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Real world evidence from a retrospective multi-center analysis on first-line therapy for metastatic papillary renal cell carcinoma: A GUARDIANS project.

496 Background: Papillary (pRCC) renal cell carcinoma is a rare cancer. We evaluated real-world treatment outcomes of 1st line treatment in these cohorts in Germany. Methods: Data were collected retrospectively from 13 GU cancer centres in Germany. Patients (pts) with advanced or metastatic pRCC were eligible. Adverse events (AEs) were reported according to CTCAE 5.0. ORR was accessed according to local standard. Progression Free Survival (PFS) were calculated from start of treatment to progression or death. Descriptive statistics and KM-plots were utilized, where appropriate. Results: 131 suitable pts (82% male) with median age of 63 years (range 22-86) were included. ECOG 0-1 was 70%, nephrectomy was performed in 78%. IMDC scores were: 0 in 18%, ≥ 1 in 53%, missing in 29%. The most common sites of metastasis were lymphatic (66%) and pulmonary (41%) metastases. 52% patients received first-line IO-combinations (IO-IO: 18%, TKI-IO: 34%) and 40% patients TKI-monotherapy, predominantly sunitinib. AEs (all grades) with IO‐based or TKI mono therapy, were reported in 86% and 74%, CTCAE grade ≥ 3 in 46% and 22%, dose modifications were required in 35% and 26.0%. ORR and survival outcomes with median follow-up of 19 months (IQR 9-35) are described in the table. Conclusions: TKI-based therapy are frequently applied in pRCC. Our data support the use of IO+ TKI as a first-line standard for patients with pRCC. Major limitations were the retrospective data capture and short follow-up of our study. Additional analyses to tailor treatment strategies in patients with metastatic pRCC is warranted. ORR and survival outcomes of study population. Parameter All therapiesN=131 IO-ION=23 IO-TKIN=45 TKI monoN=51 OtherN=12 ORR (CR+PR) 34% 35 % 40 % 31 % 8% SD 29% 17 % 33 % 29 % 17% PD 23% 35 % 13 % 29 % 17% unknown 14% 13% 13 % 10 % 58 % mOS, months,95%-CI 32 .1 (24.4-39.9) 15.6(7.5-23.7) Not reached 27.6(19.7-35.7) 32.1(21.15-42.7) mPFS, months,95%-CI 8.5(6.5-10.4) 4.9(0.5-9.4) 9.2(3.5-15.0) 9.0(6.9-11.1) 8.5(0.0-22.8)

Real-world use of bone-modifying agents (BMA) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) in the US.

95 Background: Most pts with prostate cancer with bone metastasis experience symptomatic skeletal events (SSEs) [PMID: 23884473], leading to increased morbidity and mortality. BMAs have been approved since 2007 and are recommended in mCRPC to prevent SSEs in pts with bone metastases or a high risk of osteoporotic fracture. Herein, we sought to assess the real-world trends of BMA administration in pts with mCRPC. Methods: We used the de-identified nationwide Flatiron Health electronic health record (EHR)-derived database to extract pt-level data. Inclusion criteria: pts with mCRPC with available date of diagnosis of mCRPC and information on receipt of BMA. Pts were categorized into 2 cohorts based on BMA receipt (e.g., bisphosphonates, denosumab, teriparatide, romosozumab) or not. Treatment trends of BMA by year of mCRPC diagnosis were summarized using frequency and percentages. Baseline characteristics at the time of mCRPC diagnosis (age, race-ethnicity, practice type, insurance) were compared between cohorts using the Wilcoxon rank-sum and Chi-squared tests. Results: Of 24,105 pts with metastatic prostate cancer in the dataset, 14,112 with mCRPC were eligible and included. 7,990 (56.6%) received BMA while 6,122 (43.4%) did not. In BMA receipt cohort: median age was 75 (IQR 67 – 81), majority were White (61%), treated in community practice (87%) and had commercial health plan (80%). In BMA non receipt cohort: median age was 75 (IQR 68 – 82), majority were White (61%), treated in a community practice (78%), and had commercial health plan (76%). The use of BMA decreased over time from 56% in 2013 to 46% in 2024 (Table). Statistically significant differences existed between cohorts in race-ethnicity, practice type, and insurance (p < 0.001) and will be presented at the meeting. Conclusions: Despite recommendations to use BMAs in pts with mCRPC and bone metastasis or high risk of osteoporotic fracture, our findings reveal a low utilization rate of BMAs in mCRPC setting with a notable decline over time. This highlights the need to incorporate the use of BMAs in clinical practice and improve access to these agents. Trends by year of mCRPC diagnosis in receipt of the first BMA and frequency and percentage of each agent. Year 2013N = 549 2014N = 1035 2015N = 1223 2016N = 1345 2017N = 1441 2018N = 1346 2019N = 1469 2020N = 1380 2021N = 1352 2022N = 1393 2023N = 1196 2024N = 383 Receipt of BMA, n (%) 316 (56) 674 (65) 792 (65) 837 (62) 886 (61) 766 (57) 816 (56) 766 (56) 692 (51) 713 (51) 556 (46) 176 (46) Denosumab, n (%) 190 (60.1) 450 (66.8) 557 (70.3) 599 (71.6) 606 (68.4) 533 (70) 526 (64.5) 488 (63.7) 410 (59.2) 414 (58.1) 290 (52.2) 94 (53) Zoledronic acid, n (%) 120 (38) 220 (32.6) 228 (28.7) 233 (27.8) 270 (30.5) 225 (29) 281 (34.4) 273 (35.6) 277 (40) 295 (41.4) 258 (46.4) 82 (47) Teriparatide, other bisphosphonates, n (%) 6 (1.9) 4 (0.6) 7 (1) 5 (0.6) 10 (1.1) 8 (1) 9 (1.1) 5 (0.7) 5 (0.7) 4 (0.5) 8 (1.4) 0

Phase 1/2 OMAHA-01A substudy of oral CYP11A1 inhibitor opevesostat alone or in combination with other therapies for metastatic castration-resistant prostate cancer (mCRPC).

TPS300 Background: Current treatments for mCRPC are associated with hormone dependence and the development of resistance. Therapeutic agents with novel mechanisms of action are needed for this patient population. Opevesostat (MK-5684; ODM-208) is an oral, nonsteroidal inhibitor of cytochrome P450 11A1 (CYP11A1), a catalyst of the first and rate-limiting step of steroid biosynthesis. In the phase 1/2 CYPIDES study, opevesostat demonstrated antitumor activity in patients with heavily pretreated mCRPC (1). OMAHA-U01 is an adaptive, open-label, rolling-arm, multicenter, phase 1/2 umbrella study that will evaluate the safety and efficacy of opevesostat-based investigational therapies in prostate cancer. Substudy 01A (NCT06353386) will evaluate opevesostat alone or in combination with other therapies in patients with previously treated mCRPC. Methods: Eligible patients have mCRPC that progressed during ADT ≤6 months before screening, and on/after 1-2 NHAs for metastatic or nonmetastatic hormone-sensitive prostate cancer and nonmetastatic or mCRPC. Prior treatment with ≤1 taxane for mCRPC is allowed. A safety lead-in phase for all opevesostat-based experimental combinations (~10 patients in each arm) will establish the recommended phase 2 dose (RP2D), followed by an efficacy phase (opevesostat alone, ≤100 patients; opevesostat-based combinations, ~40 patients each). Patients will be randomly assigned 1:1:1:1 to opevesostat 5 mg PO BID, opevesostat 5 mg PO BID + olaparib (RP2D), opevesostat 5 mg PO BID + docetaxel (RP2D), and opevesostat 5 mg PO BID + cabazitaxel (RP2D). The primary endpoint for the safety lead-in phase is safety and tolerability. Primary endpoints for the efficacy phase are safety and prostate-specific antigen response rate per Prostate Cancer Working Group criteria. 1. Fizazi et al. NEJM Evid. 2024. Clinical trial information: NCT06353386 .

Clinical experience with EMACO chemotherapy in male choriocarcinoma: A single-center study.

640 Background: Choriocarcinoma is an aggressive subtype of germ cell tumor that frequently metastasizes and progresses rapidly. In gestational trophoblastic tumors in females, the etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine (EMACO) regimen is commonly used, but there are limited reports of its use in male choriocarcinoma. The purpose of this study was to retrospectively describe the clinical outcomes of the EMACO regimen in male patients with pathologically confirmed or clinically highly suspected choriocarcinoma at a single institution. Methods: We conducted a retrospective review of the medical records of male patients who received at least one cycle of EMACO chemotherapy between February 2013 and September 2023 at a tertiary hospital in Korea. We analyzed their baseline characteristics, tumor response, survival outcomes, and adverse events. Resection of residual tumors following EMACO chemotherapy was also considered part of the treatment process. The evaluation of tumor response was based on radiological examinations and changes in tumor markers. Results: In total, 15 patients were included in the study with a median age of 26 years. During diagnosis, 7 patients were found to have pure choriocarcinoma cell components on pathological examination, but all patients had elevated beta-hCG levels (median 177,000 mIU/mL, range 312–11,478,883 mIU/mL). At the time of EMACO administration, lung metastasis was the most frequent, observed in 12 patients, followed by brain metastasis in 7 patients. Seven patients received EMACO chemotherapy as 1 st or 2 nd -line treatment. The median number of chemotherapy cycles was 6. Tumor marker reduction or a decrease in tumor size was observed in 11 patients. Residual tumor resection was performed immediately after EMACO treatment in 7 patients, and no recurrence was observed in 6 patients during the follow-up period. Regarding Grade 3-4 toxicity, anemia was observed in 10 patients, thrombocytopenia in 6 patients, neutropenia in all patients, and elevated alanine aminotransferase levels in 6 patients. The median OS was not reached, with a median follow-up time of 24 months and a median PFS of 10.2 months. Conclusions: EMACO chemotherapy is an effective regimen for male germ cell tumors with pathologically confirmed choriocarcinoma components or markedly elevated hCG levels, and it may offer a curative treatment option when combined with resection of residual tumors.

Validity evidence for assessing social-emotional psychological strengths in Colombian adolescents using the SEHS-S

Background Covitality is a multidimensional hierarchical construct of core psychological strengths that synergistically promote resilience and well-being and that has been shown to be effective in preventing mental health problems in individuals of different age groups. The Covitality Model consists of 12 first-order latent factors, 4 second-order factors, and one general higher-order Covitality factor. Purpose In this study, we aim at obtaining validity evidence for the assessment of Covitality in Colombian adolescents by means of the Social Emotional Health Survey-Secondary (SEHS-S). Method A sample of 1461 adolescents responded the SEHS-S and four other instruments that measure well-being and distress. The internal structure of the SEHS-S was examined through confirmatory factor analyses as well as its relations with other variables. Results The hierarchical factor structure of the SEHS-S was supported (with goodness-of-fit statistics: χ2 = 1727.6, df = 578, p < .001; RMSEA = .037; SRMSR = .044; AGFI = .962; CFI = .940; and NNFI = .935) and configural and metric invariance across gender and age was confirmed; however, the assumption of scalar invariance across males and females and across age groups was violated for some items. Furthermore, we found moderate to high correlations (r = .56 –.68) of Covitality with related constructs. Conclusion As a conclusion, the SEHS-S can be considered a valid tool to assess psychological strengths, well-being, and resilience (i.e., Covitality) in Colombian adolescents, though further research is needed to explore the differences in item functioning across gender and age.

Drug coated balloon angioplasty for de novo coronary lesions in large vessels: a systematic review and meta-analysis

Role of liquid biopsy in the detection of homologous recombination repair gene mutations (HRRm) in metastatic prostate cancer (mPC).

51 Background: The treatment landscape of mPC is rapidly evolving to include more precision therapies for patients with actionable genomic alterations. Specifically, deleterious aberrations in HRR genes (HRRm) confer sensitivity to PARP inhibitors (PARPi) which have demonstrated survival benefit in this context. Therefore, accurate identification of potentially actionable HRRm is indicated. Somatic testing for HRRm in archival tissue is inadequate due to poor DNA quality or lack of tissue availability in 30-40% of cases. We evaluated whether circulating tumor DNA (ctDNA) testing using liquid biopsies is associated with an increased rate of HRRm detection. Methods: This was a multi-institutional retrospective cohort study of mPC patients (pts) treated at the Jewish General Hospital or the McGill University Health Center, Montreal Canada, between 2021-23. Molecular data and treatment information was abstracted from chart review. Fisher’s exact test and Wilcoxon test were used to assess differences between groups. Results: We identified 282 mPC pts, mostly castration resistant (n=181, 64.2%). Median age was 67 years (43-92). Somatic and germline testing for HRRm was performed in 78.3% (n=224) and 23.4% (n=66) pts, respectively. Somatic testing was performed on tissue (n=164, 73.2%) or ctDNA from liquid biopsies (n=17, 7.5%) or both (n=43, 19.3%). Pathogenic somatic HRRm were detected in 37 pts (13.2%): BRCA2 (n=13), ATM (n=8), CHEK2 (n=4), PALB2 (n=4), CDK12 (n=4) and BRCA1 (n=2). Amongst pts with germline testing 10/66 (15.1%) had pathogenic HRRm, mostly BRCA2 (n=9) and 4/10 had detectable HRRm in tissue. The somatic HRRm detection rate was 14.6% (24/164) on tissue and 11.7% (2/17) in ctDNA, respectively. Pts who had both tissue and liquid biopsy experienced a higher detection rate (25.5%, 11/43) vs. either modality alone (P=0.064). Inconclusive results were less frequent in pts who had both liquid and tissue testing vs. tissue alone (2.3% vs 7.3%). Amongst the 10 pts who had discordant results between liquid and tissue tests, HRRm were more frequently identified in ctDNA (n=7) vs. tissue (n=3). Pts who had HRRm detected only in ctDNA, had significantly older tissue samples (median 5.1 years) compared to those who had HRRm detected only in tissue (median 0.2 years, P=0.0156). Conclusions: Our data highlight a potential role of implementing liquid biopsy to improve the detection rate of HRRm. We are currently conducting a multi-center prospective study to determine if liquid biopsy increases the rate of detection of HRRm compared to routine tissue testing, and therefore allows to identify more patients who are eligible to receive precision therapies.

Modified transurethral resection of bladder tumors: A comparison study of chemotherapy-enhanced endoscopic submucosal en bloc dissection versus conventional resection.

721 Background: High recurrence rates plague patients with nonmuscle invasive bladder cancer (NMIBC) following transurethral resection of bladder tumors (TURBT). In response, we have developed a modified TURBT procedure that integrates en bloc resection, endoscopic submucosal dissection, and the injection of chemotherapeutic drugs into the submucosa (cESD-TURBT).This study aims to determine if cESD-TURBT yields better outcomes than conventional TURBT (cTURBT). Methods: This retrospective observational study was conducted on patients diagnosed with cTa–T1 bladder cancer who received TURBT between December 2020 and July 2023 in Liaoning Cancer Hospital. Participants were grouped based on the type of treatment they received: cESD-TURBT (n=118) or conventional TURBT (cTURBT, n=105). Hydroxycamptothecin was the chemotherapeutic agent used for submucosal injections. The primary outcome was recurrence-free survival (RFS) of the treated bladder cancer. Secondary outcomes included disease recurrence within one year, operation duration, length of postoperative hospitalization, and complication rates. Statistical analyses were performed using appropriate tests, with a threshold of P < 0.05 defined as statistically significant. Results: Among the 223 patients, cESD-TURBT cohort demonstrated enhanced RFS compared to cTURBT cohort, with a median follow-up of 775 days (IQR 414-1040). The recurrence rate in the cESD-TURBT cohort was 18.64% (22/118), against 39.05% (41/105) in the cTURBT cohort, with a log-rank hazard ratio of 0.49 (95% CI 0.29-0.82; p=0.0053). Furthermore, cESD-TURBT registered fewer postoperative complications than cTURBT, markedly reducing occurrences such as the obturator reflex (2% vs. 9%). The difference in operation times was not statistically significant, with cESD-TURBT averaging 49.0 ± 21.0 minutes and cTURBT 44.3 ± 23.8 minutes, the difference being statistically negligible (p=0.127). Conclusions: For patients with NMIBC, cESD-TURBT significantly lowers recurrence rates compared to cTURBT and is associated with fewer postoperative complications. Our study reveals that the chemotherapy-enhanced ESD-TURBT technique significantly improves recurrence-free survival and reduces complications, making it a superior method over conventional TURBT for bladder tumor removal.

PSA-based intermediate endpoints to compare radiotherapy and radical prostatectomy for the treatment of localized prostate cancer.

366 Background: There is no validated PSA-based endpoint to compare oncological outcomes after radical prostatectomy (RP) and radiation therapy (RT). We aimed to define a novel PSA-based intermediate endpoint that leads to similar prostate cancer-specific mortality (PCSM) for primary treatment comparison. Methods: This population-based study included all men with cT1-3, cN0M0 prostate cancer (PCa) in Stockholm who underwent RP or RT with PSA follow-up from 2003 to 2021. Competing risk regression, accounting for non-PCa mortality, was used to compare the cumulative incidence of PCSM in patients meeting different PSA-based endpoints after RP and RT. Endpoints were predefined by systematically increasing PSA cut-offs and PSA doubling times (PSA-DT) at recurrence. The analysis was adjusted for age at diagnosis, Charlson, PSA, ISUP Gleason at biopsy, cT stage, and treatment year, and was repeated to identify endpoint combinations that resulted in similar PCSM for RT and RP (subdistribution hazard ratio [SHR] of RT vs RP close to 1). Results: 12,010 (67.7%) man underwent RP, and 5,743 (32.3%) underwent RT. The median follow-up for survivors was 91 months (IQR 70–154) after treatment. A total of 428 men died from PCa. The adjusted SHR for patients meeting the current definition of biochemical recurrence (BCR) after RT (PSA ≥ nadir + 2) was 3.35 (95% CI 2.67, 4.23) compared to RP patients with a rising PSA≥0.2. Similar results were found when comparing PSA nadir + 2 with patients reaching higher PSA cut-offs after RP (≥ 0.5 and ≥ 1 ng/ml). Further comparisons were therefore performed by lowering the PSA cut-offs for the RT endpoint (nadir + 1-0.5 ng/ml). The endpoint definition leading to similar survival rates was PSA nadir + 0.5 ng/ml after RT and PSA ≥ 0.5 ng/ml with PSA DT < 9 months after RP (SHR RT vs RP 1.00, 95% CI 0.78, 1.29). The adjusted cumulative incidence of the endpoint was higher after RT. Conclusions: We performed a systematic analysis of PSA-based early endpoints following primary treatment for PCa and found that patients who underwent RT and reached a PSA ≥ nadir + 0.5 ng/ml had similar survival rates to patients with PSA ≥ 0.5 ng/ml and PSA DT < 9 months after RP. Our results highlight that current BCR definitions are suboptimal for primary treatment comparison and present, for the first time, promising novel early endpoints suitable for further validation. Competing risk regression comparing cumulative incidence of prostate cancer specific mortality after meeting the predefined endpoints after radiotherapy or radical prostatectomy (reference group). Endpoint compared Radical Prostatectomy(reference) Radiotherapy Adjusted SHR for PCa Mortality (RT vs RP) Adjusted Coefficient for PCa Mortality (RT vs RP) SHR 95% CI P Coeff 95% CI P 1 >0.2 nadir+2 ng/ml N of Pt 2501 836 3.35 2.67, 4.23 <0.001 1.21 0.98,1.44 <0.001 2 >0.5 nadir+2 ng/ml N of Pt 1365 836 2.08 1.66, 2.60 <0.001 0.73 0.51,0.96 <0.001 3 >0.5+ DT<12 nadir+2 ng/ml N of Pt 805 836 1.68 1.32, 2.12 <0.001 0.52 0.28,0.75 <0.001 4 >0.5+ DT<9 nadir+2 ng/ml N of Pt 667 836 1.73 1.34, 2.23 <0.001 0.55 0.29,0.80 <0.001 5 >0.5+ DT<9 nadir+1 ng/ml N of Pt 667 1050 1.32 1.03, 1.70 0.030 0.28 0.03,0.53 0.030 6 >0.5+ DT<9 nadir+0.5 ng/ml N of Pt 667 1321 1.00 0.78, 1.29 0.985 0.00 -0.25,0.25 0.985 7 >0.5+ DT<6 nadir+0.5 ng/ml N of Pt 482 1321 0.97 0.74, 1.28 0.853 -0.04 -0.07,-0.00 0.040 Standardized hazard ratios (SHR) are adjusted for age at diagnosis, Charlson comorbidity, PSA, ISUP Gleason at biopsy, clinical Stage, treatment year. SHR: standardized hazard ratios; PCa: Prostate cancer; RP: Radical prostatectomy; RT: radiotherapy; DT: PSA doubling time.

¹⁸ F-PSMA-1007 PET/CT for response assessment in patients with metastatic renal cell carcinoma undergoing first line tyrosine kinase or checkpoint inhibitor therapy.

455 Background: Evaluating the effectiveness of systemic therapy in patients with metastatic renal cell carcinoma (mRCC) is crucial for timely treatment adjustments. In an earlier preliminary study on a subset of mRCC patients, we compared responses to systemic therapy using [¹⁸F]PSMA-1007 PET and conventional imaging methods. In this research, our aim was to compare response assessments using PSMA PET versus CT scans in a larger cohort of mRCC patients undergoing systemic therapy. Additionally, we investigated the potential of using PSMA-PET-derived responses to predict outcomes. Methods: We performed a retrospective single-center analysis of patients with mRCC who underwent [¹⁸F]PSMA-1007 PET/CT in the context of tyrosine kinase or checkpoint inhibition and had at least one PET avid metastatic RCC lesion at baseline. All patients were treated with IO combination therapy either in combination with a TKI or ICI. Early treatment response at a mean of 9.5 weeks after the start of systemic therapy was compared to baseline scans. PET responses and measurements were correlated with CT results, progression-free (PFS) and overall survival (OS). Survival data were analyzed using log rank testing and Kaplan-Meier analysis. Results: 25 patients with mRCC were enrolled. Median age was 65.2 years (range 24-87). Median PFS was 16.6 months (range 1.38 -58.69) and median OS 28.8 months (range 3.6 - 65.16). Median SUV, TTV, CT or PET response were not correlated with PFS or OS. Patients with a 10% reduction in SUVmax had a significant longer PFS with 23.1 months (95% CI 13.8-32.3) vs 3.6 (95% CI 1.4 – 5.9) months and OS of 36.2 months (95% CI 17.5 – 70.6) vs 11.1 months (95% CI 5.604 – 16.8) than patients without SUVmax response. SUVmax response was independent of administration of tyrosine kinase inhibitors or checkpoint inhibitors. Conclusions: Reduction of PSMA uptake on PET scans may be an independent biomarker beyond CT findings and warrants further investigation in mRCC. PSMA PET could be used for a better understanding of drug efficacy. Changes in PSMA PET are independent of the mechanism of action of systemic therapy in early prediction of therapy response and therefore might be considered a clinical biomarker.

Identifying priorities and developing collaborative action plans to improve accessible housing practice, policy, and research in Canada

This article describes the development of priorities and actions to improve the state of research, policy, and practice related to accessible housing in Canada for persons with disability or with accessible housing needs. A modified Delphi approach with an expert cross-sectoral panel was used to gain convergence on a set of priorities for advancing the accessible housing field in Canada. This included circulating an anonymous pre-meeting survey (N = 49) followed by an in-person planning meeting (N = 45). The expert panel at the in-person meeting identified three clusters of priorities from an initial list of 21 priorities, which included: 1) engaging with all levels of government to support accessible housing efforts; 2) developing educational resources to raise awareness about accessible housing, and creating services to facilitate locating and acquiring accessible housing; and 3) fostering meaningful engagement across key interest groups and sectors to find solutions to enact positive change in this space. The findings provide an initial roadmap for bringing greater cohesion to the accessible housing field, which will enable cross-sectoral partnerships and collective action towards informing the next generation of accessible housing standards, regulations and practices for people with accessible housing needs.

Decoupling chemical and mechanical signaling in colorectal cancer cell migration

Integrating aggressive variant prostate cancer–associated tumor suppressor genes (AVPC-TSG) status to refine prognosis and predict androgen-receptor pathway inhibitors (ARPI) response in metastatic hormone-sensitive prostate cancer (mHSPC).

243 Background: Alterations in AVPC-TSG (TP53, RB1, PTEN) are related with androgen insensitivity and aggressive disease. However, their role in mHSPC prognosis and treatment guidance is unclear. This retrospective study assesses the value of AVPC-TSG alterations in refining prognosis and predicting ARPI benefit in mHSPC. Methods: We included 158 mHSPC patients with available genomic tumor sequencing analysis undergoing treatment between 2013 and 2023. We compared patients with AVPC-TSGalt tumors (defined by ≥1 alterations in the TP53 gene, RB1 gene, or PTEN/PI3K/AKT pathway genes) to those without (AVPC-TSGwt tumors). Cox analyses were performed for progression-free survival (PFS) and overall survival (OS). Results: AVPC-TSGwt status was associated with improved PFS and OS in both univariate and multivariate (MV) analyses (MV PFS: HR 0.58, p=0.012; MV OS: HR 0.48, p=0.025). AVPC-TSGalt mHSPC patients seemed to derive no PFS benefit (PFS: HR 1.13, p=0.721) from the addition of an ARPI to ADT, while AVPC-TSGwt mHSPC patients did (PFS: HR 0.51, p=0.029). Integrating AVPC-TSG status with CHAARTED volume criteria enhanced prognostic and predictive discrimination in mHSPC. Three distinct subgroups were identified: "good-risk" (AVPC-TSGwt and low-volume), "intermediate-risk" (either AVPC-TSGalt or high-volume), and "poor-risk" (AVPC-TSGalt and high-volume) with median PFS of 46.8, 28.2, and 15.7 months, respectively. Among them, only the "intermediate-risk" subgroup seemed to derive PFS benefit (HR 0.36, p=0.002) from addition of an ARPI. Conclusions: Integrating AVPC-TSG status with clinical prognostic variables refines prognostication and may predict PFS benefits from the addition of an ARPI in patients with mHSPC. Patients with AVPC-TSGalt mHSPC should be considered for clinical trials exploring alternative treatments, as they may not benefit from current standard approaches. Patient characteristics. AVPC-TSGaltn=63(39.9%) AVPC-TSGwtn=95(60.1%) p-value mHSPC treatmentADT aloneADT+ARPIADT+DocetaxelADT+ARPI+Docetaxel 23(36.5%)28(44.5%)8(12.7%)4(6.3%) 32(33.6%)49(51.6%)7(7.4%)7(7.4%) p=0.64 1 De Novo disease 43(68.3%) 57 (60%) p=0.29 1 CHAARTED High Volume 36(57.1%) 52(54.7%) p=0.77 1 AVPC-TSG 1 altAVPC-TSG 2-3 alt 56(88.9%)7(11.1%) 00 p<0.012 1 median PFS (months)median OS (months) 20.568.2 39.6NR p=0.010 2 1 Pearson, 2 Log-rank test.

PUNCH01: Interim results from a phase II study of intra-arterial chemotherapy (IAC) combined with tislelizumab and bacillus Calmette-Guerin (BCG) in high-risk non-muscle-invasive bladder cancer (HR NMIBC).

767 Background: Our study was established to evaluate the efficacy and safety of IAC combined with tislelizumab and BCG as a bladder-preserving treatment for HR NMIBC pts. Methods: This open-label, single arm phase II study enrolled BCG-naïve HR NMIBC pts with papillary tumors (high-grade Ta or T1 tumors). Firstly, the papillary tumors should be removed all visible lesions by TURBT. Secondly, angiographic catheter was placed into the internal iliac arteries with Seldinger’s percutaneous technique, cisplatin (60 mg/m 2 ) and epirubicin (50 mg/m 2 ) were administered arterially in day 1 (D1), every 3 weeks for 2-4 cycles. And pts received tislelizumab 200 mg ivgtt in D1, every 3 weeks for 2-4 cycles. Finally, pts received 18 instillations of BCG plus at least 8 cycles of tislelizumab (200 mg ivgtt, every 3 weeks). Specifically, pts were started on an induction course of BCG with 6 instillations every week, followed by maintenance with 3 instillations every 2 weeks and 9 instillations every 4 weeks. The primary end point was disease-free survival(DFS) rate at 12 months. Secondary end points were bladder-preservation rate, OS and safety. Our study estimated a DFS rate at 12 months was no less than 55% and the study would enroll 29 pts. Results: By Jul. 2024, 23 eligible pts were enrolled. Twenty-two pts were analyzed (male 90.9%; median age 61 years(37-80); pure TCC 80.0%; median tumor size 3.0 cm (0.4-8.0); multiple papillary tumours=72.7%; high-gradeTa=54.5%, T1=45.5%). Median follow-up was 11.4 months (6.0-40.3), the mean number of IAC cycles was 2.7, mean number of tislelizumab cycles was 8.3, and the median BCG instillations was 10 (6-18). The DFS rate at 12month was 100.0% (95%CI, 63.8%-100%). The bladder-preservation rate at 12 months was 100% (95%CI,100%-100%). The OS rate at 12 months was 100% (95%CI, 100%-100%). 18 pts experienced treatment related adverse events, including nausea (n=6, G2), neutropenia (n=4, G2), fatigue (n=3, G2), increased AST/ALT (n=3,G2), fever (n=2, G3) and myalgia (n=1, G2). Conclusions: Our interim results supported the use of IAC combined with tislelizumab and BCG as a promising bladder-preserving strategy for HR NMIBC pts. Clinical trial information: ChiCTR2200067156 .

Five-year changes in urinary function and prostate volume in patients with localized prostate cancer treated with carbon ion radiotherapy: A prospective study.

378 Background: The potential of carbon ion radiation therapy (CIRT) as a curative treatment for localized prostate cancer (PCa) has garnered attention due to its characteristic dose distribution. There is no data on long-term urinary function or changes in prostate volume in prostate patients after CIRT. We prospectively collected and analyzed over five years to investigate the outcomes related to the urinary function of localized PCa treated with CIRT. Methods: This study included patients with localized PCa classified as T1-T3N0M0 according to the TNM staging system. A total of 309 patients who underwent carbon-ion radiotherapy (CIRT) between 2010 and 2013 were enrolled. Patients with T1c-T2bN0M0, an initial PSA < 10 ng/ml, and a Gleason score (GS) ≤ 6 were classified as the low-risk group (none androgen deprivation therapy, ADT), while those with ≥T3, an initial PSA ≥ 20 ng/ml, or a GS ≥ 8 were categorized as the high-risk group (neo adjuvant ADT 6 months and adjuvant ADT 1.5 year). The remaining patients were classified into the intermediate-risk group (neo adjuvant ADT 6 months). CIRT was administered 57.6 Gy (RBE) in 16 fractions. Pre- and post-treatment evaluations, including UFM, transrectal ultrasound, and residual urine tests, were performed, with data collected over a 5-year period. This study was approved by the Clinical Ethics Committee of Gunma University Hospital (approval number 693). Results: The median age of the patients was 66.5 years. Analysis of the UFM results showed that the maximum flow rate (mean, ml/s) significantly worsened at 1 month post-treatment (Post) compared to pre-treatment (Pre) but improved to the pre-treatment level by 3 months post-treatment (Pre: 20.0 ± 10.6 ml/s, Post: 14.5 ± 7.3 ml/s, p < 0.05, 3 m: 18.7 ± 8.9 ml/s). The mean flow rate also significantly worsened at 1 month post-treatment compared to pre-treatment but returned to pre-treatment levels at 3 months post-treatment and showed a significant improvement at 3 years post-treatment, which was maintained for up to 5 years (Pre: 8.3 ± 4.0 ml/s, Post: 6.0 ± 3.2 ml/s, p < 0.05, 3 m: 7.7 ± 4.3 ml/s, 3 y: 10.5 ± 4.9 ml/s, p < 0.05). The prostate volume in ADT (-) cases significantly decreased one year after treatment, reaching approximately 80% of the initial volume by three years and remaining stable through five years (1 year: 85.6 ± 18.6%, p < 0.05; 3 years: 78.3 ± 21.9%, p < 0.05). The multivariate analysis identified T classification (T1 vs. ≥T2, p < 0.001) and prostate volume ( p = 0.014) as significant predictive factors for late genitourinary tract complications. Conclusions: The long-term prospective study conducted over five years has elucidated the changes in urinary function and prostate volume in patients with prostate cancer following CIRT. Based on these data, it was suggested that complications in CIRT patients might be predictable through pre-treatment evaluations.

A randomized phase 3 trial of docetaxel added to ADT plus ARTA in patients with metastatic hormone-sensitive prostate cancer (Adding Docetaxel, KCSG- GU22-24).

TPS276 Background: The doublet regimen, which adds docetaxel or androgen receptor-targeted agent (ARTA) such as abiraterone, enzalutamide, or apalutamide to androgen deprivation therapy (ADT) has been a standard of care in metastatic hormone-sensitive prostate cancer (mHSPC). A triplet regimen, adding abiraterone or darolutamide to ADT and docetaxel, has also demonstrated efficacy. However, while the benefit of docetaxel in mHSPC has been established in doublet regimen (ADT + docetaxel), the efficacy of adding docetaxel to ADT + ARTA has not been confirmed. Notably, the addition of docetaxel to ADT has shown benefit primarily in patients with high-volume disease. Pivotal trials of triplet regimens were based on administering ADT + docetaxel to all mHSPC patients. However, docetaxel is associated with significant toxicity and a reduction in quality of life, especially among elderly prostate cancer patients. Considering the limited evidence for adding docetaxel to ADT + ARTA and considerable toxicity of docetaxel, this phase 3 study aims to evaluate the effectiveness of adding docetaxel to ADT + ARTA. Methods: This study is a randomized, multicenter, open-label, investigator-initiated phase 3 study. Patients diagnosed with de novo mHSPC and initiated on ADT and ARTA are enrolled and randomized within 16 weeks of starting ADT. Patients are randomized 1:1 to either the Adding-Docetaxel arm or the Non-Docetaxel arm. Randomizations is stratified by ARTA type (abiraterone vs. apalutamide vs. enzalutamide), ECOG PS (0-1 vs. 2), disease volume (high vs. low). The Adding-Docetaxel arm adds 6 cycles of docetaxel 75 mg/m 2 in addition to ADT + ARTA, while the Non-Docetaxel arm receives only ADT + ARTA. The primary endpoint is clinical progression-free survival (cCFS), which defined the time from randomization to progression of soft tissue lesions (per RECIST v1.1), development of cancer pain requiring opioids for more than 7 days, worsening of ECOG PS, need for a change in prostate cancer-specific therapy, need for radiotherapy or surgical treatment, or death. The study is designed to detect a hazard ratio of 0.7 for cPFS, with a significance level of 5%, power of 80%, and an anticipated drop-out rate of 10%. A total of 430 patients (215 per arm) will be enrolled. Patient recruitment began in November 2023. This trial has been registered on the Clinical Research Information Service (http://cris.nih.go.kr) under ID No. KCT0008726 (Release date: August 22, 2023). Clinical trial information: KCT0008726 .

Patient-Reported Outcomes among people living with Chronic Pruritus (PROs-CP): Protocol for a single-center, multistage, mixed-methods prospective cohort study in Thailand

Background Although there have been well-validated patient-reported outcome (PRO) measurements in dermatology practice, there is limited evidence of the adopted comprehensive aspects of PRO measures in long-term follow-up among people living with chronic pruritus. As such, we aim to create a cohort study of the Patient-Reported Outcomes among people living with Chronic Pruritus (PROs-CP) in Thailand. Methods and design This study is a single-center, prospective, open cohort, observational longitudinal study using a multistage, mixed-methods parallel designs to integrate both quantitative and qualitative data regarding PROs among people living with chronic pruritus (itch lasting six or more weeks). The multistage of the PROs-CP study will comprise three sub-studies: (i) study I, PROs measure development, translation, and psychometric validation; (ii) study II, perspectives of people living with chronic pruritus to gain more information regarding disease burden and unmet treatment care responses; and (iii) study III, a longitudinal study to assess the impact of chronic pruritus on long-term health outcomes. Based on a comprehensive review of a panel of stakeholders with chronic skin disease, a set of PRO measurement tools will comprise an established validated Thai version. Meanwhile, meaningful non-Thai versions or unestablished PRO instruments will be translated and developed through this study as appropriate. Quantitative data will be collected based on PRO measures regarding pruritus symptoms and severity, disease activity control and treatment satisfaction, general- and dermatology-specific health-related quality of life, mental health and psychosocial issues, and psychosomatic symptoms. Qualitative data will be obtained from the patient’s perspectives through individual interviews. Ethics and dissemination The study protocol was approved by the Ethics Committee of the Faculty of Medicine, Chiang Mai University (MED-2566-0299), Thailand. Our findings will be disseminated through scientific conferences and publications in peer-reviewed journals. Conclusion Regarding the mixed-methods approach, this open cohort, prospective longitudinal study will provide an evidence-based better understanding of patient perspectives on chronic pruritus burden and inform the utility of a comprehensive set of PROs to measure their long-term health outcomes. Trial registration Thai Clinical Trials Registry (TCTR, thaiclinicaltrials.org) registration TCTR20240327001 (registered on March 27, 2024).

Machine learning prediction of breast cancer local recurrence localization, and distant metastasis after local recurrences

Abstract Local recurrences (LR) can occur within residual breast tissue, chest wall, skin, or newly formed scar tissue. Artificial intelligence (AI) technologies can extract a wide range of tumor features from large datasets helping in oncological decision-making. Recently, machine learning (ML) models have been developed to predict breast cancer recurrence or distant metastasis (DM). However, there is still a lack of models that consider the localization of LR as a tumor feature. To address this gap, here, we analysed data from 154 patients including pathological, clinical, and follow-up data (with an average follow-up of 133.16 months) on both primary tumors (PT) and recurrences. By using ML methods we predicted the localization of LR and the occurrence of DM after LR. The performance (ROC AUC) of the best ML models was 0.75, and 0.69 for predicting LR in breast parenchyma, and surgical scar tissue, respectively, and 0.74 for predicting DM after LR. We identified recurrence localization, and the time elapsed between the detection of primary breast carcinoma and the recurrence, and adjuvant chemotherapy as the most important features associated with further DM. We conclude that combining traditional prognostic factors with ML may provide important tools in the risk assessment of patients with breast LR.

Oncological benefit of avelumab maintenance therapy for advanced or metastatic urothelial carcinoma in comparison with patients with conventional chemotherapy alone era.

711 Background: The benefit of avelumab maintenance therapy for advanced or metastatic urothelial carcinoma in real world practice remains unknown. We evaluated the oncological outcomes of avelumab maintenance therapy in comparison with conventional platinum-based 1 st line chemotherapy in real-world practice. Methods: We retrospectively evaluated 302 and 85 patients treated with and conventional platinum-based first-line chemotherapy without avelumab (chemo group) and avelumab maintenance therapy (avelumab group) between March 2004 to Sep 2024. We compared overall survival (OS) between the patients with the chemo and avelumab groups stratified by the number of cycles of first-line chemotherapy. Primary outcome was the comparison of OS in patients without progression disease (non-PD) at cycle 4 between the chemo and avelumab groups. Secondary outcomes were the impact of the administration of pembrolizumab on OS in patients with non-PD at cycle 4 in the chemo group and the comparison of OS in patients with non-PD at cycle 2-3 between the chemo and avelumab groups. Exploratory outcomes were disease-free survival (DFS) and OS based on response rate of first-line chemotherapy, first-line treatment regimen, and number of first-line chemotherapy cycles in the avelumab group. Results: We identified 124 and 49 patients with non-PD at cycle 4 in the chemo and avelumab groups, respectively. The OS from the initiation of first-line chemotherapy in the avelumab group was significantly longer than that in the chemo group (70 vs. 23 months, P = 0.009). We identified 104 and 33 patients with non-PD at cycle 2-3 in the chemo and avelumab groups, respectively. The OS from the initiation of first-line chemotherapy in the avelumab group was significantly longer than that in the chemo group (33 vs. 13 months, P = 0.002). A multivariable Cox regression analysis showed administration of avelumab was significantly associated with reduced risk of OS (hazard ratio, 0.41; P < 0.001). Of 85 patients with avelumab, the median DFS was 17 months from first-line therapy and 8.1 months from the avelumab maintenance therapy, respectively. No significant differences were observed in DFS and OS between first-line treatment regimens, and between the object response rate for first-line chemotherapy. However, the DFS and OS tended to improve in patients with first-line chemotherapy 4 cycles or more. Conclusions: We found a potential benefit of avelumab maintenance therapy on oncological outcome in real-world practice regardless of number of first-line chemotherapy. No progression within first 4 cycles of platinum-based chemotherapy might be one of the key factors for improved outcome. Further long-term follow-up is necessary.

Impact of insurance type on outcomes after radical cystectomy for bladder cancer.

679 Background: A patient’s insurance status can significantly impact their access to care, potentially altering their treatment course and outcomes. This study aimed to evaluate the potential influence of different insurance statuses on oncological outcomes, including survival. Methods: We utilized our prospectively maintained IRB-approved radical cystectomy (RC) database (#HS-01B014) to identify all muscle invasive bladder cancer (MIBC) patients who underwent neoadjuvant chemotherapy (NAC) followed by RC from 2000 to 2023. Patients were then categorized based on primary insurance type to Preferred Provider Organizations (PPO), Health Maintenance Organizations (HMO), Medicare, MediCal, and Self-Pay. We extracted demographic, clinical, and oncological outcomes data from our database. All statistical analyses were performed using SAS Version 9.4 (SAS Institute Inc., Cary, NC, USA). Results: A total of 432 patients were included in the final analyses. Patient demographics and baseline characteristics are shown in Table 1. Patients were followed for a median of 42.0 months after cystectomy. On univariate cox regression, PPO insurance was associated with improved OS (Hazards Ratio (HR) = 0.47 [95%CI: 0.29, 0.75], p = .002) and RFS (HR = 0.48 [95%CI: 0.30, 0.78], p = .003) compared to the reference group, Medicare. A multivariate cox regression demonstrated that PPO health plan could enhance OS (HR = 0.49 [95%CI: 0.30, 0.78]) even after adjusting for pathological stage. Having any other health plan had neither a beneficial, nor a detrimental effect on OS or RFS. Conclusions: Better insurance coverage is associated with improved OS and RFS. However, the single institutional design of our study limits the generalizability of our findings. Larger prospective multi-institutional studies are encouraged to better evaluate how insurance status and socioeconomic disparities can affect survival outcomes in MIBC. Demographics and baseline clinical characteristics stratified by insurance status. Variables Medicare (n = 190) HMO (n = 85) PPO (n =143) MediCal (n = 10) Self-pay (n=4) p-value Gender (Male) 148 (77.9%) 69 (81.2%) 117 (81.8%) 8 (80.0%) 3 (75.0%) .917 Age at diagnosis (yrs.) 71.5 ± 6.4 64.6 ± 10.0 60.2 ± 8.6 55.7 ± 12.9 54.8 ± 14.6 <.001 Charlson Comorbidity Index 0 30 (15.8%) 26 (30.6%) 55 (38.4%) 3 (30.0%) 1 (25.0%) <.001 1 52 (27.4%) 16 (18.8%) 35 (24.5%) 4 (40.0%) 2 (50.0%) ≥ 2 108 (56.8%) 43 (50.6%) 53 (37.1%) 3 (30.0%) 1 (25.0%) Pathological staging < (y)pT2; pN0 115 (60.5%) 59 (69.4%) 94 (65.7%) 4 (40.0%) 2 (50.0%) .515 > (y)pT2; pN0 34 (17.9%) 9 (10.6%) 25 (17.5%) 2 (20.0%) 1 (25.0%) pN+ 41 (21.6%) 17 (20.0%) 24 (16.8%) 4 (40.0%) 1 (25.0%) Income percentiles 0 - 40th 20 (10.5%) 13 (15.3%) 14 (9.8%) 4 (40.0%) 0 (0.0%) .193 40 - 60th 56 (29.5%) 26 (30.6%) 39 (27.3%) 4 (40.0%) 1 (25.0%) 60 - 80th 76 (40.0%) 33 (38.8%) 58 (40.6%) 2 (20.0%) 2 (50.0%) 80 - 100th 38 (20.0%) 13 (15.3%) 32 (22.4%) 0 (0.0%) 2 (50.0%)