Ogo, Chidiebere

Abstract Introduction: Most people who die from prostate cancer are older than 75 years. However, prostate cancer diagnosed at younger ages is often more aggressive. While epidemiologic studies have examined the association between age and survival in patients with prostate cancer overall, the clinical drivers of this relationship in patients with advanced disease remain unclear. We leveraged the International Registry of Men with Advanced Prostate Cancer (IRONMAN, NCT03151629) to (1) quantify the association between age and overall survival and (2) explore whether this association is explained by treatments. Methods: We included 3, 734 patients enrolled from 15 countries with new diagnoses of metastatic hormone sensitive (mHSPC, N=2, 642) or castration resistant prostate cancer (CRPC, N=1, 092). Age at enrollment was categorized as <55, 55-59, 60-64 (reference), 65-69, 70-74, 75-79, 80-84, 85+ years. We computed age-specific death rates (95% confidence intervals [CIs]) by disease state (mHSPC, CRPC) at enrollment. To explore whether this relationship was explained by treatment, we fitted disease state-stratified Cox models and sequentially adjusted for (1) de novo metastatic status and country, and (2) baseline treatment (androgen deprivation therapy [ADT] alone, ADT + androgen receptor pathway inhibitors [ARPI], ADT + chemotherapy, ADT + ARPI + chemotherapy, other). Results: Over 5.5 years of follow-up (median: 3.2 years, IQR: 1.7, 4.8), 995 patients died from any cause. Younger patients were more likely to have de novo metastatic disease. Among those with mHSPC at enrollment, the age-specific death rates per 1, 000 person-years followed a J-shaped pattern: 80 (95% CI: 54, 117) in patients under 55 years, 58 (46, 74) in patients aged 60-64, 102 (78, 133) in patients aged 80-84, and 172 (125, 236) in patients aged 85 and older. The death rates among those with CRPC followed a similar pattern, albeit rates were higher in magnitude: 212 (95% CI: 140, 323) in patients under 55 years, 153 (115, 202) in patients aged 60-64, 200 (155, 258) in patients aged 80-84, and 204 (142, 291) in patients aged 85 and older. After adjusting for disease state, country, and the timing of diagnosis of metastases, death rates were substantially higher for ages 75-79 (HR 1.4; 95% CI 1.1, 1.7), 80-84 years (HR 1.6; 95% CI 1.2, 2.1), and 85 years and older (HR 2.0; 95% CI: 1.5, 2.7) compared to ages 60-64 years. Patients aged under 55 years had 1.4-fold higher death rates (95% CI: 1.0, 1.9) compared to those 60-64 years. After additionally adjusting for baseline treatment, overall survival remained worse for the older patients and the youngest age group with hazard ratios remaining meaningfully unchanged. Conclusion: Age at enrollment is associated with overall survival in people with advanced prostate cancer enrolled in IRONMAN in a J-shaped pattern. This relationship is not explained by differences in baseline treatment. Citation Format: Hannah E. Guard, Michelle O. Sodipo, Colleen B. McGrath, Anna Siefkas, Lauren E. Howard, Konrad H. Stopsack, Christopher M. Sauer, Robert Dreicer, Emilio Esteban, Hassan M. Dogo, Ademola Popoola, Charles Waihenya, Anders Bjartell, Kim N. Chi, Sebastien Hotte, Richard Cathomas, Deborah Enting, Scott Tagawa, Michael Ong, Michael Kolinsky, Vincent Khoo, Joaquin Mateo, Chidiebere N. Ogo, Rana R. McKay, Stefanie Fischer, Heather H. Cheng, Russell Szmulewitz, Young E. Whang, Anand Sharma, Frédéric Pouliot, Simon Crabb, Monica S. Chatwal, Miguel A. Climent, Raymond McDermott, Ian D. Davis, Camille Ragin, Folakemi T. Odedina, Simon Anderson, Simone Badal, Natalie Greaves, Karen A. Autio, Laurel Cannon, Alyssa Chan-Cuzydlo, Marie Grant, Travis Gerke, Hannah D. McManus, Philip W. Kantoff, Daniel J. George, Lorelei A. Mucci, IRONMAN investigator team. Disentangling the association between age and overall survival in an international cohort of patients with advanced prostate cancer [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 4935.

PURPOSE There is limited cancer clinical research in sub-Saharan African countries despite the significant burden of cancers. The primary objective of this strengths, weaknesses, opportunities, and threats (SWOT) analysis was to understand and document factors affecting the successful implementation of prostate cancer (CaP) clinical research in Nigeria. METHODS The research team used a qualitative design involving International Registry of Men with Advanced Prostate Cancer (IRONMAN) study team members as participants from four regional sites in Nigeria. One-hour listening sessions were conducted via Zoom at each site, focusing on SWOT related to the IRONMAN study. All sessions were recorded, transcribed, and analyzed. Themes were inductively coded and then synthesized across all four sites. RESULTS The study teams identified several strengths and weaknesses in conducting the IRONMAN study at their respective sites. Key strengths included access to robust patient population for recruitment and the availability of essential resources, such as lab space, clinical knowledge, and adequate staffing. Weaknesses centered on the social determinants of health that hinder patient participation, such as transportation challenges, distance to clinics, limited access to care, and insufficient biorepository space for sample storage. A prominent opportunity identified was the potential for Nigerian institutions to engage in more clinical research, particularly multisite global trials. Threats included difficulties in retaining research staff and political instability. CONCLUSION This study highlights the promising research opportunities in Nigeria. The lessons learned from the IRONMAN study provide valuable insights into the feasibility of conducting CaP clinical research and trials tailored to the needs of Black men in sub-Saharan Africa. These findings offer a roadmap for future research efforts, with the potential to expand clinical trials and improve health outcomes across the region.

Abstract Background: The need to increase understanding of prostate cancer (CaP) is ever increasing. Unfortunately, there is limited understanding of how CaP affects men of African ancestry (MAA) despite significant disparities in CaP prevention, diagnosis, and treatment due to genetic and sociobehavioral factors. Conducting CaP clinical trials (CTs) in Africa presents multiple opportunities to improve upon collective knowledge of CaP in MAA experiences, expand patient access to CTs, and provide opportunities for African scientists and urologists to contribute to research on the global stage. The International Registry of Men with Advanced Prostate Cancer (IRONMAN) seeks to reduce CaP disparities by sponsoring sites throughout Africa. Four Prostate Cancer Transatlantic Consortium (CaPTC) institutions in Nigeria currently participate in IRONMAN: University of Ilorin Teaching Hospital, Federal Medical Center, University of Maiduguri, and Lagos State University Teaching Hospital. Because CTs of this scale are infrequently conducted in Africa, there are special considerations when conducting CTs in low-middle-income countries (LMICs) like Nigeria. Methods: Hourlong interviews dedicated to site staff were conducted via Zoom in Spring 2023 (four total). Interviews utilized a Strengths, Weaknesses, Opportunities, and Threats (SWOT) analysis approach. Each interview was recorded, transcribed, and validated by study staff for accuracy. Themes from each were inductively coded and then collated across all four sites. Results: The urologists, oncologists, phlebotomists, pathologists, nurses, research coordinators that make up the study teams identified the holistics of conducting the IRONMAN study at their sites. Strengths included a large patient population to recruit from and appropriate resources to conduct the study (ex., lab space, clinical knowledge, staffing levels). Weaknesses included the social determinants of health that negatively impact patient participation, limited biorepository space to store samples, and the need for patient-physician trust. The greatest opportunity presented was Nigerian institutions joining more CTs in the future, particularly multi-site global trials. Described threats included staff turnover, national stability, and increased economic disparities. Discussion: While increasing the overall number of CTs in Africa is a noble cause, sponsors and institutions should note the unique circumstances in implementing CTs in Africa when designing CTs and recruiting sites. Listening to the experiences of study teams is pivotal in ensuring CTs are Africa-minded - they will be complimentary to established research infrastructure, appropriately funded, and culturally responsive all in the name of equitable research. By doing so, ethical compliance and quality data collection will ensue and reduce disparities at the micro, mezzo, and macro levels. Citation Format: Opeyemi Oreoluwa Bolajoko, Parisa Fathi, Oluwaseyi Toye, Dottington D. Fulwood, Ademola Popoola, Chidiebere Ogo, Hassan Dogo, Omolara Fatiregun, Anthonia Sowumi, Paul Jibrin, Mutiu A. Jimoh, Faruk Mohammed, Folakemi Odedina, Prostate Cancer Transatlantic Consortium. Strengths, weaknesses, opportunities, and threats of conducting clinical trials in Nigeria: The IRONMAN study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1013.

AbstractBackgroundThrough whole‐exome sequencing of 60 formalin‐fixed paraffin‐embedded Nigerian (NGRn) benign prostatic hyperplasia (BPH) samples, we identified germline and somatic alterations in apoptotic pathways impacting BPH development and progression. Prostate enlargement is a common occurrence in male aging; however, this enlargement can lead to lower urinary tract symptoms that negatively impact quality of life. This impact is disproportionately present in men of African ancestry. BPH pathophysiology is poorly understood and studies examining non‐European populations are lacking.MethodsIn this study, NGRn BPH, normal prostate, and prostate cancer (PCa) tumor samples were sequenced and compared to characterize genetic alterations in NGRn BPH.ResultsTwo hundred and two nonbenign, ClinVar‐annotated germline variants were present in NGRn BPH samples. Six genes [BRCA1 (92%), HSD3B1 (85%), TP53 (37%), PMS2 (23%), BARD1 (20%), and BRCA2 (17%)] were altered in at least 10% of samples; however, compared to NGRn normal and tumor, the frequency of alterations in BPH samples showed no significant differences at the gene or variant level. BRCA2_rs11571831 and TP53_rs1042522 germline alterations had a statistically significant co‐occurrence interaction in BPH samples. In at least two BPH samples, 173 genes harbored somatic variants known to be clinically actionable. Three genes (COL18A1, KIF16B, and LRP1) showed a statistically significant (p < 0.05) higher frequency in BPH. NGRn BPH also had five gene pairs (PKD1/KIAA0100, PKHD1/PKD1, DNAH9/LRP1B, NWD1/DCHS2, and TCERG1/LMTK2) with statistically significant co‐occurring interactions. Two hundred and seventy‐nine genes contained novel somatic variants in NGRn BPH. Three genes (CABP1, FKBP1C, and RP11‐595B24.2) had a statistically significant (p < 0.05) higher alteration frequency in NGRn BPH and three were significantly higher in NGRn tumor (CACNA1A, DMKN, and CACNA2D2). Pairwise Fisher's exact tests showed 14 gene pairs with statistically significant (p < 0.05) interactions and four interactions approaching significance (p < 0.10). Mutational patterns in NGRn BPH were similar to COSMIC (Catalog of Somatic Mutations in Cancer) signatures associated with aging and dysfunctional DNA damage repair.ConclusionsNGRn BPH contained significant germline alteration interactions (BRCA2_rs11571831 and TP53_rs1042522) and increased somatic alteration frequencies (LMTK2, LRP1, COL18A1, CABP1, and FKBP1C) that impact apoptosis. Normal prostate development is maintained by balancing apoptotic and proliferative activity. Dysfunction in either mechanism can lead to abnormal prostate growth. This work is the first to examine genomic sequencing in NGRn BPH and provides data that fill known gaps in the understanding BPH and how it impacts men of African ancestry.

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.

Abstract Background: Prostate cancer (CaP) is a global disease with the greatest burden among Black men, including sub-Saharan African men. The International Registry to Improve Outcomes in Men with Advanced Prostate Cancer (IRONMAN) was established by the Prostate Cancer Clinical Trials Consortium (PCCTC) as a prospective, international cohort of men with advanced cancer. The goal of the study is to establish a population-based CaP registry and recruit patients across academic and community practices globally. The Prostate Cancer Transatlantic Consortium (CaPTC) joined the IRONMAN project in 2020 with active sites in Nigeria. Aim: The overall aims of the IRONMAN cohort are to develop a global picture of advanced CaP and facilitate a better understanding of the disease relative to clinical and molecular disease subtypes, treatment patterns, therapeutic regimens with associated adverse events, patient experiences and predictors of responses and unmet needs in treatment. This report presents the experiences of a low-resourced country, Nigeria, in launching the IRONMAN study. Methods: CaPTC officially launched the IRONMAN study in Nigeria in 2021. Set up included obtaining national ethics approval, training of the multidisciplinary teams from 4 sites and 7 sub-sites, and activation of all sites. Data collection includes baseline and follow-up data from patients. Patients will be followed prospectively for overall survival, clinically significant adverse events, comorbidities, changes in cancer treatments, and patient-reported outcome measures (PROMs). Physician Questionnaires are also collected from all participating sites. PCCTC maintains close monitoring of the study Results: By the 9th month of the study, the Nigerian sites had recruited 54 patients who have been followed up for 3 to 9 months. There were initial challenges with start up facilities and manpower skills. The training programs have developed a multi-disciplinary team of clinical researchers across multiple institutions, now primed to conduct clinical trials. Facilitated by CaPTC, the study has also helped strengthened multi-center national and international collaborations. Additionally, there are now several clinical trials ready sites in Nigeria, facilitated by audit of the research infrastructures across Nigeria. An added benefit is that there is an opportunity to have molecular typing of CaP in Nigeria. Conclusion: The inclusion of low-resourced sites in international studies can significantly help to improve research workforce and research capacity. The CaPTC IRONMAN sites in Nigeria are top recruiting sites for the study, underscoring the benefits of biomedical research investments in Low and Middle Income Countries. The data from Nigeria would help to better understand CaP in Black men globally. Citation Format: Ademola Alabi Popoola, Chidiebere N. Ogo, Omolara Fatiregun, Mohammed Dogo, Solomon O. Rotimi, Folakemi Odedina, Prostate Cancer Transatlantic Consortium CaPTC Investigators. International Registry for Men with Advanced Prostate Cancer (IRONMAN) study: The Nigerian experience [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr A030.

In this study, we used whole-exome sequencing of a cohort of 45 advanced-stage, treatment-naïve Nigerian (NG) primary prostate cancer tumors and 11 unmatched nontumor tissues to compare genomic mutations with African American (AA) and European American (EA) The Cancer Genome Atlas (TCGA) prostate cancer. NG samples were collected from six sites in central and southwest Nigeria. After whole-exome sequencing, samples were processed using GATK best practices. BRCA1 (100%), BARD1 (45%), BRCA2 (27%), and PMS2(18%) had germline alterations in at least two NG nontumor samples. Across 111 germline variants, the AA cohort reflected a pattern [BRCA1 (68%), BARD1 (34%), BRCA2 (28%), and PMS2 (16%)] similar to NG samples. Of the most frequently mutated genes, BRCA1 showed a statistically (P ≤ 0.05) higher germline mutation frequency in men of African ancestry (MAA) and increasing variant frequency with increased African ancestry. Disaggregating gene-level mutation frequencies by variants revealed both ancestry-linked and NG-specific germline variant patterns. Driven by rs799917 (T&gt;C), BRCA1 showed an increasing mutation frequency as African ancestry increased. BRCA2_rs11571831 was present only in MAA, and BRCA2_rs766173 was elevated in NG men. A total of 133 somatic variants were present in 26 prostate cancer–associated genes within the NG tumor cohort. BRCA2 (27%), APC (20%), ATM (20%), BRCA1 (13%), DNAJC6 (13%), EGFR (13%), MAD1L1 (13%), MLH1 (11%), and PMS2 (11%) showed mutation frequencies &gt;10%. Compared with TCGA cohorts, NG tumors showed statistically significant elevated frequencies of BRCA2, APC, and BRCA1. The NG cohort variant pattern shared similarities (cosign similarities ≥0.734) with Catalogue of Somatic Mutations in Cancer signatures 5 and 6, and mutated genes showed significant (q &lt; 0.001) gene ontology (GO) and functional enrichment in mismatch repair and non-homologous repair deficiency pathways. Here, we showed that mutations in DNA damage response genes were higher in NG prostate cancer samples and that a portion of those mutations correlate with African ancestry. Moreover, we identified variants of unknown significance that may contribute to population-specific routes of tumorigenesis and treatment. These results present the most comprehensive characterization of the NG prostate cancer exome to date and highlight the need to increase diversity of study populations. Significance: MAA have higher rates of prostate cancer incidence and mortality, however, are severely underrepresented in genomic studies. This is the first study utilizing whole-exome sequencing in NG men to identify West African ancestry-linked variant patterns that impact DNA damage repair pathways.

Abstract Men of African ancestry (MAA) have the highest global incidence and mortality of prostate cancer (PCa); however, the biology underlying this harsh disease presentation remains poorly understand, largely due to Africans and people within the African diaspora being under-represented in genomics research. MAA are younger at diagnosis, have higher tumor volume at diagnosis and have higher tumor aggression compared to European American men. Additionally, genomic profiling continues to show that PCa etiology and phenotype are influenced by higher amounts of African ancestry and that West African ancestry is associated with unique genomic alterations. Herein we utilize whole exome sequencing of a unique cohort of 45 advanced stage, treatment naïve Nigerian primary PCa tumors and 11 unmatched non-tumor tissue to compare genomic variants with African (AA) and European (EA) American TCGA PCa tumors. Nigerian samples were collected from 6 sites in central and southwest Nigeria. After whole exome sequencing, samples were processed using GATK best practices. Four genes [BRCA1 (100%), BARD1 (45%), BRCA2 (27%) and PMS2 (18%)] had germline variants in at least two Nigerian non-tumor samples. Across 111 germline variants, the AA cohort reflected a pattern [BRCA1 (68%), BARD1 (34%), BRCA2 (28%) and PMS2 (16%)] similar to Nigerian samples. Of the most frequently mutated genes, BRCA1 showed a statistically (p ≤ 0.05) higher mutation frequency in MAA. Disaggregating gene level mutation frequencies by variant revealed both ancestry linked and Nigerian specific germline variant patterns. Driven by rs799917, BRCA1 showed increasing mutation frequency as African admixture increased. BRCA2_rs11571831 was only present in MAA and BRCA2_rs766173 was increased in Nigerian men. 133 somatic variants were present in 26 PCa associated genes within the Nigerian tumor cohort. Nine genes [BRCA2 (27%), APC (20%), ATM (20%), BRCA1 (13%), DNAJC6 (13%), EGFR (13%), MAD1L1 (13%), MLH1 (11%) and PMS2 (11%)] showed mutation frequencies above 10%. Compared to TCGA cohorts, BRCA2, APC and BRCA1 showed statistically significant increases in Nigerian tumors. The Nigerian cohort variant pattern shared similarities (cosign similarities ≥ 0.734) with COSMIC signatures 5 and 6 and mutated genes showed significant (q &lt; 0.001) GO and functional enrichment in mismatch repair and non-homologous repair deficiency (HRD) pathways. Here, we show that variants in DDR genes are increased in Nigerian PCa and that a portion of those variants correlate with increased African ancestry. Moreover, we identify variants of unknown significance that may contribute to population specific routes of tumorigenesis and treatment. These results present the most comprehensive characterization of the Nigerian PCa exome to date and further highlight the need to increase study population diversity. Citation Format: Jason A. White, Ernest Kaninjing, Kayode A. Adeniji, Paul Jibrin, John O. Obafunwa, Chidiebere N. Ogo, Mohammed Faruk, Solomon Rotimi, Ademola Popoola, Omolara A. Fatiregun, Olabode P. Oluwole, Balasubramanyam Karanam, Wei Tang, Stefan Ambs, Folake T. Odedina, Damali N. Martin, Clayton Yates. Tumor only analysis of whole exome sequencing from a multi-institutional Nigerian prostate cancer cohort reveals DNA repair genes associated with African ancestry [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1507.