tbuckley/cabot-search huggingface dataset:
ACCEL: [Ac-225]-PSMA-62 phase Ia/Ib/II clinical trial to characterize efficacy, safety, tolerability, and dosimetry in oligometastatic hormone-sensitive and metastatic castration-resistant prostate cancer.
Authors: Ramy Saleh, Kim N. Chi, Di Maria Jiang, Vincent Castonguay, Farzad Abbaspour, Ur Metser, Don Wilson, Junsheng Ma, Richard Cioci, Karim Nacerddine, Jean-Mathieu Beauregard
Journal: Journal of Clinical Oncology (2025)

TPS282 Background: Actinium-225 (Ac-225)-based, prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) represents a promising treatment modality for prostate cancer. First-generation PSMA-targeting ligands (e.g., PSMA-617 and PSMA-I&amp;T) paired with Ac-225 have been associated with myelosuppression, renal toxicity, and xerostomia (1). LY4181530 (previously PNT2001) pairs Ac-225 with PSMA-62, a next-generation ligand, which was specifically designed to overcome these limitations. It employs an improved linker technology that increases cellular internalization, leading to improved biodistribution, tumor delivery of Ac-225, and efficacy in preclinical models (2). Methods: ACCEL (NCT06229366) is a multi-center, open-label, multiple-arm, Phase Ia/Ib/II study evaluating the safety, tolerability, and efficacy of [Ac-225]-PSMA-62 in patients with oligometastatic hormone-sensitive prostate cancer (OmHSPC) and metastatic castration-resistant prostate cancer (mCRPC). Eligible patients with OmHSPC have metachronous disease, up to 5 PSMA-positive lesions, and have not initiated life-long ADT. Eligible patients with mCRPC have PSMA-positive lesions and have received prior androgen receptor pathway inhibitor, taxane chemotherapy (unless ineligible or declined), and up to 3 prior systemic therapy regimens in the mCRPC setting. Prior PSMA-targeted RLT, baseline Grade ≥1 xerostomia, and Grade ≥1 xerophthalmia are not permitted. In the Phase 1a, dose escalation decisions follow the Bayesian optimal interval (BOIN) design to separately determine the maximum tolerated dose of [Ac-225]-PSMA-62 for each patient population. In the Phase 1b, patients will be randomized to 2 or more arms to optimize dosing/schedule and inform the selection of the recommended Phase II dose of [Ac-225]-PSMA-62 for each patient population. The phase II aims to evaluate the efficacy of [Ac-225]-PSMA-62 compared to best standard of care in patients with mCRPC, with the primary endpoint being radiographic progression-free survival. The study is currently enrolling in Canada with plans to open in other countries. 1. Sathekge MM. et al. Lancet Oncol . 2024 Feb;25(2):175-183. 2. Vito A. et al. EP-039. Presented at EANM Oct 2022, Barcelona, Spain. Clinical trial information: NCT06229366 .
Impact of androgen deprivation therapy with postoperative radiotherapy after radical prostatectomy on health-related quality of life.
Authors: Thilo Westhofen, Alexander Buchner, Lennert Eismann, Severin Rodler, Elena Berg, Can Aydogdu, Darjusch Askari, Armin Becker, Christian G. Stief, Alexander Kretschmer
Journal: Journal of Clinical Oncology (2025)

133 Background: There is an ongoing debate on the use and duration of androgen deprivation therapy (ADT) with postoperative radiotherapy (RT) following radical prostatectomy (RP). While there have been conflicting results regarding oncological outcome, the effect of concomitant ADT on health-related quality of life (HRQOL) remains elusive. We aimed to assess the impact of adding ADT to postoperative RT on long-term HRQOL by providing PROM data from a large contemporary cohort of patients undergoing RT following RP with a systematic follow-up of up to 10 yrs. Methods: n=1124 patients who underwent RT after previous RP at a large tertiary care center between 2010 and 2021 were identified within a prospective institutional database. Patients with previous post-op ADT were excluded. Patients were stratified by concomitant ADT (no ADT n=682; ADT n=436). PROMs were prospectively assessed preoperatively, prior and post RT and at a maximum follow-up of up to 120mo, applying the validated EORTC QLQ-C30- and the prostate cancer-specific QLQ-PR25-questionnaires. Correlation analysis and multivariable regression models were used to estimate the impact of ADT with postoperative RT on HRQOL. Results: Median duration of ADT received within the ADT-cohort was 21mo. Prior RT, no significant difference in general HRQOL assessed by the global health status domain (GHS) was found between the ADT cohort (69.6) and the no ADT cohort (68.9; p=0.88). Post RT (65.1 vs. 69.9; p=0.038) and after median follow-up of 59 months (62.8 vs. 68.1; p&lt;0.001) patients in the ADT cohort reported significantly worse general HRQOL. In multivariable regression analysis stratified by age, BMI, pT-stage, urinary continence and erectile functioning, concomitant ADT was confirmed as an independent predictor for worse general HRQOL (OR 0.68, 95% CI 0.47-0.96, p=0.03). Correlation analysis revealed a significant correlation between longer duration of ADT and worse long-term general HRQOL (p&lt;0.001). In line, multivariable linear regression analysis revealed longer duration of ADT to independently predict worse general HRQOL (p=0.041) (Table). Conclusions: In patients with postoperative RT, concomitant ADT yields worse long-term general HRQOL. A longer duration of ADT furthermore leads to worse long-term general HRQOL. Those results support careful patient selection for ADT with postoperative RT after RP. Multivariable linear regression for HRQOL. Variable B [regression coefficient] Beta [standardized regression coefficient] SE [standard error] p value Duration of ADT -0.272 -0.191 0.132 0.041 Age -0.127 -0.043 0.294 0.667 BMI -0.588 -0.120 0.444 0.188 ICIQ-SF-Score 0.914 0.012 6.729 0.892 IIEF5-Score 0.661 0.165 0.403 0.103 R² 0.341 Adjusted R² 0.336
Survival outcomes of de novo mHSPC based on hemoglobin A1C and ARPI therapy.
Authors: Rohan Agarwal, Luke Rohde, Jason M Doherty, Martin W. Schoen
Journal: Journal of Clinical Oncology (2025)

139 Background: While there has been no prospective studies, enzalutamide (enza) has better overall survival, fewer adverse events, risk of progression, and PSA response compared to the abiraterone (abi) in real-world treatment of metastatic prostate cancer with androgen receptor pathway inhibitors (ARPI)s. Diabetes (T2DM) is a major comorbidity in elderly patients, with worse glycemic control as a risk factor for and worse cancer outcomes. Studies analyzing the role of ARPIs in patients with diabetes have found enza associated with longer survival, less frequent acute hospitalizations, and likelihood of developing T2DM, compared to abi. However, there is little data in hormone sensitive population (mHSPC), where ARPIs are most commonly used. This study analyzed the association between use of APRI treatment and survival in patients with controlled versus uncontrolled diabetes based off hemoglobin A1C (hgbA1C). Methods: 1591 Patients with de novo mHSPC diagnosed between 2017-2023, treated with abiraterone or enzalutamide with 4 months of ADT, and hgbA1C within 1 year prior and up to 3 months after cancer diagnosis were retrospectively identified. Additional variables included age, BMI, base-line prostate specific antigen at diagnosis, Charlson Comorbidity Index score (CCI). Kaplan-Meier method was used to compare overall survival months based on hgbA1C and diabetes diagnosis. Cox proportional hazard modeling was performed to assess the relationship when adjusting for confounding variables. Results: The cohort included 1591 patients with de novo mHSPC, 1,196 who received abiraterone and 395 who received enzalutamide. Veterans treated with enza were older (mean 74.4 years vs. 73.0, p&lt;0.001) with higher CCI (mean 2.6 vs. 2.0, p&lt;0.001). Veterans with hgbA1C&gt;6.5 were more likely to be prescribed enzalutamide (31.1% vs. 21.6%, p&lt;0.001). Veterans with hgbA1C&lt;6.5 had significantly longer survival compared to veterans with hgbA1C&gt;6.5 (41.5 vs. 33.3 months, HR 0.79 95%, CI 0.68-0.91). Patients treated with abiraterone had a significant difference in survival based on hgbA1C (41.5 vs. 31.1, HR 0.79, CI 0.67-0.93). In patients treated with enzalutamide, there was no significant difference in survival (40.7 vs. 38.0, HR 0.80 95%, CI 0.60-1.07). A1C remained predictive of mortality (HR 1.27, 95CI 1.10-1.48) when controlled for PSA, BMI, ARPI, and age. Conclusions: In veterans with mHSPC who are treated with abiraterone, elevated hgbA1C is associated with shorter survival. No differences were seen in veterans treated with enzalutamide; however, these analyses may be underpowered. These results may help in treatment selection and support glycemic control when treating patients with mHSPC and comorbidities. ARPI A1C Median OS (months) HR 95 CI Abiraterone &lt;6.5 41.5 0.79 0.67-0.93 6.5+ 31.1 overall 39.2 Enzalutamide &lt;6.5 40.7 0.80 0.60-1.07 6.5+ 38.0 overall 39.4
Long follow-up quality of life outcomes from an investigator-initiated randomized trial of enzalutamide versus abiraterone plus prednisolone in docetaxel-untreated castration-resistant prostate cancer.
Authors: Kouji Izumi, Atsushi Mizokami
Journal: Journal of Clinical Oncology (2025)

52 Background: Head-to-head comparison between enzalutamide (ENZ) and abiraterone plus prednisolone (ABI) demonstrated similar survival benefit for castration-resistant prostate cancer. We analyzed quality of life (QOL) reported over time in each treatment arm as sub-analysis study. Methods: ENABLE study for PCa, an investigator-initiated, multicenter, phase 3 randomized controlled trial, was conducted. FACT-G QOL questionnaires were reported by patients at timepoints. We analyzed questionnaires up to 48 months, including the detailed assessment of subscales which consist of physical, social, emotional, and functional well-being. Results: In total 92 patients in each arm included, 79 and 77 in the ENZ and ABI arm answered questionnaires up to 24 months. There were no significant differences in overall survival and time to PSA progression between arms (P=0.4365 and P=0.2458). Although ENZ did not change the total score of FACT-G during treatment (P=0.8552), ABI significantly deteriorated it gradually (P=0.0002). In ABI arm, the standard dose (1000 mg/day) significantly deteriorated the total score of FACT-G chronologically (n=57, P=0.0002), meanwhile the modified dose (750 mg/day or less) did not change it during treatment (n=15, P=0.1816). In the subscale analysis, ENZ did not deteriorate any subscales, whereas ABI deteriorated social and functional well-beings (P=0.0149 and P=0.0005, respectively). Further dissection of subscale analysis revealed that the modified dose of ABI did not deteriorate social and functional well-beings (P=0.277 and P=0.4026, respectively) but the standard dose of ABI significantly deteriorated them (P=0.0010 and P&lt;0.0001, respectively). Conclusions: A head-to-head comparison of QOL between ENZ- and ABI-treated castration-resistant prostate cancer patients was performed for the first time. ABI deteriorated QOL chronologically and the standard dose of ABI was a main cause of the deterioration in QOL. The modified dose of ABI may be a better treatment option. Clinical trial information: UMIN000015529 .
Second-line platinum-based chemotherapy (PBT) in patients with metastatic urothelial carcinoma (mUC) treated with first-line pembrolizumab plus enfortumab vedotin (P/EV): A single-center, retrospective study.
Authors: Junkyu Kim, Se Hoon Park, Changgon Kim, Jiyeon Hyeon, Sung Hee Lim, Minsuk Kwon
Journal: Journal of Clinical Oncology (2025)

785 Background: Although the efficacy of PBT as first-line therapy for mUC has been known for more than 30 years, the recent integration of P/EV as a preferred first-line option prevented the use of evidence-based regimen. Since the available second-line regimens depend on what was given as first-line, we evaluate the efficacy and tolerability of second-line PBT in mUC patients treated with first-line P/EV. Methods: We retrospectively reviewed the medical records of 37 patients with mUC who were treated with first-line P/EV, mostly in clinical trials, between Jan 2022 and Jan 2024 at Samsung Medical Center (Seoul, Korea). Patients with mUC whose disease progressed during or after first-line treatment with P/EV received PBT involving gemcitabine plus either cisplatin or carboplatin (determined on the basis of cisplatin-eligibility). Primary endpoints included safety and response rates. Results: Among a total of 37 first-line P/EV patients, 10 received second-line PBT: gemcitabine plus cisplatin (n = 8) and plus carboplatin (n = 2). The median age was 68 years (range, 48 to 82 years) and the median interval from the last dose of P/EV was 50 days (range, 15 to 89 days). A total of 33 PBT cycles were given (median, 2; range 1 to 6). One patient achieved a complete response and 3 had a stable disease. Although peripheral neuropathy and gastrointestinal toxicities were the most frequently encountered adverse events, safety profile was generally manageable. Median progression-free and overall survivals were 3.4 months (95% CI, 2.3 to 4.5) and 8.0 months (95% CI, 6.1 to 19.9), respectively. Conclusions: Second-line PBT for mUC patients treated with first-line P/EV does not appear highly active but the observation of responders merits further studies in those with medically-fit, platinum-eligible patients.
Exploring the efficacy of belzutifan in the treatment of renal cell carcinoma associated with von Hippel-Lindau disease: A comparative analysis with external control arm.
Authors: W Marston Linehan, Thomas Jemielita, Jerry Cornell, Ke Chen, Mark Wayne Ball, Ramaprasad Srinivasan, Yanfang Liu, Rodolfo F. Perini, Cathy Anne Pinto
Journal: Journal of Clinical Oncology (2025)

469 Background: Randomized controlled trials are the gold standard for demonstrating treatment efficacy but are not feasible in certain disease settings. In such cases, external control arm (ECA) analysis can be an effective way to interpret experimental treatment results. Our aim, based on a natural history study (NHS), was to develop an ECA for a Phase 2 single-arm trial (LITESPARK [LS]-004) for belzutifan in 61 patients with VHL disease-associated RCC. With a median follow-up of 37.8 months in LS-004, the objective response rate (ORR) for VHL RCC patients was 64% (95%CI: 50.6, 75.8) and the median time to surgery (TTS) was not reached. Methods: The ECA was developed using NHS data for VHL RCC patients undergoing active surveillance at the US National Cancer Institute with up to 5 years of follow-up. Key LS-004 eligibility criteria (e.g., no prior systemic therapy or metastasis) were applied. Propensity score (PS) weighting was used to balance baseline characteristics (age, sex, number and size of RCC, prior surgery and time from prior surgery, VHL mutation status) between LS-004 and ECA, with balance evaluated using standardized mean difference (SMD). PS adjusted point estimates and 95% CI for ORR, assessed by independent blinded committee review using RECIST 1.1, and TTS were estimated. For the ECA, the ORR was evaluated among patients with ≥3 serial scans to allow the opportunity for a confirmed response. Results: The ECA included 244 patients with 178 patients in the ORR analysis. Prognostic factors were well balanced between the ECA and LS-004 with a SMD&lt;0.1 for all covariates. The PS adjusted ORR (95% CI) for LS-004 and the ECA was 63.9% (51.9, 76.0) and 1.5% (0.0, 3.3), respectively. Median (95% CI) TTS was 44.4 (35.7, 51.1) months in the ECA, and not yet reached in LS-004. Conclusions: The magnitude of the treatment effect with belzutifan is large compared with the ECA. Although residual confounding is still possible, including effects of unmeasured confounders, observing such a large effect is unlikely due to chance. The results support the demonstrated antitumor activity and efficacy of belzutifan in the treatment of VHL RCC.
A phase I/II study of neoadjuvant, intra-arterial administration of (177Lu)lutetium vipivotide tetraxetan in subjects with high-risk, localised or locally advanced prostate cancer (LUPUS).
Authors: Claudia Kesch, Volker Meyer, Christine Praus, Pedro Fragoso Costa, Marc Ingenwerth, Christopher Darr, Jan Philipp Radtke, Jens M Theysohn, Benedikt Schaarschmidt, Henning Reis, Wolfgang Peter Fendler, Viktor Grünwald, Boris A. Hadaschik, Ken Herrmann
Journal: Journal of Clinical Oncology (2025)

TPS431 Background: The recent LuTectomy trial suggested that intra-venous [177Lu]Lu-PSMA-617 prior to surgery in men with high-risk localised or locally advanced prostate cancer (HRCaP) is safe and effective. We hypothesise that intra-arterial infusion will further enhance target lesion uptake and efficacy without compromising safety. LUPUS is the first trial investigating (177Lu)Lutetium vipivotide tetraxetan intra-arterial infusion and will help to further evaluate if there is a role for neoadjuvant radioligand therapy in HRCaP. Methods: Phase I/II study of neoadjuvant, pre-surgical (177Lu)Lutetium vipivotide tetraxetan as intra-arterial infusion in men with HRCaP who are candidates for radical prostatectomy (EU CTR 2022-500838-28-00). Intra-arterial perfusion is performed via a catheter into A. iliaca interna without concomitant embolization. In the first cohort, 10 patients will receive one cycle of 200 mCi (7.4 GBq) (177Lu)Lutetium vipivotide tetraxetan followed by radical prostatectomy 6 weeks thereafter. If less than 4 out of 10 patients have to delay surgery or suffer from CTCAE Grade ≥3 adverse events (AEs) due to the treatment, 10 additional patients will be included and receive one cycle of 400 mCi (14.8 GBq) (177Lu)Lutetium vipivotide tetraxetan. Enrolment began in September 2024. Primary endpoints are AEs and days of delay of scheduled surgery related to intra-arterial (177Lu)Lutetium vipivotide tetraxetan therapy. Secondary endpoints are PSA-response and pathological response. Other endpoints include imaging changes, changes in quality of life and dosimetry. Clinical trial information: EU Clinical Trial no.: 2022-500838-28-00 .
Real-world U.S. county-level analysis of erectile dysfunction diagnosis following radiation therapy for localized prostate cancer: The impact of rectal spacer utilization.
Authors: Ryan Hankins, Ryoko Sato, Parthiv Mehta, Samir Bhattacharyya, Emmanuel Ezekekwu, Sean P. Collins
Journal: Journal of Clinical Oncology (2025)

365 Background: Rectal spacers have been shown to reduce side effects of prostate radiotherapy (RT) in prostate cancer (PCa) patients in clinical studies. While rectal spacing may help preserve sexual function after RT, this association has not been explored in large-scale real-world data. This study evaluated the association between rectal spacer use and the prevalence of erectile dysfunction diagnosis among PCa patients receiving prostate RT at the U.S. county level. Methods: This study utilized Medicare 5% and 100% Standard Analytic Files to analyze county-level data. The population consisted of adult PCa patients receiving RT (IMRT, brachytherapy, SBRT, or proton therapy) between 2015 and 2022. The primary outcome was the county-level proportion of patients diagnosed with erectile dysfunction in any year between 2016 and 2023. The primary explanatory variable was the proportion of patients treated with RT using rectal spacer 1 to 5 years before erectile dysfunction diagnosis. Zero-inflated Poisson regression models assessed the association between rectal spacer use and erectile dysfunction diagnosis at county level, controlling for county-level PCa patients characteristics (average age and racial composition) and general population characteristics (median age, racial composition, and median household income). State-level fixed accounted for regional variation. Data for the general population were obtained from the Agency for Healthcare Research and Quality Social Determinants of Health Database 2020. Results: The study included 247,250 PCa patients receiving prostate RT during the study period across 3,132 U.S. counties. The average annual prevalence of erectile dysfunction diagnosis among PCa patients receiving RT at the county level was 1.3%. The proportion of patients receiving rectal spacers increased from 2.9% to 18.9% over the study period. After adjusting for confounders, counties with higher rectal spacer use 4-5 years prior had a significantly lower prevalence of erectile dysfunction diagnosis. A 10-percentage point increase in rectal spacer usage at the county level was associated with a 7.7% reduction in erectile dysfunction diagnosis after 4 years (p&lt;0.001) and an 8.4% reduction after 5 years (p=0.006). Conclusions: In this first assessment of a real-world dataset, the county-level analysis suggests that increased use of rectal spacing among PCa patients receiving prostate RT is associated with a significantly lower prevalence of erectile dysfunction, with a time lag of 4 to 5 years. This finding supports the long-term benefit of rectal spacing in preserving sexual function in PCa patients undergoing prostate RT. Future research should evaluate the etiology of the longer than expected time lag between utilization and benefit.
Prospective observational study in Japanese patients with metastatic castration-sensitive prostate cancer (mCSPC) with or without intraductal carcinoma of the prostate (IDC-P).
Authors: Masashi Kato, Toyonori Tsuzuki
Journal: Journal of Clinical Oncology (2025)

87 Background: Intraductal carcinoma of the prostate (IDC-P) is a high-grade, high-volume, invasive form of prostate cancer (PCa) associated with poor clinical outcomes. The International Society of Urological Pathologists (ISUP) recommends incorporating IDC-P into the Gleason scoring system. However, existing data on survival outcomes for prostate cancer patients with IDC-P are primarily based on retrospective analyses. This study aims to prospectively evaluate the survival outcomes of Japanese patients with metastatic castration-sensitive prostate cancer (mCSPC), with and without IDC-P, using real-world data from a multi-institutional observational study. Methods: Between 2018 and 2021, we prospectively enrolled 102 de novo mCSPC patients from affiliated healthcare institutions. Eligible patients were those diagnosed with mCSPC via prostate needle biopsy and classified as high-risk according to the LATITUDE criteria. All participants underwent a standard extended biopsy (≥10 cores) to diagnose IDC-P, ensuring minimal sampling error. A single genitourinary pathologist reviewed all biopsy slides based on the 2019 ISUP grading system. Patients received treatment with androgen receptor signaling inhibitors (ARSI) with or without docetaxel. Results: The median age of the patients was 72 years (range 57–92), and the median serum PSA level was 441 ng/mL (range 3.9–9807 ng/mL). The median follow-up period was 38.3 months (range 8.2–67.4 months). All patients had a Gleason grade ≥ 3, with 66 (64.7%) exhibiting a Gleason pattern 5. Lymph node metastasis was present in 67 patients (65.7%), visceral metastasis in 23, and bone metastasis in all patients. IDC-P was identified in 86 patients (84%). Multivariate analysis revealed that elevated lactate dehydrogenase (LDH) levels and the presence of IDC-P were independent predictors of poor castration-resistant prostate cancer (CRPC)-free survival (HR 4.387, p&lt;0.001; HR 2.009, p=0.01) and progression-free survival (PFS2) (HR 6.801, p&lt;0.001; HR 1.796, p=0.016). Conclusions: This prospective observational study demonstrated that higher LDH levels and the presence of IDC-P in biopsy samples were significantly associated with poorer survival outcomes in Japanese patients with mCSPC. These findings underscore the prognostic importance of IDC-P in mCSPC management.