Physical Activity, Diet Quality, and Risk of Prostate Cancer Grade Reclassification on Active Surveillance: Results from a Prospective Cohort Study

Physical Activity, Diet Quality, and Risk of Prostate Cancer Grade Reclassification on Active Surveillance: Results from a Prospective Cohort Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Physical Activity, Diet Quality, and Risk of Prostate Cancer Grade Reclassification on Active Surveillance: Results from a Prospective Cohort Study Michelle Higgins, Zhuo Su, Mufaddal Mamawala, Yuezhou Jing, Patricia Landis, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6657111/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 18 Feb, 2026 Read the published version in Prostate Cancer and Prostatic Diseases → Version 1 posted 9 You are reading this latest preprint version Abstract Background Higher diet quality may be associated with a reduced risk of prostate cancer (PCa) grade reclassification (GR) on active surveillance (AS). However, there remain limited and conflicting data regarding whether physical activity may influence disease progression. Methods This is a prospective cohort study of men with Grade Group (GG) 1 PCa enrolled in AS. Patients completed detailed diet and physical activity surveys at time of AS enrollment. Physical activity was evaluated as metabolic equivalent of task (MET) hours per week, diet quality was measured as energy-adjusted Healthy Eating Index (E-HEI) score. Multivariable competing risk regressions were utilized to examine the association of diet and physical activity with GR on biopsy to ≥ GG2 or ≥ GG3. Results We included 828 men with a median follow up of 6.4 years. We found no significant association between MET hours per week and GR to ≥ GG2 (subdistribution hazard ratio (SHR) 1.04 per standard deviation (SD) increase in weekly MET hours, 95% confidence interval (CI) 0.90–1.21), or extreme GR to ≥ GG3 (SHR 1.03, 95% CI 0.79–1.35). Higher overall diet quality remained associated with significantly reduced risks of GR to ≥ GG2 (SHR 0.85 per SD increase in E-HEI score, 95% CI 0.73–0.99) and extreme GR (SHR 0.74, 95% CI 0.58–0.95). Conclusions In this prospective cohort study with longitudinal follow-up of men diagnosed with GG1 PCa pursuing AS, after adjusting for clinicopathological and lifestyle factors, increasing physical activity was not associated with a lower risk of PCa GR. A higher overall diet quality was associated with a reduced risk of GR for both GR outcomes. In our cohort, physical activity level does not appear to be associated with PCa progression on AS. Health sciences/Medical research/Outcomes research Biological sciences/Cancer/Urological cancer/Prostate cancer prostate cancer active surveillance physical activity exercise diet grade reclassification Introduction Among men pursuing active surveillance (AS) for favorable-risk prostate cancer (PCa), many are highly motivated to seek lifestyle modifications—such as diet and exercise—to reduce the risk of disease progression. In our institutional cohort, initial data suggest a higher overall diet quality, reflecting stricter adherence to American dietary guideline recommendations, may be associated with a reduced risk of PCa grade reclassification (GR) in men diagnosed with Grade Group 1 (GG1) disease managed with AS. 1 However, there remain limited and conflicting data regarding whether physical activity or exercise may influence the risk of disease progression during AS. The overall impact of exercise for men with PCa is encouraging; a recent meta-analysis demonstrated a marked improvement in all-cause survival and PCa specific survival associated with increased exercise levels. 2 Furthermore, both the US Department of Health and Human Services Physical Activity Guidelines for Americans and the American College of Sports Medicine specifically recommend that people with PCa exercise regularly as it may decrease cancer-specific mortality. 3 , 4 However these recommendations are based on data from all patients with PCa. In patients undergoing AS, data are more limited. A prospective randomized controlled trial (RCT), the ERASE study, demonstrated promising findings of a decrease in PSA and PSA velocity in patients undergoing a high-intensity interval training (HIIT) regimen. 5 However, the impact of exercise in retrospective studies on PCa AS are mixed. 6 – 8 In this study, we prospectively examined the association of patient self-reported physical activity level and diet quality at baseline with PCa GR on biopsy during AS. Methods Established in 1995, our institutional AS program is one of the largest, longest-running prospective PCa AS cohorts. 9 Beginning in 2005, at the time of AS enrollment participants were invited to complete the Block 1998 Food Frequency Questionnaire (FFQ; NutritionQuest), a validated questionnaire regarding usual dietary patterns, and a lifestyle questionnaire. 10 , 11 The lifestyle questionnaire collects a comprehensive list of self-reported physical activities, in accordance with the Compendium of Physical Activities , which provides a detailed coding scheme to assign metabolic equivalent intensity to each specific physical activity. 12 Consistent with our prior study of diet quality, 1 we included men enrolled between January 2005 and February 2017 who were diagnosed with GG1 disease, did not demonstrate early GR to ≥ GG2 on confirmatory biopsy typically performed within 18 months of diagnostic biopsy, and completed both questionnaires prospectively upon AS enrollment. Institutional Review Board approval and patient consent were obtained from all patients at time of AS enrollment (IRB number NA_00045103). Based on each man’s responses to the baseline FFQ, we calculated his Healthy Eating Index 1999–2000 (HEI) score at baseline, a validated measure of overall diet quality in terms of adherence to recommendations of the Dietary Guidelines for Americans . 10 An energy-adjusted HEI (E-HEI) score was obtained by adjusting the HEI score for daily total caloric intake. 13 In the baseline lifestyle questionnaire, men reported specific types of typical physical activities or exercises and numbers of hours per activity over the course of the preceding year (see Supplemental Tables 1 and 2 ). From the self-reported data, total metabolic equivalent of task (MET) hours per week was calculated. METs represent metabolic energy expenditure (Kcal/kg) as a standardized activity quantification, with coefficients assigned to adjust by type of physical activity. 12 , 14 We evaluated two outcomes: GR to ≥ GG2, and GR to ≥ GG3 (i.e. extreme GR) on any surveillance biopsy. We performed multivariable competing risk proportional hazards regressions to assess the association of self-reported baseline physical activity level, measured as total MET hours per week, and overall diet quality, reflected by E-HEI score, with either GR outcome. As described previously, 1 competing events were defined as volume reclassification only on a surveillance biopsy, elective treatment, and non-PCa mortality. The regression models additionally adjusted for smoking history (any versus none) and established AS prognostic factors at baseline 9 including year of diagnosis, age at diagnosis, self-reported race (Black versus non-Black), prostate-specific antigen (PSA) density, number of positive biopsy cores, maximum percent involvement of a core at diagnosis, and use of pre-enrollment multiparametric magnetic resonance imaging (yes versus no). Subdistribution hazard ratios (SHRs) were calculated per one standard deviation (SD) increase in MET hours per week and E-HEI score. We also evaluated MET hours per week categorized as tertiles. We performed statistical analyses using STATA version 18.0 (StataCorp LLC, College Station, TX). All tests were two sided, with statistical significance set at p < 0.05. Results In total, we included 828 men. Their baseline characteristics are summarized in Table 1 . At baseline, 41% reported any smoking history, median E-HEI score was 64 (SD 12.5), and median MET hours per week was 16.0 (SD 10.6). After median follow-up of 6.4 years (interquartile range 4.0-9.1), 174 (21%) demonstrated GR to ≥ GG2, including 53 (6.4%) with extreme GR. The cumulative incidence of GR to ≥ GG2 was 7% (95% confidence interval [CI] 5%-9%) at 3 years, 15% (95% CI 12%-18%) at 5 years, and 33% (95% CI 28%-37%) at 10 years; that of extreme GR was 2% (95% CI 1%-4%) at 3 years, 4% (95% CI 3%-6%) at 5 years, and 10% (95% CI 7%-13%) at 10 years. Median MET hours per week was 16.0 for men without GR versus 17.1 for men with GR ( p = 0.44), and median E-HEI score was 64 versus 63, respectively ( p = 0.45). Table 1 Baseline characteristics of study cohort (N = 828) Characteristic Value Year of diagnosis; median (IQR) 2010 (2008–2013) Patient age, years; median (IQR) 66 (61–69) Self-reported race; number (%) Black 49 (5.9) White 754 (91.1) Other a 25 (3.0) Total prostate-specific antigen, ng/mL; median (IQR) 4.8 (3.5–6.2) Prostate volume, mL; median (IQR) 45 (35–60) Prostate-specific antigen density, ng/mL 2 ; median (IQR) 0.10 (0.07–0.14) Number of positive biopsy cores at diagnosis; median (IQR) 1 (1–2) Maximum percent core involved with cancer, %; median (IQR) 5 (1–15) Use of pre-enrollment mpMRI; number (%) 305 (36.8) Body mass index, kg/m 2 ; median (IQR) 26.6 (24.7–29.0) Current or former smoker; number (%) 340 (41.1) Daily caloric intake, kcal; median (IQR) 1,698 (1,337–2,153) Energy-adjusted Healthy Eating Index score b ; median (IQR) 64 (55–72) MET hours per week; median (IQR) 16 (10–24) a Other includes Asian American, Hispanic, and Pacific Islander. b Score ranges from 0 to 100; a higher score reflects a higher overall diet quality. Abbreviations: IQR, interquartile range; mpMRI, multiparametric magnetic resonance imaging; MET, metabolic equivalent of task. After adjusting for baseline covariates, no statistically significant association was identified for MET hours per week with either GR to ≥ GG2 (SHR 1.04 per SD increase, 95% CI 0.90–1.21), p = 0.57, or extreme GR (SHR 1.03, 95% CI 0.79–1.35), p = 0.82,. After adjustment for physical activity, the E-HEI score remained significantly associated with lower risks of GR to ≥ GG2 (SHR 0.85 per SD increase, 95% CI 0.73–0.99), p = 0.04, and extreme GR (SHR 0.74, 95% CI 0.58–0.95), p = 0.02 (Table 2 ). Results were comparable with METs assessed as tertiles ( Supplemental Table 3 ). Table 2 Multivariable regression analysis of baseline clinicopathological and modifiable risk factors and prostate cancer grade reclassification during active surveillance Grade reclassification to ≥ GG2 Grade reclassification to ≥ GG3 (No. events/N: 167/806) (No. events/N: 51/806) Characteristic SHR 95% CI p SHR 95% CI p Clinicopathological factors Year of diagnosis 1.08 1.01–1.17 .04 1.05 0.92–1.21 .45 Patient age at diagnosis, years 1.05 1.02–1.08 .002 1.10 1.04–1.17 .001 Black race (vs. non-Black) 0.82 0.43–1.59 .56 0.24 0.03–1.74 .16 Prostate-specific antigen density (per 0.1 ng/mL 2 increase) 1.04 0.84–1.29 .71 1.06 0.73–1.53 .76 Number of positive biopsy cores at diagnosis 1.06 0.86–1.30 .58 1.03 0.77–1.38 .82 Maximum percent core involved with cancer (per 10% increase) 1.11 1.01–1.20 .02 1.04 0.90–1.22 .58 Use of pre-enrollment mpMRI (vs. not) 0.95 0.59–1.52 .82 0.96 0.35–2.64 .94 Modifiable risk factors Smoking history (vs. none) 1.02 0.75–1.39 .88 1.19 0.68–2.07 .54 Energy-adjusted Healthy Eating Index score (per SD increase a ) 0.85 0.73–0.99 .04 0.74 0.58–0.95 .02 MET hours per week (per SD increase b ) 1.04 0.90–1.21 .57 1.03 0.79–1.35 .82 Note: Multivariable regression models used complete case analysis by excluding 22 patients with missing data (2.7%); p -values <0.05 bolded. a SD = 12.5 for energy-adjusted Healthy Eating Index score b SD = 10.6 for MET hours per week Abbreviations: CI, confidence interval; GG, Grade Group; MET, metabolic equivalent of task; mpMRI, multiparametric magnetic resonance imaging; SD, standard deviation; SHR, subdistribution hazard ratio. Discussion In a prospective cohort of over 800 men with a median follow-up of over 6 years, we did not find a statistically significant association between physical activity at baseline assessed using self-reported data and risk of PCa GR during AS. Higher diet quality remained significantly associated with reduced risk of PCa GR to ≥ GG2, and ≥ GG3 on AS, 1 after adjusting for physical activity. To our knowledge, this is the only prospective cohort study to date comprehensively assessing physical activity, diet, and smoking as modifiable lifestyle factors for association with PCa GR on AS. There are limited and conflicting data regarding whether physical activity may influence PCa disease progression during AS. In a case-control study of 237 men from two AS programs who retrospectively provided lifestyle data, increased overall and vigorous physical activity were associated with significantly decreased odds of PCa reclassification, a composite outcome defined as grade or volume increase on surveillance biopsy and adverse PSA kinetics. 6 Another retrospective cohort study of 85 men also suggested that increased physical activity was associated with a reduced risk of PCa reclassification, a composite outcome similarly encompassing grade and volume increases on surveillance biopsy and clinical upstaging. 8 However, these studies were limited by recall bias due to retrospective collection of self-reported lifestyle data, modest sample sizes, and the first group excluded men who died of non-PCa causes, which may create sampling bias. The ERASE RCT prospectively randomized men on AS to a HIIT regimen versus control, and found a significant decrease in PSA and PSA velocity. 5 In addition to the ERASE RCT, several prospective trials have assessed the impact of physical activity interventions on a variety of serum biomarkers, yielding mixed results. 15 – 17 While promising, these studies involved small samples (range: 27 to 100 participants) followed for relatively short periods and assessed changes in inflammatory biomarkers, rather than PCa-related outcomes. Of note, some of these studies involve both diet and physical activity interventions, which may make distinguishing the impact of each more difficult. In comparison to the existing literature, strengths of our study include a large study cohort with long-term follow-up data, prospective collection of physical activity, diet, and lifestyle data at baseline limiting recall bias, and direct assessment of AS oncologic outcomes (i.e. any GR and extreme GR after 2 enrollment biopsies) that may be more likely to capture actual disease progression. Also, the prospective design allowed appropriate incorporation of time at risk for men who were censored or counted as competing risk events Prospective data from men diagnosed with clinically localized PCa, a much broader population than men on AS, have suggested an association for increased physical activity with improved overall survival, PCa-specific survival, and reduced disease progression. 18 , 19 Therefore, the lack of association identified in our study may be due to evaluating grade reclassification only in patients with low-risk disease managed with AS. Change from GG1 to GG2 or higher disease is a more subtle phenotypic change, in some cases representing higher grade tumor missed at initial biopsies. Thus, there is less scope for physical activity to evidence a biological impact. In men with higher-risk disease, physical activity and exercise may have a stronger, beneficial impact on reducing disease progression. For example, one meta-analysis recently showed an improvement in all-cause survival and PCa specific survival in all-comers with PCa, with exercise associated with a reduction in PCa specific mortality (pooled HR 0.73, 95% CI: 0.62—0.87). 2 Furthermore, physical activity has proven cardiovascular and overall survival benefits in the general population and should be recommended for all patients. 20 , 21 Study limitations included use of self-reported data, potential residual and unmeasured confounding inherent to an observational study design, and the single-institutional nature of our data potentially limiting generalizability. Further, we did not assess whether lifestyle behaviors changed since baseline. This is an important area of future study given the results from the aforementioned meta-analysis that showed a decreased PCa specific mortality associated with increased exercise, which focused on exercise behaviors afte r cancer diagnosis. 2 Similar to findings in the smoking literature, cancer diagnosis may represent an optimal opportunity for lifestyle modification discussion with patients regarding exercise and diet. Non-response bias was another potential limitation, although in our previous study we showed that GR rates were similar between questionnaire respondents and non-respondents. 1 Finally, the median MET hours per week of 16 (SD 10.6) in our cohort represents a relatively high activity level, exceeding the minimal activity levels (usually around 8–16 MET hours per week) recommended by current guidelines. 22 , 23 Therefore, our study group may be more active than the general population on average and/or may be over-estimating their self-reported physical activity. However, due to the prospective nature of our study, over-estimation of physical activity would likely be non-differential, causing the effect of physical activity to be under-estimated. In conclusion, in a large prospective cohort with long-term follow-up, after adjusting for patient clinicopathological and lifestyle factors, increasing physical activity was not associated with a lower risk of PCa GR. This is the first study to evaluate physical activity prospectively in men on AS. Further prospective studies involving objective measurement and tracking of physical activity and exercise throughout follow-up are warranted to further clarify the relationship between physical activity and PCa disease progression. Additional Information: Declarations Conflicts of Interest: Zhuo Tony Su reported receiving the Persky Scholarship, a Johns Hopkins Urology Intramural Grant, during the conduct of the study. Bruce J. Trock reported receiving personal fees for consulting from Emmes Inc and Myriad Genetics and grants from MDxHealth outside the submitted work. No other disclosures to report. Ethics approval and consent to participate: Institutional Review Board approval was obtained from the Johns Hopkins IRB (number NA_00045103). Patient consent was obtained from all patients at time of AS enrollment. The study was performed in accordance with the Declaration of Helsinki. Funding: This study was supported by the Patrick C. Walsh Prostate Cancer Research Fund (Bruce J. Trock). Acknowledgements: None. References Su ZT, Mamawala M, Landis PK, et al. Diet Quality, Dietary Inflammatory Potential, and Risk of Prostate Cancer Grade Reclassification. JAMA Oncol . 2024;10(12):1702. doi: 10.1001/jamaoncol.2024.4406 Ungvari Z, Fekete M, Varga P, et al. Exercise and survival benefit in cancer patients: evidence from a comprehensive meta-analysis. GeroScience . 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Supplementary Files Supplementaltablesfinal.docx Supplemental Tables Cite Share Download PDF Status: Published Journal Publication published 18 Feb, 2026 Read the published version in Prostate Cancer and Prostatic Diseases → Version 1 posted Editorial decision: revise 16 Jun, 2025 Review # 1 received at journal 08 Jun, 2025 Review # 2 received at journal 01 Jun, 2025 Reviewer # 2 agreed at journal 21 May, 2025 Reviewer # 1 agreed at journal 21 May, 2025 Reviewers invited by journal 16 May, 2025 Editor assigned by journal 16 May, 2025 Submission checks completed at journal 15 May, 2025 First submitted to journal 13 May, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Johns Hopkins School of Medicine,","correspondingAuthor":false,"prefix":"","firstName":"Carlos","middleName":"Rivera","lastName":"Lopez","suffix":""},{"id":457666594,"identity":"3124fb3f-7ac6-4ef7-90b9-ae6e52ec7bc2","order_by":8,"name":"Christian Pavlovich","email":"","orcid":"","institution":"Johns Hopkins School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Christian","middleName":"","lastName":"Pavlovich","suffix":""},{"id":457666595,"identity":"eb91e2cb-548e-43c2-88c1-13821df8d0c2","order_by":9,"name":"Bruce Trock","email":"","orcid":"","institution":"Johns Hopkins","correspondingAuthor":false,"prefix":"","firstName":"Bruce","middleName":"","lastName":"Trock","suffix":""}],"badges":[],"createdAt":"2025-05-13 15:40:28","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6657111/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6657111/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41391-026-01085-9","type":"published","date":"2026-02-18T05:00:00+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":102901178,"identity":"927216af-392b-4b0f-8807-4bdf33023c9c","added_by":"auto","created_at":"2026-02-18 08:12:26","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":584145,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6657111/v1/09494278-9ee2-4281-ad09-635c6c7b1958.pdf"},{"id":83165322,"identity":"b5208241-4fc5-4639-af7f-606617ecb476","added_by":"auto","created_at":"2025-05-20 16:02:38","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":34958,"visible":true,"origin":"","legend":"Supplemental Tables","description":"","filename":"Supplementaltablesfinal.docx","url":"https://assets-eu.researchsquare.com/files/rs-6657111/v1/d4d9f9aa1af7474f99033d19.docx"}],"financialInterests":"\u003cb\u003eYes\u003c/b\u003e there is potential conflict of interest.","formattedTitle":"Physical Activity, Diet Quality, and Risk of Prostate Cancer Grade Reclassification on Active Surveillance: Results from a Prospective Cohort Study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAmong men pursuing active surveillance (AS) for favorable-risk prostate cancer (PCa), many are highly motivated to seek lifestyle modifications\u0026mdash;such as diet and exercise\u0026mdash;to reduce the risk of disease progression. In our institutional cohort, initial data suggest a higher overall diet quality, reflecting stricter adherence to American dietary guideline recommendations, may be associated with a reduced risk of PCa grade reclassification (GR) in men diagnosed with Grade Group 1 (GG1) disease managed with AS.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e However, there remain limited and conflicting data regarding whether physical activity or exercise may influence the risk of disease progression during AS.\u003c/p\u003e \u003cp\u003eThe overall impact of exercise for men with PCa is encouraging; a recent meta-analysis demonstrated a marked improvement in all-cause survival and PCa specific survival associated with increased exercise levels.\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e Furthermore, both the US Department of Health and Human Services \u003cem\u003ePhysical Activity Guidelines for Americans\u003c/em\u003e and the American College of Sports Medicine specifically recommend that people with PCa exercise regularly as it may decrease cancer-specific mortality.\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e,\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e However these recommendations are based on data from all patients with PCa. In patients undergoing AS, data are more limited. A prospective randomized controlled trial (RCT), the ERASE study, demonstrated promising findings of a decrease in PSA and PSA velocity in patients undergoing a high-intensity interval training (HIIT) regimen.\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e However, the impact of exercise in retrospective studies on PCa AS are mixed.\u003csup\u003e\u003cspan additionalcitationids=\"CR7\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e In this study, we prospectively examined the association of patient self-reported physical activity level and diet quality at baseline with PCa GR on biopsy during AS.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eEstablished in 1995, our institutional AS program is one of the largest, longest-running prospective PCa AS cohorts.\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e Beginning in 2005, at the time of AS enrollment participants were invited to complete the Block 1998 Food Frequency Questionnaire (FFQ; NutritionQuest), a validated questionnaire regarding usual dietary patterns, and a lifestyle questionnaire.\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e,\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e The lifestyle questionnaire collects a comprehensive list of self-reported physical activities, in accordance with the \u003cem\u003eCompendium of Physical Activities\u003c/em\u003e, which provides a detailed coding scheme to assign metabolic equivalent intensity to each specific physical activity.\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e Consistent with our prior study of diet quality,\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e we included men enrolled between January 2005 and February 2017 who were diagnosed with GG1 disease, did not demonstrate early GR to \u0026ge;\u0026thinsp;GG2 on confirmatory biopsy typically performed within 18 months of diagnostic biopsy, and completed both questionnaires prospectively upon AS enrollment. Institutional Review Board approval and patient consent were obtained from all patients at time of AS enrollment (IRB number NA_00045103).\u003c/p\u003e \u003cp\u003eBased on each man\u0026rsquo;s responses to the baseline FFQ, we calculated his Healthy Eating Index 1999\u0026ndash;2000 (HEI) score at baseline, a validated measure of overall diet quality in terms of adherence to recommendations of the \u003cem\u003eDietary Guidelines for Americans\u003c/em\u003e.\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e An energy-adjusted HEI (E-HEI) score was obtained by adjusting the HEI score for daily total caloric intake.\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e In the baseline lifestyle questionnaire, men reported specific types of typical physical activities or exercises and numbers of hours per activity over the course of the preceding year (see \u003cb\u003eSupplemental Tables\u0026nbsp;1 and 2\u003c/b\u003e). From the self-reported data, total metabolic equivalent of task (MET) hours per week was calculated. METs represent metabolic energy expenditure (Kcal/kg) as a standardized activity quantification, with coefficients assigned to adjust by type of physical activity.\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e,\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eWe evaluated two outcomes: GR to \u0026ge;\u0026thinsp;GG2, and GR to \u0026ge;\u0026thinsp;GG3 (i.e. extreme GR) on any surveillance biopsy. We performed multivariable competing risk proportional hazards regressions to assess the association of self-reported baseline physical activity level, measured as total MET hours per week, and overall diet quality, reflected by E-HEI score, with either GR outcome. As described previously,\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e competing events were defined as volume reclassification only on a surveillance biopsy, elective treatment, and non-PCa mortality. The regression models additionally adjusted for smoking history (any versus none) and established AS prognostic factors at baseline\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e including year of diagnosis, age at diagnosis, self-reported race (Black versus non-Black), prostate-specific antigen (PSA) density, number of positive biopsy cores, maximum percent involvement of a core at diagnosis, and use of pre-enrollment multiparametric magnetic resonance imaging (yes versus no). Subdistribution hazard ratios (SHRs) were calculated per one standard deviation (SD) increase in MET hours per week and E-HEI score. We also evaluated MET hours per week categorized as tertiles. We performed statistical analyses using STATA version 18.0 (StataCorp LLC, College Station, TX). All tests were two sided, with statistical significance set at \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eIn total, we included 828 men. Their baseline characteristics are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. At baseline, 41% reported any smoking history, median E-HEI score was 64 (SD 12.5), and median MET hours per week was 16.0 (SD 10.6). After median follow-up of 6.4 years (interquartile range 4.0-9.1), 174 (21%) demonstrated GR to \u0026ge;\u0026thinsp;GG2, including 53 (6.4%) with extreme GR. The cumulative incidence of GR to \u0026ge;\u0026thinsp;GG2 was 7% (95% confidence interval [CI] 5%-9%) at 3 years, 15% (95% CI 12%-18%) at 5 years, and 33% (95% CI 28%-37%) at 10 years; that of extreme GR was 2% (95% CI 1%-4%) at 3 years, 4% (95% CI 3%-6%) at 5 years, and 10% (95% CI 7%-13%) at 10 years. Median MET hours per week was 16.0 for men without GR versus 17.1 for men with GR (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.44), and median E-HEI score was 64 versus 63, respectively (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.45).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline characteristics of study cohort (N\u0026thinsp;=\u0026thinsp;828)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eValue\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYear of diagnosis; median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2010 (2008\u0026ndash;2013)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient age, years; median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e66 (61\u0026ndash;69)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSelf-reported race; number (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBlack\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e49 (5.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWhite\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e754 (91.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25 (3.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal prostate-specific antigen, ng/mL; median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.8 (3.5\u0026ndash;6.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProstate volume, mL; median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e45 (35\u0026ndash;60)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProstate-specific antigen density, ng/mL\u003csup\u003e2\u003c/sup\u003e; median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.10 (0.07\u0026ndash;0.14)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of positive biopsy cores at diagnosis; median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (1\u0026ndash;2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaximum percent core involved with cancer, %; median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (1\u0026ndash;15)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUse of pre-enrollment mpMRI; number (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e305 (36.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBody mass index, kg/m\u003csup\u003e2\u003c/sup\u003e; median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26.6 (24.7\u0026ndash;29.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCurrent or former smoker; number (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e340 (41.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDaily caloric intake, kcal; median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1,698 (1,337\u0026ndash;2,153)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEnergy-adjusted Healthy Eating Index score\u003csup\u003eb\u003c/sup\u003e; median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e64 (55\u0026ndash;72)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMET hours per week; median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16 (10\u0026ndash;24)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003e\u003csup\u003ea\u003c/sup\u003e Other includes Asian American, Hispanic, and Pacific Islander.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003e\u003csup\u003eb\u003c/sup\u003e Score ranges from 0 to 100; a higher score reflects a higher overall diet quality.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e\u003cp\u003e\u003cem\u003eAbbreviations:\u003c/em\u003e IQR, interquartile range; mpMRI, multiparametric magnetic resonance imaging; MET, metabolic equivalent of task.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e \u003cp\u003eAfter adjusting for baseline covariates, no statistically significant association was identified for MET hours per week with either GR to \u0026ge;\u0026thinsp;GG2 (SHR 1.04 per SD increase, 95% CI 0.90\u0026ndash;1.21), \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.57, or extreme GR (SHR 1.03, 95% CI 0.79\u0026ndash;1.35), \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.82,. After adjustment for physical activity, the E-HEI score remained significantly associated with lower risks of GR to \u0026ge;\u0026thinsp;GG2 (SHR 0.85 per SD increase, 95% CI 0.73\u0026ndash;0.99), \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.04, and extreme GR (SHR 0.74, 95% CI 0.58\u0026ndash;0.95), \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.02 (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Results were comparable with METs assessed as tertiles (\u003cb\u003eSupplemental Table\u0026nbsp;3\u003c/b\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMultivariable regression analysis of baseline clinicopathological and modifiable risk factors and prostate cancer grade reclassification during active surveillance\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eGrade reclassification to \u0026ge;\u0026thinsp;GG2\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e \u003cp\u003eGrade reclassification to \u0026ge;\u0026thinsp;GG3\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003e(No. events/N: 167/806)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e \u003cp\u003e(No. events/N: 51/806)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSHR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e95% CI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eSHR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e95% CI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eClinicopathological factors\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYear of diagnosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.01\u0026ndash;1.17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e.04\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.92\u0026ndash;1.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e.45\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient age at diagnosis, years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.02\u0026ndash;1.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e.002\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.04\u0026ndash;1.17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBlack race (vs. non-Black)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.43\u0026ndash;1.59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.03\u0026ndash;1.74\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e.16\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProstate-specific antigen density (per 0.1 ng/mL\u003csup\u003e2\u003c/sup\u003e increase)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.84\u0026ndash;1.29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.73\u0026ndash;1.53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e.76\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of positive biopsy cores at diagnosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.86\u0026ndash;1.30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.77\u0026ndash;1.38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e.82\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaximum percent core involved with cancer (per 10% increase)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.01\u0026ndash;1.20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e.02\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.90\u0026ndash;1.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e.58\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUse of pre-enrollment mpMRI (vs. not)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.59\u0026ndash;1.52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.96\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.35\u0026ndash;2.64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e.94\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eModifiable risk factors\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSmoking history (vs. none)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.75\u0026ndash;1.39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.68\u0026ndash;2.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e.54\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEnergy-adjusted Healthy Eating Index score (per SD increase\u003csup\u003ea\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.85\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.73\u0026ndash;0.99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e.04\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.74\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.58\u0026ndash;0.95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e.02\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMET hours per week (per SD increase\u003csup\u003eb\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.90\u0026ndash;1.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.79\u0026ndash;1.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e.82\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e\u003cp\u003e\u003cem\u003eNote:\u0026nbsp;\u003c/em\u003eMultivariable regression models used complete case analysis by excluding 22 patients with missing data (2.7%); \u003cem\u003ep\u003c/em\u003e-values \u0026lt;0.05 bolded.\u003c/p\u003e\n\u003cp\u003e\u003csup\u003ea\u0026nbsp;\u003c/sup\u003eSD = 12.5 for energy-adjusted Healthy Eating Index score\u003c/p\u003e\n\u003cp\u003e\u003csup\u003eb\u0026nbsp;\u003c/sup\u003eSD = 10.6 for MET hours per week\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAbbreviations:\u003c/em\u003e CI, confidence interval; GG, Grade Group; MET, metabolic equivalent of task; mpMRI, multiparametric magnetic resonance imaging; SD, standard deviation; SHR, subdistribution hazard ratio.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn a prospective cohort of over 800 men with a median follow-up of over 6 years, we did not find a statistically significant association between physical activity at baseline assessed using self-reported data and risk of PCa GR during AS. Higher diet quality remained significantly associated with reduced risk of PCa GR to \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026ge;\u003c/span\u003e\u0026thinsp;GG2, and \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026ge;\u003c/span\u003e\u0026thinsp;GG3 on AS,\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e after adjusting for physical activity. To our knowledge, this is the only prospective cohort study to date comprehensively assessing physical activity, diet, and smoking as modifiable lifestyle factors for association with PCa GR on AS.\u003c/p\u003e \u003cp\u003eThere are limited and conflicting data regarding whether physical activity may influence PCa disease progression during AS. In a case-control study of 237 men from two AS programs who retrospectively provided lifestyle data, increased overall and vigorous physical activity were associated with significantly decreased odds of PCa reclassification, a composite outcome defined as grade or volume increase on surveillance biopsy and adverse PSA kinetics.\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e Another retrospective cohort study of 85 men also suggested that increased physical activity was associated with a reduced risk of PCa reclassification, a composite outcome similarly encompassing grade and volume increases on surveillance biopsy and clinical upstaging.\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e However, these studies were limited by recall bias due to retrospective collection of self-reported lifestyle data, modest sample sizes, and the first group excluded men who died of non-PCa causes, which may create sampling bias. The ERASE RCT prospectively randomized men on AS to a HIIT regimen versus control, and found a significant decrease in PSA and PSA velocity.\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e In addition to the ERASE RCT, several prospective trials have assessed the impact of physical activity interventions on a variety of serum biomarkers, yielding mixed results.\u003csup\u003e\u003cspan additionalcitationids=\"CR16\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e While promising, these studies involved small samples (range: 27 to 100 participants) followed for relatively short periods and assessed changes in inflammatory biomarkers, rather than PCa-related outcomes. Of note, some of these studies involve both diet and physical activity interventions, which may make distinguishing the impact of each more difficult. In comparison to the existing literature, strengths of our study include a large study cohort with long-term follow-up data, prospective collection of physical activity, diet, and lifestyle data at baseline limiting recall bias, and direct assessment of AS oncologic outcomes (i.e. any GR and extreme GR after 2 enrollment biopsies) that may be more likely to capture actual disease progression. Also, the prospective design allowed appropriate incorporation of time at risk for men who were censored or counted as competing risk events\u003c/p\u003e \u003cp\u003eProspective data from men diagnosed with clinically localized PCa, a much broader population than men on AS, have suggested an association for increased physical activity with improved overall survival, PCa-specific survival, and reduced disease progression.\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e,\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e Therefore, the lack of association identified in our study may be due to evaluating grade reclassification only in patients with low-risk disease managed with AS. Change from GG1 to GG2 or higher disease is a more subtle phenotypic change, in some cases representing higher grade tumor missed at initial biopsies. Thus, there is less scope for physical activity to evidence a biological impact. In men with higher-risk disease, physical activity and exercise may have a stronger, beneficial impact on reducing disease progression. For example, one meta-analysis recently showed an improvement in all-cause survival and PCa specific survival in all-comers with PCa, with exercise associated with a reduction in PCa specific mortality (pooled HR 0.73, 95% CI: 0.62\u0026mdash;0.87).\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e Furthermore, physical activity has proven cardiovascular and overall survival benefits in the general population and should be recommended for all patients.\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e,\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eStudy limitations included use of self-reported data, potential residual and unmeasured confounding inherent to an observational study design, and the single-institutional nature of our data potentially limiting generalizability. Further, we did not assess whether lifestyle behaviors changed since baseline. This is an important area of future study given the results from the aforementioned meta-analysis that showed a decreased PCa specific mortality associated with increased exercise, which focused on exercise behaviors afte\u003cem\u003er\u003c/em\u003e cancer diagnosis.\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e Similar to findings in the smoking literature, cancer diagnosis may represent an optimal opportunity for lifestyle modification discussion with patients regarding exercise and diet. Non-response bias was another potential limitation, although in our previous study we showed that GR rates were similar between questionnaire respondents and non-respondents.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e Finally, the median MET hours per week of 16 (SD 10.6) in our cohort represents a relatively high activity level, exceeding the minimal activity levels (usually around 8\u0026ndash;16 MET hours per week) recommended by current guidelines.\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e,\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e Therefore, our study group may be more active than the general population on average and/or may be over-estimating their self-reported physical activity. However, due to the prospective nature of our study, over-estimation of physical activity would likely be non-differential, causing the effect of physical activity to be under-estimated.\u003c/p\u003e \u003cp\u003eIn conclusion, in a large prospective cohort with long-term follow-up, after adjusting for patient clinicopathological and lifestyle factors, increasing physical activity was not associated with a lower risk of PCa GR. This is the first study to evaluate physical activity prospectively in men on AS. Further prospective studies involving objective measurement and tracking of physical activity and exercise throughout follow-up are warranted to further clarify the relationship between physical activity and PCa disease progression.\u003c/p\u003e \u003cp\u003eAdditional Information:\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eConflicts of Interest: Zhuo Tony Su reported receiving the Persky Scholarship, a Johns Hopkins Urology Intramural Grant, during the conduct of the study. Bruce J. Trock reported receiving personal fees for consulting from Emmes Inc and Myriad Genetics and grants from MDxHealth outside the submitted work. No other disclosures to report.\u003c/p\u003e\n\u003cp\u003eEthics approval and consent to participate: Institutional Review Board approval was obtained from the Johns Hopkins IRB (number NA_00045103). Patient consent was obtained from all patients at time of AS enrollment. The study was performed in accordance with the Declaration of Helsinki.\u003c/p\u003e\n\u003cp\u003eFunding: This study was supported by the Patrick C. Walsh Prostate Cancer Research Fund (Bruce J. Trock).\u003c/p\u003e\n\u003cp\u003eAcknowledgements: \u0026nbsp; None.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eSu ZT, Mamawala M, Landis PK, et al. Diet Quality, Dietary Inflammatory Potential, and Risk of Prostate Cancer Grade Reclassification. \u003cem\u003eJAMA Oncol\u003c/em\u003e. 2024;10(12):1702. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1001/jamaoncol.2024.4406\u003c/span\u003e\u003cspan address=\"10.1001/jamaoncol.2024.4406\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eUngvari Z, Fekete M, Varga P, et al. 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However, there remain limited and conflicting data regarding whether physical activity may influence disease progression.\u003c/p\u003e\u003cp\u003e\u003cb\u003eMethods\u003c/b\u003e\u003c/p\u003e \u003cp\u003eThis is a prospective cohort study of men with Grade Group (GG) 1 PCa enrolled in AS. Patients completed detailed diet and physical activity surveys at time of AS enrollment. Physical activity was evaluated as metabolic equivalent of task (MET) hours per week, diet quality was measured as energy-adjusted Healthy Eating Index (E-HEI) score. Multivariable competing risk regressions were utilized to examine the association of diet and physical activity with GR on biopsy to \u0026ge;\u0026thinsp;GG2 or \u0026ge;\u0026thinsp;GG3.\u003c/p\u003e\u003cp\u003e\u003cb\u003eResults\u003c/b\u003e\u003c/p\u003e \u003cp\u003eWe included 828 men with a median follow up of 6.4 years. We found no significant association between MET hours per week and GR to \u0026ge;\u0026thinsp;GG2 (subdistribution hazard ratio (SHR) 1.04 per standard deviation (SD) increase in weekly MET hours, 95% confidence interval (CI) 0.90\u0026ndash;1.21), or extreme GR to \u0026ge;\u0026thinsp;GG3 (SHR 1.03, 95% CI 0.79\u0026ndash;1.35). Higher overall diet quality remained associated with significantly reduced risks of GR to \u0026ge;\u0026thinsp;GG2 (SHR 0.85 per SD increase in E-HEI score, 95% CI 0.73\u0026ndash;0.99) and extreme GR (SHR 0.74, 95% CI 0.58\u0026ndash;0.95).\u003c/p\u003e\u003cp\u003e\u003cb\u003eConclusions\u003c/b\u003e\u003c/p\u003e \u003cp\u003eIn this prospective cohort study with longitudinal follow-up of men diagnosed with GG1 PCa pursuing AS, after adjusting for clinicopathological and lifestyle factors, increasing physical activity was not associated with a lower risk of PCa GR. A higher overall diet quality was associated with a reduced risk of GR for both GR outcomes. In our cohort, physical activity level does not appear to be associated with PCa progression on AS.\u003c/p\u003e","manuscriptTitle":"Physical Activity, Diet Quality, and Risk of Prostate Cancer Grade Reclassification on Active Surveillance: Results from a Prospective Cohort Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-20 16:02:33","doi":"10.21203/rs.3.rs-6657111/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"revise","date":"2025-06-16T16:01:16+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"This content is not available.","date":"2025-06-08T22:50:40+00:00","index":1,"fulltext":"This content is not available."},{"type":"editorInvitedReview","content":"This content is not available.","date":"2025-06-01T04:15:08+00:00","index":2,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2025-05-21T13:00:18+00:00","index":2,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2025-05-21T08:31:37+00:00","index":1,"fulltext":"This content is not available."},{"type":"reviewersInvited","content":"","date":"2025-05-16T13:54:21+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-05-16T13:30:22+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-05-15T14:57:06+00:00","index":"","fulltext":""},{"type":"submitted","content":"Prostate Cancer and Prostatic Diseases","date":"2025-05-13T15:35:40+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"prostate-cancer-and-prostatic-diseases","isNatureJournal":false,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"pcan","sideBox":"Learn more about [Prostate Cancer and Prostatic Diseases](http://www.nature.com/pcan/)","snPcode":"41391","submissionUrl":"https://mts-pcan.nature.com/cgi-bin/main.plex","title":"Prostate Cancer and Prostatic Diseases","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"a340212c-3069-4515-84ba-b30cf7c5df8b","owner":[],"postedDate":"May 20th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":48640276,"name":"Health sciences/Medical research/Outcomes research"},{"id":48640277,"name":"Biological sciences/Cancer/Urological cancer/Prostate cancer"}],"tags":[],"updatedAt":"2026-02-18T08:12:21+00:00","versionOfRecord":{"articleIdentity":"rs-6657111","link":"https://doi.org/10.1038/s41391-026-01085-9","journal":{"identity":"prostate-cancer-and-prostatic-diseases","isVorOnly":false,"title":"Prostate Cancer and Prostatic Diseases"},"publishedOn":"2026-02-18 05:00:00","publishedOnDateReadable":"February 18th, 2026"},"versionCreatedAt":"2025-05-20 16:02:33","video":"","vorDoi":"10.1038/s41391-026-01085-9","vorDoiUrl":"https://doi.org/10.1038/s41391-026-01085-9","workflowStages":[]},"version":"v1","identity":"rs-6657111","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6657111","identity":"rs-6657111","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}