Citations

114 Background: Oncologists have traditionally relied upon serial assessments of PSA and periodic imaging (i.e., every 2 to 3 cycles) to monitor treatment response. Early identification of disease progression allows for faster transitions to alternative therapies that might be more effective. In this study, we evaluated the utility of post-treatment SPECT/CT for earlier detection of treatment failure in patients receiving Lutetium-177–PSMA-617 (LuPSMA). Methods: We queried an IRB-approved registry including all patients starting LuPSMA at Mayo Clinic, MN, in the interval of March 2022 to March 2023. Those receiving fewer than 2 cycles of treatment and missing SPECT/CT data were excluded. We reviewed clinical notes to document the date and reason(s) for treatment discontinuation. The assembled cohort consists of patients stopping LuPSMA for progressive disease ([PD], categorized as biochemical, radiographic, or both). Results of the prior SPECT/CT imaging reports were reviewed. At our institution SPECT/CT images are typically acquired on the day after each infusion. Metrics collected from the radiology reports included: new foci of PSMA localization since the prior PSMA PET or SPECT/CT, suspicion for new non-PSMA avid disease, and a visual determination of PSMA-avid tumor volume. Results: A total of 256 patients received an initial cycle of LuPSMA. SPECT/CT imaging data for at least 2 consecutive treatment cycles was available for 68 patients who developed PD after a median (IQR) of 3 (2-4) cycles. There were 55 patients (81%) with both biochemical and radiographic evidence of PD, 7 (10%) with biochemical only progression, and 6 (9%) with radiographic only progression. The most used imaging modality for response assessment was PSMA PET/CT (n=46, 67%), followed by conventional imaging (n=9, 13%), and choline PET/CT (n=5, 7%). The median time between most recent post-therapy SPECT/CT and determination of PD was 39 days. The prior SPECT/CT had detected new foci of PSMA avid disease in 12 (18%) cases and new non-PSMA avid disease in 5 (7%) cases. Two patients had both new PSMA-avid and non-PSMA avid lesions. The most common sites of new PSMA-avid disease on SPECT/CT were bone (n=10) and liver (n=2). A total of 20 (29%) patients had visually increased tumor volume on SPECT/CT, 9 (45%) of which had no new lesions. In total, 24 of 68 patients (35%) had early detection of treatment futility detected by SPECT/CT. At a median (IQR) follow-up time of 8 (6.4-12) mo, the median OS [95% CI] was similar for patients with PD detected on SPECT/CT (7.8 [6.6 – 9] mo) compared to those without clear evidence of PD on SPECT/CT(8.4 [6.4-10.3] mo, p=0.885). Conclusions: Post-treatment SPECT/CT imaging may complement traditional forms of response assessment and provide an earlier warning of treatment failure through identification of new PSMA-avid lesions, non-PSMA avid disease, and increased tumor volume.

112 Background: We now have more than a decade of experience using Androgen Receptor Pathway Inhibitors (ARPIs) across various disease states of prostate cancer, and the safety of their combination with Lutetium-177–PSMA-617 has been demonstrated in VISION and other large randomized clinical trials. However, real-world data on treatment patterns and outcomes involving combination therapies with 177 Lu-PSMA-617 remain limited. Methods: For this analysis, we utilized the Mayo Clinic Rochester radiopharmaceutical database, a prospectively maintained retrospective database containing all patients who received 177 Lu-PSMA-617 at our institution. We focused on patients who started treatment from March 2022 to March 2023. Patients receiving an ARPI (abiraterone acetate, enzalutamide, apalutamide, or darolutamide) during the course of 177 Lu-PSMA-617 treatment were identified, inclusive of patients who continued using an ARPI prescribed as a prior line of treatment and those who started (i.e., switched) to a new ARPI. Baseline clinicopathologic and imaging characteristics were abstracted and compared using the Mann-Whitney U and Chi-square tests. Best PSA response during treatment was reported as a percent decline from baseline. Survival was calculated from the date of the first cycle of 177 Lu-PSMA-617. PSA50 response and overall survival (OS) outcomes for the two groups (concurrent use of ARPI vs. 177 Lu-PSMA-617 alone) were compared using the Chi-square test and Kaplan-Meier method, respectively. A multivariate Cox regression analysis was performed, including established prognostic factors. Results: An ARPI was prescribed to 106 of the 256 patients (41.4%) starting 177 Lu-PSMA-617 in the interval of March 2022 to March 2023. With regards to baseline characteristics, those receiving an ARPI concurrently with 177 Lu-PSMA-617 had a lower PSA (3.4 vs 29.7 ng/mL, p < 0.001) and a lower frequency of bone (77.4% vs. 87.4%, p = 0.035) and visceral metastases (18.9 vs 34%, p = 0.008) at start of treatment. Median follow-up for the overall cohort (IQR) was 19.1 months (8.7 – 23.6). Patients receiving an ARPI plus 177 Lu-PSMA-617, as compared to 177 Lu-PSMA-617 alone, were more likely to complete all 6 planned doses of treatment (63.2% vs. 48.7%, p < 0.001), though the PSA50 response rate was similar (49.1% vs 47.3%, p = 0.786). Median OS [95% CI] for the overall cohort was 21.3 [16.7 – 25.9] months and significantly longer for those receiving ARPI with 177 Lu-PSMA-617 (NR [NE – NE]) as compared to 177 Lu-PSMA-617 alone (15.3 mo [11.6 – 19.1], p < 0.001). However, on multivariate analysis including known prognostic variables, use of ARPI was not independently associated with improved survival (HR = 1.03 [CI: 0.68 to 1.55], p = 0.891). Conclusions: Patients receiving an ARPI with 177 Lu-PSMA-617 were more likely to complete all 6 cycles of treatment, but no clear differences in survival were observed on multivariate analysis.

387 Background: Level 1 evidence supports treatment of high-risk and node positive PCa using 4-9 weeks of radiotherapy (RT) combined with 18-36 months of androgen deprivation therapy (ADT) with or without abiraterone acetate plus prednisone (AAP). While effective, some cancers recur, and this prolonged treatment is associated with inconvenience and variable morbidity. We aimed to determine whether the biological synergy of stereotactic body radiotherapy (SBRT) with a 6-month combination of ADT, AAP, and the PARP inhibitor niraparib, could enable a shorter intensified, yet safe and effective, therapeutic alternative. Methods: ASCLEPIuS (NCT04194554) is a multicenter investigator-initiated phase I/II trial in high-risk or node positive, homologous recombination unselected, PCa. Patients received 6 months of ADT, AAP, niraparib and SBRT to the prostate (37.5-40 Gy) +/- pelvic lymph nodes (25 Gy). Focal prostate/nodal boosting was permitted. The phase I primary endpoint was the maximum tolerated dose (MTD) of niraparib using the time-to-event continuous reassessment method (3 dose levels: 100 mg and 200 mg held during SBRT, or 200 mg concurrent with SBRT). Dose limiting toxicities (DLT) were any persistent grade 4+ hematologic toxicity or any grade 3+ rectal/urinary toxicity at least possibly related to treatment as assessed by CTCAE v5.0. Patient reported quality of life (QOL) was assessed with the EPIC-26 short form. Linear mixed models were used to compare scores over time. Results: Accrual began in Nov. 2020 with a transition from phase I to phase II in May 2023 after enrolling 54 men. Median follow-up of the phase I cohort is 12.1 months (IQR 9.4-18.9), 80% (n=43) had Grade Group 4-5, median PSA was 17 ng/mL (range, 1-73), 15% (n=8) had cN+ disease, and 76% (n=41) received nodal RT. There were 0 DLTs to date, no grade 3+ rectal or urinary toxicities, and 5 serious adverse events at least possibly attributable to study treatment (anemia, non-rectal gastrointestinal, syncope, infection, musculoskeletal). The most common grade 3 toxicities were hypertension (n = 11, 21%) and leukopenia (n=6, 11%). Transient dose reductions or holds of AAP or niraparib occurred in 10 and 11 patients, respectively. There were no statistically significant declines in patient reported urinary QOL at 6- or 12-months post-treatment compared to baseline (all p >0.15). A transient decline in bowel QOL at 6-months occurred (p<0.01), which improved by 12-months (p=0.16). Conclusions: Our phase I findings support the short-term safety and tolerability of the combination of SBRT to the prostate and nodes, ADT, AAP, and niraparib at an MTD of 200 mg in men with high-risk or node positive PCa. Our trial completed phase II enrollment in May 2024, and longer-term safety, efficacy, and genomic correlations will be presented in the future. Clinical trial information: NCT04194554 .

382 Background: The natural history of biochemical recurrence (BCR) after radical prostatectomy (RP) is heterogeneous, with most patients not progressing to metastasis. Determining the impact and optimal timing of salvage radiation therapy (SRT) remains challenging, particularly in the absence of prospective randomized trials with a surveillance control arm. Our objective isto quantify the oncologic benefit of SRT among men with BCR after RP. Methods: Patients who underwent RP at Mayo Clinic between 1990 and 2017 and developed BCR (PSA≥0.20ng/mL) were included. Patients treated with SRT were compared to those managed with surveillance using risk-set matching with time-dependent propensity scores, accounting for covariates at BCR and post-BCR. The primary outcome was metastases, analyzed via Kaplan-Meier and Cox proportional hazard models. The number needed to treat (NNT) with SRT to prevent progression was calculated using regression outputs at 5 and 15 years post-BCR. Interaction analyses identified factors modifying SRT’s effect on metastasis. Results: Of 6,881 patients with BCR, 2,109 received SRT. At a median follow-up of 10.2 years, 1,147 patients with BCR developed metastases. After 1:1 matching, SRT was associated with lower metastasis risk than surveillance at 5 years (12.7% vs 19.3%, p<0.0001) and 15 years (28.6% vs. 31.5%, p<0.001). SRT was independently associated with decreased metastasis risk (HR 0.75, 95%CI 0.63–0.90, p=0.002) on multivariable analysis, translating to NNT of 23 and 15 at 5 and 15 years, respectively (Table). Additionally, we noted a significant interaction between PSA at SRT and the association of SRT with metastasis (p-interaction=0.02), such that the reduction in metastatic progression with SRT vs. surveillance was restricted to the cohort of patients who received SRT for PSA>0.40ng/mL (HR 0.66, 95%CI 0.54–0.80, p<0.001). Conclusions: Most patients with BCR post-RP do not develop metastases. Indeed, the NNT with SRT to reduce metastasis versus surveillance indicates a generally indolent disease course. Further, the lack of a significant association of SRT with reduction of metastases in patients with a PSA≤0.40ng/mL underscores the importance of careful patient selection when considering early SRT. Our data establish the rationale for a randomized trial comparing early SRT versus surveillance for appropriately selected patients with BCR after RP. Hazard ratios of SRT after matching by propensity scores, and number needed to treat for systemic progression, prostate cancer specific mortality and overall mortality. DiseaseOutcome Hazard Ratio(95% CI) P value Number Needed to Treat* (95% CI) 5 years 15 years Systemic progression 0.75(0.63 – 0.90) 0.002 23(17 – 41) 15(11 – 27) Prostate cancer mortality 0.81 (0.64 – 1.03) 0.086 103(62 – 494) 26(15 – 124) Overall mortality 0.79 (0.70 – 0.89) 0.0001 38(29 – 62) 12(9 – 20) *Number needed to treat (NNT) calculated using regression based absolute differences in event free survival between salvage radiation therapy (SRT) and observation.

371 Background: Prostate cancer is the most common malignancy in men globally and remains among the top five leading causes of cancer-related deaths. Emerging evidence suggests that early identification of symptoms can detect localized disease thus enabling opportunities for curative intent treatments. This study evaluates the use of the AI-powered prediction model, C the Signs, to passively screen for prostate cancer by leveraging data from electronic medical records (EMRs), offering a novel pathway for identifying high-risk individuals. Methods: A retrospective analysis was conducted using the Mayo Data Platform, encompassing 418,477 male patient records, of which 16,835 were diagnosed with prostate cancer. C the Signs identified patients at risk based solely on their EMR data, utilizing AI-driven pattern recognition. Sensitivity and specificity analyses were performed to assess the prediction model’s accuracy. Additionally, we examined the time-to-diagnosis advantage for patients flagged by the model compared to traditional physician clinical diagnoses. Results: C the Signs demonstrated a sensitivity of 83.3% and a specificity of 52.5% for identifying patients at risk of prostate cancer. Notably, 31.8% of prostate cancer cases were identified at risk up to five years earlier by the model compared to traditional physician clinical diagnosis. Conclusions: The integration of AI-driven prediction models like C the Signs into prostate cancer screening pathways provides an opportunity to enhance early detection, particularly in symptomatic individuals. Compared to prostate-specific antigen (PSA) testing, the model achieved equivalent sensitivity and 38% higher specificity, positioning it as a valuable companion tool for improving patient outcomes.

140 Background: In the phase II EXTEND iADT omPC basket, MDT+iADT improved progression-free survival (PFS) vs iADT. Here we present the primary results of the EXTEND cADT omPC basket. We further report a pre-specified combined analysis with updated results from the iADT basket and examine the effects of MDT on immunity. Methods: Patients with 1 to 5 omPC metastases were randomized 1:1 to MDT+cADT vs cADT (NCT03599765). MDT consisted of definitive local therapy. cADT consisted of ADT +/- second-generation anti-androgens. The primary endpoint was per-protocol PFS, defined by biochemical criteria (Prostate Cancer Working Group 3), radiologic measures (RECIST v1.1), clinical progression, or death. 87 patients were needed to show superiority at a one-sided P of 0.10 by log-rank test. CDR3 regions in rearranged T cell receptor (TCR) β-chains from pre- and post-enrollment peripheral blood were sequenced with immunoSEQ (Adaptive Biotech). TCR repertoire modulation was defined as having TCR expansion plus contraction using a false-discovery-corrected betabinomial model. TCR sequencing from the ORIOLE trial (NCT02680587) was assessed for external validation. Results: From 2018 to 2022, 87 randomized patients were treated per protocol (MDT+cADT: 45; cADT: 42). 39% had castrate resistant omPC. MDT was definitive radiotherapy in all cases. With median follow-up of 31 mo, median PFS was 47 mo after MDT+cADT vs 22 mo after cADT (HR 0.50; 95% CI 0.23 to 1.08; one-sided P = 0.036). In the combined analysis (N=174) with median follow-up of 42 mo, MDT+ADT improved PFS (HR 0.45; 95% CI 0.30 to 0.69; P < 0.001), radiologic PFS (HR 0.63; 95% CI 0.40 to 0.97; P = 0.038), and castration-resistance free-survival (HR 0.40; 95% CI 0.19 to 0.82; P = 0.013). MDT+ADT had higher odds of TCR repertoire modulation vs ADT (55% vs 15%, P < 0.001). This finding was validated in the ORIOLE trial (MDT: 57% vs observation: 19%, P = 0.03). Among the subset of patients with extreme responses, random forest modeling of 37 clinical/immune variables identified TCR repertoire modulation as the variable with highest importance; further, MDT+ADT induced TCR repertoire modulation in all patients with favorable responses (i.e. PFS > 4 years) and none with unfavorable responses (i.e. PFS < 1 year). Among all patients randomized to MDT+ADT, TCR repertoire modulation was associated with longer PFS (HR 0.21; 95% CI 0.06 to 0.76; P = 0.02). Conclusions: MDT+cADT met the PFS primary endpoint of the phase II EXTEND trial, warranting phase III testing. From the combined analysis, MDT+ADT may also improve longer term outcomes including radiologic PFS and castration-resistance-free survival. Improved outcomes may result from MDT-induced immunomodulation, with implications for future trial design. Clinical trial information: NCT03599765 .

136 Background: The ECOG performance status (PS) is a critical measure for evaluating functional capacity and determining clinical trial eligibility in patients with advanced prostate cancer. We aim to assess the capability of large language models (LLMs) to accurately infer ECOG PS from unstructured oncology notes. Methods: This retrospective study included patients with metastatic castration-resistant prostate cancer (mCRPC) receiving Lutetium-177–PSMA-617 ( 177 Lu) at the Mayo Clinic (2022-2023). Baseline ECOG PS scores were manually curated by a trained clinician from clinical notes recorded within four weeks prior to 177 Lu initiation. Structured zero-shot prompts were then used to prompt GPT-4 to infer ECOG PS scores from unstructured oncology notes. Total dataset was randomly sampled to prompt development (20%) and held-out test set (80%). Three experimental setups were employed to assess model performance: (i) utilizing unmasked clinical notes, (ii) clinical notes with only numerical ECOG PS scores masked while retaining narrative descriptive/assessment by oncologist of ECOG score, and (iii) clinical notes with both numerical scores and narrative ECOG descriptors masked. Final performance was assessed using evaluation metrics (precision, recall, F1 score) on the held-out test set. Results: A total of 240 patients (n: 50 prompt development; n: 190 test set) were included in the analysis. The median age was 70 (IQR: 66-76); a majority of patients were White (n: 229; 95%) and non-Hispanic (n: 233; 97%). The most prevalent ECOG PS score was 0 (n: 140; 58%), followed by 1 (n: 88; 37%), and 2 (n: 12; 5%). The performance was numerically higher when using unmasked notes (weighted average precision: 0.89; recall: 0.89; F1: 0.89), compared to using notes with masked scores only (weighted average precision: 0.76; recall: 0.79; F1: 0.75) and notes with both scores and narrative masked (weighted average precision: 0.57; recall: 0.53; F1: 0.48). Metrics by each ECOG PS score is outlined (Table). Conclusions: Large language models demonstrate significant potential in precisely extracting ECOG performance status from unstructured oncology notes, offering valuable support for treatment decision-making and clinical trial enrollment. However, model performance declines as reliance on implicit reporting within clinical notes increases. Future efforts focusing on prediction of ECOG using a series of notes over time will be the next step. ECOG Unmasked oncology notes ECOG Score masked only ECOG Score + ECOG narrative marked Precision Recall F1 Score Precision Recall F1 Score Precision Recall F1 Score 0 0.89 0.92 0.91 0.75 0.93 0.83 0.59 0.74 0.66 1 0.88 0.86 0.87 0.76 0.74 0.75 0.19 0.47 0.27 2 1.00 0.82 0.90 0.78 0.33 0.47 0.78 0.16 0.26

134 Background: Prostate cancer patients with visceral metastases at diagnosis are often treated using one-size-fits-all approach. For example, CHAARTED criteria treats any visceral metastasis as high volume. Therefore, we aimed to assess overall survival (OS) by site of visceral involvement in patients with metastatic PCa. Methods: Surveillance, Epidemiology, and End Results (SEER) database (2010-2021) was queried to obtain case listing data on metastatic PCa patients from 17 registries. The patients were categorized into three groups based on visceral metastasis at diagnosis: lung metastasis, liver metastasis, and others. Kaplan-Meier survival analysis was performed to estimate median OS with 95% confidence interval (CI). Log-rank test was conducted to assess if survival was significantly different among the groups. Cox proportional hazard regression analysis was performed to assess the magnitude of difference among the groups. P-value <0.05 established statistical significance. Results: This analysis included 21,007 metastatic PCa patients (lung: n=319; liver: n=123; brain: 107; bone: 20538). Metastatic PCa population with lung metastasis exhibited a median OS of 60 months (95% CI: 48-72) compared to 24 months (95% CI: 12-36) in population with liver metastases and to 36 months (95% CI: 36-36) in population with other metastases. The difference in OS among the groups was statistically significant (p < 0.001). Compared to population with lung metastasis, those with liver (HR: 1.91; 95% CI: 1.41-2.57) but not those with other metastases (1.16; 0.97-1.39) had significantly worse OS adjusting for Gleason score, PSA and race (Table). Conclusions: In metastatic PCa, patients with lung-only metastasis have significantly better overall survival and should be considered differently in prognostication to liver metastases. Consideration of site of visceral metastasis is critical for treatment intensification decisions. Limitations of this analysis include lack of accounting for confounding relationships at individual patient level. Variable Hazard Ratio (95% CI) Metastases (Lung) REFERENCE Metastases (Liver) 1.91 (1.41-2.57) Metastases (Other) 1.16 (0.97-1.39) Gleason score≥8 REFERENCE Gleason score <8 0.68 (0.64 -0.72) PSA - ng/dL 1.01 (1.00 – 1.01) Race (White) REFERENCE Race (Black) 0.99 (0.94 – 1.05) Race (Asian or Pacific Islander) 0.70 (0.64 – 0.76)

132 Background: Distant metastasis at the time of prostate cancer (PCa) diagnosis is associated with increased morbidity and mortality. This study aimed to assess the impact of sociodemographic characteristics on distant metastasis at the time of PCa diagnosis. Methods: The Surveillance Epidemiology and End Results (SEER) database (2000-2021), including PCa patients from 17 registries, was queried. Patients with late-stage diagnosis (LSD) were defined as those who were initially diagnosed with stage IV disease, indicating distant metastasis. Sociodemographic predictors included race, ethnicity, age, marital status, residential status, and median household income. Multicollinearity was assessed using variance inflation factors (VIF). Univariable logistic regression was performed to identify significant predictors of LSD, which were further analyzed in multivariable logistic regression using a maximum likelihood estimation approach. Odds ratios with 95% confidence intervals (CI) were computed with a p-value of <0.05 indicating a statistically significant association. Results: Of the 1,089,736 PCa patients diagnosed, 64,983 (6%) had an LSD. The majority were white (80%), non-Hispanic/Latino (HL) (91%), aged ≥65 years (60%), married (75%), residents in metropolitan areas (88%), and had an annual house income of ≥$70,000 (70%). Multivariable logistic regression identified Black (OR: 1.24; 95%CI: 1.22-1.27), Asian or Pacific Islander (1.35; 1.30-1.40), and American Indian/Alaska Native (1.70; 1.53-1.89) to have higher odds of LSD compared to White patients (Table). In addition, HL ethnicity compared to non-HL (OR: 1.45; 95% CI: 1.42-1.49), age ≥65 compared to <65 (1.68; 1.65-1.71), unmarried status compared to married (1.88; 1.85-1.91), residency in non-metropolitan areas compared to metropolitan (1.10; 1.07-1.12), and household income <$70,000 compared to ≥$70,000 (1.03; 1.01-1.05) had a significant association with LSD. Conclusions: Older, non-White (Black, Asian/Pacific Islander, American Indian/Alaska Native), Hispanic/Latino, unmarried men, residents of non-metropolitan areas, or those with lower annual household incomes have higher odds of late-stage diagnosis. Interventions targeting early detection in these at-risk groups may improve prostate cancer outcomes in the US. Variable Odds Ratio (95% CI) p-value Race (Black vs White) 1.24 (1.22-1.27) <0.01 Race (Asian or Pacific Islander vs White) 1.35 (1.31-1.40) <0.01 Race (American Indian/Alaska Native vs White) 1.70 (1.53-1.89) <0.01 Ethnicity (Hispanic/Latino vs non-/Hispanic/Latino) 1.45 (1.42-1.49) <0.01 Age (≥65 vs <65) 1.68 (1.65-1.71) <0.01 Marital status (unmarried vs married) 1.88 (1.85-1.91) <0.01 Residence status (non-metropolitan vs metropolitan) 1.10 (1.07-1.12) <0.01 Household income (<$70,000 vs ≥$70,000) 1.03 (1.01-1.05) <0.01

129 Background: Few studies have explored the use of focal therapies to address select sites of resistant disease in men receiving 177-Lu-PSMA-617 for metastatic castrate resistant prostate cancer (mCRPC). Our institutional practice is to offer SBRT for patients with up to 5 sites of oligoprogression or non-responding lesions while undergoing 177Lu-PSMA-617 (every 6 weeks for 6 cycles total). This is determined by PSMA or choline PET imaging during the course of 177Lu-PSMA-617. Herein, we evaluated the safety of adding target SBRT during treatment with 177Lu-PSMA-617. Methods: This retrospective single institution analysis was conducted via systematic chart review to evaluate for adverse events during or after treatment. Grading of treatment-related adverse events was conducted using Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE v5). Results: Thirty-one patients receiving 177Lu-PSMA-617 with 51 sites of oligoprogressive or non-responding metastatic disease were treated with SBRT. The median number of sites treated was 1 (range 1-4). Most patients received SBRT immediately after cycle 6 (32%) or after cycle 3 or 4 (42%). Bone was the most commonly treated site of disease (90%) with the majority (54%) of bone sites being spine or sacrum, followed by lymph nodes (10%). Ultimately, 84% of patients completed all 6 cycles of 177Lu-PSMA-617 (range 4-6). The median follow-up time was 19.1 months (IQR 15.5-22.4) after 177Lu-PSMA-617 therapy start. A total of 2 patients experienced a pathologic fracture within the SBRT treatment field that could possibly be related to radiotherapy. One patient experienced a grade 2 neuropathy which may have been related to radiation therapy. Other potential adverse events are listed (Table). Conclusions: Our data demonstrates a low rate of significant toxicity with the use SBRT during treatment with 177Lu-PSMA-617. Further study is indicated to determine the oncologic efficacy and potential late side effects of this treatment strategy. Adverse events. Event All Grades Grade > 3 Any Adverse Event 104 2 Anemia 29 (94%) 0 Low Platelets 11 (35.5%) 1 (3.2%) Any Pathologic Fracture 7 (22.5%) 1 (3.2%) Possible SBRT-related Pathologic Fracture 2 (6.5%) 1 (3.2%) Bone Pain Flare 3 (9.6%) 0 Neuropathy 1 (3.2%) 0