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Feasibility and safety results from RAD-IO: A multi-stage trial of durvalumab (Medi4736) with chemoradiotherapy with 5-fluorouracil and mitomycin C in patients with muscle-invasive bladder cancer.
778 Background: Immune checkpoint inhibitors have a substantial and growing role in all stages of care for bladder cancer. Durvalumab (Durva) is a humanised monoclonal antibody that inhibits binding of PD-L1. Recent phase 3 results with peri-operative durvalumab show a 25% reduction in the risk of death compared to standard of care. Methods: RADIO is a multi-stage trial comparing standard chemoradiotherapy (CRT) with 5FU & mitomycin C (MMC) +/- durvalumab given pre-CRT x1, during CRT x1 and post CRT for up to 12 months. Eligible patients T2-T4aN0-2M0 bladder cancer, neo-adjuvant chemotherapy was encouraged for suitable participants. Switch to single arm occurred after achieving feasibility criteria. We report here feasibility and toxicity data up to 3 months post randomisation. Recruitment continues in the single arm efficacy phase with results to be reported later. Results: Between Oct 2020 and May 2023, 29 participants were randomised. Median age 68 (IQR 61-75) years, 26 male, 3 female. Casemix: T2N0 21 (72.4%), T3N0 8 (27.6%), T4N0 0 (0%). 23 (79.3%) had received prior neoadjuvant chemotherapy. 10 (34.5%) were recruited to receive CRT only, 19 (65.5%) to receive CRT + Durva. All participants completed 55Gy/20# RT, 25 (86.2%) without any delays and 4 participants completed RT but with delay (1-5 days), 2 due to toxicity, 2 due to external factors. Median intensity of planned dose received: RT; 1 (IQR 1-1), MMC; 0.97 (IQR 0.94-0.99), 5FU; 0.8 (IQR 0.49-0.96), Durva; 0.97 (IQR 0.88-1). Toxicity for patients on the CRT + Durva arm, between informed consent and 3 months post the end of CRT:6 SAEs were reported, 3 of which were SARs and 0 were SUSARs. Of these SAEs, 3 were related to trial treatment (2 related to Durva, 2 related to 5FU & MMC, 1 being related to both regimens), 3 lead to discontinuation (RT; 0, MMC; 0, 5FU; 2, Durva; 1), and 2 SAEs lead to dose delays (RT; 0, MMC; 0, 5FU; 0, Durva; 2). In the CRT + Durva arm there were 9 AEs grade ≥3 (6 related to trial treatment). Results split by CRT only or CRT + Durva will be available at the time of the conference, and all figures are provisional on subsequent rounds of data cleaning. Conclusions: The schedule of neo-adjuvant, synchronous and adjuvant durvalumab was deliverable with full dose CRT to bladder. Most participants completed CRT as planned, none discontinued Durva due to toxicity, only 3 incurred toxicity related delays but continued treatment. Clinical trial information: 43698103.
GLP-1 analogues and prostate cancer incidence: A systematic review and meta-analysis.
374 Background: Preliminary evidence from preclinical and observational data suggests that GLP-1 receptor agonists (GLP-1RAs) may reduce prostate cancer (PCa) incidence. We aimed to assess the effects of GLP-1RAs on PCa risk. Methods: Embase, Medline, Web of Science, and Cochrane databases were searched from inception to identify phase III randomized controlled trials (RCTs) comparing a GLP-1 RA with placebo/non-GLP-1 RA regimens. The primary outcome was incidence of PCa. A Mantel-Haenszel random-effect meta-analysis was carried out to estimate the pooled relative risk (RR) and 95% confidence interval (CI) for the occurrence of PCa among male participants. Results: Of the 27,103 abstracts identified, 56 trials including 59,334 male participants were included. Eligibility included type 2 diabetes mellitus in 48 studies, obesity in 7 studies, and heart failure in 1 study. The GLP-1 RA’s studied included liraglutide (18), semaglutide (13), dulaglutide (6), albiglutide (6), lixisenatide (5), exenatide (4), and others (5). One study included both liraglutide and semaglutide as interventions. Follow-up durations ranged from 12 weeks to 260 weeks (5 years), with a mean of 72.5 weeks (standard deviation = 50.85). The pooled incidence of PCa was 0.55% (150 of 27,126) for the control group and 0.46% (148 of 32,208) for the GLP-1 intervention group. The pooled RR of PCa incidence with all GLP-1 RAs compared to controls was 0.86 (95% CI: 0.69-1.06, p=0.16). Conclusions: There were proportionally fewer incident PCa cases among GLP-1 RA recipients as compared with control. However, this did not achieve statistical significance. Trials were limited in duration and by the lack of pre-specification of this outcome. Further research is needed to evaluate whether GLP-1 RAs have activity against established PCa.
Timely next-generation sequencing testing in patients with metastatic prostate cancer: A comparative analysis between Medicare Advantage and traditional Medicare.
320 Background: Next-Generation Sequencing (NGS) testing has become a cornerstone of personalized medicine in cancer care. With Medicare Advantage (MA) now covering nearly half of all beneficiaries, understanding differences in access to timely NGS testing between MA and Traditional Medicare (TM) is crucial, particularly given MA’s potential restrictions. This study aims to evaluate the effectiveness of MA plans on timely NGS testing in patients with metastatic prostate cancer (mPCa). Methods: This retrospective cohort study was based on the Flatiron Health deidentified Database, comprising electronic health record-derived data from ~280 cancer practices across the US. Our study included patients aged 65 or older, diagnosed with mPCa since 2018, and exclusively enrolled in TM or MA, either before or within 90 days following mPCa diagnosis. We compared the rates between TM and MA, using three timeframes—45-, 90-, and 180-days post-mPCa diagnosis. NGS testing was defined as any tissue or liquid genomic testing resulted within the time frame of interest. Multivariate logistic regression with inverse probability of treatment weighting was used, adjusting for demographics, year of mPCa diagnosis, practice setting, and baseline ECOG score. Results: Among the 1,582 MA patients (mean age: 75.9 ± 5.8) and 2,749 TM patients (mean age: 75.4 ± 5.8), significant proportions were from community practice (MA: 78%, TM: 80%) and were characterized by being White (MA: 59%, TM: 65%), aged 75 to 85 (MA: 54%, TM: 57%), having higher socioeconomic status (SES 4 or 5: MA: 40.3%, TM: 47.5%), presenting with de-novo mPCa (MA: 53%, TM: 54%), and having better baseline functional performance (ECOG 0 or 1: MA: 70%, TM: 69%). Since 2018, 8.8%, 14.5%, 18.8% of MA patients and 10%, 14.6%, 17.6% of TM patients received NGS testing at 45, 90 and 180 days, respectively. Notably, 63.4% and 60.8% of MA and TM patients, respectively, did not have any NGS testing. After adjusting for covariation, MA was associated with a 26.2% (OR=0.74, 95%CI 0.59-0.92), 16% (OR=0.84, 95%CI 0.7-1.01), 7.8% (OR=0.92, 95%CI 0.78-1.09) lower chance to receive timely NGS testing at 45 days, 90 days and 180 days, respectively. Conclusions: Patients with mPCa enrolled in MA are less likely to receive timely NGS testing compared to TM. The high rate of delayed or no testing underscores disparities in access, especially among MA patients. Policymakers should streamline approvals to ensure timely, high-quality care for all Medicare beneficiaries.
DNA damage repair alterations as predictive biomarker for platinum-based chemotherapy in metastatic urothelial cancer.
853 Background: DNA damage repair gene alterations (DDRa), especially ERCC2 mutations, have been associated with improved clinical outcomes in patients with urothelial cancer (UC) treated with cisplatin-based neoadjuvant chemotherapy. The predictive value of DDR alterations for platinum-based chemotherapy in metastatic disease is not well-defined. Methods: We analyzed the American Association of Cancer Research (AACR) Genomics Evidence Neoplasia Information Exchange (GENIE) Biopharma Collaborative consortium (BPC), including patients with UC treated at 4 academic centers in North America between 2013 and 2018, with Next Generation Sequencing (NGS) data available. We assessed overall survival among patients treated with first line platinum-based chemotherapy for metastatic UC, and compared the outcomes based on DDRa status using Cox models adjusted with risk-set adjustment for delayed entry. DDRa were defined as any mutation defined as “likely oncogenic” or “oncogenic” in OncoKB for the genes ERCC2, ERCC5, BRCA1, BRCA2, RECQL4, ATM, ATR, RAD51C and FANCC . Results: Of 716 patients with UC, 103 (14%) had any DDRa, and 32 (4.5%) had an ERCC2 mutation. Among 566 patients (79%) who developed metastatic disease at any time during follow up, median age was 66 years, 22% were female and 25% had upper tract UC. The median overall survival (mOS) from diagnosis of metastatic disease was 15.1 months (95% CI 12.6-18.6). For patients treated with first line platinum-based chemotherapy (n=258), the presence of DDRa was associated with significantly improved mOS compared with absence of DDRa: 22.7 versus 11.2 months, hazard ratio (HR) 0.54 (95% CI 0.34-0.86, p=0.009). Similar trends were seen when analyzing patients treated with cisplatin or carboplatin, separately. Conclusions: DDRa were associated with improved survival in metastatic UC patients treated with platinum-based chemotherapy. Further studies are needed to explore the prognostic and predictive value of DDRa as the role of platinum-based chemotherapy evolves in the enfortumab vedotin and pembrolizumab era. DDRa No DDRa First Line treatment for metastatic UC N Median OS months (95% CI) N Median OS months (95% CI) HR (95% CI) P value Any platinum-based chemotherapy 32 22.7 (14.5, 66.9) 226 11.2 (9.4, 15.1) 0.54 (0.34, 0.86) 0.009 Cisplatin-based chemotherapy 22 25.9 (14.5, NR) 142 13.6 (10.4, 18.8) 0.57 (0.32, 1.01) 0.06 Carboplatin- based chemotherapy 10 17.4 (7.26, NR) 84 9.9 (6.6, 12.7) 0.53 (0.25, 1.17) 0.12 CI= Confidence interval; DDRa= DNA damage repair alteration; HR=Hazard ratio; NR=Not reached; OS= Overall survival; UC= Urothelial Carcinoma.
Cabozantinib (cabo) and nivolumab (nivo) with or without CBM588 in patients with metastatic renal cell carcinoma: Updated clinical outcomes of a phase I study.
543 Background: We previously reported that combining CBM588 ( Clostridium butyricum MIYAIRI588), a live bacterial product, with cabozantinib (cabo) and nivolumab (nivo) enhanced clinical benefit in treatment-naïve patients with mRCC (Ebrahimi et al ; Nature Medicine 2024). The current study provides updated clinical data to further evaluate the potential benefits of CBM588 in combination with cabo/nivo. Methods: This open-label, randomized trial enrolled patients aged ≥18 years old with a Karnofsky performance status ≥70% and histologically verified (clear-cell, papillary or sarcomatoid component) advanced or mRCC with no prior systemic therapy for metastatic disease. Patients were randomized in a 1:2 ratio to receive either cabo/nivo (40mg PO QD and 480mg IV monthly, respectively) alone or with CBM588 (80mg PO BID). This analysis provides updated secondary clinical endpoints with extended follow-up, including overall response rates (ORR), progression-free survival (PFS), and toxicity. Clinical benefit was defined as complete response, partial response, or stable disease, per RECIST 1.1. The association between treatment arm and ORR was evaluated using Fisher’s exact test, and PFS was estimated using the Kaplan-Meier method. Results: A total of 30 patients (20:10 M:F) were recruited, with a median age of 65 years (range, 36-84). Five patients (17%) had sarcomatoid features, and two (7%) had predominant papillary histology. As of June 1, 2024, the median follow-up was 25.8 months (interquartile range, 19.2-28.1) in the overall cohort. The ORR was significantly higher in the CBM588-containing arm compared to cabo/nivo alone arm (79% versus 20%, P =0.004). In the CBM588 arm, 17 (89%) patients, and in the control arm, 8 (80%) patients had a reduction in target lesion size, with median decreases of 51% (range, 17-94%) and 22% (range, 13-100%), respectively. Clinical benefit for at least 6 months was achieved in 80% of patients treated in experimental arm and 60% patients in the control arm. The median PFS was not reached in patients receiving CBM588, compared to 13.4 months in the control arm. The median OS was not reached in either of the arms at the time of data cutoff. Grade 3 or higher treatment-related adverse events (TRAEs) were observed in 45% of the CBM588 arm compared to 40% in the control arm. The most common TRAEs in the overall cohort were transaminitis (10%), hypertension (7%), and diarrhea (7%), with no significant differences between treatment arms. No new safety signals were detected. Conclusions: The addition of CBM588 to cabo/nivo continues to show promising efficacy in mRCC, with an improved PFS and ORR. The safety profile remains consistent with previous findings, supporting further exploration in larger trials. Further translational efforts are underway to characterize the mechanism through which CBM588 augments clinical activity. Clinical trial information: NCT05122546 .
Evaluating the therapeutic role of lymph node dissection in variant histology bladder cancer.
749 Background: Outcome benefit associated with lymph node dissection (LND) at time of radical cystectomy have been suggested in urothelial bladder cancer (BC), but have not been evaluated in variant subtype BC. Our objective was to characterize the impact of LND on survival outcomes across variant subtype BC. Methods: The National Cancer Database was queried for cases of variant histology bladder cancers using International Classification of Disease-O-3 morphologic codes managed with radical cystectomy between 2004 and 2020. Cases were stratified by variant subtype and LND status. Primary outcome was overall survival associated pathologic nodal status and receipt of LND. Kaplan Meier analysis and Cox proportional hazards analysis were performed for survival analyses. Results: A total of 30,911 patients with variant UC histology were included in our analysis. that were managed with radical cystectomy. Rates for the no-LND group (pNx) were 33.1% in the micropapillary subtype, 42.2% in sarcomatoid, 68.4% in squamous, 48.9% in adenocarcinoma, and 56.2% in the neuroendocrine subtype. Median OS was higher in those that received a nodal dissection for squamous (91.3 [89.9, 92.7] vs. 62.8 [60.1, 65.6] months p<0.001) and adenocarcinoma (83.6 [73.1, 92.1] vs. 56.3 [43.5, 69.0] months p=0.020). On Cox proportional hazards regression, in T1/2 stage disease LN dissection was associated improved OS for sarcomatoid (0.50 [0.23-0.96] p=0.048), squamous (0.67 (0.61-0.76) p<0.001), adenocarcinoma (0.45 [0.23-0.85) p=0.015), and neuroendocrine (0.425 [0.21-0.85) p=0.017) variant histologies. In T3/4 disease, nodal dissection was statistically significant improved OS only for squamous histology (0.68 [0.59-0.77] p<0.001 and 0.70 [0.59-0.83] p<0.001 respectively). The survival benefit of LND appears to be attenuated following receipt of NAC across most histologic subtypes including micropapillary and sarcomatoid histologies. Conclusions: Our data highlights the varying degrees of therapeutic benefit across variant BC. LND particularly in sarcomatoid, neuroendocrine, and adenocarcinoma VHBC is correlated with improved survival, particularly in low clinical stages. The benefit also appears to be attenuated with receipt of NAC. These data help inform a variant subtype-informed surgical approach.
Updated results from the phase 2 LITESPARK-003 study of belzutifan plus cabozantinib in patients with advanced clear cell renal cell carcinoma (ccRCC).
549 Background: In the phase 2 LITESPARK-003 study (NCT03634540), belzutifan plus cabozantinib showed antitumor activity in patients with advanced ccRCC who were treatment-naive (cohort 1) or previously treated (cohort 2). We present updated results from cohorts 1 and 2 with a median follow-up of 34.4 months and 49.9 months, respectively. Methods: Eligible patients had advanced or metastatic ccRCC and ECOG performance status of 0 or 1. Cohort 1 included patients with no prior systemic therapy. Cohort 2 included patients who had received prior immunotherapy and ≤2 systemic regimens. Starting doses for patients in both cohorts were belzutifan 120 mg PO QD + cabozantinib 60 mg PO QD. The primary end point was ORR per RECIST v1.1 by investigator assessment. Secondary end points included DOR, PFS, OS, and safety. Results: 50 patients were enrolled and treated in cohort 1 and 52 patients in cohort 2. Confirmed ORR was 70% (95% CI, 55-82; 6 CRs, 29 PRs) in cohort 1 and 31% (95% CI, 19-45; 2 CRs, 14 PRs) in cohort 2. In cohort 2, ORR was 32% (95% CI, 16-52; 1 CR, 8 PRs) in patients who received prior immunotherapy only (n = 28) and 29% (95% CI, 13-51; 1 CR, 6 PRs) in patients who received both prior immunotherapy and anti-VEGFR TKIs (n = 24). ORR by IMDC risk and baseline tumor burden subgroups is shown in the Table. Median DOR was 29.1 months (range, 1.9+ to 47.4; + indicates ongoing response at the last assessment) in cohort 1 and 30.4 months (range, 4.2+ to 45.6) in cohort 2. An estimated 62% of responders in cohort 1 and 52% in cohort 2 remained in response for ≥24 months. Median PFS was 30.3 months (95% CI, 19.4-not reached) in cohort 1 and 13.8 mo (95% CI, 9.2-19.4) in cohort 2. Median OS has not been reached in cohort 1 and was 26.7 months (95% CI, 20.0-41.1) in cohort 2. Overall, 27 (54%) patients in cohort 1 and 34 (65%) patients in cohort 2 had a grade 3 or higher treatment-related adverse event (TRAE). No patients died due to a TRAE in cohort 1 and 1 patient (2%) died due to treatment-related respiratory failure in cohort 2. Conclusions: With updated follow-up,belzutifan plus cabozantinib showed durable antitumor activity in both frontline and subsequent-line treatment of patients with RCC and a safety profile consistent with prior reports. These results support further investigation of a HIF-2α inhibitor in combination with a VEGFR-TKI as a treatment option for advanced ccRCC in both settings. Clinical trial information: NCT03634540 . Cohort 1 Cohort 2 IMDC risk category Favorable n = 33ORR, 73% (95% CI, 54-87); 5 CRs, 19 PRs n = 9ORR, 67% (95% CI, 30-93); 1 CR, 5 PRs Intermediate or poor n = 17ORR, 65% (95% CI, 38-86); 1 CR, 10 PRs n = 43ORR, 23% (95% CI, 12-39); 1 CR, 9 PRs Baseline tumor burden a Low (< median) n = 25ORR, 80% (95% CI, 59-93);3 CRs, 17 PRs n = 26ORR, 27% (95% CI, 12-48); 2 CRs, 5 PRs High (≥ median) n = 25ORR, 60% (95% CI, 39-79); 3 CRs, 12 PRs n = 26ORR, 35% (95% CI, 17-56); 0 CRs, 9 PRs a Based on the sum of diameter of the target lesions at baseline.
Evaluating the rates of surgical overtreatment of prostate cancer.
357 Background: Overtreatment of prostate cancer is a public health concern and a barrier to prostate cancer screening. In 2012 the US Preventative Task Force (USPTF) recommended against PSA screening citing overtreatment of indolent disease, and its associated morbidity, as a major limitation to the safety of widespread screening. In 2018 the USPTF updated their recommendation to PSA screening should only be pursued after an individualized discussion with the patient, emphasizing the risk of overtreatment. We sought to evaluate the rates of surgical overtreatment of prostate cancer over the last two decades. Methods: We evaluated the proportion of radical prostatectomies (RP) with pathologic Grade Group 1 (pGG1), as a surrogate for clinically insignificant disease, between 2012 and 2024 within the Michigan Urological Surgery Improvement Collaborative (MUSIC) and between 2010 and 2020 within the Surveillance Epidemiology and End Results (SEER) registry. MUSIC served as a statewide sample with a focus on urology outcomes, while SEER served as a national sample. Within MUSIC, pGG1, as a binary variable, was modeled in a mixed effects logistic model, against time while controlling for preoperative PSA, age, race, proportion and number of biopsy cores positive, and biopsy grade. We also assessed the proportion of these pGG1 RPs with preoperative higher-risk features: PSA ≥10, >50% of biopsy cores positive, or clinical Grade Group 2 on biopsy. Presence of any of these risk features was modeled as a binary variable against time, controlling for age and race. Results: Among 23,370 RPs in MUSIC and 162,558 RPs in SEER, the proportion of pGG1 decreased over the time periods examined. The proportion of patients undergoing RP with pGG1 on final pathology decreased from 21% to 2.7% from 2012 to 2024 within MUSIC and decreased from 32% to 7.8% from 2010 and 2020 within SEER. Within MUSIC, time was independently associated with a decrease in the proportion of RPs that were pGG1 (OR 0.52 per 5-years, 95% CI 0.47-0.57). During these time periods, the proportion of patients undergoing pGG1 RP with preoperative PSA ≥10 increased from 6.0% to 13% within MUSIC and increased from 8.1% to 10% within SEER. The proportion of pGG1 RPs with >50% cores positive on preoperative biopsy increased from 3.6% to 19% within MUSIC and from 11.8% to 15% within SEER. Time was independently associated with an increase in the proportion of pGG1 RP that had any pre-operative higher-risk features (OR 2.25 per 5 years, 95% CI 2.07-2.46). Conclusions: The rate of surgical overtreatment of low-risk prostate cancer has profoundly declined over the last two decades. A lower proportion of RPs are pGG1 and the pGG1 RPs being performed are more likely to have higher-risk preoperative features. Proportion of prostatectomies that were pGGG1. 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022 2023 2024 MUSIC - - 21% 18% 19% 16% 12% 8.4% 8.4% 7.2% 5.5% 5.6% 5.5% 3.7% 2.7% SEER 32% 31% 26% 23% 20% 16% 13% 11% 10% 8.8% 7.8% - - - -
Biomarker analysis in localized urothelial cancer DUART patients post-treatment.
859 Background: Patients with localized unresectable or cisplatin-ineligible urothelial cancer (UC) have limited treatment options. Biomarker identification can guide targeted therapies. In the DUART study, pre-treatment immune cell subsets were significantly linked to disease control. Our planned correlative aim was to evaluate the same biomarkers using post-adjuvant treatment (post-Rx) peripheral blood mononuclear cells (PBMCs). Methods: This was a prospective, multi-institutional study BTCRC-GU15-023. Our N=16 all had valid Post-Rx values and disease control status. Eligibility criteria: >18yrs, advanced/unresectable UC, and available tumor specimen. All received concurrent durvalumab and radiation therapy followed by adjuvant durvalumab in a Phase II study. Blood samples were taken at pretreatment, 12 weeks, and post-Rx. Biomarkers were detected using multicolor flow cytometry-based analysis of PBMCs to detect T lymphocyte subsets and by dimensionality reduction using FlowJo. Correlative objective: Evaluate post-Rx time points for biomarkers that contribute to disease progression or response. Two-sample T-tests were used to study the association. All tests were two-sided and the statistical significance level used was 0.05. Results: Standard flow cytometry analysis revealed a statistically significant increase in ICOS+ CD4 and CD8 T cells in post-Rx samples among patients with progression-free survival at one year. In addition, responder patients (CR/PR/SD, n=12) showed a significant decrease in CD8 central memory T cells compared to progressors (PD, n=4) in post-Rx samples. Although not statistically significant, additional trends were noted, including decreased PD-1+ CD4 T cells in responder patients, decreased CD4 T effector memory RA+ (TEMRA), and increased CD4 naïve T cells in responder patients. There was a slight increase in interferon gamma-producing CD8 T cell subsets in responder patients and a significant decrease in central memory CD8 T cells. tSNE analysis revealed similar trends in the data, including increased naïve CD4 T cells in responder patients and slight increases in some cytokine-producing CD8 T cell subsets. Conclusions: Our small cohort demonstrates some significant differences in post-Rx T cell populations linked to therapy response, and further evaluation in a larger cohort of patients is needed. The identification of predictive biomarkers could help a more personalized therapeutic approach.
Circulating kidney injury molecule-1 (KIM-1) in association with kidney injury biomarkers and outcomes in metastatic renal cell carcinoma.
582 Background: Kidney injury molecule-1 (KIM-1) is overexpressed in clear cell and papillary renal cell carcinoma (RCC) and in proximal tubular kidney injury. While circulating KIM-1 is a minimally invasive biomarker for RCC, it is unknown whether kidney disease, a common comorbidity among RCC patients, impacts the association of KIM-1 with RCC outcomes. We evaluated the association between KIM-1 and outcomes in metastatic RCC after adjustment for multiple kidney injury biomarkers using plasma proteomics. Methods: Plasma samples from patients with metastatic clear cell and papillary RCC were obtained prior to 1 st line systemic therapy. Samples were analyzed using a high-throughput aptamer-based proteomics assay (SomaLogic), and results were log-transformed for analysis. Clinical and laboratory data, as well as cancer outcomes, were retrospectively curated. Spearman’s ρ was used to evaluate correlations between circulating KIM-1 and kidney injury biomarkers (cystatin C, TNFR1, TNFR2, eGFR). Cox regression analyses were used to evaluate the association between KIM-1 as a continuous variable and overall survival (OS) and progression-free survival (PFS), after adjusting for kidney injury biomarkers. Performance of KIM-1 tertiles versus IMDC risk groups for prognosticating OS was evaluated using the C-index. Results: Among 210 patients, higher baseline KIM-1 was associated with worse PFS (p = 0.004) and OS (p < 0.001) in univariate Cox regression analysis (Table). The prognostic value of KIM-1 was consistent across clear cell and papillary RCC (p-value for interaction = 0.98). KIM-1 remained prognostic for PFS (p = 0.01) and OS (p < 0.001) after multivariable adjustment for kidney injury biomarkers and eGFR (Table). Median follow-up was 22.1 months. Kidney injury biomarkers (cystatin C, TNFR1, TNFR2, eGFR) were correlated with each other but not with plasma KIM-1. KIM-1 tertiles (high/medium/low) were more prognostic for OS than the IMDC risk groups (C-index, KIM-1 0.63 vs. IMDC groups 0.58) and the addition of KIM-1 to the IMDC model improved its performance (C-index, KIM-1 + IMDC groups 0.64). Conclusions: Plasma KIM-1 was associated with PFS and OS in metastatic clear cell and papillary RCC. Plasma KIM-1 was not correlated with kidney injury biomarkers, suggesting that at least in metastatic RCC, circulating KIM-1 derives predominantly from tumor rather than benign kidney. The addition of KIM-1 improves IMDC model performance and may be useful for risk prognostication in RCC. Association of KIM-1 with PFS and OS in metastatic RCC. Multivariable models are adjusted for kidney injury markers (cystatin C, TNFR1, TNFR2) and eGFR. log KIM-1 HR (95% CI) p-value OS (univariate) 1.4 (1.2 – 1.7) <0.001*** PFS (univariate) 1.2 (1.1 – 1.4) 0.004** OS (multivariate) 1.4 (1.2 – 1.6) <0.001*** PFS (multivariate) 1.2 (1.1 – 1.3) 0.01**
Efficacy of <sup>177</sup> Lu-PSMA-617 with or without ARPIs for the treatment of mCRPC: VISION secondary analysis.
121 Background: In the Phase 3 VISION trial, treatment with the prostate-specific membrane antigen (PSMA)-targeted radioligand therapy [ 177 Lu]Lu-PSMA-617 ( 177 Lu-PSMA-617) + protocol-permitted standard of care (SoC) significantly improved median radiographic progression-free survival (rPFS; 8.7 vs 3.4 months [mo]) and overall survival (OS; 15.3 vs 11.3 mo) in patients with metastatic castration-resistant prostate cancer (mCRPC) vs SoC alone. However, it is unclear how the addition of androgen receptor pathway inhibitors (ARPIs) affected 177 Lu-PSMA-617 treatment outcomes. Here we compared the efficacy and safety of 177 Lu-PSMA-617 in patients treated with vs without concomitant ARPIs. Methods: In VISION, adult patients with PSMA-positive mCRPC previously treated with ≥1 prior ARPI and 1–2 taxane chemotherapy regimens were randomized 2:1 to receive 177 Lu-PSMA-617 (7.4 GBq Q6W, 4–6 cycles) + SoC (which included ARPIs) vs SoC alone. In this secondary analysis, we assessed baseline characteristics, OS, rPFS, prostate-specific antigen (PSA) response rate, duration of PSA response, PSA-PFS, and safety among patients in the intervention arm who were treated with vs without concomitant ARPIs. Results: In total, 289 patients were treated with concomitant ARPIs and 262 patients were not (N=551). Imbalances between the groups were observed in some baseline characteristics: patients treated with concomitant ARPIs were younger, had lower ECOG performance scores, lower mean PSA and lactate dehydrogenase levels, and fewer prior taxane chemotherapy regimens. Baseline mean standardized [ 68 Ga]Ga-PSMA-11 uptake values and mean hemoglobin levels were well-balanced. A statistically significant difference in median OS was observed in patients treated with concomitant ARPIs vs those without (17.8 vs 12.4 mo; HR, 0.72; 95% CI, 0.58–0.89; nominal P=0.001). No statistically significant between-group differences were observed for rPFS, PSA response rate, duration of PSA response or PSA-PFS. The proportion of adverse events reported was similar in patients with or without concurrent ARPI, except for the number of adverse events leading to interruption of best supportive care/SoC, which was higher in patients treated with concurrent ARPIs. Conclusions: OS was significantly different in patients treated with concomitant ARPIs vs those without, while other efficacy endpoints were not. No new safety signals were observed for 177 Lu-PSMA-617 with concomitant ARPI. These findings may be confounded by varied exposure to ARPIs, or differing patient characteristics; patients who received concomitant ARPIs may represent a more favorable treatment population than those who did not. These findings should be considered as hypothesis-generating, and a multivariate analysis has been planned to ascertain the influence of these potential biases. Clinical trial information: NCT03511664 .
Phase 2 trial of immuno-ablation with intrabladder injection of N-803 or intravesical N-803 plus BCG for intermediate-risk non-muscle invasive papillary bladder cancer.
TPS905 Background: Response rates (55-65%) with bacillus Calmette-Guerin (BCG) monotherapy in papillary non-muscle invasive bladder cancer (NMIBC) are lower than rates (70-75%) for carcinoma in situ (CIS) disease, pointing to an unmet need for efficacious treatment of papillary NMIBC. We previously reported a complete response (CR) rate of 71% with combined intravesical use of the interleukin-15 (IL-15) superagonist fusion molecule N-803 (nogapendekin alfa inbakicept, NAI; ANKTIVA) and BCG in QUILT 3.032 cohort A study participants with BCG-unresponsive bladder CIS +/- Ta/T1 papillary disease and a disease-free survival (DFS) probability of 55.4% at 12 months for cohort B participants with BCG-unresponsive high-grade Ta/T1 papillary NMIBC. Based on these and other findings, the combination of N-803 plus BCG was recently approved by the FDA for BCG-unresponsive bladder CIS +/- Ta/T1 papillary disease. In a planned study, the efficacy of intrabladder N-803 immunoablative monotherapy by peritumoral injection of N-803 will be compared to intravesical N-803 plus BCG in patients with intermediate-risk BCG-naïve papillary NMIBC. The rationale for injection is based on findings from pre-clinical murine tumor models, the hypothesis that N-803 half-life will be extended by injection, and the suitability of injection for papillary disease. Methods: In the open-label phase 2 randomized study QUILT-215, adult participants with histologically-confirmed BCG-naïve intermediate-risk papillary Ta/T1 NMIBC will be enrolled into either Arm A or B. Up to 20 participants will be enrolled in each arm. In the first treatment period, Arm A participants will receive 400 µg N-803 monotherapy every 3 weeks by peritumoral intrabladder delivery and Arm B participants will receive 400 µg N-803 plus 50 mg BCG weekly for 6 weeks by intravesical delivery. The initial response assessment will be at 3 months. The second treatment period would commence at the end of month 3 and continue through month 15, with treatment depending upon the month 3 response. The primary endpoint is the CR (absence of any grade papillary NMIBC or CIS disease) rate at month 3 as determined by Investigator assessment of cystoscopy, cytology, and biopsy. The CR rate will be summarized by the number and percent and exact 95% CI using the Clopper-Pearson method. Secondary endpoints are progression-free survival (PFS), time to disease progression, overall survival (OS), disease-specific survival (DSS), duration of response (DOR) and cystectomy avoidance rate, to be analyzed using Kaplan-Meier methods. Safety will be assessed, including adverse events (AEs) and serious AEs (SAEs).
Assessing global disparities in clinical trial availability for renal cell carcinoma (RCC).
449 Background: Clinical trials are the cornerstone for developing novel therapies and diagnostic tools. Due to advancements from clinical trials, the median overall survival (OS) of patients with metastatic RCC has increased 4-fold in the last 20 years (Lancet 2024). However, clinical trial availability remains disproportionately concentrated in high-income regions, limiting the inclusion of a diverse patient population (JCO CCI 2020). We aimed to assess the current state of the global availability of clinical trials for RCC. Methods: Using the National Clinical Trials database, we identified all clinical trials enrolling patients with RCC from 6/1/2019 to 6/1/2024. We initially screened all trials and excluded those involving non-interventional studies, pediatric patients, and non-RCC neoplasms. Per trial, we annotated which countries had at least one active site. We classified them based on income using the World Bank Ranking (WBR) into high-income (HICs), upper-middle-income (UMICs), lower-middle-income (LMICs), and low-income (LICs) countries. Additionally, we registered information on RCC type, sponsor, phase, cancer stage, and primary and secondary endpoints. We used descriptive statistics to summarize the characteristics of each trial. The association between RCC trial availability and WBR was assessed using the Kruskal-Wallis test. We applied Poisson regression analysis to evaluate the association between clinical trial availability and incidence, mortality, WBR, health expenditure, and gross national income (GNI). Results: Out of 558 identified RCC trials, 357 met the eligibility criteria and 201 were exclude. The median number of countries per trial was 2.6. Most trials were conducted exclusively in HICs (76%), with fewer trials available in UMICs (23%), LMICs (3%), and none in LICs. The majority of trials included patients with clear cell RCC (52%) and metastatic disease (80%). Furthermore, 47% of trials were sponsored by academic institutions and 81% were early-phase trials. We found that the WBR was significantly associated with RCC clinical trial availability (p < .001). UMICs, LMICs, and LICs had significantly lower odds of hosting RCC clinical trials than HICs (OR 0.2, 0.05, and 0.013, respectively). Moreover, trials in non-HICs were more frequently funded by pharma (64% vs 40%), were part of multinational trials (45% vs 16%) and were late-phase trials (25% vs 8%). Poisson regression analysis revealed that GNI, health expenditure, and mortality rates were significantly associated with the number of clinical trials in a country. Conclusions: RCC clinical trials are disproportionately concentrated in HICs, with a direct association between GNI, health expenditures and trial availability. Expanding access to a broader range of trials, including early-phase and academic-sponsored studies, in underserved regions will promote more equitable advancements for all RCC patients.
Transcriptional profiling of patients with metastatic hormone-sensitive prostate cancer to uncover specific signatures linked to the transition from androgen-dependent to androgen-independent phenotype.
227 Background: Metastatic hormone-sensitive prostate cancers (mHSPC) are generally sensitive to androgen deprivation therapy (ADT). However, resistance often occurs, leading to disease progression. Understanding the transcriptomic changes underpinning the shift to antiandrogen resistance is crucial for identification of novel therapeutic vulnerabilities. Methods: Sixty patients with mHSPC undergoing ADT plus androgen receptor pathway inhibitors (ARPI) were enrolled. We defined non-responder (NR) patients (13/60) with biochemical/ radiological progression within 6 months of treatment and responder (R) (47/60) as those with stable disease or partial/complete response and eventually disease progression after 6 months. Total RNA was extracted from archived Formalin-Fixed Paraffin-Embedded (FFPE) basal prostate biopsies tissue samples using Maxwell RSC RNA FFPE Kit, and RNA was profiled using NanoString Tumor Signaling 360 Panel. Results: To identify gene signatures associated with response to ADT + ARPI, we analyzed differentially expressed genes between NR and R patients, through Rosalind platform Gene Set Analysis. Notably, NR patients exhibited significant upregulation of genes linked to cell cycle progression and DNA replication. The mitotic kinases AURKB and PLK1 were the most markedly upregulated genes in NR versus R samples (p=0.02 and p=0.01, respectively), suggesting enhanced cell cycle progression despite antiandrogen therapy. Coherent with these results, hyper-expression of KIF23 and CDC20 in NR vs R samples further confirmed aberrant cell cycle progression. Importantly, NR biopsies also exhibited increased expression of metastasis-promoting genes, such as HGF (p= 6.53 e-3 ), which may influence therapy response. Kaplan-Meier survival analysis reinforced the clinical significance of these findings, revealing that patients with hyper-expression of AURKB, KIF23, or CDC20, had shorter progression-free survival (PFS) compared to those with lower expression levels (p=0.0037, p=0.0007 and p=0.0289, respectively). These results underscore the potential of these molecular markers as predictive tools for resistance to ADT + ARPI and as potential targets for future therapeutic interventions. Conclusions: This study provides new insights into the transcriptomic landscape of mHSPC and identifies key gene signatures responsible for resistance to standard-of-care. Validation in larger cohorts is essential to confirm the predictive value of these genes and to identify patients eligible for novel combinatory treatments aimed at delaying this critical phenomenon.
Utilization, healthcare expenditures, and patient costs of definitive treatment modalities for localized prostate cancer in the United States.
370 Background: Radical prostatectomy (RP) and radiotherapy are standard-of-care treatments for localized prostate cancer. We studied the contemporary trends in utilization and costs of prostatectomy and radiotherapeutic modalities in the U.S. Methods: We analyzed the MarketScan Medicare Supplemental and Coordination of Benefits (MDCR) and Commercial Claims and Encounters (CCAE) Databases (the latter includes patients insured by employer-sponsored plans). We identified men with non-metastatic prostate cancer treated with RP, external beam radiation therapy (EBRT), brachytherapy (BT), EBRT combined with BT (EBRT+BT), stereotactic body radiation therapy (SBRT), or proton beam therapy (PBT) between 2009 and 2021. Year-to-year utilization of each treatment was compared using Kendall’s Tau-b test. Total healthcare and patient out-of-pocket payments within 12 months following treatment initiation were compared among treatment modalities using the Kruskal-Wallis test. Results: In MDCR, we identified 44,937 patients who received treatment with either RP (n=12,879), EBRT (n=26,193), BT (n=926), EBRT+BT (n=4,706), PBT (n=57), or SBRT (n=176). Between 2009 and 2021, the proportion of patients treated with EBRT increased from 52.5% to 62.2% (trend p<0.001), SBRT increased from 0.4% to 0.5% (p<0.001), BT decreased from 3.1% to 1.0% (p<0.001), and EBRT+BT decreased from 14.8% to 6.8% (p<0.001). There was no significant difference in the proportion of patients treated with RP (29.1% vs 29.4%; p=0.82) or PBT (0.1% vs 0.1%; p=0.93). In CCAE, we identified 75,626 patients treated with either RP (n=50,278), EBRT (n=16,985), BT (n=1,243), EBRT+BT (n=6,811), PBT (n=91), or SBRT (n=217). EBRT increased from 20.0% to 24.9% (p<0.001), SBRT increased from 0.1% to 0.8% (p<0.001), BT decreased from 2.5% to 0.7% (p<0.001), and EBRT+BT decreased from 10.6% to 7.4% (p<0.001). There was no significant difference in the proportion of patients treated with RP (66.8% to 66.1%; p= 0.82) or PBT (0.1% vs 0.1%; p=0.76). In both cohorts, PBT had the highest 12-month total and patient costs, while BT had the lowest total cost and SBRT had the lowest patient cost (Table). Conclusions: There is increasing use of EBRT and SBRT in the US. Despite BT being the least costly, its utilization, alone or in combination with EBRT, has declined. Distribution of inflation-adjusted total payments 12 months post diagnosis. Payment MDCR CCAE RP EBRT BT EBRT+ BT PBT SBRT P RP EBRT BT EBRT+ BT PBT SBRT P Total ($) Mean (STD) 30,149 (9,217) 56,199 (19,551) 26,241 (7,920) 38,676 (11,089) 69,719 (17,998) 47,861 (17,377) < 0.001 35,175 (4,800) 66,940 (11,397) 27,377 (3,707) 45,875 (6,620) 102,312 (12,090) 52,544 (8,027) <0.001 Patient ($) Mean (STD) 1,102 (255) 1,285 (294) 1,048 (231) 1,287 (299) 1,044 (237) 992 (325) <0.001 1,965 (671) 1,786 (636) 1,554 (569) 2,031 (695) 1,466 (477) 1,524 (536) <0.001
Presurgical treatment for inferior vena cava tumor thrombus in patients with renal cell carcinoma: A scoping review.
602 Background: To date, there is no evidence-based standard of care for the management of patients with tumor-related thrombus (TT) in the inferior vena cava (IVC) associated with renal cell carcinoma (RCC).The aim of our study is to analyze published papers on presurgical treatment and their effect on reducing the TT length, level and deintensification of surgical approach. Methods: MEDLINE, Embase, and Cochrane Central were systematically searched using PRISM-Scr checklist for studies evaluating presurgical therapies intended to decrease the TT length, and level in RCC patients as well as surgical outcome. Patient were reviewed to have the following outcomes: clinically significant (>20%) reduction in TT length, reduction in TT level by Mayo classification and deintensification of planned surgical intervention. Results: After comprehensive review of 1175 studies by PRISMA-Scr protocol, 21 studies fulfilled prespecified criteria that included 1 phase II clinical trial, 3 case series and 16 retrospective cohort studies. Among 216 patients reviewed, 178 (82.4%) had clear cell RCC, 106 (49.07%) had stage T3b and 53 (24.53%) had nodal involvement. Presurgical regimes included Thyrosine Kinase Inhibitors (TKI) (81%), TKI-Immune check point inhibitor (ICI) combination (6%), ICI monotherapy (3%), Stereotactic radiation (4%) and others (6%). Significant decrease in length in TT was reported in 40.29%, 42.86% and 84.62% of patients treated with TKI, ICI and TKI-ICI combination, respectively. Levels of TT were decreased in 30.32%, 46.15% and 14.29% patients treated with TKI, ICI and TKI-ICI combination, respectively. Among the patients reported to have less invasive surgical approach following presurgical treatment (n=34), 29.41% avoided cardiac bypass. Conclusions: Published studies have reported benefits of presurgical treatment in reducing length and level of TT as well as improving surgical outcome. However, significant heterogeneity exists and prospective studies are required to draw a meaningful conclusion.
Survival outcomes among metastatic castration-resistant prostate cancer patients treated with androgen receptor pathway inhibitor and docetaxel.
57 Background: Real-world evidence on treatment patterns and real-world overall survival (rwOS) are limited in metastatic castration-resistant prostate cancer (mCRPC) patients treated with prior androgen receptor pathway inhibitor (ARPI) and docetaxel treatment. The objective of the study was to describe distribution of ARPI switch or cabazitaxel and their rwOS in patients with mCRPC settings after ARPI and docetaxel treatment. Methods: The study analyzedConcertAI Patient 360 data with a prostate cancer diagnosis in US, derived from electronic health records and claims data between 1990 and 2023. Among the eligible adult mCRPC patients, the study population included patients who subsequently received ARPI switch or cabazitaxel in mCRPC setting. The patient number and distribution (%) by treatments and subgroups were summarized. The study used the Kaplan-Meier method to calculate rwOS (median, months; interquartile range, IQR) and rwOS rate (%) at 12, 24 and 36 months from the start date of ARPI switch or cabazitaxel (Index Date). Results: Among 945 mCRPC patients with prior ARPI and docetaxel treatment (median age: 72 years; white: 79%; baseline PSA ≥ 100 ng/mL: 41%), cabazitaxel was more commonly used (59%) compared to ARPI switch (abiraterone: 22%; enzalutamide: 19%). The rwOS was 13 months, and rwOS rates of the overall patients were 53%, 29% and 21% for at 12, 24 and 36 months, respectively. Patients with liver metastasis had 9 months of median rwOS, while patients without liver metastasis had 14 months. Conclusions: The relatively short OS demonstrated the unmet medical need in mCRPC patients who received multiple treatments including ARPI and taxane-based chemotherapy, warranting the development of more effective and innovative treatments extending patient survival. Overall survival in metastatic castration-resistant prostate cancer patients treated with androgen receptor pathway inhibitor and docetaxel. Total (N=945) Months (IQR) Median OS in total patients (Death, n=770; 81%) 13 (6 - 29) Median OS in subgroup patients by liver metastasis No 14 (6 - 30) Yes 9 (5 - 20) OS Rate % 12 months 53 24 months 29 36 months 21 IQR= interquartile range; OS=overall survival.
Boosting survival in advanced urothelial carcinoma: The power of CBM588 probiotic and pembrolizumab combination.
774 Background: Immune checkpoint inhibitors (ICIs) is now standard cares for locally advanced or metastatic Urothelial Carcinoma (UC). One of the probiotics, CBM588 (MIYAIRI 588), is widely used in clinical practice and regulates the intestinal microbiota. Recently, the relationship between ICIs and probiotics in cancer therapy has attracted attention with prolonged prognosis reported in lung and renal cancers when combined with CBM588. However, there are no reports on the usefulness in UC. Methods: We retrospectively evaluated the effect of pembrolizumab plus CBM588 in patients with unresectable UC treated with pembrolizumab as second-line therapy at our institution, with and without CBM588. The analysis was divided into two groups: those taking CBM588 (n=33) and those not taking CBM588 (n=11) at the time of pembrolizumab initiation. Progression-free survival (PFS) and overall survival (OS) were the primary endpoints. Results: The median follow-up was 12.0 months in the pembrolizumab alone group versus 12.2 months in the CBM588 group. The median PFS was 3.9 months in the pembrolizumab alone group versus 10.2 months in the CBM588 group. On multivariate analysis, the hazard ratio for the CBM588 arm was 0.074. The median OS was 12.2 months in the CBM588 arm versus 12.0 months in the pembrolizumab alone arm. On multivariate analysis, the hazard ratio for the CBM588 arm was 0.105 (95% CI 0.022-0.533, P=0.0056). Conclusions: The combination of CBM588 with pembrolizumab may prolong progression in UC. Although the sample size and follow-up period are limited, the positive outcomes observed emphasize the necessity for further studies to confirm these findings and investigate the underlying causes. Multivariate analysis of PFS and OS. Multivariate Analysis-PFS Multivariate Analysis-OS Variables Groups Hazard ratio 95% CI P-value Hazard ratio 95% CI P-value Treatment PEM reference reference PEM with CBM588 0.074 0.016-0.340 0.0008 ** 0.105 0.022-0.533 0.0056 * Age 0.947 0.901-0.995 0.030 * 0.992 0.944-1.043 0.738 Sex male reference reference female 1.410 0.546-3.643 0.4786 0.717 0.292-1.985 0.513 ECOG-PS 0 - 1 reference reference 2 - 4 0.338 0.136-0.837 0.0191 * 1.067 0.400-2.712 0.894 Tumor location (primary) Lower urinary tract reference reference Upper urinary tract 1.455 0.577-3.662 0.426 0.666 0.228-1.986 0.461 T stage (primary) 0 - 2 reference reference 3 3.634 1.340-9.835 0.011 * 1.210-8.763 0.019 * unknown 7.623 1.291-45.00 0.025 * 6.368 1.069-37.93 0.042 * N stage 0 reference reference 1 0.976 0.380-2.505 0.958 1.328 0.521-3.389 0.552 M stage 0 reference reference 1 1.407 0.298-6.652 0.666 1.579 0.313-7.944 0.579 Lung metastasis 1 0.871 0.297-2.55 0.801 0.497 0.151-1.633 0.249 Liver metastasis 1 5.465 1.516-19.70 0.0094 * 2.889 0.735-11.34 0.129 Bone metastasis 1 1.841 0.608-5.57 0.280 1.447 0.445-4.703 0.539 IrAE 1 0.133 0.03-0.586 0.0077 ** 0.277 0.056-1.359 0.114 *p < 0.05; **p < 0.008.
Validation of new prognostic factors for relapse in patients with clinical stage I seminoma.
625 Background: Patients with clinical stage I (cSI) seminomatous testicular germ cell tumors (GCT) have a relapse risk of 5 - 30% under surveillance after orchiectomy, depending on tumor size and rete testis infiltration. Recently, two studies introduced new prognostic risk models to improve clinical decision-making: the Danish Testicular Cancer database (DaTeCa) and an Individual Patient Data Analysis by the European Association of Urology (EAU) Testicular Cancer Guidelines Panel and Guidelines Office. This study aimed to validate these new prognostic risk models in an independent cohort of cSI seminoma patients. Methods: We included patients with unilateral cSI seminoma (retroperitoneal lymph nodes <10 mm in short-axis diameter), normalized serum tumor markers post-orchiectomy (β-human chorionic gonadotropin (β-hCG) and lactate dehydrogenase (LDH)), and no adjuvant therapy. All patients had at least 12 months of follow-up. Cox regression analysis was applied to evaluate the proposed prognostic factors and relapse probabilities were estimated using the Kaplan-Meier method. Results: Among 139 patients, 25 (18%) relapsed within a median follow-up of 37 months (CI 47.9–63.1). In multivariate analysis, only rete testis infiltration was confirmed as an independent predictor of relapse (p=0.039). The other prognostic factors of DaTeCa (lymphovascular invasion, elevated pre-orchiectomy β-hCG and LDH) and EAU (tumor size and lymphovascular invasion) could not be confirmed. The 5-year relapse risk according to DaTeCa risk groups was consistent with our cohort (no risk factors: 4% vs. 6%; all four risk factors: 67% vs. 62%). Similarly, the EAU classification showed comparable 5-year relapse risks for low (13% vs. 8%) and intermediate (22% vs. 20%) groups. However, the high-risk group showed a greater discrepancy (67% vs. 44%), although our study included only a limited number of high-risk patients (n=6, 4.3%). Conclusions: The risk classification models from DaTeCa and EAU demonstrated good overall reproducibility in our cohort. These models may aid in identifying seminoma patients at high-risk for relapse who might be candidates for adjuvant therapy. However, the proposed prognostic factors were mainly not independently confirmed in the multivariate analysis in our study cohort.
Interpretable machine learning for prostate biopsy: Cohort study.
333 Background: The objective of this study is to develop prediction models and provide diagnostic results for prostate biopsy among patients. Methods: This paper presents an improved tree model, called the Light gradient boosting machine model, for building a prostate cancer (PCa) risk prediction model. The research data used in this study (Waves 2008-2022) are obtained from 1987 patients who underwent transperineal biopsy at West China Hospital. All patients had biopsy indications (high levels of prostate specific antigen (PSA), suspect lesions in magnetic resonance imaging (MRI) suspect lesions). A total of 13 baseline variables were considered as candidate features, and eight machine learning models were compared in the experiment. Shapley additive explanations (SHAP) was used for explaining the prediction model. Results: The Light gradient boosting machine model demonstrated the best performance, achieving an area under the receiver operating characteristic (ROC) curve of 0.76 (CatBoost=0.71, KNN=0.65, LDA=0.61, CART=0.67, SVM=0.64, NB=0.55, XGBoost=0.71). According to the interpretable analysis, the apparent diffusion coefficient (ADC) of MRI was identified as the most important feature in the prediction model. Other important features included prostate volume, red blood cell count, neutrophil count, and platelet count. Conclusions: This study suggests that optimal models show promise in screening out patients at high risk for PCa in prostate biopsies. The decisions regarding prostate biopsies should specifically focus on the ADC of MRI, prostate volume, and blood routine indices such as RBC count, platelet count, and neutrophil count. Baseline characteristic of all patients. Mean (SD) Pca (n=1001) Non-Pca (n=986) P Age (years) 68.68(9.29) 67.99(9.32) 0.901 Blood routine RBC (10 12 /L) 4.66(0.62) 4.65(0.61) 0.56 Hemoglobin (g/L) 141.46(19.72) 141.84(17.21) 0.149 Platelet (10 9 /L) 188.49(64.65) 193.46(69.12) 0.02 WBC (10 9 /L) 6.76(6.36) 6.6(1.95) 0.56 Neutrophil count (10 9 /L) 4.15(1.52) 4.19(1.71) 0.026 Lymphocyte count (10 9 /L) 1.89(5.73) 1.75(0.76) 0.405 Monocyte count (10 9 /L) 0.48(0.16) 0.47(0.17) 0.626 Eosinophil count (10 9 /L) 0.16(0.16) 0.15(0.16) 0.781 Basophil Cell Count (10 9 /L) 0.25(1.21) 0.36(1.47) <0.001 PSA (ng/ml) 65.02(346.16) 11.32(23.01) <0.001 Prostate volume (ml) 43.96(27.66) 51.24(26.85) 0.007 PSAD (ng/ml 2 ) 1.82(12.88) 0.28(0.544) 0.001 ADC 733.13(172.09) 756.93(181.31) 0.004