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Radiotherapy and EGFR inhibition for high-risk cutaneous squamous cell carcinoma in immunosuppressed patients.
e21562 Background: Immunosuppression (IS) is a recognized risk factor for cutaneous squamous cell cancer (cSCC) incidence, recurrence and disease-specific death, though there are limited data on treatment outcomes in this population. Prior studies in unselected patients with high risk (HR) cSCC, failed to show improved outcomes from the addition of carboplatin to post-operative radiotherapy (PORT), however benefits may be better appreciated in higher risk groups. The addition of epidermal growth factor receptor inhibitors (EGFRi) to PORT has shown improved outcomes in HR-cSCC over historical controls in the general population, but its impact on patients with comorbid IS is unknown. Methods: This single institution retrospective cohort study identified all patients with a history of a solid organ transplant or autoimmune disease requiring IS or with hematologic malignancy and a diagnosis of either primary or recurrent HR-cSCC treated with concurrent EGFRi + PORT. Patients who failed to receive either modality concurrently or lost to follow-up after completion of therapy were excluded. Event-free survival (EFS) was defined as time from initiation of RT to disease recurrence, progression, or death from any cause. Results: Of 24 identified patients, 18 received concurrent EGFR inhibitor therapy and radiotherapy (mean dose 59.4 Gy delivered in 29.7 fractions) and had adequate follow-up for analysis. Fifteen patients were solid organ transplant recipients receiving immunosuppression, two had hematologic malignancies, and one had an autoimmune condition requiring chronic immunosuppression. Most patients had advanced disease, with 72.2% classified as AJCC stage III–IV and 88.9% as BWH stage T2b–T3 (T2b 50.00%; T3 38.9%). 8 of 18 (44.4%) had nodal disease involvement and 6 of 18 (33.3%) had satellite or in-transit metastases, and 2 of 18 (11.1%) had both. Median event-free survival was 5.4 months. Average follow up time was 18 months. Conclusions: IS represents a potent risk factor for cSCC recurrence or death, and outcomes remain poor even with intensification of PORT with concurrent EGFRi +RT. Such patients may benefit from a more intensified chemoRT regimen and/or the addition PD-1 inhibition in the adjuvant setting where tolerated.
The efficacy and safety of azvudine (FNC) in phase 1 investigator-initiated study in patients with advanced solid tumors.
3018 Background: Azvudine has been approved in China for treatment of AIDS and COVID-19. Serial preclinical studies demonstrated remarkable anti-tumor activity, especially in combination with anti-PD-1 therapy. The mechanistic studies have shown that FNC could significantly reduce myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment. This ongoing phase 1 investigator-initiated study aims to further confirm the nonclinical findings of FNC in cancer patients. Methods: Patients with advanced solid tumors who had progressed on standard of care (SoC) therapies were eligible in this single-arm, single-center, open-label study with the primary objective of safety and clinical efficacy. All subjects received the SoC of physician’s choice in combination with FNC which was administered orally once daily, with dose escalated across six dose levels: 3mg, 4mg, 5 mg, 6 mg, 7 mg, and 8 mg. Results: As of 31 Oct, 2025, 25 subjects were enrolled, including 22 subjects with pMMR/MSS CRC, 3 subjects with NSCLC. All CRC subjects received the triple-combination regimen of FNC, penpulimab, and fruquintinib. Among the CRC subjects, the total ORR was 18.2%, DCR was 72.7%, the mPFS was 4.3 months (95%CI: 3.32,6.31) and the mOS was 7.6 months (95% CI: 5.09,NR). Four subjects achieved the radiographic response (PR), 2 subjects from the 6 mg dose group, and one subject each from the 5 mg and 7 mg dose groups. A subgroup analysis based on liver metastasis status was performed for the 15 subjects enrolled in the 5 mg, 6 mg, and 7 mg dose groups. The ORR for the 7 subjects without liver metastases was 57.1%, the DCR was 100%, and the mean treatment duration was 33.6 weeks. In contrast, among the 8 subjects with liver metastases, the ORR was 0%, the DCR was 87.5%, and with a mean treatment duration of 16.7 weeks. No DLTs occurred in the 16 evaluable subjects during the DLT observation period. TEAEs were reported in 96.0% of patients, with a TRAE incidence of 36.0%. Most TRAEs were Grade 1/2, including hepatic dysfunction (12.0%), γ-GTP increased (8.0%), weight decreased (4.0%), diarrhoea (4.0%), insomnia (4.0%), and ALP increased (4.0%). One Grade ≥3 TRAE weight decreased occurred in the 3 mg group. SAEs were reported in 24.0% (6/25) of subjects, with only one case of weight decreased in 3 mg group considered possibly related to FNC. Two subjects (8.0%) discontinued treatment due to TEAEs, one of which was abnormal liver function, possibly related to FNC. No treatment related deaths, dose interruptions, or dose reductions were reported. Conclusions: Overall, the combination of FNC with PD-1 and VEGFR inhibitors was safe and well-tolerated, with encouraging clinical activity in advanced/metastatic pMMR/MSS CRC. Clinical trial information: chiCTR2600116125.
Double lung transplantation in patients with recent history of malignancy.
e20773 Background: Recent history of malignancy usually within five years is a contraindication for double lung transplantation (DLT). However, the relationship between a recent history of malignancy and lung transplantation outcomes is unclear. Methods: Patients with respiratory failure and a history of cancer in the last five years treated with DLT were identified between 09/2021 and 1/2026. All patients had enrolled in the DLT registry aimed for lung-limited malignancies (DREAM) study cohort C (NCT05671887). Exclusion criteria included the presence of extrapulmonary metastatic disease and medical ineligibility for DLT. Standard staging work-up confirmed the absence of distant metastasis. All patients were followed up with computed tomography every 12 weeks. Results: 19 consecutive patients who underwent DLT were included (age 27-74, 12 male, 7 female, and 13 former smokers). 11 lung (stage IA2-IIIB), three prostate (stage I-IIc), two testicular, one breast, one bladder, and one skin cancer cases were included. Among lung cancer patients, six patients had adenocarcinoma, four squamous cell carcinoma, and one poorly differentiated non-small cell carcinoma. Prior to DLT, patients received radioimmunotherapy (n = 1), chemoradiotherapy (n = 2), chemoradiotherapy plus immunotherapy (IO) (n = 2), radiotherapy alone (n = 3), and chemotherapy alone (n = 3). The duration of IO was a median of 2 (2-18) months. The IO-free interval was 11, 27, and 44 months before DLT. All patients had high oxygen requirements before DLT. The indications for DLT were COPD (n = 5), IO-related ILD (n = 3), IPF (n = 2), and COVID-related ILD (n = 1). Transplant rejection did not occur, and all patients were discharged on room air. The median overall survival after transplantation was 21 (6-59) months. 3 patients passed away at 9, 6, and 6 months post-DLT (2 died of respiratory failure, 1 died of cardiac arrest). 2 patients had new primary cancers which were surgically resected (1 had pancreatic cancer, 1 had prostate cancer). Conclusions: 19 patients, with a history of malignancy within 5 years, successfully underwent DLT for non-malignant indications of respiratory failure without significant complications. Ongoing DREAM study cohort C will continue to investigate the role of DLT in patients with a recent history of malignancy. Clinical trial information: NCT05671887 .
Efficacy of datopotamab deruxtecan after trastuzumab deruxtecan in metastatic hormone receptor–positive HER2-negative breast cancer: A real-world study.
e13040 Background: Datopotamab deruxtecan (Dato-DXd) and trastuzumab deruxtecan (T-DXd) are antibody–drug conjugates used in metastatic hormone receptor–positive HER2-negative breast cancer that target different antigens but share an identical topoisomerase I inhibitor payload. However, the activity of Dato-DXd in patients previously treated with T-DXd has not been reported. We compared the efficacy of Dato-DXd between patients with and without prior T-DXd exposure in real-world setting. Methods: This single-center retrospective study included patients who initiated Dato-DXd between March and September 2025 (data cutoff, January 2, 2026). Patients were classified as T-DXd–pretreated if they had received at least one prior dose of T-DXd and as T-DXd–naïve otherwise. The primary endpoint was disease control rate (DCR); progression-free survival (PFS) was evaluated as a secondary endpoint. DCR was defined as the proportion achieving complete response, partial response, or stable disease. PFS was defined as time from Dato-DXd initiation to progression or death. PFS was estimated using Kaplan–Meier methods, with group comparisons by log-rank test. Results: Thirty-seven patients were included; median age was 59 years (range, 41–76). At Dato-DXd initiation, ECOG performance status was 0 in 40.5%, 1 in 48.6%, and 2 in 10.8%. Fifteen patients had prior T-DXd exposure, of whom 14 received T-DXd for HER2-low disease and 1 for HER2-ultralow disease; among pretreated patients, 5 received Dato-DXd immediately after T-DXd and 10 after receiving other systemic therapies. The median proceeding number of treatment for metastatic disease was 7 (range, 4–11) in the T-DXd-pretreated group and 5.5 (range, 2-10) in the T-DXd–naïve group. DCR was 60.0% (9/15) in the T-DXd–pretreated group and 63.6% (14/22) in the T-DXd–naïve group. At a median follow-up of 6.5 months, median PFS was 4.5 months (95% CI, 1.9–7.1) overall, 4.1 months (95% CI, 2.2–6.0) in T-DXd–pretreated patients, and 8.7 months (95% CI, not evaluable) in T-DXd–naïve patients (log-rank p = 0.457). Conclusions: Dato-DXd showed clinically meaningful activity in heavily pretreated metastatic breast cancer irrespective of prior T-DXd exposure, supporting its use as a subsequent-line option and the feasibility of sequencing payload-sharing ADCs. Longer follow-up and accumulation of cases are warranted to further characterize PFS outcomes in clinical practice.
National trends and demographic disparities in mortality among adults with hepatocellular carcinoma and diabetes mellitus in the United States (1999–2020).
e16168 Background: Hepatocellular carcinoma (HCC) is a growing public health concern in the United States, particularly among individuals with diabetes mellitus (DM). The coexistence of DM can accelerate hepatic dysfunction, worsen clinical outcomes, and elevate HCC-related mortality risk. However, national trends in HCC and DM-related mortality, along with the demographic disparities remain insufficiently explored. Methods: We utilized CDC WONDER data from 1999 to 2020 to examine U.S. adults aged ≥25 years whose death certificates included both HCC (ICD-10 C22) and DM (ICD-10 E10–E14) as either underlying or contributing causes of death. Age-adjusted mortality rates (AAMRs) per 100,000 population were calculated overall and stratified by sex, age group, race/ethnicity, and state. Temporal trends were assessed using Joinpoint regression to estimate annual percent change (APC), with statistical significance defined as p≤0.05. Results: Overall, HCC among DM patients accounted for 33,955 deaths in the adult U.S. population from 1999 to 2020. The overall AAMR rose from 0.46 to 0.98, corresponding to a significant APC of 3.19% (95% CI: 2.96–3.50%, p < 0.001). Males experienced an increase in AAMR from 0.66 to 1.50 (APC 3.30%; 95% CI: 3.06–3.62), while females had rates rising from 0.32 to 0.55 (APC 2.41%; 95% CI: 1.97–2.96). Older adults accounted for the highest mortality burden (AAMR: 2.67), whereas middle-aged adults demonstrated an AAMR of 0.51. AAMRs were highest among American Indian or Alaska Native and White individuals. The American Indian or Alaska Native population exhibited the fastest rising trend (APC: 6.90%; 95% CI: 3.82–9.83). Significant increases were also observed among White (APC: 3.59%; 95% CI: 3.05–3.98), Hispanic or Latino (APC: 2.03%; 95% CI: 1.60–2.64), Black or African American (APC: 1.95%; 95% CI: 1.11–3.05), and Asian or Pacific Islander (APC: 1.40%; 95% CI: 0.48–2.76) populations. Non-metropolitan areas showed a more pronounced increase in mortality compared to metropolitan areas. Regionally, the West and South experienced the largest increases in deaths, while Texas, California, and Hawaii had the highest state-level rates. Conclusions: HCC mortality among DM patients in the United States nearly doubled from 1999–2020, with substantial disparities across sex, age, race/ethnicity, geographic region, and urban–rural status. These findings underscore the need for targeted prevention, early detection, and intervention strategies in high-risk populations to mitigate the growing burden of HCC in patients with diabetes.
Initial treatment modality and recurrence in non-metastatic leiomyosarcoma: A retrospective cohort study.
e23555 Background: Leiomyosarcoma (LMS) is an aggressive malignancy comprising 10–20% of soft tissue sarcomas, with high recurrence rates in non-metastatic cases. While surgery remains the mainstay, systemic therapy and radiation are often used for large, high-grade, or locally advanced tumors. Guidelines recommend neoadjuvant or adjuvant therapy in select non-metastatic cases, but how initial treatment influences recurrence remains unclear. We aimed to evaluate recurrence patterns by first treatment by analyzing real world data. Methods: We retrospectively reviewed non-metastatic LMS cases treated at the University of Miami. Patients were categorized by initial treatment: surgery, systemic therapy, or radiation. The primary outcome was recurrence (local or distant). Logistic regression was used to estimate odds of recurrence across treatment types. This project is part of an ongoing study that will further assess planned vs unplanned surgeries and high-risk features (e.g., high grade, large size) in systemically treated non-metastatic patients. Results: Among 151 patients, recurrence occurred in 58.1% of those receiving surgery first, 45.8% of those receiving systemic therapy first, and 50.0% of those receiving radiation first. Compared to the reference group, patients treated with systemic therapy first had significantly reduced odds of recurrence (OR 0.35, 95% CI 0.13–0.87, p=0.03). Although there was a trend toward higher recurrence odds with surgery first, the odds of recurrence were not statistically different in the surgery (OR 2.08, p=0.08) or radiation (OR 1.71, p=0.54) first groups. Conclusions: Systemic therapy as the initial treatment was significantly associated with lower odds of recurrence for patients with non-metastatic LMS. These findings support further investigation into treatment sequencing and highlight the importance of tailoring therapy based on risk features. Using real world data we can design investigator initiated trials to further validate findings and improve care in LMS.
Induction toripalimab and chemotherapy for organ preservation in locally advanced laryngeal and hypopharyngeal cancer: 3-year follow-up of the INSIGHT study.
6086 Background: This phase II study evaluated the efficacy and larynx-preservation potential of induction chemotherapy combined with the toripalimab in patients with locally advanced laryngeal and hypopharyngeal squamous cell carcinoma (LA-L/HPSCC). Primary and 1-year survival outcomes were previously reported; here we present the 3-year follow-up results. Methods: This is a single-arm phase II study. Patients with histopathologic confirmed, resectable LA-L/HPSCC and ECOG PS 0-1 were eligible. Three cycles of induction chemotherapy (paclitaxel 175mg/m 2 d1, cisplatin 25mg/m 2 d1-3) combined with toripalimab (240mg d0) were administered. Response assessment was performed after induction chemoimmunotherapy using RECIST 1.1 criteria. Patients with CR/PR of primary tumor received concurrent chemoradiation, followed by maintenance therapy of toripalimab. Otherwise, patients were referred to surgery, followed by adjuvant (chemo)radiation, and maintenance therapy of toripalimab. The primary endpoint is larynx-preservation rate at three months post-radiation. Secondary endpoints included overall survival (OS), progression-free survival (PFS), larynx preservation rate, and larynx-preservation survival (LPS), etc. Results: Twenty-seven patients were enrolled. Most cases exhibited stage IV disease (81.5%), with T4 representing 37.0%. Five patients underwent pretreatment tracheostomy. The date of data cut-off was Jan 23, 2026. With a median follow-up of 36.4 [95%CI: 33.4-39.4] months, 3-year OS rate, PFS rate, larynx preservation rate and LPS rate was 73.5%, 61.1%, 84.3% and 73.6%, respectively. Excluding patients with pretreatment tracheostomy, these rates improved to 86.4%, 70.8%, 90.2% and 81.1%. The 3-year larynx preservation rate for T2/3 and T4 disease was 92.9% and 70.0%, respectively ( p =0.081). All patients with preserved larynx at last follow-up maintained functional laryngeal status, free from tracheostomy or feeding tube dependence. Conclusions: Induction toripalimab combined with chemotherapy provided promising and durable larynx preservation rate in this cohort of extensively LA-L/HPSCC. Clinical trial information: NCT04995120 . Comparison of patients enrollment and survival among pivotal clinical trials. Study Phase Clinical Stage Larynx preservation rate at 3 year Progression-free rate at 3 year GORTEC 2000-01 III Stage III, IVHypopharynx 54.0%, larynx 46.0% 70.1% for TPF and 57.5% for PF 58% for TPF and 44% for PF Subgroup analysis ofTAX324 II Stage III 26.5%Stage IV 73.5%,Hypopharynx 46.4%, larynx l 64.5% Not available 43% for TPF and 29% for PF This study II Stage III 18.5%Stage IVa 33.3%Stage IVb 48.1%Hypopharynx 66.7%, larynx 33.3% 84.3% for whole cohort and 90.2% when excluding patients with pretreatment tracheostomy 61.1% for whole cohort and 70.8% when excluding patients with pretreatment tracheostomy
Trends and disparities in liver cancer mortality among adults with metabolic disorders in the United States, 1999–2023.
e16229 Background: Liver cancer is a leading cause of cancer-related mortality worldwide, with rising incidence linked to metabolic disorders. Conditions such as obesity, diabetes mellitus, and metabolic syndrome contribute substantially to non-viral liver carcinogenesis. However, long-term temporal trends and mortality disparities among adults with metabolic disorders in the United States remain incompletely characterized. Methods: Mortality data for liver cancer among adults with metabolic disorders were obtained from the centers for disease control and prevention (CDC) mortality database. Adults aged 25 years and older were included and age-adjusted mortality rates (AAMRs) per 100,000 were calculated. Temporal trends were evaluated using joinpoint regression and average annual percent change (AAPC) with 95% confidence intervals. Results: From 1999–2023, AAMR for liver cancer in adults with metabolic disorders rose from 0.17 to 0.65 per 100,000 in the U.S., with an overall AAPC of 5.95% [95% CI 5.2–6.7]. Men had higher absolute mortality (0.25→0.93; AAPC 5.68%), while women showed a sharper recent rise (0.11→0.41; AAPC 7.08%), peaking at 11.86% annually after 2016. Hispanic/Latino (0.27→0.89; AAPC 6.73%) and Black populations (0.15→0.75; AAPC 6.15%) experienced steady increases, whereas White mortality accelerated post-2011 (AAPC 9.37%). Regionally, the West had highest rates, the South showed highest growth, and Northeast/Midwest had sharp recent increases. Rural mortality overtook urban by 2020 (0.50 vs. 0.48). Most deaths occurred in medical facilities (48.2%) or home (33.1%), with highest state rates in Hawaii (0.56), Texas (0.47), and Rhode Island (0.47). Conclusions: Mortality from liver cancer in adults with metabolic disorders rose sharply in the U.S. since 1999, with accelerating trends and marked disparities by sex, race/ethnicity, region, and urbanization. These findings highlight an urgent need for targeted metabolic risk reduction and equity-focused prevention strategies. Trends in Age-Adjusted Mortality Rates (AAMR) from 1999 to 2023 by demographic and geographic variables. Variable AAMR 1999 (per 100,000) AAMR 2023 (per 100,000) AAPC (95% CI) Overall 0.16 0.64 5.94* (5.22 – 6.67) Males 0.25 0.92 5.67* (4.82 – 6.5) Females 0.11 0.40 7.08* (5.79 – 8.38) White 0.16 0.63 6.12* (5.41 – 6.82) Black 0.15 0.75 6.15* (5.11 – 7.19) Hispanic or Latino 0.27 0.89 6.73* (5.98 – 7.48) Variable AAMR 1999 (per 100,000) AAMR 2020 (per 100,000) AAPC (95% CI) Urban 0.16 0.47 5.38* (4.43 – 6.33) Rural 0.19 0.50 5.73* (4.48 – 6.99) AAPC denotes the average annual percent change; * indicates p < 0.05.
Quantitative baseline ctDNA as a prognostic biomarker in metastatic urothelial cancer.
e16572 Background: Detectable circulating tumor DNA (ctDNA) in patients with metastatic urothelial cancer (mUC) is associated with poor outcomes. Whether quantitative ctDNA values confer independent prognostic information beyond conventional parameters is unclear. Methods: We retrospectively analyzed patients with mUC (urothelial carcinoma [UC], variant, or mixed histology) treated at our institution who had ctDNA measured using the tumor-informed Signatera assay within 21 days prior to initiating a line of systemic therapy. Patients could contribute multiple treatment lines. ctDNA levels were reported as mean tumor molecules per milliliter (MTM/ml). The primary endpoint was overall survival (OS) from therapy initiation. Cox proportional hazards models evaluated baseline ctDNA as: (1) a quantitative continuous variable (log10-transformed), and (2) a qualitative binary variable (detectable vs. undetectable). Univariate and multivariable models estimated hazard ratios (HRs) with 95% confidence intervals (95% CIs). Multivariable models were adjusted for line of therapy, therapy class, Karnofsky Performance Status (KPS) <80% vs. ≥80%, and visceral metastases. Model comparison used Akaike Information Criterion (AIC) and likelihood ratio testing to assess incremental prognostic value of quantitative vs. qualitative ctDNA. Histologic subtype effect modification was assessed via interaction terms. Results: Among 38 unique patients with mUC, we evaluated 48 pre-treatment ctDNA timepoints (UC: n=29; variant/mixed histology: n=9). Baseline ctDNA was detectable in 89.6% of observations (43/48), with quantitative values ranging from 0 to 5879.2 MTM/ml (median 13.1 MTM/ml, interquartile range 2.5-83.6 MTM/ml). In Cox models, higher quantitative ctDNA was independently associated with worse OS adjusted for line of therapy, therapy class, KPS, and visceral metastases (Table). Quantitative ctDNA provided superior prognostic discrimination versus binary detectability thresholds, with improved AIC (ΔAIC -10.0) and likelihood ratio testing (p=0.002). No histologic subtype effect modification was observed (interaction p=0.4). Conclusions: Quantitative baseline ctDNA levels provide superior prognostic risk stratification versus qualitative detectability thresholds across therapy lines and histologic subtypes in mUC, supporting its use for prognostic assessment and as a potential stratification factor for clinical trials. Association of baseline quantitative ctDNA with OS using Cox proportional hazards models (log10[ctDNA + 1]). HR >1 indicates increased risk of death. Model HR (95% CI) P-value Unadjusted 2.6 (1.5–4.4) <0.001 Adjusted for line of therapy 2.6 (1.5–4.3) <0.001 Adjusted for KPS 2.6 (1.5–4.5) 0.001 Adjusted for visceral metastases 2.7 (1.5–4.9) <0.001 Adjusted for therapy class 2.4 (1.4–4.2) 0.001 Fully adjusted 3.0 (1.5–5.8) 0.002
Neurosensory deficits and functional outcomes in childhood cancer survivors: A report from the Childhood Cancer Survivor Study (CCSS).
10046 Background: Survivors of childhood cancer are at risk for neurosensory deficits secondary to their disease and treatment. Previous research has characterized system-specific (e.g., visual) impairments; however, the prevalence of multisystem neurosensory deficits and their functional impact remain unknown. Methods: Adult 5-year survivors (n=20037, median age 36 [range 18-69] years, 53.4% male) and sibling controls (n=4121) reported neurosensory deficits related to vision, hearing, vestibular, and neuropathy. Comorbidities were graded using modified CTCAE v5 and defined as having at least one grade 1 neurosensory deficit in one, two, and three/four systems. Survivors reported neurocognitive function (CCSS Neurocognitive questionnaire; impairment: <10 th %ile of sibling distribution), emotional distress (BSI-18; impairment: T score ≥63), quality of life (SF-36; impairment: T score <40), and functional independence. Multivariable models estimated the prevalence of neurosensory comorbidities, adjusted for age, sex, and race. Multivariable models further adjusted for other chronic conditions and neurotoxic therapies examined associations between comorbidities and functional outcomes in survivors. Results: Survivors had higher prevalence of neurosensory deficits in one (31% vs. 24%; prevalence ratio [PR] 1.4, 95% confidence interval [CI] 1.3-1.5), two (14% vs. 8%; 2.2, 1.9-2.5) and three/four systems (9% vs. 3%; 3.3, 2.9-4.1) than siblings. Neurosensory comorbidities were associated with greater risk of neurocognitive impairment (task efficiency and memory), emotional distress (anxiety) and poor quality of life (physical and social function) in a dose-dependent manner in survivors (Table). Similar effects were observed for indicators of functional independence: assistance with personal care/routine needs (one system: relative risk [RR] 2.7, 95% CI 2.2-3.3; two systems: 4.1, 3.3-5.0; three/four systems: 6.5, 5.4-7.9), interference with job/school (2.5, 2.2-3.0; 3.8, 3.2-4.5; 6.1, 5.2-7.1), no driver’s license (1.5, 1.3-1.8; 2.4, 2.1-2.8; 3.8, 3.2-4.4), and non-independent living (1.3, 1.2-1.4; 1.8, 1.6-2.0; 2.1, 1.9-2.4). Conclusions: Adult survivors of childhood cancer have high rates of comorbid neurosensory deficits that have a dose-dependent impact on functional outcomes. Survivors with multisystem deficits should be prioritized for interventions to support functional independence. Relative risk (95% CI) of impaired outcomes in survivors with neurosensory comorbidities. Neurosensory comorbidities(# organ systems) Memory TaskEfficiency Anxiety Physical Function Social Function 0 (ref.) - - - - - 1 1.6 (1.4-1.8) 1.8 (1.6-2.0) 2.6 (2.2-3.1) 2.2 (1.9-2.6) 1.9 (1.7-2.1) 2 2.2 (2.0-2.5) 2.4 (2.2-2.7) 3.4 (2.8-4.1) 3.1 (2.7-3.5) 2.5 (2.2-2.8) 3/4 3.1 (2.7-3.4) 3.3 (3.0-3.7) 5.2 (4.4-6.3) 4.4 (3.8-5.0) 3.2 (2.9-3.7)
Has early detection improved?: Trends in localized PDAC diagnoses in the U.S. (2004-2022).
e16454 Background: Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest cancers in the United States; most patients are not diagnosed until they present with symptomatic, advanced-stage disease. However, advances in imaging, endoscopic techniques, biomarker development, liquid biopsy, and high-risk screening programs may have helped shift detection toward earlier stages. National trends in stage-specific PDAC incidence were analyzed to determine the trends in stage-at-diagnosis over time. Methods: A retrospective cohort study was conducted using the NCI’s SEER database. Patients aged 15-84 years old diagnosed with PDAC between 2004 and 2022 were included. Age-adjusted incidence and mortality rates were calculated per 100,000 people. Trends were assessed using Joinpoint regression to estimate annual percent change (APC). Multivariable Poisson regression was used to estimate incidence rate ratios (IRRs) adjusting for age, sex, race/ethnicity, stage, and calendar year. Results: Between 2004 and 2022 the incidence of localized PDAC was 0.97 per 100,000 versus 1.33 for regional and 5.62 for distant disease. In stage-stratified models, incidence of localized PDAC increased 5% annually, compared with only a 1% increase for both regional and distant stages. Notably, from 2015 to 2022 the APC of localized PDAC was 10.2%. Further stratification by age, sex, and race demonstrated stage-consistent results including a rising with age, lower risk in females, and disparities by race (Black > White; Hispanic, AI/AN, and Asian/PI < White). APC plots confirmed this positive trend towards localized PDAC diagnosis across all subgroups. Conclusions: There has been clear improvement in the ability to diagnose PDAC earlier. While most patients are still diagnosed with distant disease, the increasing rate of localized PDAC diagnoses likely reflect multiple factors. Widespread use of high-resolution CT and MRI has led to more incidental detection of asymptomatic PDAC. The roll out of high-risk surveillance programs targeting individuals with familial or genetic predispositions have enabled earlier diagnosis and improved outcomes. Endoscopic ultrasound (EUS) has improved the ability to detect small or cystic lesions. Liquid biopsy has also begun to demonstrate promise as a non-invasive way to detect early PDAC. These factors, along with heightened clinical awareness, have resulted in a measurable stage shift. These findings support continued investment in early detection strategies to ultimately improve survival. PDAC Incidence trends and annual percent change by stage (2004 – 2022). Stage at Diagnosis Incidence* Incidence Rate Ratio (IRR)* Annual Percent Change (APC)* Localized 0.97 1.05 (1.05-1.06) 5.71 (p < 0.001) Regional 1.33 1.01 (1.00-1.01) 1.83 (p = 0.039) Distant 5.62 1.01 (1.01-1.01) 0.91 (p < 0.001) *95% CI; per 100k people.
Pembrolizumab–lenvatinib beyond immunotherapy progression in endometrial cancer: A real-world analysis.
5612 Background: The integration of immune checkpoint inhibitors (ICIs) into frontline therapy for advanced or recurrent endometrial cancer (aEC) has transformed treatment paradigms. However, the management of patients who experience disease progression after ICI-based therapy remains challenging. In the absence of prospective guidance, ICI rechallenge and ICI-based combinations beyond progression are already being used in clinical practice. In this real- world study, we aimed to evaluate the effectiveness of pembrolizumab-lenvatinib (PL) beyond ICI progression in patients with aEC. Methods: A retrospective study was conducted using the TriNetX database, defining two cohorts of aEC patients: 527 patients who received PL and 2,582 patients who did not receive PL but were treated with either paclitaxel or doxorubicin (chemotherapy, CHT cohort). Both cohorts had received an ICI-based regimen within the previous three years. Patients with any other malignancy were excluded. Propensity score matching (PSM) was used to balance cohorts for age, race, body mass index (BMI), major comorbidities, mismatch repair (MMR) status and prior olaparib exposure. The primary endpoint was overall survival (OS); secondary endpoints were treatment-related toxicities, including hypothyroidism and heart failure. OS was estimated using Kaplan–Meier methods, with hazard ratio (HR) used to compare OS and odds ratio (OR) used to compare toxicities. Results: After PSM, 521 matched pairs of patients (mean age +/- standard deviation: 66,4 +/- 9,6 years) were included in the PL and CHT cohorts, respectively, with well-balanced baseline characteristics. Asian patients were similarly represented in the two groups (7.3% vs 7.4%), most patients were obese (BMI ≥30: 59,3% vs 57,8%), only a small proportion had known MMR-deficient disease (2.1% and 1.9%), and just few of them were previously treated with olaparib (1.9%). After a median follow-up of 8.6 months (interquartile range, IQR 14.3) in the PL cohort and 11.5 months (IQR 16.7) in the CHT cohort; median OS was 27,4 months with PL and was not reached with CHT (HR = 2.25, 95% CI 1.76–2.89; p<0.001). Conclusions: The rise of ICIs in frontline therapy for aEC marks a paradigm shift and raises the question on how to manage patients who progress after prior immunotherapy. This is the first large, real-world cohort analysis to evaluate PL beyond immunotherapy progression in aEC. In this study, PL did not improve OS compared with CHT in patients previously exposed to ICIs. These findings suggest that PL may not be the optimal choice in this setting, and further work is needed to clarify the best post-ICI sequencing strategies and to develop approaches to overcome resistance.
Microbial dysbiosis as predictor of benefit from CBM588 as an adjunct to immune checkpoint blockade (ICB)–based first line therapies in metastatic renal cell carcinoma (mRCC).
4519 Background: The Clostridium butyricum -based live biotherapeutic, CBM588, demonstrated signals for enhanced clinical activity with first-line ICB combinations in two randomized phase I trials for mRCC. However, impact of microbial dysbiosis on the benefit of CBM588 supplementation is unclear. Herein, we examined prognostic and predictive value of microbial dysbiosis with CBM588. Methods: We analyzed clinical outcomes and stool whole-genome sequencing data from a combined cohort from two randomized phase I clinical trials. Both enrolled treatment-naïve patients with mRCC and randomized them to receive nivolumab/ipilimumab (NCT03829111) or nivolumab/cabozantinib (NCT05122546) alone (standard of care [SOC]), or with CBM588 (SOC+CBM588). Baseline TOPOSCORE, a stool metagenomic dysbiosis index linked to ICB outcomes, was analyzed continuously (S score positively correlated with dysbiosis) and categorically (SIG1+ [dysbiosis phenotype] vs SIG2+ [non-dysbiosis]). Associations with progression free survival (PFS) and objective response rate (ORR, per RECIST 1.1) with SOC and SOC + CBM588 were assessed. Results: Fifty-nine patients were included: 39 in the SOC + CBM588 arm and 20 in the SOC arm. Median age was 65 (range 36-90), with the majority male (69.5%), clear-cell (88.1%) and intermediate/poor risk (67.8%) mRCC. Baseline clinical characteristics were comparable across arms. ORR was 66.7% in SOC+CBM588 arm versus 20.0% in the SOC arm (p = 0.001). Median PFS was 32.1 months (95% CI 16.6-NR) with SOC+CBM588 versus 3.7 months (95% CI 2.6-17.0) with SOC (HR 0.36 [95% CI 0.19, 0.67], p = 0.001). At baseline, S score was similar across arms (p = 0.16), and SIG1+ was seen in 55.6% of patients in the SOC+CBM588 arm versus 44.4% in the SOC arm (p = 0.441). While differences in PFS were not statistically significant in the SIG2+ cohort between SOC+CBM588 and SOC alone (32.0 vs 10.9 months, HR 0.49 [95% CI 0.19-1.3], p = 0.149), in the SIG1+ setting, a PFS improvement was seen for SOC+CBM588 versus SOC alone (24.9 vs 2.8 months, HR 0.19 [95% CI 0.07-0.53], p < 0.001). Notably, S score was associated with response to SOC+CBM588 among patients who received nivolumab/ipilimumab backbone (median S score 0.668 in response vs 0.540 in no response, p = 0.046), while no such association was observed in patients treated with nivolumab/cabozantinib backbone (median S score 0.681 vs 0.821, p = 0.554, respectively). Conclusions: Addition of CBM588 to ICB-based first-line combinations conferred a disproportionately greater benefit in patients with a dysbiotic stool phenotype, underscoring actionability of TOPOSCORE as a potential predictive biomarker in this setting. The upcoming phase III randomized placebo-controlled BIOFRONT trial will assess clinical activity of CBM588 and advance microbiome-based predictive biomarker development in mRCC.
Impact of endometrial cancer surgery on the development of cardiovascular risk factors in women under 51.
e17645 Background: In younger patients, the rising burden of endometrial cancer (EC) intersects with cardiovascular (CV) disease, now a predominant driver of non-cancer mortality in gynecologic oncology. Abrupt loss of ovarian function after hysterectomy with bilateral salpingo-oophorectomy (BSO) may unmask or accelerate cardiometabolic vulnerability. Here, we assess the incidence of new CV risk factors among women under 51 years of age who underwent BSO for EC compared to those who underwent BSO for benign indications. Methods: Patients under 51 years of age who underwent hysterectomy with BSO at a single academic center between January 1, 2017 to September 1, 2023 were identified from the electronic health record. They were classified into an exposure cohort of those surgically treated for EC and a comparison cohort of those who underwent the same procedure for borderline pathology or risk-reducing indications. Demographic and clinical variables, including age at surgery, body mass index (BMI), smoking status, and baseline CV history, were abstracted. The primary endpoint was incident or progressive CV risk, defined as new-onset hypertension, hyperlipidemia, or atrial fibrillation, or initiation/intensification of antihypertensive, lipid-lowering, antiplatelet (aspirin), or anticoagulant therapy. Associations between EC status and the primary endpoint were evaluated using multivariable models adjusted for age, BMI, and smoking. A p-value <0.05 was considered statistically significant. Analyses were performed using SAS version 9.4 (SAS Institute, Cary, NC). Results: In our cohort of 399 patients, 281 (70.4%) carried an EC diagnosis and 118 (29.6%) a benign diagnosis. EC patients were more likely to be younger, belong to a minority race/ethnicity, have a higher BMI, and smoke (p<0.01). EC patients were more likely to develop a new CV comorbidity, with 83 (29.6%) of the EC group diagnosed at a median time of 19.4 months and 25 (21.2%) of non-EC patients diagnosed at 32.9 months (p<0.05). There was a greater 5-year cumulative incidence of the primary outcome in EC patients (46%, 95% CI: 38-55%) compared with non-EC patients (30%, 95% CI: 22-41%). Gray’s test confirmed a statistically significant difference in the cumulative incidence functions between groups (p=0.01). After adjustment, EC patients had a 51% increase in risk of the primary outcome, though this did not reach statistical significance (adjHR 1.51, 95% CI: 0.95-2.40, p=0.08). Among patients who developed at least one new CV risk factor, 49% of EC patients had an increase in anti-hypertensive or lipid-lowering therapy compared to 0% in the non-EC group (p<0.01). Conclusions: Young patients with EC had a higher and earlier burden of new CV risk factors than those undergoing surgery for benign indications. This highlights the need to incorporate systematic CV risk assessment as an integral part of routine EC surveillance.
Leisure-time physical activity among US cancer survivors, 2020-2024.
10623 Background: Physical activity (PA) after a cancer diagnosis reduces treatment-related side effects and improves quality of life and cancer outcomes. Historical data show that most cancer survivors do not meet recommended levels of aerobic and strength training PA. However, the recent pattern of PA in people with cancer remained unexamined. Methods: This pooled cross-sectional study analyzed data from the 2020, 2022, and 2024 National Health Interview Survey to examine the prevalence and predictors of meeting PA guidelines among US cancer survivors vs. non-cancer adults. The analytic sample included adults aged ≥18 years with available cancer history. Data were collected on frequency and duration of aerobic and strength training PA. Age-adjusted prevalence of meeting aerobic (≥150 minutes per week of moderate-intensity activity or ≥75 minutes per week of vigorous-intensity activity) and strength training (≥2 days per week) PA guidelines were estimated across sociodemographic and health characteristics among cancer survivors and non-cancer adults. Multivariable logistic regression models were fitted to identify factors associated with meeting PA guidelines among cancer survivors. Results: The final sample included 8,974 cancer survivors (Mean age: 65.7 [SE: 0.21]; 57.3% female) and 79,036 non-cancer adults (Mean age: 46.6 [SE: 0.11]; 51.1% female). After age-adjustment, 44.5% of cancer survivors met guidelines for aerobic exercise (95% CI: 41.8-47.3), 28.9% for strength training (26.3-31.6), and 22.2% for both (19.8-24.7%), significantly lower than the non-cancer group (48.3%, 32.5%, and 26.0%; all p <0.01). Patterns of lower prevalence were consistent across aerobic, strength training, and combined guidelines. Among cancer survivors, age-adjusted prevalence of meeting PA guidelines was significantly lower among those who were female, non-Hispanic Black or Hispanic, had lower levels of education or income, lived alone, were unemployed, had BMI ≥ 25, or were current smokers (all p<0.05). Survivors of gynecological and lung cancers had significantly lower age-adjusted prevalence of meeting both aerobic and strength training guidelines, while gastrointestinal cancer survivors had lower prevalence of meeting strength training guidelines only (all p<0.01). After adjustment for all covariates, not meeting PA guidelines in cancer survivors remained significantly associated with older age, female, lower education level, BMI ≥ 25, current smoking, and presence of cardiovascular disease or diabetes (all p<0.05). Conclusions: During 2020 and 2024, fewer than 1 in 4 cancer survivors met both aerobic and strength training PA guidelines. These findings underscore a critical need to integrate PA interventions into standard oncology survivorship care, with particular attention to addressing socioeconomic barriers and tailoring programs for survivors with comorbidities and high-risk cancer types.
Antibody-drug conjugate adoption in triple-negative breast cancer through community-based quality improvement.
e23328 Background: Community oncology settings face challenges adopting evidence-based protocols for integrating novel therapies such as antibody-drug conjugates (ADCs) into workflows. These challenges are exacerbated by limited experience with new agents, variability in adverse event (AE) management, and lack of standardized workflows, ultimately affecting treatment sequencing, supportive care, and shared decision-making. Methods: In 2025, 51 healthcare professionals (HCPs) from 6 US oncology clinics within a large community network completed surveys assessing practice patterns/barriers related to integration of novel therapies, AE management, supportive care, and patient (pt) education. Site-specific audit-feedback sessions were conducted to identify root causes of gaps and develop action plans, including implementing a TNBC treatment pocket guide. An ensuing network-wide summit was held to share key insights and lessons learned, and develop strategies to address gaps. Results: At baseline, few HCPs reported high confidence integrating ADCs (31%) or determining optimal treatment sequencing (25%). Top barriers included limited experience with agents (35%), uncertainty about sequencing (22%), and concerns about AE management (19%). The toxicities HCPs found most difficult to manage were diarrhea (39%), interstitial lung disease (37%), nausea/vomiting (31%), and neutropenia (29%). Despite known neutropenia risk with sacituzumab govitecan, G-CSF use varied with 27% using primary prophylaxis in high-risk pts, 20% as primary prophylaxis in all pts, 29% as secondary prophylaxis, and 12% reporting no use. About half (51%) of HCPs consistently used supportive care protocols for ADC AE management. While most provided pt education on AE management (82%) and treatment expectations (71%), fewer addressed biomarkers (49%), caregiver education (39%), behavioral health (24%), or clinical trials (20%). Barriers to shared decision-making included difficulty tailoring communication to pt understanding (39%) and limited staff resources (37%). HCPs identified improved supportive care focus (43%) and multidisciplinary communication (45%) as key opportunities to improve care. These findings informed site-specific action plans and network-wide alignment on implementing clinical workflows to improve guideline-aligned care and ADC AE management, integrating the TNBC treatment guide, establishing order sets for supportive care, and developing new patient education resources. Conclusions: Significant gaps in confidence, AE management, and care standardization limit effective ADC integration in community settings. A network-based QI approach and dedicated resources enhanced alignment on practical strategies to improve guideline-concordant, multidisciplinary, and pt-centered care. Ongoing evaluation will assess the impact of these interventions over time.
Upfront low-dose diet-modified nilotinib versus standard imatinib in Indian patients with newly diagnosed chronic-phase chronic myeloid leukemia: The NILLOW phase II randomised trial.
6584 Background: Upfront use of second-generation tyrosine kinase inhibitors in chronic myeloid leukemia (CML) is limited in resource-constrained settings due to cost, fasting requirements, and tolerability concerns. Food increases nilotinib bioavailability, enabling effective dose reduction. Methods: NILLOW was a single-center, open-label, randomized phase II study. Newly diagnosed CML-CP patients were randomized 1:1 to receive nilotinib 150 mg twice daily with meals or imatinib 400 mg once daily. The primary endpoint was EMR at 3 months (BCR-ABL1 IS ≤10%). Safety and hematologic recovery were evaluated as secondary endpoints. Results: EMR at 3 months was significantly higher with nilotinib compared to imatinib (73.8% vs 46.2%; absolute difference 27.6%; p=0.001). Patients receiving nilotinib demonstrated faster hemoglobin recovery during follow-up (p<0.01). Grade 3/4 anemia was lower with nilotinib (5.5% vs 17.8%; p=0.02). Imatinib was associated with higher rates of peripheral edema, periorbital edema, rash, pruritus, and headache (all p<0.05). Conclusions: Low-dose fed nilotinib improves early molecular response with superior tolerability compared to imatinib. This approach represents a cost-effective frontline strategy for CML in low-resource settings. Further studies as phase 3 maybe be followed up to confirm the signal. Clinical trial information: CTRI/2024/03/064707.
Incidence of early-onset colorectal cancer in the United States: A population-based analysis (2000-2019).
e15676 Background: The incidence of colorectal cancer (CRC) among individuals younger than 50 years has been increasing in the United States, while rates among older adults have declined. Understanding demographic patterns of early-onset CRC is essential to inform prevention and screening strategies. We examined temporal trends in early onset CRC incidence overall and stratified by sex and race using population-based cancer registry data. Methods: We conducted a descriptive epidemiologic study using data from the Surveillance, Epidemiology, and End Results (SEER) 17 registries. Incident cases of malignant colorectal cancer diagnosed between 2000 and 2019 were identified. Early-onset CRC was defined as diagnosis before age 50 years; late-onset CRC was defined as diagnosis at age 50 years or older. Age-adjusted incidence rates per 100,000 person-years were calculated using SEER*Stat and standardized to the 2000 US standard population. Incidence rates were summarized across predefined calendar periods (2000–2004, 2005–2009, 2010–2014, and 2015–2019) and stratified by sex and race. Temporal changes were assessed descriptively using absolute and relative differences in incidence rates. Results: Between 2000 and 2019, 93,186 early-onset and 746,447 late-onset CRC cases were identified. Among individuals younger than 50 years, age-adjusted CRC incidence increased steadily from 6.0 per 100,000 in 2000–2004 to 8.4 per 100,000 in 2015–2019, representing an approximate 40% increase. In contrast, incidence among individuals aged 50 years and older declined from 173.1 to 116.1 per 100,000 over the same period. Early-onset CRC incidence was consistently higher among males than females, increasing from 6.4 to 8.7 per 100,000 in males and from 5.6 to 8.0 per 100,000 in females between 2000–2004 and 2015–2019. Racial disparities were observed, with Black individuals experiencing the highest incidence across all periods (7.6 to 8.6 per 100,000), while White individuals demonstrated a substantial increase over time (5.8 to 8.6 per 100,000). Asian or Pacific Islander populations had lower incidence overall but showed steady increases. Estimates among American Indian/Alaska Native individuals were based on small case counts and were less stable. Conclusions: Early-onset colorectal cancer incidence increased substantially in the United States from 2000 to 2019, in contrast to declining incidence among older adults. Rising rates were observed across sexes and racial groups, with persistently higher incidence among males and Black individuals and notable increases among White individuals. These findings highlight a growing public health burden of early-onset CRC and underscore the need for targeted prevention strategies and continued evaluation of age-based screening recommendations.
Interrupting sedentary time to improve cardiometabolic health and toxicity in patients with lymphoma receiving chemotherapy: The iSTAND trial.
TPS12173 Background: Among lymphoma patients treated with steroids, hyperglycemia is a common side effect. Episodes of hyperglycemia increase the likelihood of chemotherapy alterations, infection risk, and decreased overall survival. Interrupting sedentary time (IST) helps manage glycemic control in the diabetic population but is understudied among lymphoma patients. Additionally, there is preliminary evidence that IST during a chemotherapy infusion may reduce chemotherapy-related adverse effects. Therefore, we designed the iSTAND study to assess the feasibility of a 12-week IST intervention at home and during chemotherapy infusion appointments, and the preliminary efficacy on said intervention on a) cardiometabolic biomarkers and b) chemotherapy completion and toxicities among lymphoma patients. Methods: The iSTAND study is a prospective study aiming to recruit 24 patients diagnosed with lymphoma receiving either R-CHOP or POLA-R-CHP chemotherapy regimens. The first 3 enrolled patients will automatically be assigned to the intervention group to pilot the intervention (pre-pilot group). The remaining 21 patients will be randomly assigned IST intervention (n = 14) or control (n = 7). Five patients have been enrolled thus far (January 2026). The 12-week intervention will include a supervised component completed during chemotherapy infusion appointments and a self-directed home-based component. The in-clinic component will involve 2-minutes of walking every 30-minutes at 65-70% age predicted heart rate maximum, and two lower body resistance exercises every hour (1 set, 5-12 repetitions, 6-7 RPE) repeated for up to 4 hours of the infusion appointment. The home-based component will involve walking 250 steps per hour and alternating two lower and two upper body resistance exercises every hour (6 days/week for 6-12 hours/day). Patients will receive a Fitbit and resistance bands. Additionally, patients will receive daily movement prompts via Fitbit and text messages to encourage and assess adherence. Outcomes will be assessed at baseline prior to the second infusion and post-intervention after the 12-week intervention period. The primary outcome will be feasibility assessed via completion of ≥70% of prescribed activities, ≤50% rate of refusal, ≥70% retention rate, and ≥70% acceptance rate via acceptability of intervention questionnaire. Secondary outcomes include glucose levels and insulin assessed via continuous glucose monitor and fasting blood. Exploratory outcomes include quality of life, sleep quality, chemotherapy completion rate, and chemotoxicities assessed via questionnaires and medical records. Clinical trial information: NCT06923397 .
Real-World outcome of apalutamide therapy in mHSPC patients depending on age, dose reduction, and PSA decline: Data from the German AmPel trial.
e17094 Background: Data from the Titan Trial (apalutamide + ADT) showed a benefit for mHSPC patients who achieved low ( < 0.2 ng/ml) and ultra-low (UL-1 0.02–0.2 ng/ml / UL-2 < 0.02 ng/ml) PSA levels under apalutamide (APA) therapy. The AmPel study (Use of Apalutamide in Prostate Cancer in Middle-Hesse) has been collecting data from mHSPC patients in urology practices since November 2021. Methods: In this multicenter investigator initiated trial (IIT), patient data (demographic and tumor-specific) as well as outcomes (PSA response/course including UL ( < 0.2 ng/ml), UL-1 (0.02-0.2 ng/ml), UL-2 ( < 0.02 ng/ml)), side effects, and dose modifications are recorded. A positive approval from the ethics committee is available. Results: 127 pat (73 y, range 43-87, ECOG 0/1/2/3: 33.1/50.4/9.4/4.7%) were documented from 9 specialized urology practices (med FU 14 months). Synchronous mHSPC was present in 67.7%, an initial Gleason score ≥ 8 was observed in 65.3%, high-volume mHSPC in 56.7%, and the median PSA before starting APA was 15.4 ng/ml. After 3 months PSA decreased by 98.5% and after 12 months by 99.5%. There was no PFS difference neither in older pat ( > 75 years, p = 0.46) nor in case of dose reduction (15%) of APA (p = 0.7). After 12 months, 32.6% of pat reached a UL-2 PSA and nearly the same number (31.6%) reached a UL-1 PSA. There was a significant PFS advantage for UL-1 PSA (HR 0.28) and UL-2 PSA (HR 0.06). In the overall cohort, PFS has not been reached yet. Currently, 77.2% are still receiving APA. In 22.8% treatment was discontinued after a median of 8 months: in 9.4% due to progression. Overall, 7 pat died – 2 (1.6%) due to PCA. Conclusions: Our Real World Data show that APA therapy is highly effective in mHSPC and achieving UL-PSA quickly and sustainably (64.2% after 12 months) as well as PSA decrease of > 95% (91.6% after 12 months) - associated with significantly improved PFS in an unselected patient population and good tolerability in daily practice.