression (rDP) on 2nd HT. In univariate and multivariate analyses, we investigated factors associated with rPD and CSM. Results We included 75 patients (52 in Group A, 23 in Group B) in the analytic cohort. Baseline clinico-demographic characteristics, including median age, primary Gleason score risk group, median pre-treatment PSA, disease burden, site of metastases, and pre-treatment ECOG score were not statistically different between the two groups. Median follow up time was 30 months and the median time to radiographic disease progression was 28.1 and 12.5 months (p = 0.002) in cohorts A and B, respectively. On univariate and multivariate analyses, both PSA reduction ≥ 50% and volume of metastatic disease were significantly associated with a decreased risk of radiographic disease progression (HR 0.41, 95% CI 0.21–0.80, p = 0.0113) as well as a decreased risk of cancer-specific mortality (HR 0.29, 95% CI 0.09–0.87, p = 0.0325). Conclusion PSA reduction ≥ 50% within 3 months of starting 2nd HT was associated with significantly improved radiographic disease progression-free survival and 3-year cancer-specific mortality. This suggests using PSA 50%-decline metric in surveillance patients with on 2nd HT and identifies patients who require further evaluation with imaging.

192 Background: In the setting of disease progression of metastatic castrate resistant prostate cancer (mCRPC) on docetaxel, abiraterone acetate (AA) and enzalutamide are two commonly used second line therapies with data demonstrating survival benefits. Less is known about patient specific factors that contribute to success with these therapies. The objective of this study is to improve patient selection for post-docetaxel second generation hormone therapy (AA or enzalutamide) by evaluating whether overall metastatic burden is associated with treatment response in this setting. Methods: By retrospective chart review, patients with mCRPC treated with AA or enzalutamide following docetaxel failure (defined as PSA rise and radiographic progression) were identified. Patients were categorized into low volume and high volume metastatic disease based on the number of pre-treatment metastatic lesions; where low volume disease describes patients with ≤ 5 metastatic lesions (e.g. oligometastatic disease), and high volume disease represents patients with > 5 individual lesions. The primary endpoint was cancer-specific mortality and the secondary endpoint was radiographic progression free survival. Median follow-up time was 29.5 months. Results: 75 patients were identified and included in our analysis: 39 with high volume metastatic disease, and 36 with low volume metastatic disease. Baseline characteristics of age and pre-treatment ECOG were not statistically different between these groups. Pre-treatment high-volume disease burden was significantly associated with increased risk of radiographic disease progression (HR 4.21, 95%CI 1.97-8.99, p < 0.0001) and cancer specific mortality (HR 5.84, 95% CI 1.58-21.53, p = 0.0026) during treatment with second generation androgen deprivation therapy. Conclusions: High volume metastatic disease burden is associated with significantly increased cancer specific mortality and decreased progression free survival for patients on second line therapy with AA or enzalutamide following docetaxel treatment failure.

189 Background: The objective of this study is to evaluate the prognostic value of early PSA decline following initiation of second-generation hormone therapy (2nd HT), namely abiraterone acetate or enzalutamide, in the post-chemotherapy setting in patients with metastatic castrate-resistant prostate cancer (mCRPC). Methods: We retrospectively identified 75 m-CRPC patients treated with 2nd HT following docetaxel failure (defined as PSA rise and radiographic progression). Patients were categorized into two groups based on first PSA within 3 months after initiation of therapy: PSA reduction ≥ 50% (Group A) and PSA reduction < 50% (Group B). The primary endpoint was cancer-specific mortality and the secondary endpoint was radiographic progression free survival. Results: There were 75 patients (52 in group A, 23 in group B) in the analytic cohort. Baseline clinical and demographic characteristics, including median age, primary Gleason score risk group, median pre-treatment PSA, disease burden, site of metastases, and pre-treatment ECOG score were not statistically different between the two groups. PSA reduction ≥50% was significantly associated with decreased risk of radiographic disease progression (HR 0.41, 95%CI 0.21-0.80, p = 0.0113) as well as decreased risk of cancer-specific mortality (HR 0.29, 95%CI 0.09-0.87, p = 0.0325). Conclusions: PSA reduction ≥50% within 3 months of starting 2nd HT for patients with mCRPC who have failed first-line docetaxel is associated with significantly improved 3-year cancer-specific mortality and progression free survival. Our data supports the use of PSA as an early prognosticating marker for patient outcomes on this second line therapy. [Table: see text]

AbstractBackgroundThe clinical course in metastatic castrate‐resistant prostate cancer (mCRPC) can be complicated when patients have disease progression after prior treatment with second generation hormone therapy (second HT), such as enzalutamide or abiraterone. Currently, limited data exist regarding the optimal choice of chemotherapy for mCRPC after failing second generation hormone therapy. We sought to evaluate three common chemotherapy regimens in this setting.MethodsWe retrospectively identified 150 mCRPC patients with disease progression on enzalutamide or abiraterone. Of these 150 patients, 92 patients were chemo‐naïve while 58 patients had previously received docetaxel chemotherapy before being started on second HT. After failing second HT, 90 patients were assigned for docetaxel‐alone (group A), 33 patients received carboplatin plus docetaxel (group B), while 27 patients received cabazitaxel‐alone (Group C). A favorable response was defined by more than or equal to 50% reduction in prostate‐specific antigen from the baseline level after a complete course of chemotherapy. Survival outcomes were assessed for 30‐month overall survival.ResultsPatients in group (B) were 2.6 times as likely to have a favorable response compared to patients in group (A) (OR = 2.625, 95%CI: 1.15‐5.99) and almost three times compared to patients in group (C) (OR = 2.975, 95%CI: 1.04–8.54) (P = .0442). 30‐month overall survival was 70.7%, 38.9% and 30.3% for group (B), (A), and (C), respectively (P = .008). We report a Hazard Ratio of 3.1 (95% CI, 1.31‐7.35; P = .0037) between patients in group (A) versus those in group (B) and a Hazard Ratio of 4.18 (95% CI, 1.58‐11.06; P = .0037) between patients in group (C) compared to those in group (B)ConclusionThis data demonstrates improved response and overall survival in treatment‐refractory mCRPC with a chemotherapy regimen of docetaxel plus carboplatin when compared to docetaxel alone or cabazitaxel alone. Further investigations are required.

143 Background: Systemic treatment in the management of metastatic prostate cancer is inevitable. However, there is a growing interest in metastases-directed therapy (MDT). We sought to investigate the efficacy of MDT in treating patients with solitary metastatic prostate cancer and hence, delaying initiation of systemic treatment (i.e., Androgen deprivation therapy or chemotherapy). Methods: We retrospectively identified 61 patients treated with targeted therapy in the form of surgery (n = 30), stereotactic body radiation therapy (SBRT) (n = 25), or cryotherapy (n = 7) for their solitary metastases prostate cancer. Complete response was defined by achieving a PSA value of ≤0.2 ng/ml plus resolution of the solitary metastatic lesion on C-11 choline PET choline scan, while incomplete response was defined by a residual PSA of > 0.2 ng/ml and/or radiographic evidence of disease following metastases-targeted therapy. Results: Mean (±SD) age was 68.4 (±7.8) yrs., median (IQR) primary Gleason Score was 7 (7-9) and median (IQR) pre-MDT PSA was 2 (1.3-3.8) ng/ml. Median (IQR) time from primary treatment of the prostate to MDT was 5.1 (2.7-10.1) years. None of the patients were on hormone therapy at the time of presentation with solitary metastases prostate cancer. 30 patients had bone metastases, 29 patients had lymph node metastases, 1 patient had soft tissue metastasis (pelvic metastatic mass), and another patient had visceral metastasis (to the lung). 42% of the patients (n = 26) achieved complete response to targeted therapy. Median time to initiation of 2nd line systemic treatment following MDT was 17.8 months for the complete responders versus 9.3 months for incomplete responders. 11% of the patients (n = 7) did not require 2nd line therapy after their MDT for a mean (±SD) time of 56.9 (±22.5) months. Conclusions: The use of targeted therapy in the management of patients with solitary metastatic disease or low-volume metastatic disease can provide comparable outcomes to those of systemic treatment. Further studies are warranted.