Background Radium-223 (Ra-223) has been approved for the treatment of metastatic castration-resistant prostate cancer (mCRPC) with predominant osseous metastases. PSA flare phenomenon with Ra-223 limits its use as a prognostic tool to predict treatment response. Currently, there is a lack of diagnostic tools to predict treatment response to Ra-223. Therefore, we sought to investigate the role of mid treatment C-11 choline PET/CT scan in predicting overall response to Ra-223. In a single institute retrospective study, we identified 32 patients who were treated with a full course of 4-6 cycles of Ra-223 and were evaluated with PSA, and C-11 choline PET scan before treatment, at mid-treatment point, and after complete course of Ra-223 between 2013 and 2018. Ra-223 was used as a salvage therapy for their predominant bone disease after failing chemotherapy and 2nd generation hormone therapy. Blind repeat radiographic evaluation of patients' scans has been done by a radiologist specialized in nuclear medicine. Favorable response was defined by achieving partial response or stable disease on imaging, while unfavorable response was defined by showing progressive disease on imaging. Results Mean age (+/- SD) at starting Radium223 was 67.6 (+/- 7.1) years, median (IQR) primary Gleason score was 9 (8-9), and median (IQR) pretreatment PSA was 13.5 (5.4-39.6) ng/ml. 78% of the patients (n = 25) completed 6 cycles of Ra-223, and 15% of the patients (n = 5) completed 5 cycles while 6% (n = 2) received only 4 cycles. At mid treatment scanning, 25% of the patient (n = 8) showed favorable response (Group A), while 75% of the patients (n = 24) showed unfavorable response (B). After complete course of treatment, 50% of patients (n = 4) in Group (A) continued to show favorable response, versus only 8.3% of patients (n = 2) in Group (B) showed favorable response (p-value = 0.023). Conclusion Mid treatment evaluation with C-11 choline PET/CT scan can predict overall response to Radium 223. Patients with progressive disease at mid- treatment evaluation are very likely not going to respond to their treatment. Further studies and clinical trials are warranted.

Pleomorphic giant cell carcinoma (PGCC) of the prostate is an extremely rare and aggressive malignancy with limited treatment options. We present a case report of metastatic PGCC patients treated with 177Lu-PSMA-617 radioligand therapy (Pluvicto) after progression on standard therapies. Both patients had PSMA-avid tumors on imaging. Molecular profiling revealed mutations in hallmark tumor suppressors including TP53, RB1, and PTEN. Both patients initially experienced partial radiographic response, in which one patient achieved stable disease for 9 months posttherapy. These findings suggest that PSMA-radioligand therapy may be a reasonable treatment for PGCC patients, but underscore the need for additional therapeutic options.

Aims Schistosomiasis remains endemic in various parts of the world, and insights into pathogen immunobiology are mainly based on experimental models, while studies on human tissues are limited. Methods We explored the role of immune checkpoint pathway by evaluating the immunohistochemical expression of programmed death-ligand 1 (PD-L1) in a retrospective cohort of patients with bilharzial cystitis. Inflammation severity by conventional histology and staining intensity by immunohistochemistry were assigned three-tier scores (0/1+/2+), and a cut-off for staining percentage was set at 5%. Results 38 biopsies from 31 patients were considered adequate for evaluation, and positive staining was detected in 80.6% of patients (34 biopsies). High expressors (22.6%) showed strong positive membranous staining (score 2+) with high staining density (more than 5% of inflammatory cells). Low expressors (58.1%) showed mild/moderate staining (score 1+) predominantly in less than 5% of the cells (91.6%) or expressed restricted cytoplasmic staining (6/31). All high expressors showed severe inflammation (score 2+) (p<0.001), and viable ova were only observed in these cases. Calcified ova were associated with mild/moderate inflammation or absent/minimal inflammation, correlating with low expressors or non-expressors (19.4%), respectively. Conclusion Schistosomal granuloma exhibits upregulated PD-L1 expression proportional to inflammation severity and pathogen viability, highlighting a critical immune checkpoint engagement in disease pathology.

PurposeRadioligand therapy (RLT) with [177Lu] Lu-PSMA-617 has shown significant benefits in metastatic castration-resistant prostate cancer (mCRPC), including prolonged overall survival (OS) and progression-free survival (PFS), as well as improved quality of life. For patients previously treated with [177Lu]Lu-PSMA-617 who subsequently experience disease progression, retreatment with [177Lu] Lu-PSMA-617 has emerged as a potential approach, yet data on the outcomes of RLT retreatment remains limited. This study aimed to assess the efficacy and safety of retreatment RLT in mCRPC.MethodsClinical and imaging data of patients who underwent at least two cycles of [177Lu] Lu-PSMA-617, followed by a second course of treatment with [177Lu] Lu-PSMA-617 between March 2018 and December 2024, were retrospectively reviewed. Endpoints included biochemical response, imaging response, toxicity, PSA-PFS, rPFS, and OS. Radiologic and biochemical responses were evaluated using RECIST 1.1 criteria and PSA levels, respectively.ResultsA total of 589 patients underwent [177Lu] Lu-PSMA-617 RLT, of whom 20 (3.4%, 20/589) received RLT retreatment. The median age was 71.3 years (range: 63.7–95.2), and the median follow-up was 73.3 months (95% CI, 35.7–77.2 months) after the initial treatment and 21.7 months (95% CI, 16.9–26.0 months) after retreatment. The initial treatment involved a median of 4.5 cycles (range: 2–6). Following the first course of RLT, 15 patients (75%, 15/20) had exhibited a >50% decline in PSA levels, including 9 who achieved a >90% decrease. Additionally, 12 patients (60%, 12/20) had demonstrated a complete or partial imaging response, while 3 (15%, 3/20) patients had stable disease, and 5 (25%, 5/20) patients had progressive radiologic disease. Patients received a median of 4 retreatment cycles (range, 1–6), and the median interval between initial RLT and retreatment RLT was 33.1 months (IQR, 16.2–48.9 months; range, 10.7–58.8 months). A PSA decline of ≥50% was observed in 9 out of 20 patients (45%, 9/20). An imaging response was observed in 10 patients (50%, 10/20), with 4 achieving a complete response and 6 achieving a partial response, whereas 10 patients (50%, 10/20) showed progression. The median PSA-PFS was 9.8 months (95% CI, 4.1–17.9 months), and the median rPFS was 8.2 months (95% CI, 3.3–17.9 months). Eight deaths occurred during follow-up. The estimated Kaplan Meier OS rates were 83.6% at 12 months (95% CI, 57.3%–94.4%) and 53.7% at 24 months (95% CI, 28.3%–73.7%). Grade 2 renal toxicity was observed in one patient (5%, 1/20). Three patients (15%, 3/20) developed Grade 2 anemia. Notably, no grade 3 or grade 4 adverse events were observed during either treatment period.ConclusionIn our cohort, retreatment with [¹77Lu]Lu-PSMA-617 RLT was associated with biochemical and imaging responses in some patients, with observed survival outcomes that support further investigation. However, given the retrospective single-arm design and small sample size, large prospective studies are needed to more rigorously evaluate the safety, efficacy, and optimal patient selection for retreatment RLT.

Purpose This study investigates the prognostic impact of metastatic disease volume on clinical outcomes in metastatic castration-resistant prostate cancer (mCRPC) patients treated with [& sup1;Lu-7(7)]Lu-PSMA-617 radioligand therapy ([Lu-177]Lu-PSMA-617 RLT), aiming to refine patient selection and optimize treatment strategies. Methods This study included 264 mCRPC patients who received a taxane-based therapy and at least one cycle of [Lu-177]Lu-PSMA-617 RLT at Mayo Clinic between October 2017 and February 2024. Patients were stratified into high-volume (n = 176) or low-volume (n = 88) disease groups per CHAARTED criteria (visceral metastases or >= 4 skeletal lesions, with one beyond the vertebral bodies/pelvis). Primary endpoints were overall survival (OS) and PSA response rate (PSA-RR, >= 50% PSA decline), with secondary endpoints of PSA progression-free survival (PSA-PFS) and radiographic progression-free survival (rPFS). Statistical differences between the two sub cohorts were assessed using the Mann-Whitney U test. Kaplan-Meier analysis and Cox proportional hazard models assessed survival differences. Univariable and multivariable Cox proportional hazards regression analyses were performed to evaluate prognostic factors. A two-sided p-value < 0.05 was considered statistically significant. All statistical analyses were performed using R statistical software. Results The median age was 71 years in both cohorts. Low-volume patients exhibited superior OS (median 68.1 vs. 27.5 months, p < 0.05) and PSA-RR (71% vs. 55%, p < 0.0001) compared to high-volume patients, with a trend toward improved rPFS (19 vs. 12 months, p = 0.04) and PSA-PFS (21 vs. 13 months, p = 0.01). Multivariable Cox regression analysis identified selected clinical variables as significant prognostic factors for survival outcomes. Baseline PSA, hemoglobin, and alkaline phosphatase levels also differed significantly between groups (p < 0.0001). The median follow-up time was 14.8 months. Conclusion Metastatic disease volume significantly affects [Lu-177]Lu-PSMA-617 RLT outcomes, with low-volume patients showing better survival and response. While both groups benefited, high-volume patients' poorer prognosis suggests reduced efficacy, possibly due to tumor heterogeneity or tumor sink effect. Volume-based stratification could optimize therapy, with combination strategies warranting further study to improve high-volume mCRPC outcomes.

BACKGROUND AND OBJECTIVE:Salvage lymph node dissection (sLND) is a treatment for prostate cancer patients with lymph node recurrence. However, there is a lack of comprehensive data regarding subsequent patterns of recurrence and long-term survival outcomes. This study aims to explore those patterns of recurrence following sLND in patients with oligorecurrent disease. Additionally, we investigate factors associated with disease progression after sLND. METHODS:Utilizing the prospectively maintained C11 choline positron emission tomography (PET)/computed tomography (CT) scan registry, we identified patients who underwent salvage lymph node dissection for oligorecurrent disease detected by C11 choline PET/CT. Primary objective was to characterize the patterns of recurrence after sLND. Recurrence sites following the procedure were classified into 3 categories: local recurrence, locoregional lymph node recurrence, and progression to distant metastatic spread. Secondary objective was to identify factors associated with disease progression to distant metastases. The median follow-up duration was 111 months. RESULTS:We identified 152 patients who underwent sLND for nodal recurrence prostate cancer. At time of sLND, the median (interquartile range [IQR]) age was 65 years (59.4-70.6), median (IQR) prostate-specific antigen of 2.1 ng/dl (1.3-3.9), and 27% of patients had castration-resistant prostate cancer. The median (IQR) number of lymph nodes dissected was 18 (12-27), while the median (IQR) number of positive lymph nodes was 3 (1-5). The anatomical distribution of sites of recurrence after sLND demonstrated approximately 6.4% of local recurrence in the prostate bed, 34.5% of loco-regional nodal recurrent, and 59% metastatic disease. In univariable and multivariable analyses of factors associated with disease progression to metastatic disease, only the number of positive lymph nodes at sLND was associated with increased risk of progression to distant metastatic disease with 14% increased risk for each positive lymph node. CONCLUSIONS:The role of sLND in patients with oligorecurrent disease remains investigational. Recurrence is anatomically diverse, including progression to distant metastatic disease. The number of positive nodes at sLND serves as a useful predictor of progression and can help guide decisions on adjuvant therapies, supporting a more personalized postoperative approach.

INTRODUCTION:Advanced prostate cancer treatments carry substantial financial toxicity, which may be mitigated by generic alternatives. We characterize Medicare spending trends on branded vs generic abiraterone to estimate the impact of generic adoption on cost and access. METHODS:Medicare Part D data (2013-2023) were analyzed for all abiraterone formulations and compared with enzalutamide, which carries similar indications but no generic alternative. Annual percent change (APC) was analyzed using joinpoint regression. RESULTS:Generic abiraterone became available in 2018. Medicare spending on all abiraterone formulations increased from $470 million to $1.5 billion from 2013 to 2018 (APC 19.3%, P = .02) and then decreased from $1.5 billion to $910 million from 2018 to 2023 (APC -10.4%, P = .06). From 2013 to 2023, the number of beneficiaries receiving abiraterone annually increased from 14,188 to 46,411 (APC 12.3%, P < .01). From 2013 to 2017, the annual cost per beneficiary grew from $33,094 to $48,978 (APC 12.2%, P = .02) and then decreased to $19,610 in 2023 (APC -17.7%, P < .01). The per-refill cost of generic abiraterone decreased significantly after its introduction in 2018 (APC -17.2%, P = .01). Generic abiraterone adoption yielded total Medicare cost savings of $7.3 billion from 2018 to 2023. By contrast, enzalutamide displayed steady increases in total Medicare spending (APC 18.5%, P < .01) and per-beneficiary cost (APC 9.3%, P < .01) throughout the study period. CONCLUSIONS:Generic abiraterone adoption led to significant reductions in Medicare spending and cost per beneficiary, while maintaining a trend of increased utilization. These benefits were not seen with enzalutamide, which does not have a generic alternative. These findings underscore the importance of timely generic entry in controlling Medicare spending while preserving access to life-prolonging therapeutics.

This study investigates the prognostic impact of metastatic disease volume on clinical outcomes in metastatic castration-resistant prostate cancer (mCRPC) patients treated with [¹⁷⁷Lu]Lu-PSMA-617 radioligand therapy ([177Lu]Lu-PSMA-617 RLT), aiming to refine patient selection and optimize treatment strategies. This study included 264 mCRPC patients who received a taxane-based therapy and at least one cycle of [177Lu]Lu-PSMA-617 RLT at Mayo Clinic between October 2017 and February 2024. Patients were stratified into high-volume (n = 176) or low-volume (n = 88) disease groups per CHAARTED criteria (visceral metastases or ≥ 4 skeletal lesions, with one beyond the vertebral bodies/pelvis). Primary endpoints were overall survival (OS) and PSA response rate (PSA-RR, ≥ 50

Purpose/objectives:Metastasis directed therapy (MDT) with stereotactic body radiotherapy (SBRT) has demonstrated clinical benefit among select oligometastatic prostate cancer (PCa) patients. The outcomes of SBRT to the left supraclavicular lymph nodes (SCLNs) are examined. Materials/methods:Between 2017 and 2024, 16 (3.8%) of 419 patients with PCa metastatic to lymph nodes were found by prostate-specific PET to have SCLN involvement. Survival, relapse patterns, and toxicity are analyzed. Results:At initial PCa diagnosis, median PSA was 6.7 ng/mL (range 2.1-315) with 50% of patients having Gleason score of 8-10. Mean time from initial diagnosis to SCLN metastasis was 10.4 years with median PSA of 2.0 ng/mL and median number of involved SCLNs of 1.5 (range 1-10). The most common fractionation scheme was 35 Gy in 5 fractions daily (44%) with 81% of patients receiving concurrent hormonal therapy. No grade ≥ 2 toxicities were reported. Local relapse-free survival at 5 years was 90.9%. Mean distant progression-free survival was 16.7 months (95% CI: 7.9-25.5). Mean prostate cancer-specific survival (PCSS) and overall survival were 4.6 years (95% CI: 3.6-5.6) and 4.0 years (95% CI: 2.8-5.1), respectively. Patients with castration-sensitive disease had 100% 5-year PCSS, and 58.3% for those with mCRPC. Conclusion:SBRT to SCLNs was well tolerated with no significant toxicity. Durable local control was satisfactory. The presence of SCLN metastases is frequently a harbinger of additional metastatic progression which suggests that patients require close monitoring and could benefit from the addition or intensification of systemic therapy.

Radium-223 (Ra-223) has been approved for the treatment of metastatic castration-resistant prostate cancer (mCRPC) with predominant osseous metastases. PSA flare phenomenon with Ra-223 limits its use as a prognostic tool to predict treatment response. Currently, there is a lack of diagnostic tools to predict treatment response to Ra-223. Therefore, we sought to investigate the role of mid treatment C-11 choline PET/CT scan in predicting overall response to Ra-223. In a single institute retrospective study, we identified 32 patients who were treated with a full course of 4–6 cycles of Ra-223 and were evaluated with PSA, and C-11 choline PET scan before treatment, at mid-treatment point, and after complete course of Ra-223 between 2013 and 2018. Ra-223 was used as a salvage therapy for their predominant bone disease after failing chemotherapy and 2nd generation hormone therapy. Blind repeat radiographic evaluation of patients’ scans has been done by a radiologist specialized in nuclear medicine. Favorable response was defined by achieving partial response or stable disease on imaging, while unfavorable response was defined by showing progressive disease on imaging. Mean age (± SD) at starting Radium223 was 67.6 (± 7.1) years, median (IQR) primary Gleason score was 9 (8–9), and median (IQR) pretreatment PSA was 13.5 (5.4–39.6) ng/ml. 78

To identify imaging and clinical features that aid in distinguishing metastatic lesions from benign or physiologic uptake on PSMA PET, using correlation with scrotal ultrasound. This IRB-approved retrospective study included prostate cancer (PCa) patients who underwent PSMA PET-CT or PET-MRI between July 2021 and May 2025, with a scrotal ultrasound performed within 100 days of the scan. PSMA-avid lesions were assessed for uptake intensity (mild vs. intense), distribution (diffuse vs. focal), laterality (unilateral vs. bilateral), scan indication (initial staging vs. restaging), and SUVmax. Ultrasound findings were reviewed, and metastasis was confirmed by pathology or clinical consensus by three board-certified radiologists. Multivariable logistic regression using LASSO was performed to identify predictors of testicular or paratesticular metastasis. Of 114 patients (mean age 70), 24 (21

INTRODUCTION/BACKGROUND:Approval of [177Lu]Lu-PSMA-617 has changed the usual sequencing of treatments for metastatic castration-resistant prostate cancer (mCRPC). There is limited data on outcomes and safety of therapies used after its administration. METHODS:We conducted a retrospective, multi-institutional analysis including patients with mCRPC who received Radium-223 (Ra-223) after [177Lu]Lu-PSMA-617. Patients from Mayo Clinic and Dana-Farber Cancer Institute were evaluated for multiple efficacy and tolerability endpoints, with particular attention given to hematologic toxicities and skeletal-related events. RESULTS:Among 21 patients analyzed, 19% (n = 4) completed all 6 planned Ra-223 cycles. Reasons for early treatment discontinuation included: disease progression (n = 13, 62%) and toxicity (n = 2, 10%). Hematologic toxicity included grade ≥ 3 anemia and thrombocytopenia in 33% (n = 7) and 19% (n = 4) of patients, respectively, and 38% (n = 8) required transfusions, all of which occurred within 30 days following the final Ra-223 cycle. Four patients (19%) developed new skeletal-related events after starting Ra-223. One PSA50 response was observed and ≥ % reduction in alkaline phosphatase levels occurred in 42% of patients (n=9). The median PSA progression-free survival was 2.5 months (95% CI; 1.4 - 3.8 months). The median overall survival was 10.6 months (95% CI; 5.2 - 20.4 months) and 76% (n = 16) of patients survived six months beyond their first dose of Ra-223. CONCLUSION:These data suggest that Ra-223 after [177Lu]Lu-PSMA-617 is feasible with efficacy even amongst heavily pre-treated patients. The observed hematologic toxicities and fractures underscore the need for careful patient selection and monitoring.

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.

BACKGROUND:Circulating tumor DNA (ctDNA) genomic testing is increasingly used in advanced prostate cancer (aPC) to identify actionable alterations, however the longitudinal nature of tumor mutation burden (TMB) remains poorly characterized. Current guidelines recommend somatic testing at diagnosis of metastatic hormone-sensitive or castration-resistant disease, but do not address serial testing. While prior studies suggest modest increases in TMB with advanced disease, longitudinal trends and treatment-associated changes have not been systematically examined. Here we evaluate how TMB changes over time and in relation to treatment exposures in a large real-world aPC cohort. METHODS:We retrospectively identified 714 men with aPC who underwent ≥ 1 ctDNA-based genomic profiling test with evaluable TMB between November 2018 and May 2025. For patients with multiple tests, sequential TMB values were mapped to discrete treatment episodes, used as a surrogate for lines of therapy. Univariable linear mixed-effects models with fixed effects for timeframe and treatment exposures, and random intercepts for repeated measurements, assessed associations between TMB, episode number, age, individual therapies, and treatment combinations. An exploratory multivariable mixed-effects model was also performed. RESULTS:Median age at diagnosis was 63.3 years (interquartile ranges [IQR] 56.8-69.0); median prostate specific antigen 13.9 ng/mL (IQR 6.8-60.9). Median first-test TMB was 7.8 mutations per megabase (mut/Mb) (IQR 4.8-11.2). TMB increased significantly across episodes (P = .001). Age was associated with higher TMB (+ 0.20 mut/Mb per year, P < .0001). In univariable analyses, radiotherapy (RT) was associated with higher TMB (+ 1.9 mut/Mb, P = .004). In multivariable models adjusting for age and treatment episode, RT remained associated with higher TMB (+ 2.4 mut/Mb, 95% confidence intervals 1.1-3.7; P = .0004). Combination regimens, particularly androgen deprivation therapy + androgen receptor pathway inhibitors + RT, were associated with marked increases in absolute TMB. CONCLUSIONS:We demonstrate that TMB is dynamic and rises over time and with select treatment exposures. These findings reinforce how TMB should be interpreted within the broader context and not necessarily viewed as a standalone threshold for initiating immunotherapy in advanced prostate cancer.