Publications by authors named "Charles J Ryan"

177 Publications

Feasibility, safety, and acceptability of a remotely monitored exercise pilot CHAMP: A Clinical trial of High-intensity Aerobic and resistance exercise for Metastatic castrate-resistant Prostate cancer.

Cancer Med 2021 Nov 12;10(22):8058-8070. Epub 2021 Oct 12.

University of California, San Francisco, San Francisco, California, USA.

Background: Exercise may improve clinical and quality of life outcomes for men with prostate cancer. No randomized controlled trials (RCTs) have examined the feasibility, safety, and acceptability of remote exercise training in men with metastatic castrate-resistant prostate cancer (mCRPC).

Methods: We conducted a pilot RCT (1:1:1 aerobic or resistance exercise 3x/week or usual care) to determine the feasibility, safety, and acceptability of remotely monitored exercise over 12 weeks in 25 men with mCRPC. A prescribed exercise program was based on baseline testing including high- and moderate-intensity aerobic exercise or resistance exercise completed at a local exercise facility. Feasibility was based on attendance, adherence, and tolerance; safety on adverse events; and acceptability on participant interviews.

Results: Between March 2016 and March 2020, 25 patients were randomized (8 aerobic, 7 resistance, and 10 control). Twenty-three men (82%) completed the 12-week study. Men who completed the remote intervention attempted 90% and 96% of prescribed aerobic and resistance training sessions, respectively, and 86% and 88% of attempted sessions were completed as or more than prescribed. We observed changes in performance tests that corresponded with the exercise prescription. No safety concerns were identified. Ninety percent of participants interviewed were satisfied with the program and would recommend it to others.

Conclusions: Remotely monitored exercise training is feasible, safe, and acceptable in men with mCRPC; there was no difference in these outcomes by mode of exercise. Through this research, we provide direction and rationale for future studies of exercise and clinical outcomes in patients with metastatic prostate cancer.
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http://dx.doi.org/10.1002/cam4.4324DOI Listing
November 2021

Response to Rucaparib in BRCA-Mutant Metastatic Castration-Resistant Prostate Cancer Identified by Genomic Testing in the TRITON2 Study.

Clin Cancer Res 2021 Oct 1. Epub 2021 Oct 1.

Genitourinary Oncology Service, Memorial Sloan Kettering Cancer Center, New York, New York.

Purpose: The PARP inhibitor rucaparib is approved in the United States for patients with metastatic castration-resistant prostate cancer (mCRPC) and a deleterious germline and/or somatic or (BRCA) alteration. While sequencing of tumor tissue is considered the standard for identifying patients with BRCA alterations (BRCA), plasma profiling may provide a minimally invasive option to select patients for rucaparib treatment. Here, we report clinical efficacy in patients with BRCA mCRPC identified through central plasma, central tissue, or local genomic testing and enrolled in TRITON2.

Patients And Methods: Patients had progressed after next-generation androgen receptor-directed and taxane-based therapies for mCRPC and had BRCA alterations identified by central sequencing of plasma and/or tissue samples or local genomic testing. Concordance of plasma/tissue BRCA status and objective response rate and prostate-specific antigen (PSA) response rates were summarized.

Results: TRITON2 enrolled 115 patients with BRCA identified by central plasma ( = 34), central tissue ( = 37), or local ( = 44) testing. Plasma/tissue concordance was determined in 38 patients with paired samples and was 47% in 19 patients with a somatic BRCA alteration. No statistically significant differences were observed between objective and PSA response rates to rucaparib across the 3 assay groups. Patients unable to provide tissue samples and tested solely by plasma assay responded at rates no different from patients identified as BRCA by tissue testing.

Conclusions: Plasma, tissue, and local testing of mCRPC patients can be used to identify men with BRCA mCRPC who can benefit from treatment with the PARP inhibitor rucaparib.
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http://dx.doi.org/10.1158/1078-0432.CCR-21-2199DOI Listing
October 2021

Acceptability and Feasibility of Collecting Sexual Orientation and Expanded Gender Identity Data in Urology and Oncology Clinics.

LGBT Health 2021 Aug-Sep;8(6):420-426. Epub 2021 Aug 4.

Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA.

We evaluated the acceptability and feasibility of collecting sexual orientation and gender identity (SOGI) data in oncology and urology clinical settings. We surveyed 101 urology and 104 oncology clinic patients with a standardized sexual orientation question with six response options, "lesbian, gay, or homosexual;" "straight or heterosexual;" "bisexual;" "something else;" "do not know;" and "choose not to disclose." Next, we added the sexual orientation question and an expanded gender identity question to the electronic medical record (EMR) and analyzed data on the first 450 urology and 103 oncology patients. Acceptability and feasibility were assessed based on responses to the survey and patient intake forms. In the acceptability survey, only 3% of urology and 4% of oncology patients selected "choose not to disclose." Over 90% of patients in both clinics assessed the sexual orientation question as understandable and easy to answer. In all, 79% of urology and 73% of oncology patients stated they would answer it in their EMR, but only 56% of urology and 54% of oncology patients described the information as important. Sexual minority patients were as likely as heterosexual patients to state they would answer the question. Only 5% of patients selected "choose not to disclose" for sexual orientation, and <1% for the expanded gender identity question. Adding SOGI questions to the EMR appears to be acceptable and feasible and the sexual orientation question was understandable to a large majority of urology and oncology patients. ClinicalTrials.gov ID: NCT03343093.
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http://dx.doi.org/10.1089/lgbt.2020.0256DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8591059PMC
October 2021

Combined Longitudinal Clinical and Autopsy Phenomic Assessment in Lethal Metastatic Prostate Cancer: Recommendations for Advancing Precision Medicine.

Eur Urol Open Sci 2021 Aug 2;30:47-62. Epub 2021 Jul 2.

Faculty of Medicine and Health Technology, Prostate Cancer Research Center, Tampere University and Tays Cancer Center, Tampere, FI-33014, Finland.

Background: Systematic identification of data essential for outcome prediction in metastatic prostate cancer (mPC) would accelerate development of precision oncology.

Objective: To identify novel phenotypes and features associated with mPC outcome, and to identify biomarker and data requirements to be tested in future precision oncology trials.

Design Setting And Participants: We analyzed deep longitudinal clinical, neuroendocrine expression, and autopsy data of 33 men who died from mPC between 1995 and 2004 (PELICAN33), and related findings to mPC biomarkers reported in the literature.

Intervention: Thirty-three men prospectively consented to participate in an integrated clinical-molecular rapid autopsy study of mPC.

Outcome Measurements And Statistical Analysis: Data exploration with correction for multiple testing and survival analysis from the time of diagnosis to time to death and time to first occurrence of severe pain as outcomes were carried out. The effect of seven complications on the modeled probability of dying within 2 yr after presenting with the complication was evaluated using logistic regression.

Results And Limitations: Feature exploration revealed novel phenotypes related to mPC outcome. Four complications (pleural effusion, severe anemia, severe or controlled pain, and bone fracture) predict the likelihood of death within 2 yr. Men with Gleason grade group 5 cancers developed severe pain sooner than those with lower-grade tumors. Surprisingly, neuroendocrine (NE) differentiation was frequently observed in the setting of high serum prostate-specific antigen (PSA) levels (≥30 ng/ml). In 4/33 patients, no controlled (requiring analgesics) or severe pain was detected, and strikingly, 14/15 metastatic sites studied in these men did not express NE markers, suggesting an inverse relationship between NE differentiation and pain in mPC. Intracranial subdural metastasis is common (36%) and is usually clinically undetected. Categorization of "skeletal-related events" complications used in recent studies likely obscures the understanding of spinal cord compression and fracture. Early death from prostate cancer was identified in a subgroup of men with a low longitudinal PSA bandwidth. Cachexia is common (body mass index <0.89 in 24/31 patients) but limited to the last year of life. Biomarker review identified 30 categories of mPC biomarkers in need of winnowing in future trials. All findings require validation in larger cohorts, preferably alongside data from this study.

Conclusions: The study identified novel outcome subgroups for future validation and provides "vision for mPC precision oncology 2020-2050" draft recommendations for future data collection and biomarker studies.

Patient Summary: To better understand variation in metastatic prostate cancer behavior, we assembled and analyzed longitudinal clinical and autopsy records in 33 men. We identified novel outcomes, phenotypes, and aspects of disease burden to be tested and refined in future trials.
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http://dx.doi.org/10.1016/j.euros.2021.05.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8317817PMC
August 2021

A multidisciplinary team-based approach with lifestyle modification and symptom management to address the impact of androgen deprivation therapy in prostate cancer: A randomized phase II study.

Urol Oncol 2021 10 23;39(10):730.e9-730.e15. Epub 2021 Jul 23.

Division of Hematology Oncology, University of California San Francisco, San Francisco, CA.

Background: Androgen deprivation therapy (ADT) is associated with numerous toxicities that are potentially modifiable. We sought to evaluate the impact of participation in a multidisciplinary clinic, STAND (Supportive Therapy in Androgen Deprivation) Clinic, designed to provide individualized lifestyle modification and management of ADT-related side effects.

Methods: This phase II study recruited men with prostate cancer who had started ADT <6 months prior to enrollment, and in whom ADT was planned for at least 12 months following enrollment. Patients were randomized in a 1:1 ratio to either the STAND Clinic or usual care. Patients randomized to the STAND Clinic were provided monthly multidisciplinary assessment and counseling on exercise, nutrition, and symptom management for 12 months on a rotating schedule. Primary outcome was change from baseline to 12 months in percent body fat. Feasibility outcomes were also assessed by measuring percentage of completed visits. Secondary outcomes included change from baseline to 12 months in 3 domains: (1) metabolic impact and bone health, (2) quality of life (QOL), and (3) physical activity.

Results: A total of 25 men were randomized to STAND clinic, and 23 were randomized to usual care. The study did not meet its accrual target of 32 men in each arm and was closed early due to lack of financial support. Overall, 91% (295 of 325) of STAND clinic visits were completed. Eighteen out of the 25 patients in STAND clinic arm (72%) completed all 12 months of STAND clinic visits, and 80% (20 of 25) completed the first 6 months. For all primary and secondary outcomes, there were no statistically significant differences between treatment arms.

Conclusion: Individualized and comprehensive management of ADT toxicities in a multidisciplinary clinic was well attended by patients. However, we did not find any differences in the outcomes assessed between the intervention arm and control.
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http://dx.doi.org/10.1016/j.urolonc.2021.05.032DOI Listing
October 2021

Management of Patients with Metastatic Castration-Sensitive Prostate Cancer in the Real-World Setting in the United States.

J Urol 2021 Dec 23;206(6):1420-1429. Epub 2021 Jul 23.

Division of Urology, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, California.

Purpose: This study provides a contemporary assessment of the treatment patterns, health care resource utilization (HRU) and costs among metastatic castration-sensitive prostate cancer (mCSPC) patients in the U.S.

Materials And Methods: Adults with mCSPC were selected from Optum's de-identified Clinformatics® Data Mart Database (Commercial insurance/Medicare Advantage [COM/MA]; January 1, 2014-July 31, 2019) or Medicare Fee-for-Service (FFS; January 1, 2014-December 31, 2017). The index date was the first metastatic disease diagnosis date on/after the first prostate cancer diagnosis (without prior evidence of castration resistance). Patients were observed for 12 months pre-index (baseline) through their mCSPC period (from index until castration resistance or followup end). First-line (1L) mCSPC therapy was assessed during the mCSPC period; all-cause HRU and health plan-paid costs per-patient-per-year (PPPY) were measured during baseline and mCSPC periods.

Results: Among 6,517 COM/MA and 13,324 Medicare-FFS mCSPC patients over ∼10 months (median mCSPC period), 38% and 48% remained untreated/deferred treatment, and 45% and 46% received 1L androgen deprivation therapy (ADT) monotherapy, respectively. 1L abiraterone acetate and docetaxel were used among 7% and 6% of COM/MA and 1% and 2% of Medicare-FFS patients, respectively. HRU increased from baseline to mCSPC period, resulting in increased health plan-paid costs from $21,201 to $108,767 in COM/MA and from $16,819 to $69,639 PPPY in Medicare-FFS.

Conclusions: This study highlights the limited use of newer therapies that improve survival in men with mCSPC in the U.S. HRU and costs increased substantially after onset of metastasis. Given the emergence of newer effective mCSPC therapies, further evaluation of future real-world mCSPC treatment patterns and outcomes is warranted.
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http://dx.doi.org/10.1097/JU.0000000000002121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8584208PMC
December 2021

Novel immune engagers and cellular therapies for metastatic castration-resistant prostate cancer: do we take a BiTe or ride BiKEs, TriKEs, and CARs?

Prostate Cancer Prostatic Dis 2021 Dec 25;24(4):986-996. Epub 2021 May 25.

Department of Medicine, Division of Hematology, Oncology, and Transplantation, University of Minnesota, Minneapolis, MN, USA.

Background: Checkpoint inhibitors and currently approved cellular products for metastatic castration-resistant prostate cancer have not resulted in revolutionary changes in outcomes compared to other solid tumors. Much of this lack of progress is attributed to the unique tumor microenvironment of prostate cancer that is often immunologically cold and immunosuppressive. These unique conditions emphasize the need for novel therapeutic options. In this review, we will discuss progress made in design of T- and NK cell immune engagers in addition to chimeric antigen receptor products specifically designed for prostate cancer that are currently under investigation in clinical trials.

Methods: We searched peer-reviewed literature on the PubMed and the ClinicalTrials.gov databases for active clinical trials using the terms "bispecific T-cell engager," "bispecific killer engager," "trispecific killer engager," "chimeric antigen receptor," "metastatic castration-resistant prostate cancer," and "neuroendocrine prostate cancer."

Results: Ten bispecific T-cell engager studies and nine chimeric antigen receptor-based products were found. Published data were compiled and presented based on therapeutic class.

Conclusions: Multiple immune engagers and cell therapies are in the development pipeline and demonstrate promise to address barriers to better outcomes for metastatic castration-resistant prostate cancer patients.
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http://dx.doi.org/10.1038/s41391-021-00381-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8613314PMC
December 2021

Prostate Cancer Mortality Associated with Aggregate Polymorphisms in Androgen-Regulating Genes: The Atherosclerosis Risk in the Communities (ARIC) Study.

Cancers (Basel) 2021 Apr 19;13(8). Epub 2021 Apr 19.

Division of Hematology, Oncology and Transplantation, University of Minnesota Medical School, Minneapolis, MN 55455, USA.

Genetic variations in androgen metabolism may influence prostate cancer (PC) prognosis. Clinical studies consistently linked PC prognosis with four single nucleotide polymorphisms (SNPs) in the critical androgen-regulating genes: 3-beta-hydroxysteroid dehydrogenase () rs1047303, 5-alpha-reductase 2 () rs523349, and solute carrier organic ion () rs1789693 and rs12422149. We tested the association of four androgen-regulating SNPs, individually and combined, with PC-specific mortality in the ARIC population-based prospective cohort. Men diagnosed with PC (N = 622; 79% White, 21% Black) were followed for death (N = 350) including PC death (N = 74). Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95%CI adjusting for center, age, stage, and grade at diagnosis using separate hazards for races. A priori genetic risk score (GRS) was created as the unweighted sum of risk alleles in the four pre-selected SNPs. The gain-of-function rs1047303C allele was associated PC-specific mortality among men with metastatic PC at diagnosis (HR = 4.89 per risk allele, = 0.01). Higher GRS was associated with PC-specific mortality (per risk allele: HR = 1.26, = 0.03). We confirmed that the gain-of-function allele in rs1047303 is associated with greater PC mortality in men with metastatic disease. Additionally, our findings suggest a cumulative effect of androgen-regulating genes on PC-specific mortality; however, further validation is required.
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http://dx.doi.org/10.3390/cancers13081958DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072683PMC
April 2021

Efficacy and Adverse Events of Docetaxel for Metastatic, Hormone-sensitive Prostate Cancer Among Elderly Men: A Post Hoc Analysis of the CHAARTED Trial.

Clin Genitourin Cancer 2021 10 19;19(5):388-395. Epub 2021 Mar 19.

Northwestern University, Feinberg School of Medicine, Department of Medicine, Chicago, IL. Electronic address:

Background: Combination therapy with docetaxel and androgen deprivation therapy (ADT) prolongs overall survival (OS) in men with metastatic hormone-sensitive prostate cancer. We assessed the benefits and adverse effects of docetaxel and ADT in relation to advancing age.

Methods: We performed a post hoc analysis of the CHAARTED trial comparing docetaxel and ADT vs. ADT alone (n = 773). Patients were stratified in age groups <60, 60-70, and >70 years old. Multivariable-adjusted progression-free survival (PFS) and OS were assessed using Kaplan-Meier curves and compared using multivariable Cox regressions with calculated interaction terms between age group and treatment arm. In the combination arm, the incidence of ≥1 adverse event (grade ≥3) and the number of adverse events per patient were compared for each age group using multivariable logistic and linear regressions, respectively.

Results: After adjusting for clinical variables, docetaxel's effect did not vary by age group for PFS and OS. There was no significant difference in the odds ratio of ≥1 adverse event (P > .1 for age groups 60-70 and >70 years old compared with <60 years old). However, men age >70 years old experienced +0.37 more adverse events per patient compared with men age <60 years old (95% CI, 0.11-0.64; P = .006).

Conclusions: PFS and OS were similar across age groups for the combination of docetaxel and ADT compared with ADT. Older men experienced a modest increase in adverse events per patient, highlighting the importance of balancing treatment benefits and adverse effects in this age group.
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http://dx.doi.org/10.1016/j.clgc.2021.03.016DOI Listing
October 2021

Genomic Analysis of Circulating Tumor DNA in 3,334 Patients with Advanced Prostate Cancer Identifies Targetable BRCA Alterations and AR Resistance Mechanisms.

Clin Cancer Res 2021 Jun 8;27(11):3094-3105. Epub 2021 Feb 8.

Foundation Medicine Inc., Cambridge, Massachusetts.

Purpose: Comprehensive genomic profiling (CGP) is of increasing value for patients with metastatic castration-resistant prostate cancer (mCRPC). mCRPC tends to metastasize to bone, making tissue biopsies challenging to obtain. We hypothesized CGP of cell-free circulating tumor DNA (ctDNA) could offer a minimally invasive alternative to detect targetable genomic alterations (GA) that inform clinical care.

Experimental Design: Using plasma from 3,334 patients with mCRPC (including 1,674 screening samples from TRITON2/3), we evaluated the landscape of GAs detected in ctDNA and assessed concordance with tissue-based CGP.

Results: A total of 3,129 patients (94%) had detectable ctDNA with a median ctDNA fraction of 7.5%; was mutated in 295 (8.8%). In concordance analysis, 72 of 837 patients had mutations detected in tissue, 67 (93%) of which were also identified using ctDNA, including 100% of predicted germline variants. ctDNA harbored some BRCA1/2 alterations not identified by tissue testing, and ctDNA was enriched in therapy resistance alterations, as well as possible clonal hematopoiesis mutations (e.g., in and ). Potential androgen receptor resistance alterations were detected in 940 of 2,213 patients (42%), including amplifications, polyclonal and compound mutations, rearrangements, and novel deletions in exon 8.

Conclusions: Genomic analysis of ctDNA from patients with mCRPC recapitulates the genomic landscape detected in tissue biopsies, with a high level of agreement in detection of mutations, but more acquired resistance alterations detected in ctDNA. CGP of ctDNA is a compelling clinical complement to tissue CGP, with reflex to tissue CGP if negative for actionable variants..
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http://dx.doi.org/10.1158/1078-0432.CCR-20-4805DOI Listing
June 2021

Identification of patients with metastatic castration-sensitive or metastatic castration-resistant prostate cancer using administrative health claims and laboratory data.

Curr Med Res Opin 2021 04 13;37(4):609-622. Epub 2021 Feb 13.

Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN, USA.

Objective: To develop algorithms to identify metastatic castration-sensitive prostate cancer (mCSPC) patients and castration-resistant prostate cancer (mCRPC) patients, using health claims data and laboratory test results.

Methods: A targeted literature review summarized mCSPC and mCRPC patient selection criteria previously used in real-world retrospective studies. Novel algorithms to identify mCSPC and mCRPC were developed based on diagnosis codes indicating hormone sensitivity/resistance, prostate-specific antigen (PSA) test results, and claims for castration and mCRPC-specific treatments. These algorithms were applied to claims data from Optum Clinformatics Extended DataMart (Date of Death) Databases (commercial insurance/Medicare Advantage [COM/MA]; 01 January 2014-31 July 2019) and Medicare Fee-for-Service (Medicare-FFS; 01 January 2014-31 December 2017).

Results: Previous real-world studies identified mCSPC primarily based on metastasis diagnosis codes, and mCRPC based on mCRPC-specific drugs. Using the current study's algorithms, 7034 COM/MA and 19,981 Medicare-FFS patients were identified as having mCSPC, and 2578 COM/MA and 11,554 Medicare-FFS as having mCRPC. Most mCSPC patients were identified based on evidence of being hormone/castration-naive. Patients were identified as having mCRPC most commonly based on rising PSA (COM/MA), or at the metastasis diagnosis date if it occurred after castration (Medicare-FFS). Among patients with mCSPC, 14-17% had evidence of progression to castration resistance during a median 1-year follow-up period, mostly based on use of mCRPC-specific drugs.

Conclusions: Comprehensive algorithms based on claims and laboratory data were developed to identify and distinguish patients with mCSPC and mCRPC. This will facilitate appropriate identification of mCSPC and mCRPC patients based on health claims data and better understanding of patient unmet needs in real-world settings.
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http://dx.doi.org/10.1080/03007995.2021.1879753DOI Listing
April 2021

Prostate Cancer Foundation Hormone-Sensitive Prostate Cancer Biomarker Working Group Meeting Summary.

Urology 2021 Sep 26;155:165-171. Epub 2020 Dec 26.

Genitourinary Malignancies Research Center, Cleveland Clinic, Cleveland, OH; Department of Urology, Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH; Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH. Electronic address:

Androgen deprivation therapy remains the backbone therapy for the treatment of metastatic hormone-sensitive prostate cancer (mHSPC). In recent years, several treatments, including docetaxel, abiraterone + prednisone, enzalutamide, and apalutamide, have each been shown to demonstrate survival benefit when used upfront along with androgen deprivation therapy. However, treatment selection for an individual patient remains a challenge. There is no high level clinical evidence for treatment selection among these choices based on biological drivers of clinical disease. In August 2020, the Prostate Cancer Foundation convened a working group to meet and discuss biomarkers for hormone-sensitive prostate cancer, the proceedings of which are summarized here. This meeting covered the state of clinical and biological evidence for systemic therapies in the mHSPC space, with emphasis on charting a course for the generation, interrogation, and clinical implementation of biomarkers for treatment selection.
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http://dx.doi.org/10.1016/j.urology.2020.12.021DOI Listing
September 2021

Resetting the Bar of Castration Resistance - Understanding Androgen Dynamics in Therapy Resistance and Treatment Choice in Prostate Cancer.

Clin Genitourin Cancer 2021 06 29;19(3):199-207. Epub 2020 Aug 29.

Masonic Cancer Center, University of Minnesota Medical School, Minneapolis, MN.

This review discusses impact of advancements in biologic understanding of prostate cancer (PCa) on definition and diagnosis of castration-resistant PCa (CRPC), predictive factors for progression to CRPC and treatment strategies. More sensitive assays confirm that bilateral orchiectomy reduces serum testosterone (T) closer to < 20 ng/dL than < 50 ng/dL, and evidence suggests that achieving T < 20 ng/dL improves outcomes and delays CRPC emergence. Regular T assessments will evaluate whether T is adequately suppressed in the setting of potential progression to CRPC, given that late dosing may result in T escape. More advanced imaging modalities and biomarker assays allow earlier detection of disease progression. Predictive factors for progression to CRPC include Gleason grade, extent of metastatic spread, germline hereditary factors such as gene mutations affecting androgen receptor amplification or DNA repair deficiency mutations, prostate-specific antigen kinetics, and biomarker analyses. Treatment options for CRPC have expanded beyond androgen deprivation therapy to include therapies that suppress T or inhibit its activity through varying mechanisms. Future directions include therapies with novel biological targets, drug combinations and personalized treatments. Advanced PCa management aims to delay progression to CRPC and prolong survival. With redefinition of castration and advancements in understanding of the biology of disease progression, diagnosis and treatment strategies should be re-evaluated. Definition of CRPC could be updated to reflect the T < 20 ng/dL requirement as this is a 'true' castrate level and may improve outcomes. It is important that androgen deprivation therapy as foundational therapy is continued even as new CRPC therapies are introduced.
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http://dx.doi.org/10.1016/j.clgc.2020.08.008DOI Listing
June 2021

Practical Considerations and Challenges for Germline Genetic Testing in Patients With Prostate Cancer: Recommendations From the Germline Genetics Working Group of the PCCTC.

JCO Oncol Pract 2020 12 28;16(12):811-819. Epub 2020 Sep 28.

Department of Medicine, University of California at San Diego Moores Cancer Center, La Jolla, CA.

Germline genetic testing is now routinely recommended for patients with prostate cancer (PCa) because of expanded guidelines and options for targeted treatments. However, integrating genetic testing into oncology and urology clinical workflows remains a challenge because of the increased number of patients with PCa requiring testing and the limited access to genetics providers. This suggests a critical unmet need for genetic services outside of historical models. This review addresses current guidelines, considerations, and challenges for PCa genetic testing and offers a practical guide for genetic counseling and testing delivery, with solutions to help address potential barriers and challenges for both providers and patients. As genetic and genomic testing become integral to PCa care, developing standardized systems for implementation in the clinic is essential for delivering precision oncology to patients with PCa and realizing the full scope and impact of genetic testing.
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http://dx.doi.org/10.1200/OP.20.00431DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7735040PMC
December 2020

NK-Cell-Mediated Targeting of Various Solid Tumors Using a B7-H3 Tri-Specific Killer Engager In Vitro and In Vivo.

Cancers (Basel) 2020 Sep 18;12(9). Epub 2020 Sep 18.

Department of Medicine, Division of Hematology, Oncology, and Transplantation, University of Minnesota, Minneapolis, MN 55455, USA.

We improved the bispecific antibody platform that primarily engages natural killer (NK) cells to kill cancer cells through antibody-dependent cellular cytotoxicity (ADCC) by adding IL-15 as a crosslinker that expands and self-sustains the effector NK cell population. The overall goal was to target B7-H3, an established marker predominantly expressed on cancer cells and minimally expressed on normal cells, and prove that it could target cancer cells in vitro and inhibit tumor growth in vivo. The tri-specific killer engager (TriKE) was assembled by DNA shuffling and ligation using DNA encoding a camelid anti-CD16 antibody fragment, a wild-type IL-15 moiety, and an anti-B7-H3 scFv (clone 376.96). The expressed and purified cam1615B7H3 protein was tested for in vitro NK cell activity against a variety of tumors and in vivo against a tagged human MA-148 ovarian cancer cell line grafted in NSG mice. cam1615B7H3 showed specific NK cell expansion, high killing activity across a range of B7-H3+ carcinomas, and the ability to mediate growth inhibition of aggressive ovarian cancer in vivo. cam1615B7H3 TriKE improves NK cell function, expansion, targeted cytotoxicity against various types of B7-H3-positive human cancer cell lines, and delivers an anti-cancer effect in vivo in a solid tumor setting.
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http://dx.doi.org/10.3390/cancers12092659DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7564091PMC
September 2020

Triple Aberrant Prostate Cancer (TAPC) - Aggregate role of aberrations in , and on ETS gene fusions and prognosis in metastatic castrate resistant prostate cancer.

Am J Clin Exp Urol 2020 15;8(4):106-115. Epub 2020 Aug 15.

Division of Hematology, Oncology & Transplantation, Department of Medicine, University of Minnesota Minneapolis, USA.

Background: Aberrations in , and are key drivers of therapy resistance in prostate cancer. Up to 50% of prostate cancers harbor ETS gene rearrangements, a potentially compounding aggressive biological event. Little is known about the impact of aggregate aberrations and gene fusion events in prostate cancer.

Methods: Using cBioportal for Cancer Genomics, an open-access resource for exploration of multidimensional cancer genomics data, we integrate whole-exome sequencing, gene expression, and histopathology with longitudinal clinical outcomes. Subsets of prostate tumors with aberrations in all three genes , and were identified and correlated with prevalence of gene fusions. Prostate tumors with aberrations in , , and were termed "triple aberrant prostate cancer" (TAPC).

Results: Of 479 metastatic prostate tumors, 195 (40.7%) were TAPC, versus 21 of 594 (3.5%) of primary prostate tumors. Patients with metastatic TAPC showed a trend toward poorer overall survival than patients harboring 0, 1 or 2 of these aberrations. Twenty-five distinct fusions were identified, all involving ETS transcription factors. Both primary and metastatic prostate cancers with ETS fusions were significantly more likely to be TAPC than those without ETS fusions.

Conclusions: This study identified a unique molecular signature consisting of combined aberrations in , and that is associated with poorer overall survival, as well as increasing prevalence of ETS gene fusions and differential gene expression patterns favoring aggressive disease and tumor progression. Identification of this subset of patients could inform prognostic decisions and provide a rationale for more aggressive or unique therapeutic approaches.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7486539PMC
August 2020

Rucaparib in Men With Metastatic Castration-Resistant Prostate Cancer Harboring a or Gene Alteration.

J Clin Oncol 2020 11 14;38(32):3763-3772. Epub 2020 Aug 14.

Medical Oncology, Guy's Hospital, London, United Kingdom.

Purpose: or () alterations are common in men with metastatic castration-resistant prostate cancer (mCRPC) and may confer sensitivity to poly(ADP-ribose) polymerase inhibitors. We present results from patients with mCRPC associated with a alteration treated with rucaparib 600 mg twice daily in the phase II TRITON2 study.

Methods: We enrolled patients who progressed after one to two lines of next-generation androgen receptor-directed therapy and one taxane-based chemotherapy for mCRPC. Efficacy and safety populations included patients with a deleterious alteration who received ≥ 1 dose of rucaparib. Key efficacy end points were objective response rate (ORR; per RECIST/Prostate Cancer Clinical Trials Working Group 3 in patients with measurable disease as assessed by blinded, independent radiology review and by investigators) and locally assessed prostate-specific antigen (PSA) response (≥ 50% decrease from baseline) rate.

Results: Efficacy and safety populations included 115 patients with a alteration with or without measurable disease. Confirmed ORRs per independent radiology review and investigator assessment were 43.5% (95% CI, 31.0% to 56.7%; 27 of 62 patients) and 50.8% (95% CI, 38.1% to 63.4%; 33 of 65 patients), respectively. The confirmed PSA response rate was 54.8% (95% CI, 45.2% to 64.1%; 63 of 115 patients). ORRs were similar for patients with a germline or somatic alteration and for patients with a or alteration, while a higher PSA response rate was observed in patients with a alteration. The most frequent grade ≥ 3 treatment-emergent adverse event was anemia (25.2%; 29 of 115 patients).

Conclusion: Rucaparib has antitumor activity in patients with mCRPC and a deleterious alteration, but with a manageable safety profile consistent with that reported in other solid tumor types.
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http://dx.doi.org/10.1200/JCO.20.01035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7655021PMC
November 2020

Examining initial treatment and survival among men with metastatic prostate cancer: An analysis from the CaPSURE registry.

Urol Oncol 2020 10 8;38(10):793.e1-793.e11. Epub 2020 Aug 8.

Department of Medicine, Division of Hematology/Oncology and Transplantation, University of Minnesota, Minneapolis, MN.

Background: New data is emerging to guide initial treatment of patients with metastatic prostate cancer (CaP). This study utilizes the Cancer of the Prostate Strategic Urologic Research Endeavor registry to evaluate variations in survival based on initial treatment received by men with metastatic disease at diagnosis or after progression.

Materials And Methods: Cancer of the Prostate Strategic Urologic Research Endeavor is a national registry of men diagnosed with CaP and managed at 43 community, academic, and Veteran's centers. We examined socio-demographic factors, disease biology, initial and subsequent therapy received, and survival among patients who presented with de novo or recurrent metastatic disease stratified by receipt of initial local therapy vs. combined local and hormonal therapy. The outcome was prostate cancer specific mortality (PCSM). We performed Fine and Gray competing risks regression analysis to evaluate the association between timing of metastasis and PCSM, adjusted for age, initial treatment, and subsequent therapy.

Results: Of the 14,753 patients diagnosed with CaP from 1990 to 2016, 669 (5%) had metastatic disease. Among the examined patients, 303 (45%) had metastatic disease at diagnosis and 366 (55%) progressed to metastatic disease. Overall, 461 (69%) were ≥65 years old, 582 (87%) had Medicare, and 227 (34%) had an annual income < $30,000. Prostate-specific antigen at diagnosis was >20 ng/ml for 342 (51%) patients and biopsy Gleason grade was ≥4 + 3 for 386 (58%) patients. Among patients with metastatic disease at diagnosis, 31 (10%) received initial local therapy and 272 (90%) received initial hormonal therapy. Among patients who progressed to metastatic disease, 239 (65%) received initial local therapy and 127 (35%) received initial systemic hormonal therapy. Among patients with metastatic disease, the multivariate competing risks model, after adjusting for sociodemographics, marital status, diagnosis year, and comorbidities, revealed a significantly lower risk of PCSM among patients with de novo vs. recurrent metastatic disease (Hazard Ratio 0.66 (95% Confidence Interval 0.51, 0.85) P = 0.002). In the stratified analysis, no difference was seen for patients treated with initial hormonal vs. combined local and hormonal therapy.

Conclusions: In this analysis of a nationwide cohort of men treated for CaP with all types of therapy over 25 years, we observed that among men with metastatic CaP, the risk of PCSM was lower for de novo vs. recurrent metastatic disease. Additionally, no difference was observed based on initial treatment with combined local and hormonal therapy vs. hormonal therapy alone.
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http://dx.doi.org/10.1016/j.urolonc.2020.07.012DOI Listing
October 2020

Optimizing the management of castration-resistant prostate cancer patients: A practical guide for clinicians.

Prostate 2020 10 11;80(14):1159-1176. Epub 2020 Aug 11.

Integra Connect, West Palm Beach, Florida.

Background: Advanced prostate cancer (PC) patients, especially those with metastatic prostate cancer (mPC), often require complex management pathways. Despite the publication of clinical practice guidelines by leading urological and oncological organizations that provide a substantial and comprehensive framework, there are numerous clinical scenarios that are not always addressed, especially as new treatments become available, new imaging modalities are developed, and advances in genetic testing continue.

Methods: A 14-member expert review panel comprised of urologists and medical oncologists were chosen to provide guidance on addressing specific topics and issues regarding metastatic castration-resistant prostate cancer (mCRPC) patients. Panel members were chosen based upon their experience and expertise in the management of PC patients. Four academic members (two urologists and two medical oncologists) of the panel served as group leaders; the remaining eight panel members were from Large Urology Group Practice Association (LUGPA) practices with proven experience in leading their advanced PC clinics. The panel members were assigned to four separate working groups, each assigned a specific mCRPC topic to review and discuss with the entire panel.

Results: This article describes the practical recommendations of an expert panel on the management of mCRPC patients. The target reading audience for this publication is all providers (urologists, medical oncologists, radiation oncologists, or advanced practice providers) who evaluate and manage advanced PC patients, regardless of their practice setting.

Conclusion: The panel has provided recommendations for managing mCRPC with regard to specific issues: (a) biomarker monitoring and the role of genetic and molecular testing; (b) rationale, current strategies, and optimal sequencing of the various approved therapies, including hormonal therapy, cytotoxic chemotherapy, radiopharmaceuticals and immunotherapy; (c) adverse event management and monitoring; and (d) imaging advanced PC patients. These recommendations seek to complement national guidelines, not replace them, and a discussion of where the panel agreed or disagreed with national guidelines is included.
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http://dx.doi.org/10.1002/pros.24053DOI Listing
October 2020

The Movember Prostate Cancer Landscape Analysis: an assessment of unmet research needs.

Nat Rev Urol 2020 Sep 22;17(9):499-512. Epub 2020 Jul 22.

Movember, Melbourne, Victoria, Australia.

Prostate cancer is a heterogeneous cancer with widely varying levels of morbidity and mortality. Approaches to prostate cancer screening, diagnosis, surveillance, treatment and management differ around the world. To identify the highest priority research needs across the prostate cancer biomedical research domain, Movember conducted a landscape analysis with the aim of maximizing the effect of future research investment through global collaborative efforts and partnerships. A global Landscape Analysis Committee (LAC) was established to act as an independent group of experts across urology, medical oncology, radiation oncology, radiology, pathology, translational research, health economics and patient advocacy. Men with prostate cancer and thought leaders from a variety of disciplines provided a range of key insights through a range of interviews. Insights were prioritized against predetermined criteria to understand the areas of greatest unmet need. From these efforts, 17 research needs in prostate cancer were agreed on and prioritized, and 3 received the maximum prioritization score by the LAC: first, to establish more sensitive and specific tests to improve disease screening and diagnosis; second, to develop indicators to better stratify low-risk prostate cancer for determining which men should go on active surveillance; and third, to integrate companion diagnostics into randomized clinical trials to enable prediction of treatment response. On the basis of the findings from the landscape analysis, Movember will now have an increased focus on addressing the specific research needs that have been identified, with particular investment in research efforts that reduce disease progression and lead to improved therapies for advanced prostate cancer.
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http://dx.doi.org/10.1038/s41585-020-0349-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7462750PMC
September 2020

Transcriptional profiling identifies an androgen receptor activity-low, stemness program associated with enzalutamide resistance.

Proc Natl Acad Sci U S A 2020 06 18;117(22):12315-12323. Epub 2020 May 18.

Department of Microbiology, Immunology, and Molecular Genetics at the David Geffen School of Medicine, University of California, Los Angeles, CA 90095

The androgen receptor (AR) antagonist enzalutamide is one of the principal treatments for men with castration-resistant prostate cancer (CRPC). However, not all patients respond, and resistance mechanisms are largely unknown. We hypothesized that genomic and transcriptional features from metastatic CRPC biopsies prior to treatment would be predictive of de novo treatment resistance. To this end, we conducted a phase II trial of enzalutamide treatment (160 mg/d) in 36 men with metastatic CRPC. Thirty-four patients were evaluable for the primary end point of a prostate-specific antigen (PSA)50 response (PSA decline ≥50% at 12 wk vs. baseline). Nine patients were classified as nonresponders (PSA decline <50%), and 25 patients were classified as responders (PSA decline ≥50%). Failure to achieve a PSA50 was associated with shorter progression-free survival, time on treatment, and overall survival, demonstrating PSA50's utility. Targeted DNA-sequencing was performed on 26 of 36 biopsies, and RNA-sequencing was performed on 25 of 36 biopsies that contained sufficient material. Using computational methods, we measured AR transcriptional function and performed gene set enrichment analysis (GSEA) to identify pathways whose activity state correlated with de novo resistance. gene alterations were more common in nonresponders, although this did not reach statistical significance ( = 0.055). gene alterations and AR expression were similar between groups. Importantly, however, transcriptional measurements demonstrated that specific gene sets-including those linked to low AR transcriptional activity and a stemness program-were activated in nonresponders. Our results suggest that patients whose tumors harbor this program should be considered for clinical trials testing rational agents to overcome de novo enzalutamide resistance.
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http://dx.doi.org/10.1073/pnas.1922207117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7275746PMC
June 2020

Androgen hazards with COVID-19.

Endocr Relat Cancer 2020 04 24;27(6):E1-E3. Epub 2020 Apr 24.

Division of Hematology, Oncology and Transplantation, University of Minnesota Medical School, Minneapolis, Minnesota, USA.

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http://dx.doi.org/10.1530/ERC-20-0133DOI Listing
April 2020

Androgens and Overall Survival in Patients With Metastatic Castration-resistant Prostate Cancer Treated With Docetaxel.

Clin Genitourin Cancer 2020 06 17;18(3):222-229.e2. Epub 2019 Oct 17.

Duke University Medical Center, Durham, NC.

Background: Pre-treatment androgen levels are associated with overall survival (OS) in patients with metastatic castration-resistant prostate cancer (CRPC) treated with androgen synthesis inhibitors. The current study sought to determine whether pre-treatment serum androgens predict clinical outcome among patients with metastatic CRPC treated with docetaxel chemotherapy.

Materials And Methods: Data were obtained from 1050 men who were chemotherapy-naive prior to treatment with docetaxel, prednisone, and either bevacizumab or placebo (CALGB 90401). Pretreatment serum assays for testosterone, androstenedione, and dehydroepiandrosterone (DHEA) were performed with tandem liquid chromatography-mass spectrometry.

Results: Median values for testosterone, androstenedione, and DHEA were 1.00, 13.50, and 8.12 ng/dL, respectively. The median was used to define the midpoint between low and high values. In univariate analysis, median OS for low versus high levels was 21.4 and 24.2 months for testosterone, 23.8 and 21.9 months for androstenedione, and 20.2 and 25.2 months for DHEA (P = NS). In multivariable analysis of all androgens, baseline DHEA was prognostic of ≥ 50% PSA decline from baseline (P = .008). In multivariable analysis adjusting for 10 known prognostic values and prior ketoconazole use for metastatic CRPC, a 10-unit increase in baseline testosterone increased risk of death (hazard ratio, 1.11; 95% confidence interval, 1.01-1.23; P = .039), whereas a 10-unit increase in androstenedione lowered risk of death (hazard ratio, 0.92; 95% confidence interval, 0.88-0.97; P = .001).

Conclusion: Consistent with prior studies, higher androstenedione levels in patients with metastatic CRPC treated with docetaxel are associated with improved survival. However pretreatment levels of other androgen levels are associated with varied effects on clinical outcome in chemotherapy-treated patients.
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http://dx.doi.org/10.1016/j.clgc.2019.10.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7252587PMC
June 2020

Addressing Cardiovascular Risk of Prostate Cancer Hormonal Therapy.

JACC CardioOncol 2020 Mar 17;2(1):82-83. Epub 2020 Mar 17.

Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.

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http://dx.doi.org/10.1016/j.jaccao.2020.02.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8351975PMC
March 2020

Non-BRCA DNA Damage Repair Gene Alterations and Response to the PARP Inhibitor Rucaparib in Metastatic Castration-Resistant Prostate Cancer: Analysis From the Phase II TRITON2 Study.

Clin Cancer Res 2020 06 21;26(11):2487-2496. Epub 2020 Feb 21.

Medical Oncology, Guy's Hospital and Sarah Cannon Research Institute, London, United Kingdom.

Purpose: Genomic alterations in DNA damage repair (DDR) genes other than may confer synthetic lethality with PARP inhibition in metastatic castration-resistant prostate cancer (mCRPC). To test this hypothesis, the phase II TRITON2 study of rucaparib included patients with mCRPC and deleterious non- DDR gene alterations.

Patients And Methods: TRITON2 enrolled patients who had progressed on one or two lines of next-generation androgen receptor-directed therapy and one taxane-based chemotherapy for mCRPC. Key endpoints were investigator-assessed radiographic response per modified RECIST/PCWG3 and PSA response (≥50% decrease from baseline).

Results: TRITON2 enrolled 78 patients with a non- DDR gene alteration [ ( = 49), ( = 15), ( = 12), and other DDR genes ( = 14)]. Among patients evaluable for each endpoint, radiographic and PSA responses were observed in a limited number of patients with an alteration in [2/19 (10.5%) and 2/49 (4.1%), respectively], [0/10 (0%) and 1/15 (6.7%), respectively], or [1/9 (11.1%) and 2/12 (16.7%), respectively], including no radiographic or PSA responses in 11 patients with confirmed biallelic loss or 11 patients with germline mutations. Responses were observed in patients with alterations in the DDR genes , and .

Conclusions: In this prospective, genomics-driven study of rucaparib in mCRPC, we found limited radiographic/PSA responses to PARP inhibition in men with alterations in , or . However, patients with alterations in other DDR-associated genes (e.g., ) may benefit from PARP inhibition..
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http://dx.doi.org/10.1158/1078-0432.CCR-20-0394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8435354PMC
June 2020

Management of Patients with Advanced Prostate Cancer: Report of the Advanced Prostate Cancer Consensus Conference 2019.

Eur Urol 2020 04 27;77(4):508-547. Epub 2020 Jan 27.

Division of Medical Oncology, National Cancer Centre, Singapore.

Background: Innovations in treatments, imaging, and molecular characterisation in advanced prostate cancer have improved outcomes, but there are still many aspects of management that lack high-level evidence to inform clinical practice. The Advanced Prostate Cancer Consensus Conference (APCCC) 2019 addressed some of these topics to supplement guidelines that are based on level 1 evidence.

Objective: To present the results from the APCCC 2019.

Design, Setting, And Participants: Similar to prior conferences, experts identified 10 important areas of controversy regarding the management of advanced prostate cancer: locally advanced disease, biochemical recurrence after local therapy, treating the primary tumour in the metastatic setting, metastatic hormone-sensitive/naïve prostate cancer, nonmetastatic castration-resistant prostate cancer, metastatic castration-resistant prostate cancer, bone health and bone metastases, molecular characterisation of tissue and blood, inter- and intrapatient heterogeneity, and adverse effects of hormonal therapy and their management. A panel of 72 international prostate cancer experts developed the programme and the consensus questions.

Outcome Measurements And Statistical Analysis: The panel voted publicly but anonymously on 123 predefined questions, which were developed by both voting and nonvoting panel members prior to the conference following a modified Delphi process.

Results And Limitations: Panellists voted based on their opinions rather than a standard literature review or formal meta-analysis. The answer options for the consensus questions had varying degrees of support by the panel, as reflected in this article and the detailed voting results reported in the Supplementary material.

Conclusions: These voting results from a panel of prostate cancer experts can help clinicians and patients navigate controversial areas of advanced prostate management for which high-level evidence is sparse. However, diagnostic and treatment decisions should always be individualised based on patient-specific factors, such as disease extent and location, prior lines of therapy, comorbidities, and treatment preferences, together with current and emerging clinical evidence and logistic and economic constraints. Clinical trial enrolment for men with advanced prostate cancer should be strongly encouraged. Importantly, APCCC 2019 once again identified important questions that merit assessment in specifically designed trials.

Patient Summary: The Advanced Prostate Cancer Consensus Conference provides a forum to discuss and debate current diagnostic and treatment options for patients with advanced prostate cancer. The conference, which has been held three times since 2015, aims to share the knowledge of world experts in prostate cancer management with health care providers worldwide. At the end of the conference, an expert panel discusses and votes on predefined consensus questions that target the most clinically relevant areas of advanced prostate cancer treatment. The results of the voting provide a practical guide to help clinicians discuss therapeutic options with patients as part of shared and multidisciplinary decision making.
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http://dx.doi.org/10.1016/j.eururo.2020.01.012DOI Listing
April 2020

How current reporting practices may mask differences: A call for examining cancer-specific demographic enrollment patterns in cancer treatment clinical trials.

Contemp Clin Trials Commun 2019 Dec 28;16:100476. Epub 2019 Oct 28.

University of California at San Francisco, Division of General Internal Medicine, United States.

Background: A lack of diversity among clinical trial (CT) participants remains a critical problem. Few studies have examined recruitment variability in cancer treatment CTs by cancer type. Given the increasing organ-specific specialization of oncologic care, an understanding of this variability may affect institutional recruitment practices.

Methods: This study examines three data sources from 2010 through 2014. The analyzed sample includes 3,580 CT participants identified in the institutional Clinical Trials Management System (CTMS) database and 20,305 incident cases of invasive cancer within a Comprehensive Cancer Center (CCC) institutional catchment area. A total of 341,114 incident cases of primary invasive cancer were identified through the California Cancer Registry (CCR). The primary study measurements were sociodemographic characteristics of the three populations (age, sex, race/ethnicity, and health insurance).

Results: Racial/ethnic disparities were observed, with more incident cases of Whites seen in cancer center (68%) and enrolled in CTs (72%) compared to incident cases in catchment area (67%) (p < 0.001) overall. More older adults (65) were enrolled in prostate cancer CTs (58%) than seen in cancer center (45%) (p < 0.001). Alternatively, fewer older adults were enrolled in breast and colorectal CTs than seen in cancer center (p < 0.001). Among colon (p < 0.001), breast (p < 0.001), and prostate (p<0.001) cancer types, insurance type significantly varied between incident cases in catchment area, cancer center, and among CT participants. For colorectal cancer, no difference in sex distribution was observed overall. A significant difference in insurance type within each cancer type was observed (p < 0.001).

Conclusions: These findings suggest that reporting overall recruitment frequencies may mask differences by cancer type.
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http://dx.doi.org/10.1016/j.conctc.2019.100476DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6915794PMC
December 2019

Improving research for prostate cancer survivorship: A statement from the Survivorship Research in Prostate Cancer (SuRECaP) working group.

Urol Oncol 2020 03 14;38(3):83-93. Epub 2019 Nov 14.

Division of Hematology, Medical Oncology, and Transplantation, University of Minnesota, Minneapolis, MN. Electronic address:

Survivorship care for patients with prostate cancer requires careful consideration of unique disease-specific factors, including the prolonged natural disease history, the potential for competing health risks, and the consequences of long-term androgen deprivation therapy. However, current prostate cancer survivorship research is unfortunately limited by the lack of a robust supportive evidence base, variability in the definitions and measurement of survivorship outcomes, and a heavy reliance on expert opinion. As a result, the conduct of quality prostate cancer survivorship research is of increasing importance for patients, medical providers, and other key stakeholders. This manuscript harmonizes a path forward for improving prostate cancer survivorship by defining prostate cancer survivorship and survivorship research, as well as by highlighting key research priorities and cooperative mechanisms for survivorship studies within prostate cancer, with a particular focus on men with advanced disease.
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http://dx.doi.org/10.1016/j.urolonc.2019.10.006DOI Listing
March 2020

Diet and lifestyle considerations for patients with prostate cancer.

Urol Oncol 2020 03 18;38(3):105-117. Epub 2019 Jul 18.

Department of Urology, University of California San Francisco, San Francisco, CA. Electronic address:

Purpose: To review the literature and provide recommendations on diet and lifestyle considerations in patients with prostate cancer using evidence from randomized controlled trials (RCTs) with additional considerations based on observational evidence.

Materials And Methods: We initiated our search on ClinicalTrials.gov combining the term "prostate cancer" with a variety of diet and lifestyle factors. We then supplemented our summary of publications from registered trials by including other publications available on Pubmed.

Results: There is a well-established benefit of exercise for improving functional outcomes and pelvic floor muscle training for improving treatment-related adverse effects. Multimodality interventions that integrate several factors (e.g., low-saturated fat, plant-based, whole-food diets with exercise, and stress reduction) appear to have the most clinically significant benefit for patients with prostate cancer. Ongoing multimodality interventions are including the efficacy of implementation strategies as observed outcomes. Limited RCT evidence suggests a clinically significant benefit for guided imagery/progressive muscle relaxation, Pilates, and lycopene-rich diets and a modest benefit for green tea, qigong, massage, and avoidance of nonprescribed vitamin and mineral supplements. Observational and single arm trial evidence indicates a need for further exploration of acupuncture, coffee, cruciferous vegetables, fish, Larrea tridentata, mushrooms, and vegetable-derived fats and avoidance of eggs, dairy, poultry with skin, processed red meat, and saturated fat. Published trials suggest no benefit from hypnosis, milk thistle, pomegranate, soy, or omega-3 fatty acid supplementation.

Conclusions: Our search demonstrated that most diet and lifestyle factors identified from observational studies have limited data from RCTs. Few items have shown early evidence of benefit. The best recommendation for patients with prostate cancer is to form a habit of wellness through healthy eating, aerobic and resistance exercise, and psychological well-being. Future trial development should consider how interventions can be implemented into real world practice.
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http://dx.doi.org/10.1016/j.urolonc.2019.06.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7293879PMC
March 2020

Germline Genetic Testing in Advanced Prostate Cancer; Practices and Barriers: Survey Results from the Germline Genetics Working Group of the Prostate Cancer Clinical Trials Consortium.

Clin Genitourin Cancer 2019 08 18;17(4):275-282.e1. Epub 2019 Apr 18.

Department of Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA. Electronic address:

Background: Germline genetic testing increasingly identifies advanced prostate cancer (PCa) patients who are candidates for precision therapies. The Prostate Cancer Clinical Trials Consortium (PCCTC) established the Germline Genetics Working Group to provide guidance and resources to expand effective use of germline genetic testing.

Materials And Methods: A 14-item questionnaire was e-mailed to academic oncologists at 43 PCCTC sites to collect information on germline genetic testing patterns, including patients considered, choice of assays, barriers slowing adoption, and actions to overcome barriers.

Results: Twenty-six genitourinary oncologists from 19 institutions responded. Less than 40% (10 of 26) reported referring patients to a genetics department, whereas the remainder take personal responsibility for genetic testing and counseling; 16 (62%) consider testing all metastatic PCa patients, whereas 3 (12%) consider testing all patients with high-risk local disease; and 7 (27%) use multigene comprehensive pan-cancer panels, and 14 (54%) use smaller or targeted cancer gene panels. Barriers to widespread use are: (1) delayed or limited access to genetic counseling; (2) no insurance coverage; (3) lack of effective workflows; (4) insufficient educational materials; and (5) time and space constraints in busy clinics. The primary limitation was the <50% (19 of 43) response from PCCTC sites and no coverage of nonacademic cancer treatment facilities.

Conclusion: Joint efforts by urologists, oncologists, genetics counselors, insurers, and cancer centers can accelerate implementation of integrated germline genetic services for personalized treatment and clinical trial eligibility for PCa patients.
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http://dx.doi.org/10.1016/j.clgc.2019.04.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6662206PMC
August 2019
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