Publications by authors named "June M Chan"

127 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 Oct 12. 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
October 2021

Factors Associated with Time to Conversion from Active Surveillance to Treatment for Prostate Cancer in a Multi-Institutional Cohort.

J Urol 2021 11 10;206(5):1147-1156. Epub 2021 Sep 10.

Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, Illinois.

Purpose: We examined the demographic and clinicopathological parameters associated with the time to convert from active surveillance to treatment among men with prostate cancer.

Materials And Methods: A multi-institutional cohort of 7,279 patients managed with active surveillance had data and biospecimens collected for germline genetic analyses.

Results: Of 6,775 men included in the analysis, 2,260 (33.4%) converted to treatment at a median followup of 6.7 years. Earlier conversion was associated with higher Gleason grade groups (GG2 vs GG1 adjusted hazard ratio [aHR] 1.57, 95% CI 1.36-1.82; ≥GG3 vs GG1 aHR 1.77, 95% CI 1.29-2.43), serum prostate specific antigen concentrations (aHR per 5 ng/ml increment 1.18, 95% CI 1.11-1.25), tumor stages (cT2 vs cT1 aHR 1.58, 95% CI 1.41-1.77; ≥cT3 vs cT1 aHR 4.36, 95% CI 3.19-5.96) and number of cancerous biopsy cores (3 vs 1-2 cores aHR 1.59, 95% CI 1.37-1.84; ≥4 vs 1-2 cores aHR 3.29, 95% CI 2.94-3.69), and younger age (age continuous per 5-year increase aHR 0.96, 95% CI 0.93-0.99). Patients with high-volume GG1 tumors had a shorter interval to conversion than those with low-volume GG1 tumors and behaved like the higher-risk patients. We found no significant association between the time to conversion and self-reported race or genetic ancestry.

Conclusions: A shorter time to conversion from active surveillance to treatment was associated with higher-risk clinicopathological tumor features. Furthermore, patients with high-volume GG1 tumors behaved similarly to those with intermediate and high-risk tumors. An exploratory analysis of self-reported race and genetic ancestry revealed no association with the time to conversion.
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http://dx.doi.org/10.1097/JU.0000000000001937DOI Listing
November 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

Cell-Free DNA Detection of Tumor Mutations in Heterogeneous, Localized Prostate Cancer Via Targeted, Multiregion Sequencing.

JCO Precis Oncol 2021 27;5. Epub 2021 Apr 27.

Department of Epidemiology and Biostatistics, University of California, San Francisco, CA.

Cell-free DNA (cfDNA) may allow for minimally invasive identification of biologically relevant genomic alterations and genetically distinct tumor subclones. Although existing biomarkers may detect localized prostate cancer, additional strategies interrogating genomic heterogeneity are necessary for identifying and monitoring aggressive disease. In this study, we aimed to evaluate whether circulating tumor DNA can detect genomic alterations present in multiple regions of localized prostate tumor tissue.

Methods: Low-pass whole-genome and targeted sequencing with a machine-learning guided 2.5-Mb targeted panel were used to identify single nucleotide variants, small insertions and deletions (indels), and copy-number alterations in cfDNA. The majority of this study focuses on the subset of 21 patients with localized disease, although 45 total individuals were evaluated, including 15 healthy controls and nine men with metastatic castration-resistant prostate cancer. Plasma cfDNA was barcoded with duplex unique molecular identifiers. For localized cases, matched tumor tissue was collected from multiple regions (one to nine samples per patient) for comparison.

Results: Somatic tumor variants present in heterogeneous tumor foci from patients with localized disease were detected in cfDNA, and cfDNA mutational burden was found to track with disease severity. Somatic tissue alterations were identified in cfDNA, including nonsynonymous variants in , and . Detection of these overlapping variants was associated with seminal vesicle invasion ( = .019) and with the number of variants initially found in the matched tumor tissue samples ( = .0005).

Conclusion: Our findings demonstrate the potential of targeted cfDNA sequencing to detect somatic tissue alterations in heterogeneous, localized prostate cancer, especially in a setting where matched tumor tissue may be unavailable (ie, active surveillance or treatment monitoring).
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http://dx.doi.org/10.1200/PO.20.00428DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8232833PMC
April 2021

Post-diagnostic coffee and tea consumption and risk of prostate cancer progression by smoking history.

Cancer Causes Control 2021 Jun 9;32(6):635-644. Epub 2021 Apr 9.

Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA.

Purpose: Post-diagnostic coffee and tea consumption and prostate cancer progression is understudied.

Methods: We examined 1,557 men from the Cancer of the Prostate Strategic Urologic Research Endeavor who completed a food frequency questionnaire a median of 28 months post-diagnosis. We estimated associations between post-diagnostic coffee (total, caffeinated, decaffeinated) and tea (total, non-herbal, herbal) and risk of prostate cancer progression (recurrence, secondary treatment, bone metastases, or prostate cancer death) using Cox proportional hazards regression. We also examined whether smoking (current, former, never) modified these associations.

Results: We observed 167 progression events (median follow-up 9 years). Higher coffee intake was associated with higher risk of progression among current smokers (n = 95). The hazard ratio (HR) [95% confidence interval (CI)] for 5 vs 0 cups/day of coffee was 0.5 (CI 0.2, 1.7) among never smokers, but 4.5 (CI 1.1, 19.4) among current smokers (p-interaction: 0.001). There was no association between total coffee intake and prostate cancer progression among never and former smokers. However, we observed an inverse association between decaffeinated coffee (cups/days) and risk of prostate cancer progression in these men (HR  : 1.1 (CI 0.7, 1.8); HR: 0.7 (CI 0.3, 1.4); HR: 0.6 (CI 0.3, 1.1); p-trend = 0.03). There was no association between tea and prostate cancer progression, overall or by smoking status.

Conclusion: Among non-smoking men diagnosed with localized prostate cancer, moderate coffee and tea consumption was not associated with risk of cancer progression. However, post-diagnostic coffee intake was associated with increased risk of progression among current smokers.
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http://dx.doi.org/10.1007/s10552-021-01417-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8189293PMC
June 2021

Post-Diagnostic Dietary and Lifestyle Factors and Prostate Cancer Recurrence, Progression, and Mortality.

Curr Oncol Rep 2021 03 10;23(3):37. Epub 2021 Mar 10.

Department of Epidemiology & Biostatistics, University of California, San Francisco, 550 16th Street, San Francisco, CA, USA.

Purpose Of Review: This study aimed to summarize evidence published between 1999 and June 2020 examining diet and lifestyle after prostate cancer (PC) diagnosis in relation to risk of biochemical recurrence, PC progression, and PC-specific mortality.

Recent Findings: Secondary prevention is an important research area in cancer survivorship. A growing number of studies have reported associations between post-diagnostic modifiable behaviors and risk of PC outcomes. Evidence on modifiable lifestyle factors and PC remains limited. Where multiple studies exist, findings are often mixed. However, studies consistently suggest that smoking and consumption of whole milk/high-fat dairy are associated with higher risk of PC recurrence and mortality. In addition, physical activity and ½ to 1 glass of red wine/day have been associated with lower risk of recurrence and PC-specific mortality. Greater inclusion of racially/ethnically diverse groups in future research is necessary to understand these relationships in populations most impacted by adverse PC outcomes.
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http://dx.doi.org/10.1007/s11912-021-01017-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946660PMC
March 2021

Cell-free DNA concentration and fragment size as a biomarker for prostate cancer.

Sci Rep 2021 Mar 3;11(1):5040. Epub 2021 Mar 3.

Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA.

Prostate cancer is the most commonly diagnosed neoplasm in American men. Although existing biomarkers may detect localized prostate cancer, additional strategies are necessary for improving detection and identifying aggressive disease that may require further intervention. One promising, minimally invasive biomarker is cell-free DNA (cfDNA), which consist of short DNA fragments released into circulation by dying or lysed cells that may reflect underlying cancer. Here we investigated whether differences in cfDNA concentration and cfDNA fragment size could improve the sensitivity for detecting more advanced and aggressive prostate cancer. This study included 268 individuals: 34 healthy controls, 112 men with localized prostate cancer who underwent radical prostatectomy (RP), and 122 men with metastatic castration-resistant prostate cancer (mCRPC). Plasma cfDNA concentration and fragment size were quantified with the Qubit 3.0 and the 2100 Bioanalyzer. The potential relationship between cfDNA concentration or fragment size and localized or mCRPC prostate cancer was evaluated with descriptive statistics, logistic regression, and area under the curve analysis with cross-validation. Plasma cfDNA concentrations were elevated in mCRPC patients in comparison to localized disease (OR = 1.34, P = 0.027) or to being a control (OR = 1.69, P = 0.034). Decreased average fragment size was associated with an increased risk of localized disease compared to controls (OR = 0.77, P = 0.0008). This study suggests that while cfDNA concentration can identify mCRPC patients, it is unable to distinguish between healthy individuals and patients with localized prostate cancer. In addition to PSA, average cfDNA fragment size may be an alternative that can differentiate between healthy individuals and those with localized disease, but the low sensitivity and specificity results in an imperfect diagnostic marker. While quantification of cfDNA may provide a quick, cost-effective approach to help guide treatment decisions in advanced disease, its use is limited in the setting of localized prostate cancer.
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http://dx.doi.org/10.1038/s41598-021-84507-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930042PMC
March 2021

Feasibility and Acceptability of a Remotely Delivered, Web-Based Behavioral Intervention for Men With Prostate Cancer: Four-Arm Randomized Controlled Pilot Trial.

J Med Internet Res 2020 12 31;22(12):e19238. Epub 2020 Dec 31.

Oregon Health and Science University, Portland, OR, United States.

Background: Diet and exercise may be associated with quality of life and survival in men with prostate cancer.

Objective: This study aimed to determine the feasibility and acceptability of a remotely delivered web-based behavioral intervention among men with prostate cancer.

Methods: We conducted a multi-site 4-arm pilot randomized controlled trial of a 3-month intervention (TrueNTH Community of Wellness). Eligibility included self-reported prostate cancer diagnosis, having a personal device that connected to the internet, age ≥18 years, and ability to read English and receive text messages and emails. Men receiving chemotherapy or radiation, or those who reported contraindications to exercise, could participate with physician clearance. Participants were randomized (1:1:1:1) to additive intervention levels: website; website and personalized diet and exercise prescription; website, personalized prescription, Fitbit, and text messages; and website, personalized prescription, Fitbit, text messages, and 2 30-minute phone calls-one with an exercise trainer and one with a registered dietician. Primary outcomes were feasibility (accrual and attrition) and acceptability (survey data and website use). We described self-reported diet and exercise behavior at the time of enrollment, 3 months, and 6 months as secondary outcomes.

Results: In total, 202 men consented and were randomized between August 2017 and September 2018 (level 1: 49, level 2: 51, level 3: 50, level 4: 52). A total of 160 men completed the onboarding process and were exposed to their randomly assigned intervention (38, 38, 42, and 42 in levels 1, 2, 3, and 4, respectively). The follow-up rate was 82.7% (167/202) at 3 months and 77.2% (156/202) at 6 months. Participants had a median age of 70 years and were primarily White and college educated. Website visit frequency over the 3-month intervention period increased across levels (median: 2, 9, 11, and 16 visits for levels 1, 2, 3, and 4, respectively). Most were satisfied or very satisfied with the intervention (20/39, 51%; 27/42, 64%; 23/44, 52%; and 27/42, 64% for levels 1, 2, 3, and 4, respectively). The percentage of men who reported being very satisfied was highest among level 4 participants (10/42, 24% vs 4/39, 10%; 5/42, 12%; and 5/44, 11% for levels 1, 2, and 3, respectively). Dissatisfaction was highest in level 1 (5/39, 13% vs 1/42, 2%; 3/44, 7%; and 2/42, 5% for levels 2, 3, and 4, respectively). We observed small improvements in diet and physical activity at 3 months among men in level 4 versus those in level 1.

Conclusions: A web-based, remotely delivered, tailored behavioral intervention for men with prostate cancer is feasible. Future studies are warranted to increase the effect of the intervention on patient behavior while maintaining sustainability and scalability as well as to design and implement interventions for more diverse populations.

Trial Registration: ClinicalTrials.gov NCT03406013; http://clinicaltrials.gov/ct2/show/NCT03406013.
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http://dx.doi.org/10.2196/19238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7808895PMC
December 2020

Web-Based Lifestyle Interventions for Prostate Cancer Survivors: Qualitative Study.

JMIR Cancer 2020 Nov 10;6(2):e19362. Epub 2020 Nov 10.

University of California, San Francisco, San Francisco, CA, United States.

Background: Exercise and a healthy diet can improve the quality of life and prognosis of prostate cancer survivors, but there have been limited studies on the feasibility of web-based lifestyle interventions in this population.

Objective: This study aims to develop a data-driven grounded theory of web-based engagement by prostate cancer survivors based on their experience in the Community of Wellness, a 12-week randomized clinical trial designed to support healthy diet and exercise habits.

Methods: TrueNTH's Community of Wellness was a four-arm pilot study of men with prostate cancer (N=202) who received progressive levels of behavioral support (level 1: website; level 2: website with individualized diet and exercise recommendations; level 3: website with individualized diet and exercise recommendations, Fitbit, and text messages; and level 4: website with individualized diet and exercise recommendations, Fitbit and text messages, and separate phone calls with an exercise trainer and a registered dietitian). The primary aim of the study is to determine the feasibility and estimate the effects on behaviors (results reported in a separate paper). Following the 12-week intervention, we invited participants to participate in 4 focus groups, one for each intervention level. In this report, we used grounded theory analyses including open, axial, and selective coding to generate codes and themes from the focus group transcripts. Categories were refined across levels using embodied categorization and constant comparative methods.

Results: In total, 20 men with prostate cancer participated in the focus groups: 5, 4, 5, and 6 men in levels 1, 2, 3, and 4, respectively. Participants converged on 5 common factors influencing engagement with the intervention: environment (home environment, competing priorities, and other lifestyle programs), motivation (accountability and discordance experienced within the health care system), preparedness (technology literacy, health literacy, trust, and readiness to change), program design (communication, materials, and customization), and program support (education, ally, and community). Each of these factors influenced the survivors' long-term impressions and habits. We proposed a grounded theory associating these constructs to describe the components contributing to the intuitiveness of a web-based lifestyle intervention.

Conclusions: These analyses suggest that web-based lifestyle interventions are more intuitive when we optimize participants' technology and health literacy; tailor interface design, content, and feedback; and leverage key motivators (ie, health care providers, family members, web-based coach) and environmental factors (ie, familiarity with other lifestyle programs). Together, these grounded theory-based efforts may improve engagement with web-based interventions designed to support prostate cancer survivorship.
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http://dx.doi.org/10.2196/19362DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7685923PMC
November 2020

Opportunities and challenges for research on low-carbohydrate diets in prostate cancer.

Nat Rev Urol 2020 Aug;17(8):437-438

Department of Epidemiology & Biostatistics, University of California San Francisco, San Francisco, CA, USA.

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http://dx.doi.org/10.1038/s41585-020-0326-8DOI Listing
August 2020

The Problem of Underrepresentation: Black Participants in Lifestyle Trials Among Patients with Prostate Cancer.

J Racial Ethn Health Disparities 2020 10 20;7(5):996-1002. Epub 2020 Feb 20.

Department of Urology, University of California, San Francisco, San Francisco, CA, USA.

Introduction: Healthy lifestyle behaviors are an essential component of prostate cancer survivorship; however, it is unknown whether Black participants are adequately represented in randomized controlled trials (RCTs) on lifestyle interventions. The goal of this study was to identify types of lifestyle RCTs that may require improved recruitment resources to enhance generalizability of lifestyle recommendations to Black patients.

Materials And Methods: ClinicalTrials.gov was used to identify lifestyle RCTs among patients with prostate cancer. Using racial distribution data from the Surveillance, Epidemiology, and End Results (SEER) program as a reference, one-sample proportion tests were performed to assess adequate recruitment of Black participants.

Results: Of 31 lifestyle trials, one trial reported race-specific results. Proportion of Black participants was acquired from 26 trials. Compared to the US population, Black participants were overrepresented in the overall study population (17% versus 15%, p = 0.019). Black participants were underrepresented in trials exploring exercise interventions (9% versus 15%, p = 0.041), trials among patients with advanced disease (9% versus 16%, p < 0.001), and in university-funded trials (12% versus 15%, p = 0.026).

Conclusions: The reporting of race data, and race-specific results when feasible, is essential for clinicians to accurately generalize findings from lifestyle trials. Additional resources may be necessary to aid in strategic recruitment of Black participants for trials on exercise interventions, trials among patients with advanced disease, and in university-funded trials.
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http://dx.doi.org/10.1007/s40615-020-00724-8DOI Listing
October 2020

Feasibility and Acceptability of a Web-Based Dietary Intervention with Text Messages for Colorectal Cancer: A Randomized Pilot Trial.

Cancer Epidemiol Biomarkers Prev 2020 04 15;29(4):752-760. Epub 2020 Jan 15.

UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, California.

Background: Diet is associated with colorectal cancer survival. Yet, adherence to nutrition guidelines is low among colorectal cancer survivors.

Methods: We conducted a pilot trial among colorectal cancer survivors to evaluate a 12-week remote dietary intervention. Participants received print materials and were randomized (1:1) to intervention (website, text messages) or wait-list control. Primary outcomes included feasibility and acceptability. We also explored change in diet from 0 to 12 and 24 weeks and change from 0 to 12 weeks in anthropometry and circulating biomarkers (Trial Registration: NCT02965521).

Results: We randomized 50 colorectal cancer survivors (25 intervention, 25 control). Retention was 90% at 12 weeks and 84% at 24 weeks. Participants had a median age of 55 years and were 66% female, 70% non-Hispanic white, and 96% had a college degree. The intervention arm responded to a median 15 (71%) of 21 text messages that asked for a reply [interquartile range (IQR) = 8, 19] and visited the website a median of 13 (15%) days (IQR = 1, 33) of the 84 study days.

Conclusions: We developed a Web-based dietary intervention for colorectal cancer survivors. Our pilot results suggest that colorectal cancer survivors may engage more with text messages than a study website. Research to improve tailoring of text messages, while maintaining scalability, is needed.

Impact: Remote dietary interventions using text messages may be feasible for colorectal cancer survivors.
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http://dx.doi.org/10.1158/1055-9965.EPI-19-0840DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7125029PMC
April 2020

Development and pilot evaluation of a personalized decision support intervention for low risk prostate cancer patients.

Cancer Med 2020 01 12;9(1):125-132. Epub 2019 Nov 12.

Department of Urology, University of California, San Francisco, CA, USA.

Objectives: Development and pilot evaluation of a personalized decision support intervention to help men with early-stage prostate cancer choose among active surveillance, surgery, and radiation.

Methods: We developed a decision aid featuring long-term survival and side effects data, based on focus group input and stakeholder endorsement. We trained premedical students to administer the intervention to newly diagnosed men with low-risk prostate cancer seen at the University of California, San Francisco. Before the intervention, and after the consultation with a urologist, we administered the Decision Quality Instrument for Prostate Cancer (DQI-PC). We hypothesized increases in two knowledge items from the DQI-PC: How many men diagnosed with early-stage prostate cancer will eventually die of prostate cancer? How much would waiting 3 months to make a treatment decision affect chances of survival? Correct answers were: "Most will die of something else" and "A little or not at all."

Results: The development phase involved 6 patients, 1 family member, 2 physicians, and 5 other health care providers. In our pilot test, 57 men consented, and 44 received the decision support intervention and completed knowledge surveys at both timepoints. Regarding the two knowledge items of interest, before the intervention, 35/56 (63%) answered both correctly, compared to 36/44 (82%) after the medical consultation (P = .04 by chi-square test).

Conclusions: The intervention was associated with increased patient knowledge. Data from this pilot have guided the development of a larger scale randomized clinical trial to improve decision quality in men with prostate cancer being treated in community settings.
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http://dx.doi.org/10.1002/cam4.2685DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6943165PMC
January 2020

Obesity at Diagnosis and Prostate Cancer Prognosis and Recurrence Risk Following Primary Treatment by Radical Prostatectomy.

Cancer Epidemiol Biomarkers Prev 2019 11 28;28(11):1917-1925. Epub 2019 Aug 28.

Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California.

Background: The association of obesity at diagnosis with prostate cancer progression is uncertain. This study aimed to examine the relationship between body mass index (BMI; 18.5-<25, 25-<30, 30-<35, ≥35 kg/m) and prognostic risk at diagnosis, compare the concordance between prognostic risk assessed at diagnostic biopsy versus pathologic risk assessed at surgery across BMI categories, and investigate the association between obesity and prostate cancer recurrence and all-cause death.

Methods: We examined men enrolled in CaPSURE who underwent radical prostatectomy between 1995 and 2017. Multiple imputation methods were used to handle missing data and reported along with complete case findings.

Results: Participants ( = 5,200) were followed for a median of 4.5 years; 685 experienced recurrence. Obesity was associated with higher prognostic risk at time of diagnosis (OR = 1.5; OR = 1.7) and upward reclassification of disease between biopsy and surgery, driven by change in tumor stage (OR = 1.3; OR = 1.6). We observed an association between BMI and recurrence with adjustment for disease severity using diagnostic factors (HR = 1.7); this association disappeared when adjusting for disease severity factors obtained at surgery.

Conclusions: Our findings suggest that residual confounding may partially explain the conflicting evidence regarding obesity's influence on prostate cancer progression. Assessing T-stage via digital rectal exam may be complicated in larger men, potentially affecting clinical treatment decisions. A strong association with all-cause mortality demonstrates healthier BMI at diagnosis may still improve overall survival.

Impact: Patients with greater BMI are prone to more advanced disease at diagnosis and may be more likely to have their tumor stage underestimated at diagnosis.
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http://dx.doi.org/10.1158/1055-9965.EPI-19-0488DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6825577PMC
November 2019

Decipher identifies men with otherwise clinically favorable-intermediate risk disease who may not be good candidates for active surveillance.

Prostate Cancer Prostatic Dis 2020 03 27;23(1):136-143. Epub 2019 Aug 27.

Department of Urology, University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA.

Background: We aimed to validate Decipher to predict adverse pathology (AP) at radical prostatectomy (RP) in men with National Comprehensive Cancer Network (NCCN) favorable-intermediate risk (F-IR) prostate cancer (PCa), and to better select F-IR candidates for active surveillance (AS).

Methods: In all, 647 patients diagnosed with NCCN very low/low risk (VL/LR) or F-IR prostate cancer were identified from a multi-institutional PCa biopsy database; all underwent RP with complete postoperative clinicopathological information and Decipher genomic risk scores. The performance of all risk assessment tools was evaluated using logistic regression model for the endpoint of AP, defined as grade group 3-5, pT3b or higher, or lymph node invasion.

Results: The median age was 61 years (interquartile range 56-66) for 220 patients with NCCN F-IR disease, 53% classified as low-risk by Cancer of the Prostate Risk Assessment (CAPRA 0-2) and 47% as intermediate-risk (CAPRA 3-5). Decipher classified 79%, 13% and 8% of men as low-, intermediate- and high-risk with 13%, 10%, and 41% rate of AP, respectively. Decipher was an independent predictor of AP with an odds ratio of 1.34 per 0.1 unit increased (p value = 0.002) and remained significant when adjusting by CAPRA. Notably, F-IR with Decipher low or intermediate score did not associate with significantly higher odds of AP compared to VL/LR.

Conclusions: NCCN risk groups, including F-IR, are highly heterogeneous and should be replaced with multivariable risk-stratification. In particular, incorporating Decipher may be useful for safely expanding the use of AS in this patient population.
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http://dx.doi.org/10.1038/s41391-019-0167-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076042PMC
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

Trends in Complementary and Alternative Medicine Use among Patients with Prostate Cancer.

J Urol 2019 10 6;202(4):689-695. Epub 2019 Sep 6.

Department of Urology, University of California-San Francisco, San Francisco, California.

Purpose: We explored the prevalence and trends of self-reported complementary and alternative medicine use among patients with prostate cancer using CaPSURE™ (Cancer of the Prostate Strategic Urologic Research Endeavor).

Materials And Methods: A total of 7,989 CaPSURE participants completed questionnaires between 1996 and 2016 on the use of nearly 70 complementary and alternative medicine types. Participants were defined as users if they indicated that they had ever used complementary and alternative medicines. To evaluate trends among 7,696 patients with newly diagnosed prostate cancer we considered complementary and alternative medicine use within 24 months of diagnosis and calculated the percent change in complementary and alternative medicine use between groups defined by the year of diagnosis.

Results: Of patients with prostate cancer 56% reported complementary and alternative medicine use on at least 1 questionnaire. Multivitamin and omega-3 fatty acid use was common at 40% and 24% of patients, respectively. Compared to nonusers greater proportions of complementary and alternative medicine users were college educated, had a higher household income and lived in the West and Midwest. Median prostate specific antigen at diagnosis was 5.8 (IQR 4.4-8.4) and 6.2 ng/ml (IQR 4.7-10.1) among users and nonusers, respectively (p <0.01). Between those diagnosed in 1996 to 2000 and 2011 to 2016, complementary and alternative medicine use increased 128% from 24% to 54%. When comparing participants diagnosed in 2006 to 2010 with those diagnosed in 2011 to 2016, a 108% increase was seen in supplemental vitamin D use and a -48% decrease was seen in supplemental vitamin E use.

Conclusions: Many patients with prostate cancer reported complementary and alternative medicine use. Multivitamins and omega-3 fatty acids were commonly ingested and vitamin D use increased dramatically from 2006 to 2010 compared to 2011 to 2016. These data can guide clinical discussions and decision making such as nutritionist referral and help prioritize future research.
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http://dx.doi.org/10.1097/JU.0000000000000336DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7017721PMC
October 2019

A 17-Gene Genomic Prostate Score as a Predictor of Adverse Pathology in Men on Active Surveillance.

J Urol 2019 10 6;202(4):702-709. Epub 2019 Sep 6.

Department of Urology, University of California-San Francisco Helen Diller Family Comprehensive Cancer Center, University of California-San Francisco, San Francisco, California.

Purpose: The GPS (Oncotype Dx® Genomic Prostate Score) test is a RNA expression assay which can be performed on prostate biopsies. We sought to determine whether the GPS was associated with an increased risk of adverse pathology findings in men enrolled on active surveillance who later underwent radical prostatectomy.

Materials And Methods: We identified all patients on active surveillance at University of California-San Francisco who had Gleason score 3 + 3 or low volume (33% or fewer positive cores) Gleason score 3 + 4 prostate cancer, GPS testing at diagnostic or confirmatory biopsy, clinical stage T1/T2, prostate specific antigen less than 20 and a clinical CAPRA (Cancer of the Prostate Risk Assessment) score less than 6. The primary outcome was adverse pathology, defined as Gleason score 4 + 3 or greater, stage pT3a or greater, or pN1. The secondary outcome was biochemical recurrence, defined as 2 consecutive prostate specific antigen measurements greater than 0.05 ng/ml following radical prostatectomy.

Results: Of the 215 men 179 (83%) were at low risk and 36 (17%) were at intermediate risk by CAPRA scoring. The median GPS was 26.4 (IQR 18.8-34.6). On multivariate analysis a higher GPS was associated with an increased risk of adverse pathology at delayed radical prostatectomy (HR/5 units 1.16, 95% CI 1.06-1.26, p <0.01). A higher GPS was also associated with an increased risk of biochemical recurrence (HR/5 units 1.10, 95% CI 1.00-1.21, p=0.04).

Conclusions: In patients who undergo radical prostatectomy after a period on active surveillance, as in those who undergo immediate prostatectomy, a higher GPS is associated with an increased risk of adverse pathology. The GPS is also associated with biochemical recurrence following radical prostatectomy in such patients.
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http://dx.doi.org/10.1097/JU.0000000000000290DOI Listing
October 2019

Alcohol Intake and Risk of Lethal Prostate Cancer in the Health Professionals Follow-Up Study.

J Clin Oncol 2019 06 26;37(17):1499-1511. Epub 2019 Apr 26.

3 University of California, San Francisco, San Francisco, CA.

Purpose: It is unknown whether alcohol intake is associated with the risk of lethal (metastatic or fatal) prostate cancer. We examine (1) whether alcohol intake among men at risk of prostate cancer is associated with diagnosis of lethal prostate cancer and (2) whether intake among men with nonmetastatic prostate cancer is associated with metastasis or death.

Methods: This prospective cohort study uses the Health Professionals Follow-Up Study (1986 to 2012). Our analysis of alcohol intake among men at risk of prostate cancer included 47,568 cancer-free men. Our analysis of alcohol intake among men with prostate cancer was restricted to 5,182 men diagnosed with nonmetastatic prostate cancer during follow-up. We examine the association of total alcohol, red and white wine, beer, and liquor with lethal prostate cancer and death. Multivariate Cox proportional hazards regression estimated hazard ratios (HRs) and 95% CIs.

Results: Alcohol drinkers had a lower risk of lethal prostate cancer (any none: HR, 0.84 [95% CI, 0.71 to 0.99]) without a dose-response relationship. Total alcohol intake among patients with prostate cancer was not associated with progression to lethal prostate cancer (any none: HR, 0.99 [95% CI, 0.57 to 1.72]), whereas moderate red wine intake was associated with a lower risk (any none: HR, 0.50 [95% CI, 0.29 to 0.86]; trend = .05). Compared with none, 15 to 30 g/d of total alcohol after prostate cancer diagnosis was associated with a lower risk of death (HR, 0.71 [95% CI, 0.50 to 1.00]), as was red wine (any none: HR, 0.74 [95% CI, 0.57 to 0.97]; trend = .007).

Conclusion: Cancer-free men who consumed alcohol had a slightly lower risk of lethal prostate cancer compared with abstainers. Among men with prostate cancer, red wine was associated with a lower risk of progression to lethal disease. These observed associations merit additional study but provide assurance that moderate alcohol consumption is safe for patients with prostate cancer.
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http://dx.doi.org/10.1200/JCO.18.02462DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6599404PMC
June 2019

Aspirin Use and Lethal Prostate Cancer in the Health Professionals Follow-up Study.

Eur Urol Oncol 2019 03 31;2(2):126-134. Epub 2018 Jul 31.

Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.

Background: Aspirin use probably protects against some malignancies but its effects on lethal prostate cancer (PC) are unclear.

Objective: To investigate the association between regular aspirin use and lethal PC.

Design, Setting, And Participants: Participants were aged 40-75 yr at baseline in 1986 and have been followed with biennial questionnaires. The risk analysis includes 49 409 men. The survival analysis includes 5980 PC patients without metastatic disease at diagnosis.

Outcome Measurements And Statistical Analysis: We used Cox proportional hazards regression to examine the association between current, past, or never regular aspirin use (≥2 d/wk) in relation to lethal (metastatic or fatal) PC. We also examined years of use among current users and years since stopping among past users. In the risk analysis, aspirin was updated throughout follow-up. In the survival analysis, aspirin use after diagnosis was assessed.

Results And Limitations: Some 29% of participants used aspirin regularly at baseline, which increased to 60% by 2010. In the risk analysis, 804 men were diagnosed with lethal PC. Current regular aspirin was associated with a lower risk of lethal prostate cancer (hazard ratio [HR] 0.80, 95% confidence interval [CI] 0.66-0.96) compared to never users. In the survival analysis, 451 of the men diagnosed with nonmetastatic PC later developed lethal disease. Current postdiagnostic aspirin was associated with a lower risk of lethal PC (HR 0.80, 95% CI 0.64-1.00) and overall mortality (HR 0.79, 95% CI 0.69-0.90). When restricted to highly screened men, the risk analysis associations were stronger and survival analysis associations remained statistically significant. Reverse causation and residual confounding remain concerns, as demonstrated by the attenuated results in sensitivity analyses.

Conclusions: Regular aspirin use was associated with a lower risk of lethal PC. Postdiagnostic use was associated with better survival after diagnosis.

Patient Summary: We found that it may be advisable for prostate cancer patients to take aspirin to improve their survival for both prostate cancer mortality and other mortality outcomes.
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http://dx.doi.org/10.1016/j.euo.2018.07.002DOI Listing
March 2019

Stability of a 17-Gene Genomic Prostate Score in Serial Testing of Men on Active Surveillance for Early Stage Prostate Cancer.

J Urol 2019 10 6;202(4):696-701. Epub 2019 Sep 6.

Department of Urology, University of California-San Francisco, San Francisco, California.

Purpose: Genomic testing may improve risk stratification in men with prostate cancer managed by active surveillance. We aimed to characterize the stability and usefulness of serial genomic test scores in men undergoing serial biopsies during active surveillance.

Materials And Methods: We compiled clinical and disease characteristics of men on active surveillance using an institutional Urologic Outcomes Database. We included patients initially diagnosed with Gleason 3 + 3 prostate cancer who elected active surveillance and received 2, 17-gene GPS (Genomic Prostate Score) results. We examined the association of GPS results and Gleason grade reclassification (Gleason 3 + 4 or greater) with definitive treatment using multivariable Cox proportional hazards regression models.

Results: We identified 111 men who underwent serial genomic testing. There were 49 grade reclassification events (44%) at a median followup of 64 months. The mean ± SD GPS change between the first and second biopsies was 2.1 ± 10.3. The GPS at first biopsy (per 5 units HR 1.04, 95% CI 1.00-1.07, p=0.03) was associated with an upgrade at second biopsy, although the second GPS was not (HR 1.02, 95% CI 0.99-1.05, p=0.13). The first and second GPSs (HR 1.09, 95% CI 1.04-1.14 and HR 1.09, 95% CI 1.04-1.14, each p <0.01) were associated with active treatment.

Conclusions: The GPS undergoes small changes with time. Absolute GPS results at the first and second biopsies were associated with Gleason upgrading and transition from active surveillance to active treatment.
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http://dx.doi.org/10.1097/JU.0000000000000271DOI Listing
October 2019

The associations of anthropometric, behavioural and sociodemographic factors with circulating concentrations of IGF-I, IGF-II, IGFBP-1, IGFBP-2 and IGFBP-3 in a pooled analysis of 16,024 men from 22 studies.

Int J Cancer 2019 12 4;145(12):3244-3256. Epub 2019 Apr 4.

Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.

Insulin-like growth factors (IGFs) and insulin-like growth factor binding proteins (IGFBPs) have been implicated in the aetiology of several cancers. To better understand whether anthropometric, behavioural and sociodemographic factors may play a role in cancer risk via IGF signalling, we examined the cross-sectional associations of these exposures with circulating concentrations of IGFs (IGF-I and IGF-II) and IGFBPs (IGFBP-1, IGFBP-2 and IGFBP-3). The Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group dataset includes individual participant data from 16,024 male controls (i.e. without prostate cancer) aged 22-89 years from 22 prospective studies. Geometric means of protein concentrations were estimated using analysis of variance, adjusted for relevant covariates. Older age was associated with higher concentrations of IGFBP-1 and IGFBP-2 and lower concentrations of IGF-I, IGF-II and IGFBP-3. Higher body mass index was associated with lower concentrations of IGFBP-1 and IGFBP-2. Taller height was associated with higher concentrations of IGF-I and IGFBP-3 and lower concentrations of IGFBP-1. Smokers had higher concentrations of IGFBP-1 and IGFBP-2 and lower concentrations of IGFBP-3 than nonsmokers. Higher alcohol consumption was associated with higher concentrations of IGF-II and lower concentrations of IGF-I and IGFBP-2. African Americans had lower concentrations of IGF-II, IGFBP-1, IGFBP-2 and IGFBP-3 and Hispanics had lower IGF-I, IGF-II and IGFBP-3 than non-Hispanic whites. These findings indicate that a range of anthropometric, behavioural and sociodemographic factors are associated with circulating concentrations of IGFs and IGFBPs in men, which will lead to a greater understanding of the mechanisms through which these factors influence cancer risk.
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http://dx.doi.org/10.1002/ijc.32276DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6745281PMC
December 2019

Self-monitoring and reminder text messages to increase physical activity in colorectal cancer survivors (Smart Pace): a pilot randomized controlled trial.

BMC Cancer 2019 Mar 11;19(1):218. Epub 2019 Mar 11.

Division of Hematology/Oncology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.

Background: Over 1.3 million people live with colorectal cancer in the United States. Physical activity is associated with lower risk of colorectal cancer recurrence and mortality. Interventions are needed to increase physical activity in colorectal cancer survivors.

Methods: We conducted a 2-arm non-blinded pilot randomized controlled trial at the University of California, San Francisco among 42 individuals who had completed curative-intent treatment for colorectal cancer to determine the feasibility and acceptability of a 12-week (84 days) physical activity intervention using a Fitbit Flex™ and daily text messages. Participants were randomized 1:1 to receive the intervention with print educational materials or print educational materials alone. We explored the impact of the intervention versus usual care on physical activity using ActiGraph GT3X+ accelerometers pre-/post-intervention.

Results: We screened 406 individuals and randomized 42 to intervention (n = 21) or control (n = 21) groups. During the 12-week study, the intervention arm wore their Fitbits a median of 74 days [88% of days in study period, interquartile range: 23-83 days] and responded to a median of 34 (out of 46) text messages that asked for a reply (interquartile range: 13-38 text messages). Among the 16 intervention participants who completed the feedback survey, the majority (88%) reported that the intervention motivated them to exercise and that they were satisfied with their experience. No statistically significant difference in change in moderate-to-vigorous physical activity was found from baseline to 12 weeks between arms.

Conclusion: A 12-week physical activity intervention with a Fitbit and text messages was feasible and acceptable among colorectal cancer patients after curative treatment. Larger studies are needed to determine whether the intervention increases physical activity.

Trial Registration: Clinicaltrials.gov Identifier NCT02966054 . Registered 17 November 2016, retrospectively registered.
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http://dx.doi.org/10.1186/s12885-019-5427-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6417122PMC
March 2019

Feasibility, Acceptability, and Behavioral Outcomes from a Technology-enhanced Behavioral Change Intervention (Prostate 8): A Pilot Randomized Controlled Trial in Men with Prostate Cancer.

Eur Urol 2019 06 10;75(6):950-958. Epub 2019 Jan 10.

Department of Urology, University of California, San Francisco, CA, USA; Department of Epidemiology & Biostatistics, University of California, San Francisco, CA, USA.

Background: Increasing evidence suggests that lifestyle factors may decrease the risk of prostate cancer progression. Lifestyle guidelines and tools may support lifestyle modification after diagnosis.

Objective: To determine the feasibility and acceptability of a digital lifestyle intervention among men with prostate cancer.

Design, Setting, And Participants: A 12-wk pilot randomized controlled trial among 76 men with clinical stage T1-T3a prostate cancer. Eligibility included Internet access, no contraindications to aerobic exercise, and engaging in four or fewer of eight targeted behaviors at baseline.

Intervention: Website, Fitbit One, and text messaging to facilitate adoption of eight behaviors: vigorous activity, smoking cessation, and six diet improvements.

Outcome Measurements And Statistical Analysis: Our primary outcomes were feasibility and acceptability based on recruitment and user data, and surveys, respectively. Secondarily, we evaluated the change in eight lifestyle behaviors, and also objective physical activity. Each factor was assigned one point, for an overall "P8 score" (range 0-8). Analysis of covariance (ANCOVA) was conducted. Exploratory outcomes included quality of life, anthropometrics, and circulating biomarkers after 12wk, and behaviors after 1yr.

Results And Limitations: At baseline, men in both arms met a median of three targeted behaviors. Sixty-four men (n=32 per arm) completed the study; 88% completed 12-wk assessments (intervention, 94%; control, 82%). Intervention participants wore their Fitbits a median of 82d (interquartile range [IQR]: 72-83), replied to a median of 71% of text messages (IQR: 57-89%), and visited the website a median of 3d (IQR: 2-5) over 12wk. Median (IQR) absolute changes in the P8 score from baseline to 12wk were 2 (1, 3) for the intervention and 0 (-1, 1) for the control arm. The estimated mean score of the intervention arm was 1.5 (95% confidence interval: 0.7, 2.3) higher than that of the control arm at 12wk (ANCOVA p<0.001). Changes were driven by diet rather than exercise. Limitations include self-reported diet and exercise data.

Conclusions: Overall, in this novel pilot trial, the intervention was feasible and acceptable to men with prostate cancer. Next steps include improving the intervention to better meet individuals' needs and focusing on increasing physical activity in men not meeting nationally recommended physical activity levels.

Patient Summary: Tailored print materials combined with technology integration, including the use of a website, text messaging, and physical activity trackers, helped men with prostate cancer adopt healthy lifestyle habits, in particular recommended dietary changes, in the Prostate 8 pilot trial.
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http://dx.doi.org/10.1016/j.eururo.2018.12.040DOI Listing
June 2019

Effect of Increasing Levels of Web-Based Behavioral Support on Changes in Physical Activity, Diet, and Symptoms in Men With Prostate Cancer: Protocol for a Randomized Controlled Trial.

JMIR Res Protoc 2018 Nov 15;7(11):e11257. Epub 2018 Nov 15.

Department of Urology, University of California, San Francisco, San Francisco, CA, United States.

Background: More than 3.1 million men in the United States are prostate cancer survivors. These men may improve their physical function, quality of life, and potentially their prognosis by adopting healthier lifestyle habits. The internet provides a scalable mechanism to deliver advice and support about improving physical activity and dietary habits, but the feasibility and acceptability of a Web-based lifestyle intervention and the dose of support necessary to improve health behaviors are not yet known.

Objectives: The Community of Wellness is a Web-based intervention focused on supporting exercise and healthy dietary practices for men with prostate cancer. The objectives of this study were to determine the feasibility, acceptability, and preliminary efficacy of the Community of Wellness Web portal among prostate cancer survivors by conducting a randomized controlled trial (RCT) comparing 4 levels of additive Web-based content and interaction with participants: Level 1 (Teaching; Control), Level 2 (Teaching + Tailoring), Level 3 (Teaching + Tailoring + Technology), and Level 4 (Teaching + Tailoring + Technology + Touch).

Methods: This is a single-blinded RCT comparing 3 levels of behavioral support within the Community of Wellness Web portal intervention (Levels 2 to 4) with each other and with the control condition (Level 1). The control condition receives general static Web-based educational information only on physical activity and dietary habits, self-efficacy for behavior change, motivation for physical activity, and changes in anxiety and treatment-related side effects. We will enroll and randomize 200 men with prostate cancer equally to 4 levels of the Community of Wellness Web-based intervention for 3 months (50 men per level). Surveys will be completed by self-report at baseline, 3 months (immediately postintervention), and 6 months (3 months postintervention). Feasibility and acceptability will be assessed by enrollment statistics, Web-based usage metrics, and surveys at the 3-month time point. We will also conduct focus groups after the postintervention follow-up assessment in a sample of enrolled participants to evaluate elements of usability and acceptability that cannot be obtained via surveys.

Results: Enrollment is ongoing, with 124 enrolled. Study completion (6-month follow-up) is expected by July 2019.

Conclusions: The goal of the study is to identify the level of support that is feasible, acceptable, promotes behavior change, and improves health in men with prostate cancer to inform future efforts to scale the program for broader reach.

Trial Registration: ClinicalTrials.gov NCT03406013; https://clinicaltrials.gov/ct2/show/NCT03406013 (Archived by WebCite at http://www.webcitation.org/73YpDIoTX).

International Registered Report Identifier (irrid): PRR1-10.2196/11257.
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http://dx.doi.org/10.2196/11257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6265599PMC
November 2018

A Collaborative Analysis of Individual Participant Data from 19 Prospective Studies Assesses Circulating Vitamin D and Prostate Cancer Risk.

Cancer Res 2019 01 13;79(1):274-285. Epub 2018 Nov 13.

The Medical School, University of Western Australia, Perth, Australia.

Previous prospective studies assessing the relationship between circulating concentrations of vitamin D and prostate cancer risk have shown inconclusive results, particularly for risk of aggressive disease. In this study, we examine the association between prediagnostic concentrations of 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)D] and the risk of prostate cancer overall and by tumor characteristics. Principal investigators of 19 prospective studies provided individual participant data on circulating 25(OH)D and 1,25(OH)D for up to 13,462 men with incident prostate cancer and 20,261 control participants. ORs for prostate cancer by study-specific fifths of season-standardized vitamin D concentration were estimated using multivariable-adjusted conditional logistic regression. 25(OH)D concentration was positively associated with risk for total prostate cancer (multivariable-adjusted OR comparing highest vs. lowest study-specific fifth was 1.22; 95% confidence interval, 1.13-1.31; trend < 0.001). However, this association varied by disease aggressiveness ( = 0.014); higher circulating 25(OH)D was associated with a higher risk of nonaggressive disease (OR per 80 percentile increase = 1.24, 1.13-1.36) but not with aggressive disease (defined as stage 4, metastases, or prostate cancer death, 0.95, 0.78-1.15). 1,25(OH)D concentration was not associated with risk for prostate cancer overall or by tumor characteristics. The absence of an association of vitamin D with aggressive disease does not support the hypothesis that vitamin D deficiency increases prostate cancer risk. Rather, the association of high circulating 25(OH)D concentration with a higher risk of nonaggressive prostate cancer may be influenced by detection bias. SIGNIFICANCE: This international collaboration comprises the largest prospective study on blood vitamin D and prostate cancer risk and shows no association with aggressive disease but some evidence of a higher risk of nonaggressive disease.
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http://dx.doi.org/10.1158/0008-5472.CAN-18-2318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6330070PMC
January 2019

The Immune Landscape of Prostate Cancer and Nomination of PD-L2 as a Potential Therapeutic Target.

J Natl Cancer Inst 2019 03;111(3):301-310

Department of Radiation Oncology, Helen Diller Comprehensive Cancer Center, University of California at San Francisco, San Francisco, CA.

Background: Immunotherapy has been less successful in treating prostate cancer than other solid tumors. We sought to better understand the immune landscape in prostate cancer and identify immune-related biomarkers and potential therapeutic targets.

Methods: We analyzed gene expression data from 7826 prospectively collected prostatectomy samples (2013-2016), and 1567 retrospective samples with long-term clinical outcomes, for a total of 9393 samples, all profiled on the same commercial clinical platform in a CLIA-certified lab. The primary outcome was distant metastasis-free survival (DMFS). Secondary outcomes included biochemical recurrence-free survival (bRFS), prostate cancer-specific survival (PCSS), and overall survival (OS). All statistical tests were two-sided.

Results: Unsupervised hierarchical clustering of hallmark pathways demonstrated an immune-related tumor cluster. Increased estimated immune content scores based on immune-specific genes from the literature were associated with worse bRFS (hazard ratio [HR] = 1.26 [95% confidence interval [CI] = 1.12 to 1.42]; P < .001), DMFS (HR = 1.34 [95% CI = 1.13 to 1.58]; P < .001), PCSS (HR = 1.53 [95% CI = 1.21 to 1.92]; P < .001), and OS (HR = 1.27 [95% CI = 1.07 to 1.50]; P = .006). Deconvolution using Cibersort revealed that mast cells, natural killer cells, and dendritic cells conferred improved DMFS, whereas macrophages and T-cells conferred worse DMFS. Interestingly, while PD-L1 was not prognostic, consistent with its low expression in prostate cancer, PD-L2 was expressed at statistically significantly higher levels (P < .001) and was associated with worse bRFS (HR = 1.17 [95% CI = 1.03 to 1.33]; P = .01), DMFS (HR = 1.25 [95% CI = 1.05 to 1.49]; P = .01), and PCSS (HR = 1.45 [95% CI = 1.13 to 1.86]; P = .003). PD-L2 was strongly associated with immune-related pathways on gene set enrichment analysis suggesting that it is playing an important role in immune modulation in clinical prostate cancer samples. Furthermore, PD-L2 was correlated with radiation response pathways, and also predicted response to postoperative radiation therapy (PORT) on multivariable interaction analysis (P = .03).

Conclusion: In the largest study of its kind to date, these results illustrate the complex relationship between the tumor-immune interaction, prognosis, and response to radiotherapy, and nominate PD-L2 as a potential novel therapeutic target in prostate cancer, potentially in combination with radiotherapy.
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http://dx.doi.org/10.1093/jnci/djy141DOI Listing
March 2019
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