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Background Individual health behaviours have been associated with fatal prostate cancer (PCa). Their combined association with fatal PCa after diagnosis is unknown. Methods This prospective cohort included 4518 men diagnosed with nonmetastatic PCa from the Health Professionals Follow-up Study. Exposures included a three-factor score integrating post-diagnostic fatal PCa risk factors (“2021 PCa Behaviour Score”), six-factor score integrating incident aggressive PCa risk factors (“2015 PCa Behaviour Score”), and two scores integrating recommendations for cancer prevention and survival, respectively. Multivariable Cox models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for fatal PCa. Results Over a median 10.2 years, we observed 219 PCa deaths. Each additional point of one of the PCa-specific health behaviour scores (2015 PCa Behaviour Score) was associated with a 19% reduced fatal PCa risk (HR: 0.81, 95%CI: 0.68–0.97). The 2021 PCa Behaviour Score and scores integrating national recommendations were not associated with fatal PCa. Conclusions While a PCa-specific health behaviour score was associated with a reduced risk of fatal PCa, we did not otherwise observe strong evidence of associations between post-diagnostic scores and fatal PCa. Avoiding tobacco, healthy body size, and physical activity may decrease PCa death risk, but further research is needed to inform cancer survivorship recommendations.

Background Individual behaviours are associated with prostate cancer (PC) progression. Behavioural scores, comprised of multiple risk factors, allow assessment of the combined impact of multiple behaviours. Methods We examined the association between six a priori scores and risk of PC progression and mortality among 2156 men with PC in the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) cohort: two scores developed based on the PC survivorship literature (‘2021 Score [+ Diet]’); a score developed based on pre-diagnostic PC literature (‘2015 Score’); and three scores based on US recommendations for cancer prevention (‘WCRF/AICR Score’) and survival (‘ACS Score [+ Alcohol]’). Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for progression and PC mortality via parametric survival models (interval censoring) and Cox models, respectively. Results Over a median (IQR) of 6.4 (1.3, 13.7) years, we observed 192 progression and 73 PC mortality events. Higher (i.e., healthier) 2021 Score + Diet and WCRF/AICR Scores were inversely associated with risk of PC progression (2021 + Diet: HRcontinuous = 0.76, 95% CI: 0.63–0.90. WCRF/AICR: HRcontinuous = 0.83, 95% CI: 0.67–1.02) and mortality (2021 + Diet: HRcontinuous = 0.65, 95% CI: 0.45–0.93. WCRF/AICR: HRcontinuous = 0.71; 95% CI: 0.57–0.89). The ACS Score + Alcohol was only associated with progression (HRcontinuous = 0.89, 95% CI: 0.81–0.98) while the 2021 Score was only associated with PC mortality (HRcontinuous = 0.62, 95% CI: 0.45–0.85). The 2015 was not associated with PC progression or mortality. Conclusion Findings strengthen the evidence that behavioural modifications following a prostate cancer diagnosis may improve clinical outcomes.

Diabetes mellitus (DM) has been proposed to be positively associated with breast cancer (BCa) risk due to shared risk factors, metabolic dysfunction, and use of antidiabetic medications. We conducted a systematic review and meta-analysis to evaluate the association between DM and BCa risk. We searched PubMed, Embase, and Web of Science for cohort and case-control studies assessing the association between DM and BCa published before December 10, 2021. Two reviewers independently screened the studies for inclusion, abstracted article data, and rated study quality. Random effects models were used to estimate summary risk ratios (RRs) and 95% confidence intervals (CIs). From 8396 articles identified in the initial search, 70 independent studies were included in the meta-analysis. DM was associated with an overall increased risk of BCa (RR=1.20, 95% CI: 1.11-1.29). The 24 case-control studies demonstrated a stronger association (RR=1.26, 95% CI: 1.13-1.40) than the 46 cohort studies (RR=1.15, 95% CI: 1.05-1.27). Studies reporting risk by menopausal status found that postmenopausal women had an elevated risk of developing BCa (RR=1.12, 95% CI: 1.07-1.17). No association between DM and BCa risk was observed among premenopausal women (RR=0.95, 95% CI: 0.85-1.05). In addition, DM was associated with significantly increased risks of estrogen receptor (ER)+ (RR=1.09, 95% CI: 1.00-1.20), ER- (RR=1.16, 95% CI: 1.04-1.30), and triple negative BCa (RR=1.41, 95% CI: 1.01-1.96). The association estimate for human epidermal growth factor 2- positive BCa was also positive (RR=1.21, 95% CI: 0.52-2.82), but the confidence interval was wide and crossed the null. Our meta-analysis confirms a modest positive association between DM and BCa risk. In addition, our results suggest that the DM and BCa association may be modified by menopausal status, and DM may be differentially associated with BCa subtypes defined by receptor status. Additional studies are warranted to investigate the mechanisms underlying these associations and any influence of DM on BCa receptor expression.

Supplemental Table 1: Minor allele frequencies and Hardy Weinberg Equilibrium (HWE) p-values for SNPs across antioxidant & transport related genes. Supplemental Table 2: Full results for the associations between antioxidant SNPs x selenium supplementation. Supplemental Table 3: Full results for the associations between antioxidant, transport, & DNA repair SNPs x vitamin E supplementation and risk of high-grade and overall prostate cancer (N=1,538) in SELECT. Supplemental Table 4: Full results for the independent associations of SNPs and risk high-grade and overall prostate cancer in the placebo arm of SELECT.

Supplementary material and methods: supplementary information on data collection, statistical analyses, and presentation of results in the figures.

Supplementary Figure Legends for Figures S1-S15.

The role of insulin-like growth factors (IGF) in prostate cancer development is not fully understood. To investigate the association between circulating concentrations of IGFs (IGF-I, IGF-II, IGFBP-1, IGFBP-2, and IGFBP-3) and prostate cancer risk, we pooled individual participant data from 17 prospective and two cross-sectional studies, including up to 10,554 prostate cancer cases and 13,618 control participants. Conditional logistic regression was used to estimate the ORs for prostate cancer based on the study-specific fifth of each analyte. Overall, IGF-I, IGF-II, IGFBP-2, and IGFBP-3 concentrations were positively associated with prostate cancer risk (Ptrend all ≤ 0.005), and IGFBP-1 was inversely associated weakly with risk (Ptrend = 0.05). However, heterogeneity between the prospective and cross-sectional studies was evident (Pheterogeneity = 0.03), unless the analyses were restricted to prospective studies (with the exception of IGF-II, Pheterogeneity = 0.02). For prospective studies, the OR for men in the highest versus the lowest fifth of each analyte was 1.29 (95% confidence interval, 1.16–1.43) for IGF-I, 0.81 (0.68–0.96) for IGFBP-1, and 1.25 (1.12–1.40) for IGFBP-3. These associations did not differ significantly by time-to-diagnosis or tumor stage or grade. After mutual adjustment for each of the other analytes, only IGF-I remained associated with risk. Our collaborative study represents the largest pooled analysis of the relationship between prostate cancer risk and circulating concentrations of IGF-I, providing strong evidence that IGF-I is highly likely to be involved in prostate cancer development. Cancer Res; 76(8); 2288–300. ©2016 AACR.

Background: Epidemiologic studies and secondary analyses of randomized trials supported the hypothesis that selenium and vitamin E lower prostate cancer risk. However, the Selenium and Vitamin E Cancer Prevention Trial (SELECT) showed no benefit of either supplement. Genetic variants involved in selenium or vitamin E metabolism or transport may underlie the complex associations of selenium and vitamin E.Methods: We undertook a case–cohort study of SELECT participants randomized to placebo, selenium, or vitamin E. The subcohort included 1,434 men; our primary outcome was high-grade prostate cancer (N = 278 cases, Gleason 7 or higher cancer). We used weighted Cox regression to examine the association between SNPs and high-grade prostate cancer risk. To assess effect modification, we created interaction terms between randomization arm and genotype and calculated log likelihood statistics.Results: We noted statistically significant (P < 0.05) interactions between selenium assignment, SNPs in CAT, SOD2, PRDX6, SOD3, and TXNRD2, and high-grade prostate cancer risk. Statistically significant SNPs that modified the association of vitamin E assignment and high-grade prostate cancer included SEC14L2, SOD1, and TTPA. In the placebo arm, several SNPs, hypothesized to interact with supplement assignment and risk of high-grade prostate cancer, were also directly associated with outcome.Conclusion: Variants in selenium and vitamin E metabolism/transport genes may influence risk of overall and high-grade prostate cancer, and may modify an individual man's response to vitamin E or selenium supplementation with regards to these risks.Impact: The effect of selenium or vitamin E supplementation on high-grade prostate cancer risk may vary by genotype. Cancer Epidemiol Biomarkers Prev; 25(7); 1050–8. ©2016 AACR.

Supplementary tables and figures showing study and assay characteristics, correlations between analytes, and the relationships of the analytes with prostate cancer risk overall, by study and study design, and subdivided by clinical and other characteristics.

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)2D] 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)2D 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; P trend < 0.001). However, this association varied by disease aggressiveness (Pheterogeneity = 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)2D 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.

Purpose We aimed to estimate the effect of a 12-week web-based dietary intervention with text messages on quality of life (QoL) among colorectal cancer (CRC) survivors. Methods Between 2017 and 2018, 50 CRC survivors were randomized (1:1) to receive a 12-week web-based dietary intervention with daily text messages or wait-list control. Health-related QoL was assessed using the European Organization for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire–Core 30 (QLQ-C30) and colorectal quality of life module (QLQ-CR29) at baseline, 12, and 24 weeks. Within- and between-group mean changes in health-related QoL with 95% confidence intervals (CI) were calculated for both arms. Results Compared to the controls, participants receiving the intervention had an improvement in emotional functioning (mean change: 14.3; 95% CI: 3.0, 25.6) at 12 weeks and social functioning (mean change: 13.8; 95% CI: 2.1, 25.5) at 24 weeks. A decrease of fatigue from baseline was also observed in the intervention arm (mean change: − 9.1; 95% CI: − 17.1, − 1.1) at 24 weeks. No other changes in QoL scores were associated with the intervention. Conclusion CRC survivors randomized to receive a web-based dietary intervention with text messages experienced higher emotional and social functioning. Further study with a larger population may be warranted. Trial registration clinicaltrials.gov, NCT02965521. Registered 16 November 2016, https://clinicaltrials.gov/ct2/keydates/NCT02965521

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., We conducted a 3‐arm pilot randomized controlled trial to determine the feasibility, safety, and acceptability of two modes of remotely monitored exercise (resistance or aerobic) over 12 weeks compared to usual care in 25 men with metastatic castrate‐resistant prostate cancer (mCRPC). We report that remotely monitored exercise training is feasible, safe, and acceptable in this patient population, with a high satisfaction rate. Through this research we provide direction and rationale for future studies of exercise and clinical outcomes for people with metastatic cancer.

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.

Background: Technology-based interventions are increasingly used to improve physical activity (PA) and diet. Methods: We conducted a systematic review of randomized controlled trials (RCTs) published up to August 2021 that tested mobile health (mHealth) PA and/or dietary interventions among cancer survivors and reported on the feasibility, satisfaction, behavioral change, and/or quality of life (QOL) outcomes. Results: In total, 61 articles were identified on PubMed, and 23 of those met the inclusion criteria. The most common cancers were breast (n = 1000), prostate (n = 713), and colorectal (n = 650). Participants were predominantly White (median: 84%, interquartile range (IQR): 20%) and college-educated (58%). The interventions varied, but the most common combination of components (six studies) was a website/mobile app with an activity tracker and coaching. In terms of duration, 70% (n = 16) of the interventions lasted 12 weeks. The median total tracker wear was 87% of the study days (IQR: 6%) and the median text-message reply rate was 73% (IQR 4%). Most participants (median: 87%; IQR: 16%) were satisfied with at least one intervention component. Eleven out of 18 studies examining behavioral change reported significant between-group differences and six out of 11 studies examining QoL reported significant improvements. Conclusions: mHealth interventions are a promising approach to improving the PA and diets of cancer survivors. Research in racially/ethnically and socioeconomically diverse populations is needed.

Colorectal cancer (CRC) is the 2nd leading cause of cancer death in the United States. The American Cancer Society (ACS) Nutrition and Physical Activity Guidelines are associated with longer survival among CRC survivors, but few report behaviors consistent with the guidelines.The Tools To Be Fit study, based on the Multiphase Optimization Strategy (MOST) framework, is a full factorial experimental to optimize a remotely delivered 48-week diet and physical activity intervention for non-metastatic CRC survivors. The intervention includes a core component (booklet and personal report). CRC survivors (N = 400) are additionally randomly assigned to one of 16 combinations of four candidate components, each with 2 options: 1) text messaging (on/off); 2) self-monitoring modality (digital/paper); 3) health coaching (on/off); and 4) support person coaching (on/off).Our primary outcome is adherence to the ACS guidelines after 48 weeks using a score that includes physical activity from accelerometers, dietary intake from a food frequency questionnaire, and body mass index (BMI) measured by a technician. Secondary outcomes include the ACS score after 24 weeks and score components at 24 and 48 weeks. Exploratory outcomes include adherence and change in Social Cognitive Theory constructs. We will explore moderation by sociodemographic, clinical, and psychological/behavioral factors; and change in the ACS score in relation to change in levels of insulin, insulin sensitivity, inflammation, gut microbiome structure, fatigue, depression, and sleep disturbance.The proposed study aims to inform a randomized controlled trial to determine whether an optimized intervention reduces risk of recurrence among CRC survivors.

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.

Abstract Purpose We sought to determine whether adherence to the American Cancer Society (ACS) Nutrition and Physical Activity Guidelines was associated with better bowel function among colon cancer survivors. Methods This prospective cohort study included patients surgically treated for stage I–IV colon cancer enrolled in the Lifestyle and Outcomes after Gastrointestinal Cancer (LOGIC) study between February 2017 and May 2021. Participants were assigned an ACS score (0–6 points) at enrollment. Stool frequency (SF) was assessed every 6 months using the EORTC QLQ-CR29. Higher SF is an indication of bowel function impairment. ACS score at enrollment was examined in relation to SF at enrollment and over a 3-year period. Secondarily, we examined associations between the ACS score components (body mass index, dietary factors, and physical activity) and SF. Multivariable models were adjusted for demographic and surgical characteristics. Results A total of 112 people with colon cancer (59% women, mean age 59.5 years) were included. Cross-sectionally, for every point increase in ACS score at enrollment, the odds of having frequent stools at enrollment decreased by 43% (CI 0.42–0.79; p Conclusions Colon cancer survivors who more closely followed the ACS nutrition and physical activity guidelines had lower SF, an indication of better bowel function. Implications for Cancer Survivors Our findings highlight the value of interventions that support health behavior modification as part of survivorship care for long-term colon cancer survivors.

Following a prostate cancer diagnosis, disease and treatment-related symptoms may result in diminished quality of life (QoL). Whether exercise improves QoL in men with metastatic castrate-resistant prostate cancer (mCRPC) is not fully understood.We conducted a 3-arm pilot randomized controlled trial to assess the feasibility, acceptability, safety, and efficacy of a 12-week remotely monitored exercise program among men with mCRPC. Here we report qualitative changes in QoL, consistent with the guidelines for pilot trials. Men were randomized to control, aerobic exercise, or resistance exercise. Exercise prescriptions were based on baseline cardiorespiratory and strength assessments. QoL outcomes were evaluated using self-reported questionnaires (e.g., QLQ-C30, PROMIS Fatigue, Pittsburgh Sleep Quality Index (PSQI), EPIC-26) collected at baseline and 12 weeks.A total of 25 men were randomized (10 control, 8 aerobic, 7 resistance). Men were predominately white (76%) with a median age of 71 years (range: 51-84) and 10.5 years (range: 0.9-26.3) post prostate cancer diagnosis. The men reported poor sleep quality and high levels of fatigue at enrollment. Other baseline QoL metrics were relatively high. Compared to the controls at 12 weeks, the resistance arm reported some improvements in social function and urinary irritative/obstruction symptoms while the aerobic arm reported some improvements in social function and urinary incontinence, yet worsening nausea/vomiting. Compared to the resistance arm, the aerobic arm reported worse urinary irritative/obstruction symptoms and self-rated QoL, yet some improvements in emotional function, insomnia, and diarrhea.The 3-month exercise intervention pilot appeared to have modest effects on QoL among mCRPC survivors on ADT. Given the feasibility, acceptability, and safety demonstrated in prior analyses, evaluation of the effect of the intervention on QoL in a larger sample and for extended duration may still be warranted.

Background: Inflammatory and insulin pathways have been linked to prostate cancer; postdiagnostic behaviors activating these pathways may lead to poor outcomes. The empirical dietary inflammatory pattern (EDIP), empirical dietary index for hyperinsulinemia (EDIH), and empirical dietary index for insulin resistance (EDIR), and associated lifestyle indices (ELIH, ELIR) predict biomarkers of inflammation (EDIP: IL6, TNFaR2, CRP) and insulin secretion (EDIH/ELIH: c-peptide; EDIR/ELIR: TAG:HDL) from whole foods and behaviors. Methods: Associations of these indices with time to prostate cancer progression (primary, n = 2,056) and prostate cancer–specific mortality (PCSM; secondary, n = 2,447) were estimated among men diagnosed with nonmetastatic prostate cancer in the Cancer of the Prostate Strategic Urologic Research Endeavor cohort diet and lifestyle sub-study. Because the true (versus clinically documented) date of progression is unobserved, we used parametric (Weibull) survival models to accommodate interval-censoringand estimated adjusted HR and 95% confidence intervals (CI) for prostate cancer progression per 1-SD increase in index. Cox proportional hazards models were used to estimate PCSM associations. Results: During a median [interquartile range (IQR)] 6.4 years (IQR, 1.3–12.7), 192 progression and 73 PCSM events were observed. Inflammatory (EDIP: HR, 1.27; CI, 1.17–1.37), hyperinsulinemic (EDIH: HR, 1.24; CI, 1.05–1.46. ELIH: HR, 1.34; CI, 1.17–1.54), and insulin-resistant (EDIR: HR, 1.22; CI, 1.00–1.48. ELIR: HR, 1.36; CI, 1.12–1.64) indices were positively associated with risk of prostate cancer progression. There was no evidence of associations between the indices and PCSM. Conclusions: Both inflammatory and insulinemic dietary and lifestyle patterns are associated with risk of prostate cancer progression. Impact: For men with prostate cancer, consuming dietary patterns that limit chronic systemic inflammation and insulin hypersecretion may improve survivorship, especially when coupled with active lifestyle and healthy body weight. See related commentary by Kucuk, p. 1673

Background While there is a robust literature on environmental exposure to iodine-131 (131I) in childhood and adolescence and the risk of thyroid cancer and benign nodules, little is known about its effects on thyroid volume. Methods To assess the effect of 131I dose to the thyroid on the volume of the thyroid gland, we examined the data from the baseline screening of the Belarusian-American Cohort Study of residents of Belarus who were exposed to the Chernobyl fallout at ages ≤18 years. Thyroid dose estimates were based on individual thyroid activity measurements made shortly after the accident and dosimetric data from questionnaires obtained 10-15 years later at baseline screening. During baseline screening, thyroid gland volume was assessed from thyroid ultrasound measurements. The association between radiation dose and thyroid volume was modeled using linear regression where radiation dose was expressed with power terms to address non-linearity. The model was adjusted for attained age, sex, and place of residence, and their modifying effects were examined. Results The analysis was based on 10,703 subjects. We found a statistically significant positive association between radiation dose and thyroid volume (P P P Conclusions This is the first study to examine the association between 131I dose to the thyroid gland and thyroid volume in a population of individuals exposed during childhood and systematically screened 10-15 years later. It provides evidence for a moderate statistically significant increase in thyroid volume among those who were ≥ 18 years at screening. Given that this effect was observed at very low doses and was restricted to a narrow dose range, further studies are necessary to better understand the effect.

Background: Following a prostate cancer (PC) diagnosis, treatment-related symptoms may result in diminished quality of life (QoL). Improved diet and increased exercise may improve QoL in men with PC. Methods: We conducted a 4-arm pilot randomized trial to assess feasibility and acceptability of a 3-month web-based diet and exercise intervention, among men (>18 years of age) with PC (reported elsewhere). The purpose of this study is to describe the change in QoL measured by surveys (eg, QLQ-C30, PROMIS Fatigue) at enrollment and following the intervention. Men were randomized 1:1:1:1 to increasing levels of web-based behavioral support: Level 1: website; Level 2: Level 1 plus personalized diet and exercise prescription; Level 3: Levels 1-2 plus Fitbit and text messages; Level 4: Levels 1-3 plus 2 30-minute coaching calls. T-tests were used to compare pre-post change in mean QoL scores between each Level and Level 1. Results: Two hundred and two men consented and were randomized (n = 49, 51, 50, 52 for Levels 1-4, respectively). Men were predominantly white (93%), with a median age of 70 years (Intra-quartile Range [IQR]: 65,75) and 3 years (IQR: 1,9) post primary treatment for mostly localized disease (74% with T1-2). There were no meaningful changes in QoL, but there were notable trends. Level 3 participants had small improvements in QLQ-C30 Global Health (5.46; 95% CI: −0.02, 10.95) compared to Level 1. In contrast, Level 2 participants trended toward decreasing Global QoL (−2.31, 95% CI: −8.05, 3.42), which may reflect declines in function (eg, Cognitive: −6.94, 95% CI: −13.76, −0.13) and higher symptom burden (eg, Diarrhea: 4.63, 95% CI: −1.48, 10.74). Conclusions: This short, web-based intervention did not appear to have an impact on PC survivors’ QoL. Most men were several years past treatment for localized disease; the potential for this approach to reduce symptoms and improve QoL in men who have worse health may still be warranted.

392 Background: Plant-based diets have been linked to multiple health benefits. For prostate cancer (PC), individual plant foods (e.g., tomatoes with lycopene) appear to reduce PC incidence and mortality. However, less is known about plant-based dietary patterns and PC survivorship. Methods: We examined 2038 men diagnosed with T1-T3a PC who were enrolled in the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) and had completed a food frequency questionnaire (FFQ) a median of 31.5 months post-diagnosis. “Overall” and “healthy plant-based” dietary indices (PDI and hPDI, respectively,) were calculated from the FFQ. Multivariable Cox proportional hazards models estimated adjusted hazard ratios (HR) and 95% confidence intervals (CI) for associations between plant-based diets and risk of PC progression (recurrence, secondary treatment, bone metastases, or PC death) as the primary outcome, and PC recurrence as a secondary outcome. We also examined whether age, stage, grade, and walking pace modified associations. Results: We observed 204 progression events (169 due to biochemical recurrence) over a median follow up of 7.4 years after the FFQ. Men in the highest quintile of PDI had a 52% lower risk of progression (HR 0.48, 95% CI 0.36-0.65, p-trend0.05), men in the higher quintiles had statistically significant reductions in risk of recurrence. Among men >65 years, greater consumption of a healthful plant-based diet was associated with lower risk of PC recurrence (HR 0.41, 95% CI 0.24-0.7, p-trend=0.03). In addition, among those with a brisk/fast walking pace (>3 h/wk), men in the highest PDI quintile had a 56% (HR 0.33, 95% CI 0.26, 0.73) lower risk of PC progression, and a 59% (HR 0.41, 95% CI 0.25, 0.68) decrease in risk of PC recurrence. Grade and stage did not modify associations between either index and PC progression or recurrence. Conclusions: This study indicates that plant-based dietary patterns are associated with lower risk of PC progression and recurrence, particularly among older men and those who reported a higher intensity walking pace. PC survivors may be recommended diet and exercise counseling to improve clinical outcomes after PC diagnosis.

262 Background: While active surveillance (AS) is the preferred management strategy for men diagnosed with low-risk prostate cancer (PCa), the inability to distinguish indolent from aggressive tumors in clinically low-risk patients complicates decision-making. Genomic classifiers (GCs) were introduced to improve risk stratification, based on their ability to predict the risk of upgrading or upstaging (UG/US) in this setting. We assessed the impact of GCs on UG/US risk prediction added to a rich clinical model to better guide management decision-making for low-risk patients. Methods: We used multivariate logistic regression and receiver operating characteristic (ROC) curves to develop a prediction model for UG/US in men with low-risk, low-volume intermediate-risk PCa who were potential candidates for AS. The model was developed among 864 men and validated in an independent cohort of 2,267 men with similar risk profiles. After computing areas under the ROC curve (AUC) from these probabilities, we tested the model’s predictive ability with the addition of a series of GCs (OncoType Dx Genomic Prostate Score, Decipher score, and selected Decipher GRID scores) using the logistic model constructed for the development cohort to estimate the predicted probability of UG/US. Results: The prediction model for the development cohort included five diagnostic variables that were significantly associated with risk of UG/US: diagnostic grade (OR 5.83, 95% CI 3.73-9.10), PSA (OR 1.10, 95% CI 1.01-1.20), percent positive cores (OR 1.01, 95% CI 1.01-1.02), TRUS prostate volume (OR 0.98, 95% CI 0.97-0.99), and age (OR 1.05, 95% CI 1.02-1.07). The pooled AUC was 0.72 for 10 iterations of the model. When the addition of GCs was applied to this model, Genomic Prostate Score was independently associated with risk of UG/US (OR 1.42, 95%CI 0.016-0.066, p=0.017). However, the pooled AUC was 0.71, indicating comparable predictive performance to the risk prediction model. Conclusions: The addition of GCs to a validated rich model incorporating detailed clinical variables, when applied to favorable-risk PCa patients, did not substantially improve prediction of UG/US. Our findings suggest that widespread use of biomarkers to guide management or the intensity of follow up may not be supported in men with low-risk, low-volume disease pursuing AS.

Nutrition and physical activity are associated with prostate cancer recurrence and mortality. Few randomized controlled trials (RCT) have examined the effects of long-term exercise and diet changes on prostate cancer clinical, biological, and patient-reported outcomes.Prostate 8-II is a 4-arm RCT among 200 men with prostate cancer who chose radical prostatectomy (RP) as their primary treatment. Men are enrolled prior to RP and randomized to exercise-only, diet-only, exercise + diet, or usual care (50/arm). Participants begin their assigned intervention 0-5 weeks prior to RP and continue for 24-months following surgery. The 3 active intervention arms receive access to a web-portal and text messages, coaching calls, and other intervention resources (e.g., heart rate sensor and resistance bands and/or recipe booklet). Weekly exercise goals for the exercise intervention groups are 150 min moderate or 75 min vigorous aerobic exercise, 2 strength sessions, and 2 flexibility sessions. Diet intervention groups work with a dietitian to customize their goals (e.g., increase cruciferous vegetables, cooked tomatoes, healthy fats, fish; limit processed meats, whole milk). The primary endpoint is biochemical recurrence. Secondary endpoints include change in tumor biomarkers from biopsy to RP as well as patient-reported outcomes (e.g., quality-of-life), blood and urine biomarkers, and anthropometry at 0, 6, 12, and 24 months.This 4-arm RCT will examine the impact of change in exercise and diet (alone or in combination) on prostate cancer recurrence, biology, and quality-of-life.

BACKGROUND Plant-based diets are associated with multiple health benefits and a favorable environmental impact. For prostate cancer, previous studies suggest a beneficial role of specific plant-based foods (e.g., tomatoes) and a potentially harmful role of specific animal-based foods (e.g., meat, dairy). However, less is known about plant-based dietary patterns. OBJECTIVE To examine the relationship between Plant-based Diet Indices and prostate cancer risk, including clinically relevant disease. DESIGN This was a prospective cohort study including 47,239 men in the Health Professionals Follow-up Study (1986-2014). Overall and healthful Plant-based Diet Indices were calculated from food frequency questionnaires. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) to examine the risk of incident prostate cancer (total and by clinical category), among men ages

Summary Men diagnosed with low-risk prostate cancer (PC) are increasingly electing active surveillance (AS) as their initial management strategy. While this may reduce the side effects of treatment for PC, many men on AS eventually convert to active treatment. PC is one of the most heritable cancers, and genetic factors that predispose to aggressive tumors may help distinguish men who are more likely to discontinue AS. To investigate this, we undertook a multi-institutional genome-wide association study (GWAS) of 5,222 PC patients and 1,139 other patients from replication cohorts, all of whom initially elected AS and were followed over time for the potential outcome of conversion from AS to active treatment. In the GWAS we detected 18 variants associated with conversion, 15 of which were not previously associated with PC risk. With a transcriptome-wide association study (TWAS), we found two genes associated with conversion (MAST3, p = 6.9 × 10−7 and GAB2, p = 2.0 × 10−6). Moreover, increasing values of a previously validated 269-variant genetic risk score (GRS) for PC was positively associated with conversion (e.g., comparing the highest to the two middle deciles gave a hazard ratio [HR] = 1.13; 95% confidence interval [CI] = 0.94–1.36); whereas decreasing values of a 36-variant GRS for prostate-specific antigen (PSA) levels were positively associated with conversion (e.g., comparing the lowest to the two middle deciles gave a HR = 1.25; 95% CI, 1.04–1.50). These results suggest that germline genetics may help inform and individualize the decision of AS—or the intensity of monitoring on AS—versus treatment for the initial management of patients with low-risk PC., Genetic factors may distinguish who should receive active surveillance (AS) versus treatment following prostate cancer diagnosis. We undertook the first study to investigate this and report novel variants, genes, and risk scores associated with AS outcomes. These findings could help inform and individualize the decision of AS.

INTRODUCTION AND OBJECTIVE:Plant-based diets are associated with multiple health benefits as well as a favorable environmental impact. For prostate cancer, previous studies suggest a beneficial rol...

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.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.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, p0.01). 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).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.

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.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.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 p0.01) were associated with active treatment.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.

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.

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 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.

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.

BACKGROUND We conducted a pilot 2-arm randomized controlled trial to assess the feasibility of a digital health intervention to increase moderate-to-vigorous physical activity in patients with colorectal cancer (CRC) during chemotherapy. OBJECTIVE This study aimed to determine whether a digital health physical activity intervention is feasible and acceptable during chemotherapy for CRC. METHODS Potentially eligible patients with CRC expected to receive at least 12 weeks of chemotherapy were identified in person at the University of California, San Francisco, and on the web through advertising. Eligible patients were randomized 1:1 to a 12-week intervention (Fitbit Flex, automated SMS text messages) versus usual care. At 0 and 12 weeks, patients wore an Actigraph GT3X+ accelerometer for 7 days and completed surveys, body size measurements, and an optional 6-minute walk test. Participants could not be masked to their intervention arm, but people assessing the body size and 6-minute walk test outcomes were masked. The primary outcomes were adherence (eg, Fitbit wear and text response rate) and self-assessed acceptability of the intervention. The intervention would be considered feasible if we observed at least 80% complete follow-up and 70% adherence and satisfaction, a priori. RESULTS From 2018 to 2020, we screened 240 patients; 53.3% (128/240) of patients were ineligible and 26.7% (64/240) declined to participate. A total of 44 patients (44/240, 18%) were randomized to the intervention (n=22) or control (n=22) groups. Of these, 57% (25/44) were women; 68% (30/44) identified as White and 25% (11/44) identified as Asian American or Pacific Islander; and 77% (34/44) had a 4-year college degree. The median age at enrollment was 54 years (IQR 45-62 years). Follow-up at 12 weeks was 91% (40/44) complete. In the intervention arm, patients wore Fitbit devices on a median of 67 out of 84 (80%) study days and responded to a median of 17 out of 27 (63%) questions sent via SMS text message. Among 19 out of 22 (86%) intervention patients who completed the feedback survey, 89% (17/19) were satisfied with the Fitbit device; 63% (12/19) were satisfied with the SMS text messages; 68% (13/19) said the SMS text messages motivated them to exercise; 74% (14/19) said the frequency of SMS text messages (1-3 days) was ideal; and 79% (15/19) said that receiving SMS text messages in the morning and evening was ideal. CONCLUSIONS This pilot study demonstrated that many people receiving chemotherapy for CRC are interested in participating in digital health physical activity interventions. Fitbit adherence was high; however, participants indicated a desire for more tailored SMS text message content. Studies with more socioeconomically diverse patients with CRC are required. CLINICALTRIAL ClinicalTrials.gov NCT03524716; https://clinicaltrials.gov/ct2/show/NCT03524716

Purpose There are over 1.3 million colorectal cancer (CRC) survivors in the USA, many of whom report lower health-related quality of life (HRQoL) years after treatment. This study aimed to explore the effect of digital health tools on HRQoL in CRC survivors. Methods We conducted a two-arm, randomized controlled trial of 42 subjects who had completed treatment for CRC. Participants in the intervention arm received a Fitbit Flex™ and daily text messages for 12 weeks. HRQoL was assessed as a secondary endpoint in both arms at enrollment and 12 weeks using the Medical Outcomes Study Short Form Survey (SF-36) and the Functional Assessment of Cancer Therapy–Colorectal (FACT-C). Survey score changes from enrollment to 12 weeks were compared between the two arms using independent t tests, and scores at enrollment and 12 weeks were compared using paired t tests. Results An increase in the FACT-C functional well-being subscale was observed in individuals in the intervention arm pre- to post-intervention (median difference, 2; interquartile range (IQR), 1, 4; P = .02). Although the between-group comparison was not statistically significant, no change in the functional well-being subscale was observed in the control arm (median difference, 0; IQR, 1, 1; P = .71). No other measures of HRQoL appeared to differ within arm across time points or between arms. Conclusion A 12-week digital physical activity intervention may improve functional well-being among CRC survivors. Larger randomized studies are needed to determine if digital health tools improve functional well-being among CRC survivors and if this improvement can be sustained over time. Trial registration NCT02966054; registration date, November 17, 2016

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 (OR5ng/mL = 1.34, P = 0.027) or to being a control (OR5ng/mL = 1.69, P = 0.034). Decreased average fragment size was associated with an increased risk of localized disease compared to controls (OR5bp = 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.