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1. Refining Risk Stratification of High-risk and Locoregional Prostate Cancer: A Pooled Analysis of Randomized Trials

Author

Ravi, Praful, Xie, Wanling, Buyse, Marc, Halabi, Susan, Kantoff, Philip W., Sartor, Oliver, Attard, Gert, Clarke, Noel, D'Amico, Anthony, Dignam, James, James, Nicholas, Fizazi, Karim, Gillessen, Silke, Parulekar, Wendy, Sandler, Howard, Spratt, Daniel E., Sydes, Matthew R., Tombal, Bertrand, Williams, Scott, and Sweeney, Christopher J.

Published
2024
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2. Characterising the contribution of rare protein-coding germline variants to prostate cancer risk and severity in 37,184 cases

Author

Mitchell, Jonathan, primary, Camacho, Niedzica, additional, Shea, Patrick, additional, Stopsack, Konrad, additional, Joseph, Vijai, additional, Burren, Oliver Simon, additional, Dhindsa, Ryan, additional, Nag, Abhishek, additional, Berchuck, Jacob, additional, O'Neill, Amanda, additional, Abbasi, Ali, additional, Zoghbi, Anthony, additional, Alegre-Diaz, Jesus, additional, Kuri-Morales, Pablo, additional, Berumen, Jaime, additional, Tapia-Conyer, Roberto, additional, Emberson, Jonathan, additional, Torres, Jason, additional, Collins, Rory, additional, Wang, Quanli, additional, Goldstein, David, additional, Matakidou, Athena, additional, Haefliger, Carolina, additional, Anderson-Dring, Lauren, additional, March, Ruth, additional, Jobanputra, Vaidehi, additional, Dougherty, Brian, additional, Carss, Keren, additional, Petrovski, Slave, additional, Kantoff, Philip, additional, Offit, Kenneth, additional, Mucci, Lorelei, additional, Pomerantz, Mark, additional, and Fabre, Margarete, additional

Published
2024
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3. FIGURE 1 from Pain and Its Association with Survival for Black and White Individuals with Advanced Prostate Cancer in the United States

Author

Rencsok, Emily M., primary, Slopen, Natalie, primary, McManus, Hannah D., primary, Autio, Karen A., primary, Morgans, Alicia K., primary, McSwain, Lawrence, primary, Barata, Pedro, primary, Cheng, Heather H., primary, Dreicer, Robert, primary, Gerke, Travis, primary, Green, Rebecca, primary, Heath, Elisabeth I., primary, Howard, Lauren E., primary, McKay, Rana R., primary, Nowak, Joel, primary, Pileggi, Shannon, primary, Pomerantz, Mark M., primary, Rathkopf, Dana E., primary, Tagawa, Scott T., primary, Whang, Young E., primary, Ragin, Camille, primary, Odedina, Folakemi T., primary, Kantoff, Philip W., primary, Vinson, Jake, primary, Villanti, Paul, primary, Haneuse, Sebastien, primary, Mucci, Lorelei A., primary, and George, Daniel J., primary

Published
2024
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4. Data from Pain and Its Association with Survival for Black and White Individuals with Advanced Prostate Cancer in the United States

Author

Rencsok, Emily M., primary, Slopen, Natalie, primary, McManus, Hannah D., primary, Autio, Karen A., primary, Morgans, Alicia K., primary, McSwain, Lawrence, primary, Barata, Pedro, primary, Cheng, Heather H., primary, Dreicer, Robert, primary, Gerke, Travis, primary, Green, Rebecca, primary, Heath, Elisabeth I., primary, Howard, Lauren E., primary, McKay, Rana R., primary, Nowak, Joel, primary, Pileggi, Shannon, primary, Pomerantz, Mark M., primary, Rathkopf, Dana E., primary, Tagawa, Scott T., primary, Whang, Young E., primary, Ragin, Camille, primary, Odedina, Folakemi T., primary, Kantoff, Philip W., primary, Vinson, Jake, primary, Villanti, Paul, primary, Haneuse, Sebastien, primary, Mucci, Lorelei A., primary, and George, Daniel J., primary

Published
2024
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5. ArCH: improving the performance of clonal hematopoiesis variant calling and interpretation

Author

Chan, Irenaeus C C, primary, Panchot, Alex, additional, Schmidt, Evelyn, additional, McNulty, Samantha, additional, Wiley, Brian J, additional, Liu, Jie, additional, Turner, Kimberly, additional, Moukarzel, Lea, additional, Wong, Wendy S W, additional, Tran, Duc, additional, Beeler, J Scott, additional, Batchi-Bouyou, Armel Landry, additional, Machiela, Mitchell J, additional, Karyadi, Danielle M, additional, Krajacich, Benjamin J, additional, Zhao, Junhua, additional, Kruglyak, Semyon, additional, Lajoie, Bryan, additional, Levy, Shawn, additional, Patel, Minal, additional, Kantoff, Philip W, additional, Mason, Christopher E, additional, Link, Daniel C, additional, Druley, Todd E, additional, Stopsack, Konrad H, additional, and Bolton, Kelly L, additional

Published
2024
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6. Data from Marital Status, Living Arrangement, and Survival among Individuals with Advanced Prostate Cancer in the International Registry for Men with Advanced Prostate Cancer

Author

Chen, Naiyu, primary, McGrath, Colleen B., primary, Ericsson, Caroline I., primary, Vaselkiv, Jane B., primary, Rencsok, Emily M., primary, Stopsack, Konrad H., primary, Guard, Hannah E., primary, Autio, Karen A., primary, Rathkopf, Dana E., primary, Enting, Deborah, primary, Bitting, Rhonda L., primary, Mateo, Joaquin, primary, Githiaka, Charles W., primary, Chi, Kim N., primary, Cheng, Heather H., primary, Davis, Ian D., primary, Anderson, Simon G., primary, Badal, Simone Ann Marie, primary, Bjartell, Anders, primary, Russnes, Kjell M., primary, Heath, Elisabeth I., primary, Pomerantz, Mark M., primary, Henegan, John C., primary, Hyslop, Terry, primary, Esteban, Emilio, primary, Omlin, Aurelius, primary, McDermott, Ray, primary, Fay, Andre P., primary, Popoola, Ademola Alabi, primary, Ragin, Camille, primary, Nowak, Joel, primary, Gerke, Travis, primary, Kantoff, Philip W., primary, George, Daniel J., primary, Penney, Kathryn L., primary, and Mucci, Lorelei A., primary

Published
2024
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7. Supplementary Table 1. from Marital Status, Living Arrangement, and Survival among Individuals with Advanced Prostate Cancer in the International Registry for Men with Advanced Prostate Cancer

Author

Chen, Naiyu, primary, McGrath, Colleen B., primary, Ericsson, Caroline I., primary, Vaselkiv, Jane B., primary, Rencsok, Emily M., primary, Stopsack, Konrad H., primary, Guard, Hannah E., primary, Autio, Karen A., primary, Rathkopf, Dana E., primary, Enting, Deborah, primary, Bitting, Rhonda L., primary, Mateo, Joaquin, primary, Githiaka, Charles W., primary, Chi, Kim N., primary, Cheng, Heather H., primary, Davis, Ian D., primary, Anderson, Simon G., primary, Badal, Simone Ann Marie, primary, Bjartell, Anders, primary, Russnes, Kjell M., primary, Heath, Elisabeth I., primary, Pomerantz, Mark M., primary, Henegan, John C., primary, Hyslop, Terry, primary, Esteban, Emilio, primary, Omlin, Aurelius, primary, McDermott, Ray, primary, Fay, Andre P., primary, Popoola, Ademola Alabi, primary, Ragin, Camille, primary, Nowak, Joel, primary, Gerke, Travis, primary, Kantoff, Philip W., primary, George, Daniel J., primary, Penney, Kathryn L., primary, and Mucci, Lorelei A., primary

Published
2024
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8. FIGURE 2 from Pain and Its Association with Survival for Black and White Individuals with Advanced Prostate Cancer in the United States

Author

Rencsok, Emily M., primary, Slopen, Natalie, primary, McManus, Hannah D., primary, Autio, Karen A., primary, Morgans, Alicia K., primary, McSwain, Lawrence, primary, Barata, Pedro, primary, Cheng, Heather H., primary, Dreicer, Robert, primary, Gerke, Travis, primary, Green, Rebecca, primary, Heath, Elisabeth I., primary, Howard, Lauren E., primary, McKay, Rana R., primary, Nowak, Joel, primary, Pileggi, Shannon, primary, Pomerantz, Mark M., primary, Rathkopf, Dana E., primary, Tagawa, Scott T., primary, Whang, Young E., primary, Ragin, Camille, primary, Odedina, Folakemi T., primary, Kantoff, Philip W., primary, Vinson, Jake, primary, Villanti, Paul, primary, Haneuse, Sebastien, primary, Mucci, Lorelei A., primary, and George, Daniel J., primary

Published
2024
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9. Supplementary Table S4 from Pain and Its Association with Survival for Black and White Individuals with Advanced Prostate Cancer in the United States

Author

Rencsok, Emily M., primary, Slopen, Natalie, primary, McManus, Hannah D., primary, Autio, Karen A., primary, Morgans, Alicia K., primary, McSwain, Lawrence, primary, Barata, Pedro, primary, Cheng, Heather H., primary, Dreicer, Robert, primary, Gerke, Travis, primary, Green, Rebecca, primary, Heath, Elisabeth I., primary, Howard, Lauren E., primary, McKay, Rana R., primary, Nowak, Joel, primary, Pileggi, Shannon, primary, Pomerantz, Mark M., primary, Rathkopf, Dana E., primary, Tagawa, Scott T., primary, Whang, Young E., primary, Ragin, Camille, primary, Odedina, Folakemi T., primary, Kantoff, Philip W., primary, Vinson, Jake, primary, Villanti, Paul, primary, Haneuse, Sebastien, primary, Mucci, Lorelei A., primary, and George, Daniel J., primary

Published
2024
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10. Supplementary Figure S2 from Pain and Its Association with Survival for Black and White Individuals with Advanced Prostate Cancer in the United States

Author

Rencsok, Emily M., primary, Slopen, Natalie, primary, McManus, Hannah D., primary, Autio, Karen A., primary, Morgans, Alicia K., primary, McSwain, Lawrence, primary, Barata, Pedro, primary, Cheng, Heather H., primary, Dreicer, Robert, primary, Gerke, Travis, primary, Green, Rebecca, primary, Heath, Elisabeth I., primary, Howard, Lauren E., primary, McKay, Rana R., primary, Nowak, Joel, primary, Pileggi, Shannon, primary, Pomerantz, Mark M., primary, Rathkopf, Dana E., primary, Tagawa, Scott T., primary, Whang, Young E., primary, Ragin, Camille, primary, Odedina, Folakemi T., primary, Kantoff, Philip W., primary, Vinson, Jake, primary, Villanti, Paul, primary, Haneuse, Sebastien, primary, Mucci, Lorelei A., primary, and George, Daniel J., primary

Published
2024
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11. TABLE 1 from Pain and Its Association with Survival for Black and White Individuals with Advanced Prostate Cancer in the United States

Author

Rencsok, Emily M., primary, Slopen, Natalie, primary, McManus, Hannah D., primary, Autio, Karen A., primary, Morgans, Alicia K., primary, McSwain, Lawrence, primary, Barata, Pedro, primary, Cheng, Heather H., primary, Dreicer, Robert, primary, Gerke, Travis, primary, Green, Rebecca, primary, Heath, Elisabeth I., primary, Howard, Lauren E., primary, McKay, Rana R., primary, Nowak, Joel, primary, Pileggi, Shannon, primary, Pomerantz, Mark M., primary, Rathkopf, Dana E., primary, Tagawa, Scott T., primary, Whang, Young E., primary, Ragin, Camille, primary, Odedina, Folakemi T., primary, Kantoff, Philip W., primary, Vinson, Jake, primary, Villanti, Paul, primary, Haneuse, Sebastien, primary, Mucci, Lorelei A., primary, and George, Daniel J., primary

Published
2024
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12. TABLE 3 from Pain and Its Association with Survival for Black and White Individuals with Advanced Prostate Cancer in the United States

Author

Rencsok, Emily M., primary, Slopen, Natalie, primary, McManus, Hannah D., primary, Autio, Karen A., primary, Morgans, Alicia K., primary, McSwain, Lawrence, primary, Barata, Pedro, primary, Cheng, Heather H., primary, Dreicer, Robert, primary, Gerke, Travis, primary, Green, Rebecca, primary, Heath, Elisabeth I., primary, Howard, Lauren E., primary, McKay, Rana R., primary, Nowak, Joel, primary, Pileggi, Shannon, primary, Pomerantz, Mark M., primary, Rathkopf, Dana E., primary, Tagawa, Scott T., primary, Whang, Young E., primary, Ragin, Camille, primary, Odedina, Folakemi T., primary, Kantoff, Philip W., primary, Vinson, Jake, primary, Villanti, Paul, primary, Haneuse, Sebastien, primary, Mucci, Lorelei A., primary, and George, Daniel J., primary

Published
2024
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13. TABLE 4 from Pain and Its Association with Survival for Black and White Individuals with Advanced Prostate Cancer in the United States

Author

Rencsok, Emily M., primary, Slopen, Natalie, primary, McManus, Hannah D., primary, Autio, Karen A., primary, Morgans, Alicia K., primary, McSwain, Lawrence, primary, Barata, Pedro, primary, Cheng, Heather H., primary, Dreicer, Robert, primary, Gerke, Travis, primary, Green, Rebecca, primary, Heath, Elisabeth I., primary, Howard, Lauren E., primary, McKay, Rana R., primary, Nowak, Joel, primary, Pileggi, Shannon, primary, Pomerantz, Mark M., primary, Rathkopf, Dana E., primary, Tagawa, Scott T., primary, Whang, Young E., primary, Ragin, Camille, primary, Odedina, Folakemi T., primary, Kantoff, Philip W., primary, Vinson, Jake, primary, Villanti, Paul, primary, Haneuse, Sebastien, primary, Mucci, Lorelei A., primary, and George, Daniel J., primary

Published
2024
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14. TABLE 2 from Pain and Its Association with Survival for Black and White Individuals with Advanced Prostate Cancer in the United States

Author

Rencsok, Emily M., primary, Slopen, Natalie, primary, McManus, Hannah D., primary, Autio, Karen A., primary, Morgans, Alicia K., primary, McSwain, Lawrence, primary, Barata, Pedro, primary, Cheng, Heather H., primary, Dreicer, Robert, primary, Gerke, Travis, primary, Green, Rebecca, primary, Heath, Elisabeth I., primary, Howard, Lauren E., primary, McKay, Rana R., primary, Nowak, Joel, primary, Pileggi, Shannon, primary, Pomerantz, Mark M., primary, Rathkopf, Dana E., primary, Tagawa, Scott T., primary, Whang, Young E., primary, Ragin, Camille, primary, Odedina, Folakemi T., primary, Kantoff, Philip W., primary, Vinson, Jake, primary, Villanti, Paul, primary, Haneuse, Sebastien, primary, Mucci, Lorelei A., primary, and George, Daniel J., primary

Published
2024
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15. Marital status, living arrangement, and survival among individuals with advanced prostate cancer in the International Registry for Men with Advanced Prostate Cancer

Author

Chen, Naiyu, primary, McGrath, Colleen B., additional, Ericsson, Caroline I., additional, Vaselkiv, Jane B., additional, Rencsok, Emily M., additional, Stopsack, Konrad H., additional, Guard, Hannah E., additional, Autio, Karen A., additional, Rathkopf, Dana E., additional, Enting, Deborah, additional, Bitting, Rhonda L., additional, Mateo, Joaquin, additional, Githiaka, Charles Waihenya., additional, Chi, Kim N., additional, Cheng, Heather H., additional, Davis, Ian D., additional, Anderson, Simon G., additional, Badal, Simone Ann Marie., additional, Bjartell, Anders, additional, Russnes, Kjell M., additional, Heath, Elisabeth I., additional, Pomerantz, Mark M., additional, Henegan, John C., additional, Hyslop, Terry, additional, Esteban, Emilio, additional, Omlin, Aurelius, additional, McDermott, Ray, additional, Fay, Andre P., additional, Popoola, Ademola Alabi., additional, Ragin, Camille, additional, Nowak, Joel, additional, Gerke, Travis, additional, Kantoff, Philip W., additional, George, Daniel J., additional, Penney, Kathryn L., additional, and Mucci, Lorelei A., additional

Published
2024
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16. Supplementary Methods S1 from Pain and Its Association with Survival for Black and White Individuals with Advanced Prostate Cancer in the United States

Author

Rencsok, Emily M., primary, Slopen, Natalie, primary, McManus, Hannah D., primary, Autio, Karen A., primary, Morgans, Alicia K., primary, McSwain, Lawrence, primary, Barata, Pedro, primary, Cheng, Heather H., primary, Dreicer, Robert, primary, Gerke, Travis, primary, Green, Rebecca, primary, Heath, Elisabeth I., primary, Howard, Lauren E., primary, McKay, Rana R., primary, Nowak, Joel, primary, Pileggi, Shannon, primary, Pomerantz, Mark M., primary, Rathkopf, Dana E., primary, Tagawa, Scott T., primary, Whang, Young E., primary, Ragin, Camille, primary, Odedina, Folakemi T., primary, Kantoff, Philip W., primary, Vinson, Jake, primary, Villanti, Paul, primary, Haneuse, Sebastien, primary, Mucci, Lorelei A., primary, and George, Daniel J., primary

Published
2024
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17. Quantifying Y chromosome loss in primary and metastatic prostate cancer by chromosome painting.

Author

Rajanala, Sai Harisha, Ghale, Romina, Nandakumar, Subhiksha, Chadalavada, Kalyani, Lee, Gwo-Shu Mary, Stopsack, Konrad H., Chen, Yu, Nanjangud, Gouri J., Chakraborty, Goutam, and Kantoff, Philip W.

Subjects
Y chromosome, CASTRATION-resistant prostate cancer, PROSTATE cancer, METASTASIS, CHROMOSOMES, NUDITY
Abstract

Somatic Y chromosome loss in hematopoietic cells is associated with higher mortality in men. However, the status of the Y chromosome in cancer tissue is not fully known due to technical limitations, such as difficulties in labelling and sequencing DNA from the Y chromosome. We have developed a system to quantify Y chromosome gain or loss in patient-derived prostate cancer organoids. Using our system, we observed Y chromosome loss in 4 of the 13 (31%) patient-derived metastatic castration-resistant prostate cancer (mCRPC) organoids; interestingly, loss of Yq (long arm of the Y chromosome) was seen in 38% of patient-derived organoids. Additionally, potential associations were observed between mCRPC and Y chromosome nullisomy. The prevalence of Y chromosome loss was similar in primary and metastatic tissue, suggesting that Y chromosome loss is an early event in prostate cancer evolution and may not a result of drug resistance or organoid derivation. This study reports quantification of Y chromosome loss and gain in primary and metastatic prostate cancer tissue and lays the groundwork for further studies investigating the clinical relevance of Y chromosome loss or gain in mCRPC. [ABSTRACT FROM AUTHOR]

Published
2024
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18. Development and Optimization of a Subtraction-Normalized Immunocyte Profiling Signature for Prostate Cancer Active Surveillance Risk Stratification.

Author

Van Neste, Leander, Henao, Ricardo, Wojno, Kirk J., Signes, Jorge, DeHart, Jessica, Busta, Angela, Marriott, Elyse, Willing, Marian, Argentini, Andrea, Hurley, Patrick M., Korman, Howard, Hafron, Jason, Putzi, Mathew, Pieczonka, Chris M., Karsh, Lawrence I., Morris, David S., Kassis, Amin I., and Kantoff, Philip W.

Abstract

Purpose: Less invasive decision support tools are desperately needed to identify occult high-risk disease in men with prostate cancer (PCa) on active surveillance (AS). For a variety of reasons, many men on AS with low- or intermediate-risk disease forgo the necessary repeat surveillance biopsies needed to identify potentially higher-risk PCa. Here, we describe the development of a blood-based immunocyte transcriptomic signature to identify men harboring occult aggressive PCa. We then validate it on a biopsy-positive population with the goal of identifying men who should not be on AS and confirm those men with indolent disease who can safely remain on AS. This model uses subtraction-normalized immunocyte transcriptomic profiles to risk-stratify men with PCa who could be candidates for AS. Materials and Methods: Men were eligible for enrollment in the study if they were determined by their physician to have a risk profile that warranted prostate biopsy. Both training (n = 1017) and validation cohort (n = 1198) populations had blood samples drawn coincident to their prostate biopsy. Purified CD2D and CD14D immune cells were obtained from peripheral blood mononuclear cells, and RNA was extracted and sequenced. To avoid overfitting and unnecessary complexity, a regularized regression model was built on the training cohort to predict PCa aggressiveness based on the National Comprehensive Cancer Network PCa guidelines. This model was then validated on an independent cohort of biopsy-positive men only, using National Comprehensive Cancer Network unfavorable intermediate risk and worse as an aggressiveness outcome, identifying patients who were not appropriate for AS. Results: The best final model for the AS setting was obtained by combining an immunocyte transcriptomic profile based on 2 cell types with PSA density and age, reaching an AUC of 0.73 (95% CI: 0.69-0.77). The model significantly outperforms (P < .001) PSA density as a biomarker, which has an AUC of 0.69 (95% CI: 0.65-0.73). This model yields an individualized patient risk score with 90% negative predictive value and 50% positive predictive value. Conclusions: While further validation in an intended-use cohort is needed, the immunocyte transcriptomic model offers a promising tool for risk stratification of individual patients who are being considered for AS. [ABSTRACT FROM AUTHOR]

Published
2024
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19. SLCO1B3 and SLCO2B1 genotypes, androgen deprivation therapy, and prostate cancer outcomes: a prospective cohort study and meta-analysis.

Author

Rajanala, Sai Harisha, Plym, Anna, Vaselkiv, Jane B, Ebot, Ericka M, Matsoukas, Konstantina, Lin, Zhike, Chakraborty, Goutam, Markt, Sarah C, Penney, Kathryn L, Lee, Gwo-Shu M, Mucci, Lorelei A, Kantoff, Philip W, and Stopsack, Konrad H

Abstract

Solute carrier organic anion (SLCO) transporters (OATP transporters) are involved in cellular uptake of drugs and hormones. Germline variants in SLCO1B3 and SLCO2B1 have been implicated in prostate cancer progression and therapy response, including to androgen deprivation and statin medications, but results have appeared heterogeneous. We conducted a cohort study of five single-nucleotide polymorphisms (SNPs) in SLCO1B3 and SLCO2B1 with prior evidence among 3208 men with prostate cancer who participated in the Health Professionals Follow-up Study or the Physicians' Health Study, following participants prospectively after diagnosis over 32 years (median, 14 years) for development of metastases and cancer-specific death (lethal disease, 382 events). Results were suggestive of, but not conclusive for, associations between some SNPs and lethal disease and differences by androgen deprivation and statin use. All candidate SNPs were associated with SLCO mRNA expression in tumor-adjacent prostate tissue. We also conducted a systematic review and harmonized estimates for a dose-response meta-analysis of all available data, including 9 further studies, for a total of 5598 patients and 1473 clinical events. The A allele of the exonic SNP rs12422149 (14% prevalence), which leads to lower cellular testosterone precursor uptake via SLCO2B1, was associated with lower rates of prostate cancer progression (hazard ratio per A allele, 0.80; 95% confidence interval, 0.69–0.93), with little heterogeneity between studies (I 2, 0.27). Collectively, the totality of evidence suggests a strong association between inherited genetic variation in SLCO2B1 and prostate cancer prognosis, with potential clinical use in risk stratification related to androgen deprivation therapy. [ABSTRACT FROM AUTHOR]

Published
2024
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20. A Phase I Study of Everolimus and Docetaxel in Patients With Castration-Resistant Prostate Cancer

Author

Courtney, Kevin D., Manola, Judith B., Elfiky, Aymen A., Ross, Robert, Oh, William K., Yap, Jeffrey T., Van den Abbeele, Annick D., Ryan, Christopher W., Beer, Tomasz M., Loda, Massimo, Priolo, Carmen, Kantoff, Philip, and Taplin, Mary-Ellen

Abstract

Activation of the phosphoinositide 3-kinase signaling cascade, often through loss of the phosphatase and tensin homologue deleted on chromosome 10 (PTEN) tumor suppressor, is frequent in castration-resistant prostate cancer (CRPC). We assessed the safety and efficacy of combining the mammalian target of rapamycin (mTOR) inhibitor everolimus with docetaxel in a phase I clinical trial of men with metastatic CRPC, and evaluated the ability of fluorine–18-fluorodeoxyglucose (FDG) positron emission tomography (PET) to predict response to treatment. The observed clinical activity of tolerable dose levels of everolimus with docetaxel was low. FDG-PET might serve as a biomarker for target inhibition by mTOR inhibitors in metastatic CRPC.

Published
2024
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21. Germline DNA damage repair variants and prognosis of patients with high-risk or metastatic prostate cancer.

Author

Stopsack KH, Vijai J, Conry M, Berchuck JE, Kemel Y, Vasselman SE, Freeman DA, Lee GM, Mandelker D, Solit DB, Morris MJ, Penney KL, Abida W, Offit K, Mucci LA, Kantoff PW, and Pomerantz MM

Abstract

Purpose: Deleterious germline variants in certain DNA repair genes are risk factors for developing aggressive prostate cancer. The objective was to quantify their prognostic impact after prostate cancer diagnosis., Methods: Men with prostate cancer, predominantly of European ancestry, were included from four cohorts with long-term follow-up. Pathogenic or likely pathogenic germline variants in 26 DNA repair genes were assessed in relation to metastasis-free survival in high-risk, localized prostate cancer and to overall survival in metastatic castration-sensitive prostate cancer (mCSPC) and metastatic castration-resistant prostate cancer (mCRPC)., Results: Among 3,525 patients initially diagnosed with non-metastatic prostate cancer, 2,594 had high-risk localized prostate cancer, 429 mCSPC, and 502 mCRPC at inclusion. BRCA2 variant carriers did not have worse metastasis-free survival in high-risk localized prostate cancer (hazard ratio [HR] 1.01, 95% confidence interval [CI] 0.69, 1.46) or overall survival in mCSPC (HR 0.46, 95% CI 0.14, 1.45) or mCRPC (HR 0.60, 95% CI 0.31, 1.17) compared to non-carriers of DNA repair variants. Among 868 additional patients with de novo metastatic (M1) prostate cancer, BRCA2 variant carriers tended to have worse overall survival (HR 1.59, 95% CI 1.01, 2.51). BRCA2 prognostic associations were not explained by radiation, PARP inhibitor, or platinum therapy. Results for other genes were limited in precision because variants were less common., Conclusions: Among patients with high-risk or metastatic prostate cancer who were initially diagnosed with and treated for non-metastatic tumors, germline DNA repair variants in BRCA2 do not confer a substantially worse prognosis.

Published
2024
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22. Characterising the contribution of rare protein-coding germline variants to prostate cancer risk and severity in 37,184 cases.

Author

Mitchell J, Camacho N, Shea P, Stopsack KH, Joseph V, Burren O, Dhindsa R, Nag A, Berchuck JE, O'Neill A, Abbasi A, Zoghbi AW, Alegre-Díaz J, Kuri-Morales P, Berumen J, Tapia-Conyer R, Emberson J, Torres JM, Collins R, Wang Q, Goldstein D, Matakidou A, Haefliger C, Anderson-Dring L, March R, Jobanputra V, Dougherty B, Carss K, Petrovski S, Kantoff PW, Offit K, Mucci LA, Pomerantz M, and Fabre MA

Abstract

The etiology of prostate cancer, the second most common cancer in men globally, has a strong heritable component. While rare coding germline variants in several genes have been identified as risk factors from candidate gene and linkage studies, the exome-wide spectrum of causal rare variants remains to be fully explored. To more comprehensively address their contribution, we analysed data from 37,184 prostate cancer cases and 331,329 male controls from five cohorts with germline exome/genome sequencing and one cohort with imputed array data from a population enriched in low-frequency deleterious variants. Our gene-level collapsing analysis revealed that rare damaging variants in SAMHD1 as well as genes in the DNA damage response pathway ( BRCA2 , ATM and CHEK2 ) are associated with the risk of overall prostate cancer. We also found that rare damaging variants in AOX1 and BRCA2 were associated with increased severity of prostate cancer in a case-only analysis of aggressive versus non-aggressive prostate cancer. At the single-variant level, we found rare non-synonymous variants in three genes ( HOXB13 , CHEK2 , BIK ) significantly associated with increased risk of overall prostate cancer and in four genes ( ANO7 , SPDL1 , AR , TERT ) with decreased risk. Altogether, this study provides deeper insights into the genetic architecture and biological basis of prostate cancer risk and severity., Competing Interests: Competing Interests J.M., N.C., O.B., R.D., A.N., A.O., A.A., Q.W., L.A.-D., R.M., B.D., K.C., S.P., M.A.F. are current employees and/or stockholders of AstraZeneca. A.W.Z receives grant funding and consulting fees from AstraZeneca. L.A.M. is on the advisory board and holds equity interest in Convergent Therapeutics. A.M. is a former employee of AstraZeneca and current employee of GSK and a stockholder of AstraZeneca and GSK. C.H. was an employee and stockholder of AZ at the time of study. P.W.K. is a co-founder and employee of Convergent Therapeutics.

Published
2024
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23. Pain and Its Association with Survival for Black and White Individuals with Advanced Prostate Cancer in the United States.

Author

Rencsok EM, Slopen N, McManus HD, Autio KA, Morgans AK, McSwain L, Barata P, Cheng HH, Dreicer R, Gerke T, Green R, Heath EI, Howard LE, McKay RR, Nowak J, Pileggi S, Pomerantz MM, Rathkopf DE, Tagawa ST, Whang YE, Ragin C, Odedina FT, Kantoff PW, Vinson J, Villanti P, Haneuse S, Mucci LA, and George DJ

Subjects
Humans, Male, Black or African American, Prospective Studies, Quality of Life, United States epidemiology, White, Survival Rate, Prostatic Neoplasms complications, Cancer Pain
Abstract

Bone pain is a well-known quality-of-life detriment for individuals with prostate cancer and is associated with survival. This study expands previous work into racial differences in multiple patient-reported dimensions of pain and the association between baseline and longitudinal pain and mortality. This is a prospective cohort study of individuals with newly diagnosed advanced prostate cancer enrolled in the International Registry for Men with Advanced Prostate Cancer (IRONMAN) from 2017 to 2023 at U.S. sites. Differences in four pain scores at study enrollment by race were investigated. Cox proportional hazards models and joint longitudinal survival models were fit for each of the scale scores to estimate HRs and 95% confidence intervals (CI) for the association with all-cause mortality. The cohort included 879 individuals (20% self-identifying as Black) enrolled at 38 U.S. sites. Black participants had worse pain at baseline compared with White participants, most notably a higher average pain rating (mean 3.1 vs. 2.2 on a 10-point scale). For each pain scale, higher pain was associated with higher mortality after adjusting for measures of disease burden, particularly for severe bone pain compared with no pain (HR, 2.47; 95% CI: 1.44-4.22). The association between pain and all-cause mortality was stronger for participants with castration-resistant prostate cancer compared with those with metastatic hormone-sensitive prostate cancer and was similar among Black and White participants. Overall, Black participants reported worse pain than White participants, and more severe pain was associated with higher mortality independent of clinical covariates for all pain scales., Significance: Black participants with advanced prostate cancer reported worse pain than White participants, and more pain was associated with worse survival. More holistic clinical assessments of pain in this population are needed to determine the factors upon which to intervene to improve quality of life and survivorship, particularly for Black individuals., (© 2024 The Authors; Published by the American Association for Cancer Research.)

Published
2024
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