Heath, Elisabeth I.

Abstract Background: Accurate staging is essential for treatment selection, prognosis assessment, and trial eligibility. While prior studies attempted automating pathological (p) staging, few address clinical (c) staging and no studies have compared LLM-derived staging with clinician staging during clinical visit and retrospective cancer registry staging. Methods: We developed a multi-agent framework using Gemini-2.0-Flash-001 and GPT-5 to (1) identify reports (2) extract key data, and (3) apply AJCC 8th edition staging criteria. LLM staging was compared with clinician documentation and registry staging in breast cancer patients. Clinician-registry agreement served as the reference standard. Two independent breast oncologists reviewed discordant cases. Results: We analyzed 122 randomly selected breast cancer patients across all three Mayo Clinic sites from 2018 - 2023. LLM performance matched or exceeded human inter-rater agreement for pathological staging (95-99.2% vs. 95-98.4%). Clinical staging was more challenging, with LLM concordance of 73-77.9% for cT and 87-89.3% for cN versus 87.8% and 91.0% clinician-registry agreement. Among 89 patients with clinician-registry concordance, LLM concordance was 98.9% for pT/pN, 79.8% for cT, and 91.0% for cN. Experts favored LLM staging in 27.8% (5/18) of cT and 25.0% (2/8) of cN discordances. Error analysis revealed LLM challenges in handling non-mass enhancements (6 cases), selecting radiologic measurements (2 cases), identifying discrete masses (2 cases), and miscellaneous (3 cases). Conclusion: LLMs achieved human-level performance for pathological staging (98%), supporting human-in-the-loop deployment. For clinical staging (79.8% cT, 91.0% cN), future work must enhance multimodal reasoning and integrate physical examination data. Prospective validation is needed to assess real-world impact. With targeted refinements and oversight, automated staging can transform registry workflows while augmenting clinical decision-making. Citation Format: Arshad Mohammed, Umair Ayub, Pooja Advani, Shakeela W. Bahadur, Amye J. Tevaarwerk, Tufia C. Haddad, Elisabeth I. Heath, Brenda J. Ernst, Ben Zhou, Cui Tao, Sara J. Holton, Karthik V. Giridhar, Irbaz B. Riaz. Automating clinical and pathological staging for breast cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 2744.

88 Background: The VISION (NCT03511664) and PSMAfore (NCT04689828) clinical trials have demonstrated the effectiveness of 177 Lu-PSMA-617 in patients with mCRPC who have previously received androgen receptor pathway inhibitors (ARPIs) with or without taxane-based chemotherapy. Sipuleucel-T is used for treatment of mCRPC in routine clinical practice, particularly among community urologists; however, to date, there are no data available to understand the effectiveness of 177 Lu-PSMA-617 in patients previously treated with sipuleucel-T. Methods: This was a retrospective, observational study of adult patients with a diagnosis of mCRPC who received 177 Lu-PSMA-617 between March 23, 2022, and June 27, 2025, and had a history of treatment with sipuleucel-T. Data were obtained from the PRECISION data platform, a harmonized dataset of patients with advanced prostate cancer in the US that integrates electronic health records and claims data from community, academic, urology, and medical oncology settings. The index date was the date of 177 Lu-PSMA-617 initiation. Patient characteristics and prostate-specific antigen (PSA) response rates were evaluated descriptively. Progression-free survival (PFS), defined as the time from 177 Lu-PSMA-617 initiation to disease progression or death, was analyzed using Kaplan–Meier curves. Results: A total of 290 patients met the inclusion criteria, of whom 72% were White and 12% were Black. At index, 32% of patients were treated in urology and 68% in oncology settings. The median age was 74 years, the median baseline PSA was 35.3 ng/mL (interquartile range [IQR] 10.0–99.2 ng/mL), and 57% of patients had a Gleason score of ≥8. In addition to sipuleucel-T, prior to 177 Lu-PSMA-617, 97% of patients had received ≥1 ARPI and 79% had received ≥1 taxane. The median follow-up for this cohort was 9.4 months (IQR 5.3–17.5 months). Among 144 patients with available PSA values both before and during 177 Lu-PSMA-617 treatment (representing 50% of the cohort), PSA response rates were as follows: a ≥50% reduction in PSA from baseline (PSA50) was observed in 60%, PSA80 in 42%, and PSA90 in 33% of patients. Overall, the median PFS was 15.2 months (95% confidence interval [CI] 11.6–19.4 months). Conclusions: In this real-world analysis of patients who received 177 Lu-PSMA-617 after sipuleucel-T treatment, the median PFS was similar to that observed in clinical trials, suggesting that 177 Lu-PSMA-617 can be sequenced after sipuleucel-T treatment in appropriate patients.

81 Background: In the PSMAfore clinical trial, 177 Lu-PSMA-617 achieved a PSA50 (defined as a ≥50% reduction in prostate-specific antigen [PSA] from baseline) response rate in 58%, a median radiographic progression-free survival (PFS) of 12 months, and a median overall survival (OS) of 25 months among taxane-naïve patients with mCRPC who had received one prior androgen receptor pathway inhibitor (ARPI). The aim of the present study was to evaluate the real-world effectiveness of 177 Lu-PSMA-617 in taxane-naïve patients with mCRPC who had received one or more prior ARPIs. Methods: This retrospective, observational study included taxane-naïve adults with mCRPC initiating 177 Lu-PSMA-617 between March 23, 2022, and June 27, 2025, after ≥1 prior ARPI. All data for the study were extracted from the PRECISION data platform, a harmonized dataset of patients with advanced prostate cancer in the US treated in a variety of clinical settings. The index date was the date of 177 Lu-PSMA-617 initiation. Patient characteristics and PSA response rates were evaluated descriptively. PFS, defined as the time from 177 Lu-PSMA-617 initiation to progression or death, was estimated using Kaplan–Meier methodology. Results: A total of 500 patients were included. The median age was 75 years, 75% of patients were White and 8% Black, and 18% were treated in urology centers while 82% were treated in oncology centers. The most common site of metastasis was bone (77%), followed by lymph node (21%), visceral (12%), and unknown (5%). Overall, 51% had received 1 previous ARPI while 49% had received ≥2. The median baseline PSA was 26.7 ng/mL (interquartile range [IQR] 10−105 ng/mL) and the median time from mCRPC diagnosis to 177 Lu-PSMA-617 initiation was 23.6 months. The median number of 177 Lu-PSMA-617 cycles received was 4 (IQR 2−6). Among 219 patients with available PSA measurements both before and during 177 Lu-PSMA-617 treatment (representing 44% of the cohort), PSA response rates were as follows: PSA50 in 137 (63%), PSA80 in 86 (39%), and PSA90 in 56 (26%) patients. Overall, the median PFS was 13.5 months (95% confidence interval 11.7–14.7 months). Conclusions: The effectiveness of 177 Lu-PSMA-617 as a standard-of-care treatment in real-world, taxane-naïve patients with mCRPC who had received prior treatment with ≥1 ARPI is consistent with results from the PSMAfore trial, confirming the applicability of those findings to the real-world population now eligible for 177 Lu-PSMA-617. Further research on sequencing 177 Lu-PSMA-617 after one or more prior ARPIs in taxane-naïve patients with mCRPC is needed to guide optimal treatment sequencing in clinical practice.

79 Background: In March 2025, the indication for 177 Lu-PSMA-617 was expanded to include prostate-specific membrane antigen (PSMA)-positive patients with mCRPC treated with ≥1 androgen receptor pathway inhibitor (ARPI) and considered appropriate to delay taxane-based chemotherapy. With 177 Lu-PSMA-617 moving earlier in the treatment journey, it is important to understand the clinical activity of other systemic therapies after 177 Lu-PSMA-617. The aim of this study was to evaluate the clinical outcomes among patients with mCRPC receiving a systemic therapy after 177 Lu-PSMA-617 treatment. Methods: This retrospective, observational study used real-world data from the PRECISION data platform, a proprietary dataset developed by Novartis representative of patients with advanced prostate cancer in the US from diverse clinical settings. Patients with mCRPC treated with 177 Lu-PSMA-617 who received a systemic therapy ≥14 days after treatment with 177 Lu-PSMA-617 between March 23, 2022, and June 27, 2025, were included. Systemic therapies included ARPIs (abiraterone, enzalutamide, darolutamide, apalutamide); chemotherapy (cabazitaxel, docetaxel, carboplatin, cisplatin, etoposide, mitoxantrone); immunotherapy (pembrolizumab, sipuleucel-T); poly (ADP-ribose) polymerase (PARP) inhibitors (niraparib, olaparib, talazoparib, rucaparib); and radium-223. Patient characteristics and prostate-specific antigen (PSA) response were evaluated descriptively. Progression-free survival (PFS) from subsequent therapy initiation was estimated using Kaplan–Meier methodology. Results: A total of 442 patients receiving any subsequent systemic therapy after 177 Lu-PSMA-617 were included. Overall, 95% of patients received ≥1 ARPI and 76% ≥1 taxane pre- 177 Lu-PSMA-617. The median age was 73 years. Most patients received a taxane (n = 188), an ARPI (n = 176), or a PARP inhibitor (n = 33) as their subsequent therapy. The median time to subsequent therapy initiation was 70 days (interquartile range 38−137 days) from the last 177 Lu-PSMA-617 administration. Among 299 patients receiving a systemic therapy after 177 Lu-PSMA-617 with PSA values available both pre-index and during subsequent treatment, 48% achieved a ≥50% reduction in PSA from baseline (PSA50), 31% a PSA80, and 18% a PSA90. The median PFS from the initiation of subsequent therapy was 8.6 months in the entire cohort; this was 10.7 months with a subsequent ARPI, 7.2 months with a subsequent taxane, and 7.1 months with a subsequent PARP inhibitor. Conclusions: In this real-world analysis, meaningful clinical responses were observed in a subset of patients who received subsequent systemic therapies after 177 Lu-PSMA-617.

78 Background: 177 Lu-PSMA-617 is currently under investigation in combination with an ARPI in those with metastatic hormone-sensitive prostate cancer (PSMAddition trial: NCT04720157). This observational study was performed to assess the effectiveness of 177 Lu-PSMA-617 in combination with an ARPI in patients with mCRPC in the real-world setting. Methods: This was a retrospective cohort study of adults with mCRPC in the PRECISION data platform, a comprehensive database of prostate cancer patients compiled from diverse clinical settings in the US. Patients who received 177 Lu-PSMA-617 during March 23, 2022–June 27, 2025 were identified, among whom two cohorts were selected for inclusion: those who had evidence of ARPI use (apalutamide, darolutamide, abiraterone, or enzalutamide) at any time during 177 Lu-PSMA-617 treatment (concomitant ARPI cohort), and those who had no other treatment for mCRPC during 177 Lu-PSMA-617 treatment (no concomitant therapy cohort). The index date was initiation of 177 Lu-PSMA-617. Patient characteristics and prostate-specific antigen (PSA) responses were evaluated descriptively. Progression-free survival (PFS), defined as the time from 177 Lu-PSMA-617 initiation to disease progression or death, was estimated using Kaplan–Meier analysis. Results: A total of 1,880 patients treated with 177 Lu-PSMA-617 were identified, 140 in the concomitant ARPI cohort and 1,740 in the no concomitant therapy cohort. The median age was 74 years. Demographic characteristics were balanced between the groups, except that median baseline PSA was lower in the concomitant ARPI cohort when compared with patients in the no concomitant therapy cohort (18 ng/mL vs. 32 ng/mL). Before 177 Lu-PSMA-617 initiation, 94.3% and 73.6% of patients in the concomitant ARPI and 80.9% and 56.7% in the no concomitant therapy cohort had received ≥1 prior ARPI and ≥1 prior taxane, respectively. PSA response rates were broadly comparable between cohorts. The median (95% confidence interval) PFS was 14.7 (11.7–21.3) months among patients in the concomitant ARPI cohort vs 12.5 (11.5–13.6) months in the no concomitant therapy cohort. Ongoing follow-up aims to evaluate the impact of combining ARPI with 177 Lu-PSMA-617 on long-term clinical outcomes, including overall survival. Conclusions: The results of this study demonstrate that 177 Lu-PSMA-617 delivers clinical benefits inpatients with mCRPC with or without ARPI; however, addition of an ARPI may potentially improve these benefits. Prospective randomized controlled studies are needed to confirm this.

77 Background: The incidence of metastatic hormone-sensitive prostate cancer (mHSPC) is increasing in the US, likely due to a decrease in screening practices. There has also been a rapid increase in recent years in the number of treatment options that can improve progression-free and overall survival (OS) for these patients. The objective of the current study was to evaluate the clinical outcomes among patients with mHSPC treated in contemporary US clinical practice (2020 to 2025). Methods: This retrospective, observational cohort study used data from PRECISION, a harmonized dataset on advanced prostate cancer in patients in the US treated in a range of clinical settings. Patients aged ≥18 years who were diagnosed with mHSPC during 01/01/2020–01/01/2024 and who initiated ≥1 therapy (index date = first-line [1L] treatment initiation) were included. The study period was from 01/01/2010 to 06/30/2025. Patient characteristics at mHSPC diagnosis and treatment utilization were evaluated descriptively. Castration resistance-free survival (CRFS; defined as the time to castration-resistant prostate cancer or death) and OS were evaluated from index using Kaplan–Meier analysis. Results: A total of 27,708 patients were included (median age, 72 years); 20,015 (72%) were treated in community urology, 4994 (18%) in community oncology, and 2669 (10%) in academic oncology centers at index. Almost half of patients (47%) initiated 1L treatment with androgen-deprivation therapy (ADT) monotherapy, 44% initiated a 1L doublet regimen (36% ADT + androgen receptor pathway inhibitor [ARPI], 5% 1L ADT + radiotherapy, 2% 1L ADT + docetaxel), and 5% a 1L triplet regimen (ADT + radiotherapy + ARPI or docetaxel); the remaining patients received other regimens. The 5-year CRFS rate was 41%; this was significantly higher in patients with a 1L doublet (45%) or triplet (58%) regimen compared with patients with 1L ADT monotherapy (31%; p<0.001). Similarly, the 5-year OS rate was 59% overall and was significantly higher in patients with a 1L doublet (61%) or triplet (59%) regimen compared with patients with 1L ADT monotherapy (55%; p<0.001) (Table). Conclusions: Though both CRFS and OS rates appear to be increasing among real-world patients with mHSPC, >40% of patients in this study died within 5 years of initiating 1L treatment. Patients who received guideline-recommended combined systemic treatment regimens experienced improved CRFS and OS, confirming the importance of implementing therapies in practice that prolong survival. CRFS and OS rates from start of 1L therapy, by therapy type. CRFS rate (%) OS rate (%) 1 y 2 y 3 y 4 y 5 y 1 y 2 y 3 y 4 y 5 y Overall 68 58 51 46 41 93 84 76 67 59 ADT monotherapy 59 49 41 36 31 92 83 74 65 55 Doublet therapy 72 62 55 49 45 94 85 76 68 61 Triplet therapy 85 77 70 68 58 94 89 82 74 59

75 Background: Although the number of life-prolonging treatment options for pts with mHSPC has increased, initial real-world evidence has demonstrated slow uptake. This study utilized a large, contemporary, real-world dataset to evaluate the characteristics and treatment utilization among US pts with mHSPC in recent years. Methods: This retrospective, observational study used data from PRECISION, a harmonized dataset on pts with advanced prostate cancer. Adult men who were diagnosed with mHSPC during 01/01/2020–01/01/2024 (index date) and who initiated ≥1 therapy were included; the study period was 01/01/2010–06/30/2025. Pt characteristics were described at index. Treatment utilization was evaluated from index until progression to metastatic castration-resistant prostate cancer, death, or last follow-up. If an androgen receptor pathway inhibitor (ARPI), docetaxel, or radiotherapy was started within 4 months of index/androgen-deprivation therapy (ADT) start, it was considered a first-line (1L) combination; if it was started after >4 months, it was considered treatment intensification. All analyses were descriptive. Results: Among the 27,708 pts who met the inclusion criteria in PRECISION, 72%, 18%, and 10% were treated in community urology, community oncology, and academic oncology centers at index, respectively. Median age was 72 years; 62% were White; 43% were from the US South; 53% had synchronous and 54% had metachronous metastases (2% unknown). Median prostate-specific antigen level was 9 ng/mL (mean, 130 ng/mL). Prior to mHSPC diagnosis, 19% of pts had a prostatectomy and 17% had radiotherapy. Almost half of pts (47%) initiated 1L treatment with ADT monotherapy; 36% initiated 1L ADT + ARPI, 5% 1L ADT + radiotherapy, 2% 1L ADT + docetaxel, 5% 1L ADT + radiotherapy + ARPI or docetaxel, and 5% other regimens. From 2020 to 2023, 1L ADT monotherapy use decreased, while 1L combination use increased (Table). In addition, 19% of pts with 1L ADT monotherapy had evidence of subsequent treatment intensification, mainly the addition of an ARPI. Conclusions: In this study, use of 1L ADT monotherapy declined over time, accompanied by an increase in 1L combinations and treatment intensification. Nonetheless, approximately 1/3 of pts still did not receive a combination or intensification. Further research is needed to understand treatment trends in pts with mHSPC. Treatment patterns by index year. Pts, % 2020(n=5278) 2021(n=6203) 2022(n=7701) 2023(n=8526) 1L ADT monotherapy* 54 52 45 40 Subsequent treatment intensification* 18 19 20 18 1L ADT + ARPI* 29 33 38 42 1L ADT + radiotherapy 5 5 5 6 1L ADT + docetaxel* 3 2 2 1 1L ADT + radiotherapy + ARPI or docetaxel* 3 3 5 7 *p<0.001 for trend across years.

567 Background: Selecting adjuvant therapy after nephrectomy for renal cell carcinoma (RCC) requires reviewing scattered electronic health records (EHR) and performing accurate eligibility and risk assessments. Large Language Models (LLMs) may assist physicians by extracting key clinical data and generating evidence-based recommendations between active surveillance and adjuvant pembrolizumab. Methods: We selected RCC patients who underwent nephrectomy at Mayo Clinic in Arizona, Florida, and Minnesota between December 2021 and September 2025. Data extraction from EHRs was performed by a HIPAA-compliant LLM (GPT-5 and Gemini 2.0-Flash-001) and compared to human labels. Data on patients’ demographics, medical history, pathology, laboratory results, and imaging were collected. GPT-5 generated treatment recommendations using a structured prompt that incorporated patients’ features and relevant clinical information that is available to clinicians. Concordance between the human labels and LLM was evaluated for extraction. For treatment recommendations, agreement between the LLM’s output and physician’s documented recommendation in clinical notes was assessed, with disagreements reviewed independently by two blinded genitourinary oncologists. Results: The dataset included 85 patients, median (range) age of 65 (34-84) years; 24.7% were females. Patients who declined adjuvant treatment for personal reasons were excluded. LLM achieved an extraction accuracy of 95% for presenting symptoms, 97% for BMI and ECOG, and > 99% for pathology variables. Concordance between LLM and physician treatment recommendations was 84.7% (72/85). Among 13 discrepant cases, one oncologist agreed with the LLM in 9 cases and the other in 8. The main reasons for disagreement between the physicians and the LLM were that the LLM favored active surveillance for patients with declining renal function, whereas physicians still considered adjuvant pembrolizumab appropriate in such cases. Additionally, the LLM demonstrated hesitancy to recommend pembrolizumab for patients with low performance status. Overall, the 13 discrepant cases were nuanced and challenging, with disagreement observed between the two oncologists themselves in three instances. Conclusions: LLMs demonstrated high accuracy in extracting clinically relevant variables and generating objective, evidence-based adjuvant treatment recommendations for RCC after nephrectomy. Importantly, LLM did not generate any inappropriate or potentially harmful recommendations. Our pipeline can serve as a supportive decision tool to enhance consistency in post-nephrectomy management and assist physicians in choosing between active surveillance and adjuvant pembrolizumab. However, final treatment decisions should remain the responsibility of the treating physician after comprehensive patient evaluation.

352 Background: Glucagon-like peptide 1 (GLP1) receptor expression in prostate cancer tissue has raised concerns that GLP1 receptor agonists (GLP1A) may influence tumor growth or progression. We compared prostate cancer severity at diagnosis among patients receiving GLP1A versus other glucose lowering therapies. Methods: A retrospective chart review identified patients who received GLP1A or alternative second-line glucose lowering agents (DPP4/SGLT2 inhibitors) and were subsequently diagnosed with prostate cancer. Patients receiving both drug classes were excluded. Baseline demographics (race, ethnicity, age), comorbidities (diabetes, myocardial infarction, peripheral vascular disease) concomitant medications (insulin, metformin, statins), appointments (within past year) and laboratory values (HbA1c, eGFR) at therapy initiation were recorded. Primary outcomes included Gleason grade group and metastatic presentation within three months of diagnosis. Propensity score matching balanced baseline characteristics between groups. Mann-Whitney U tests compared grade groups. Chi-square tests compared metastatic presentation, reporting odds ratios (OR) with 95% confidence intervals (CI). Multivariable logistic regression identified predictors of grade group (low-grade: 1-2; high-grade: ≥3) and metastatic presentation, reporting OR with 95% CI. A p value <0.05 indicated a significant association. Results: Of 260 propensity-matched patients (GLP1A: 130, comparison: 130), 87% were White and 95% were Non-Hispanic/Non-Latino in each group. Median HbA1c was 7% (IQR: 6.4-8) in GLP1A group versus 7.5% (6.2-8.5) in comparison group. Median eGFR was 75mL/min/1.73m 2 (IQR: 61.5-90.0) in GLP1A group versus 60.0 (52.0-80.5) in comparison group. High-grade disease occurred in 33 (25%) GLP1A patients and 37 (29%) comparison patients. Among patients with available imaging (GLP1A: 40; comparison: 32), metastatic presentation occurred in 7 (18%) GLP1A group and 7 (22%) comparison group patients. No significant differences were observed in grade group (GLP1A median: 2; IQR: 1-2 vs. comparison median: 2; 1-3; p=0.44) or metastatic presentation (OR: 1.32; 95%CI: 0.41-4.25; p=0.64) between groups. In multivariable analysis, higher HbA1c was associated with high-grade disease in GLP1A group (OR: 1.83; 95%CI: 1.07-3.35; p=0.03) while higher eGFR was associated with low-grade disease in the comparison group (0.97; 0.93-0.99; p=0.04). Conclusions: GLP1A use was not associated with prostate cancer grade or metastatic presentation at diagnosis compared to alternative glucose-lowering agents. However, the association between elevated HbA1c and high-grade disease in GLP1A patients suggests a potential impact of poor glycemic control on tumor biology. Prospective studies are needed to elucidate the relationship between metabolic dysregulation and prostate cancer severity.

127 Background: Bone metastases affect up to 90 % of patients with metastatic hormone-resistant prostate cancer (mHRPC) and cause substantial morbidity from skeletal-related events (SREs) such as fracture, spinal-cord compression, and palliative interventions. Bone-modifying agents (BMAs) including bisphosphonates and denosumab reduce SRE risk and are NCCN-recommended, however, real-world use remains inconsistent. Methods: Patients with mHRPC treated from January 2017-September 2024 across Mayo Clinic sites were identified using SQL-based EHR queries confirmed by manual chart review. Bone Metastases were detected through keyword searchers of radiology reports and confirmed through manual chart review. SRE-prevention dosing was defined as zoledronic acid 4mg IV or denosumab 120mg SC; osteoporosis dosing was excluded. SREs were identified using diagnosis codes and text-pattern searches for radiotherapy, surgery, fracture, and spinal-cord compression. Descriptive statistics summarized BMA utilization and SRE incidence. Categorical variables were compared using Chi-square tests, and a risk ratio (RR) with 95% confidence intervals was calculated to evaluate association between early BMA initiation and SRE risk. Results: Among 778 patients with mHRPC, 685 (88 %) had bone metastases (mean age 70.5 years). Of these, 169 (24.7 %) had an SRE, and 261 (38.1 %) received BMAs at SRE-prevention doses (denosumab n = 157 [60 %]; zoledronic acid n = 104 [40 %]). Based on a chi-square test, combined SRE incidence did not differ significantly (No BMA 23 %, denosumab 23 %, zoledronic 33 %; p = 0.069). Bone pain at baseline was more common in patients who later received a BMA (136 [68 %]) than in those who did not (82 [41 %]; p < 0.001). Among 200 randomly sampled non-BMA patients, 83 had no recorded BMA discussion (66 also lacked bone pain), 38 lacked dental clearance, 32 had uncompleted plans and 18 declined therapy. Early BMA initiation (before first bone metastases) was associated with fewer SREs (16 % vs 29 %; RR 0.56, 95 % CI 0.33–0.96). Conclusions: Less than half of bone-metastatic mHRPC patients received BMAs. Non-initiation was often linked to modifiable factors such as delayed dental clearance or lack of treatment discussions, highlighting the need for system-level strategies to improve timely bone-directed care. SREs were common, affecting one quarter of patients. Small sample size precluded meaningful comparison of the impact of BMAs on SRE incidence however early BMA initiation may lower SREs. Incidence of SREs stratified by no BMA vs BMA treatment. SRE No BMA BMA Overall Pathological Fracture 6.4% (27/424) 4.9% (13/261) 5.8% (40/685) Radiotherapy to Bone 13.9% (59/424) 18.8% (49/261) 15.7% (108/685) Spinal Cord Compression 0.7% (3/424) 3.1% (8/261) 1.6% (11/685) Surgery to Bone 2.1% (9/424) 0.3% (1/261) 1.5% (10/685) Combined 23% (98/424) 27.2% (71/261) 24.7% (169/685)