Ragin, Camille

Abstract Introduction: The standard of care for metastatic hormone-sensitive prostate cancer (mHSPC) has evolved with the expanded approval of androgen receptor pathway inhibitors (ARPIs) alongside androgen deprivation therapy (ADT). ADT alone has been shown to affect cognitive function. However, the cognitive impact of distinct treatment combinations remains unclear. We investigated the association between first-line systemic treatments and the trajectory of subjective cognitive function among mHSPC survivors in the International Registry for Men with Advanced Prostate Cancer (IRONMAN). Methods: This analysis included 2435 newly diagnosed mHSPC patients enrolled across 15 countries between July 2017 and August 2024. Treatments were reported by site personnel and physicians. For this analysis, we focused on first-line systemic treatment and classified treatment groups at enrollment as ADT monotherapy (referent), ADT + ARPIs, or ADT + chemotherapy. Subjective cognitive function was assessed via the EORTC QLQ-C30 Cognitive Function subscale, with patient-reported scores (range 0-100) collected at enrollment and every 3 months for up to 5 years; higher scores reflect better cognitive function. Associations were estimated using linear mixed effects models with clustering by study site and country to examine differences at enrollment and across trajectories of subjective cognitive function by first-line treatment, adjusting for demographic and clinical factors. Results: Median age at enrollment was 70 years, with a median follow-up of 1.7 years. 724 (30%) participants were treated with ADT monotherapy, 1317 (54%) with ADT + ARPIs, and 394 (16%) with ADT + chemotherapy. Mean cognitive function scores at enrollment were 85.4 (Standard Deviation [SD] 19.5) for participants treated with ADT monotherapy, 86.7 (SD 17.3) for ADT + ARPIs, and 86.7 (SD 18.0) for ADT + chemotherapy. Cognitive function scores decreased by -0.60 points (95% Confidence Interval [CI] -0.72, -0.48) per year among those treated with ADT monotherapy, with similar rates observed for those treated with ADT + chemotherapy. Participants treated with ADT + ARPIs had a slower decline in cognitive function, with scores decreasing by -0.36 points (95% CI -0.60, -0.08) per year. Conclusion: In this international cohort of mHSPC survivors, subjective cognitive function scores were generally high at enrollment but declined over time. There was no evidence of worse cognitive function in those treated with ADT + ARPIs nor ADT + chemotherapy over time compared to ADT monotherapy. Cognitive functioning is a key component of survivorship, and defining cognitive trajectories associated with first-line treatment can inform supportive interventions, patient treatment decision-making, and clinical guidelines. Citation Format: Michelle O. Sodipo, Alicia K. Morgans, Erica T. Warner, Emily M. Rencsok, Lauren E. Howard, Colleen B. McGrath, Anna Siefkas, Konrad H. Stopsack, Christopher Sauer, Robert Drecier, Emilio Esteban, Hassan M. Dogo, Ademola Popoola, Charles Waihenya, Anders Bjartell, Kim Chi, Sebastien Hotte, Richard Cathomas, Deborah Enting, Scott Tagawa, Michael Ong, David Lorente, Elisabeth Heath, Rana McKay, Stefanie Fischer, Heather H. Cheng, Young E. Whang, Frederic Pouliot, Simon Crabb, Monica Chatwal, Miguel A. Climent, Raymond McDermott, Ian D. Davis, Camille Ragin, Folakemi Odedina, Natalie Greaves, Simone Badal, Simon Anderson, Sharon Harrison, Karen Autio, Laurel Cannon, Marie Grant, Alyssa Chan-Cuzydlo, Travis Gerke, Hannah D. McManus, Philip W. Kantoff, Daniel George, Sebastien Haneuse, Lorelei A. Mucci, on behalf of the IRONMAN Registry. First-line therapies and subjective cognitive function trajectories among international metastatic hormone-sensitive prostate cancer survivors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3630.

Background Men of African ancestry experience higher burden from prostate cancer compared to men of other ancestral backgrounds. Limitations in the availability of high-quality biospecimens hinder the inclusion of this population in genetic studies of prostate cancer. The use of formalin-fixed paraffin-embedded (FFPE) tissues represent a potential rich source of genetic material particularly in some international settings, where fresh frozen tissue is difficult to obtain. In this study, we investigate the feasibility of using FFPE biospecimens acquired from various international sites for utility in next-generation sequencing. Methods A total of 976 FFPE blocks were collected between 2002 and 2017 from six international sites in Africa and the Caribbean representing three consortia: Prostate Cancer Transatlantic Consortium; African-Caribbean Cancer Consortium; and Men of African Descent and Carcinoma of the Prostate. Genomic DNA was checked for quality and quantity. Differences in mean quality control (QC) for pre-and-post pathology training were assessed using t-test. Pearson chi-square with trend analysis examined association between time-category and QC success status. Association of continuous DNA quality (Q129/Q41 ratio) and time of specimen collection was estimated with linear regression. Samples with a DNA quantity >0.2µg and a Q129/Q41 ratio >0.00225 were submitted for whole exome sequencing (WES). Results There was a positive relative percentage change in DNA quantity from 2002 to 2017 for Jamaica, Kenya and Senegal. There was a decline in DNA quantity over the same time period for Nigeria. There was a statistically significant improvement in quality of samples from Kenya ( P =0.032), Nigeria ( P <.001) and Senegal ( P =0.043). There was a significant improvement in the collected DNA sample quality over time with an R 2 of 0.12. Conclusions FFPE samples from low-resource settings could potentially provide sufficient DNA for WES. Improvements in biospecimen collection processing and storage for research are needed in some of these settings.

AbstractObjectiveThe purpose of this study was to assess differences in reported information about treatment, integration into care, and respect by self‐identified Black and White individuals with advanced prostate cancer in the United States.Patients and MethodsThis is a prospective cohort study of 701 participants (20% identifying as Black) enrolled in the International Registry for Men with Advanced Prostate Cancer at 37 US sites from 2017 to 2022. Participants were asked six questions from the Cancer Australia National Cancer Control Indicators about their experience with care at study enrollment. Prevalence differences by self‐reported race were estimated using marginal standardization of logistic‐normal mixed effects models (adjusted for age at enrollment and disease state at enrollment), and 95% CIs were estimated using parametric bootstrapping.ResultsMost participants reported a high quality of care for each question. Black participants generally reported higher care quality compared with White participants. Black participants reported more frequently that they were offered a written assessment and care plan (71%) compared with White participants (58%; adjusted difference, 13 percentage points; 95% CI, 4–23). Black participants also reported more frequently being given the name of nonphysician personnel who would support them (64%) than White participants (52%; adjusted difference, 10; 95% CI, 1–20). Prevalence differences did not differ by disease state at enrollment.ConclusionsBlack participants generally reported a higher quality of care compared with White participants. This study calls attention to the need to study potential mediating factors and interpersonal aspects of care in this population to improve survivorship.