Abstract Background: Interest in fasting related to cancer has increased as evidence suggests fasting may have anti-cancer benefits. Fasting has been shown to deprive cancer cells of nutrients, thereby inhibiting their growth and proliferation and making them more sensitive to chemotherapy in preclinical studies. Clinical trials incorporating fasting have grown over the years; however, recruiting participants remains challenging due to eligibility criteria, protocol complexities, and public interest. Identifying public interest in fasting and cancer, as well as in cancer-fasting clinical trials could help improve methods to raise awareness of the importance of fasting clinical trials and increase the number of trials to improve cancer. Objective: To determine if public interest in fasting and cancer corresponds with cancer fasting clinical trials. Methods: U.S. Google Trends data were queried by region from January 2004 to October 2025 to identify public interest in fasting overall (across all categories) and by cancer. Data are presented using relative search interest (RSI) ranging from 0 to 100, with 100 indicating the most searched, 50 representing half as many searches, and zero or null indicating insufficient data. Data from clinicaltrials.gov and Surveillance, Epidemiology, and End Results (SEER) Program were queried and used for trend analysis. Results: Public interest in fasting in general, not restricted to cancer, across all categories was low prior to 2011 (RSI generally <20). RSI began to increase slightly after 2011 and grew to 30 by 2016. There was a sharper increase after 2016 with interest peaking in November 2019 (RSI=100) but has remained consistently high since (RSI range 50-80 since 2019). When examining only cancer interest, fasting related to cancer remained low with occasional spikes, but began to increase after 2016, in-line with the increased interest in fasting not limited to cancer. Indeed, interest in fasting and cancer largely mirrored general interest in fasting trends. Among all states with data, most had an RSI of 75 or higher for fasting across all categories. From 1991 to the present, 255 clinical trials have been initiated on fasting and cancer. The number of new trials per year slightly rose from 2000 to 2008, then dipped a bit, and then grew again slightly from 2013 (15 new trials in 2013) to 2025 (18 new cancer-fasting trials in 2025). Conclusions: Public interest in fasting and cancer in the past ∼12 years has grown 2-3-fold and been sustained at a high level over the past ∼8 years. In contrast, the number of new trials started per year has barely changed over this time. While the reasons fasting trial numbers have lagged public interest are unknown, we speculate challenges enrolling and receiving funding for dietary trials may play a role. Given promising preclinical data coupled with public health interest, there should be increased funding and support for fasting trials in patients with cancer. Citation Format: Alanna Burwell, Maria Mogollon, Alexander Hernandez, Nadine Friedrich, Pao-hwa Lin, Stephen J. Freedland. Examining trends of public interest in fasting and cancer-fasting clinical trials in the U.S [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 925.

We investigated the real-world criteria and thresholds physicians use to classify patients with nonmetastatic castration-sensitive prostate cancer with biochemical recurrence as high risk, and how these align with guidelines. Descriptive analyses were conducted using data abstracted from an independent, retrospective, cross-sectional survey completed by urologists and radiation oncologists in the USA between April and November 2023. Physicians provided their perspectives and extracted chart data for the last 6–8 patients they diagnosed with high-risk biochemical recurrence. The cohort included 87 physicians (79

5071 Background: Olaparib, a targeted therapy for metastatic castration-resistant prostate cancer (mCRPC), has demonstrated clinical benefits in patients with homologous recombination repair (HRR) gene alterations, as shown in the PROfound trial. As the largest integrated healthcare system in the US, the Veteran’s Health Administration (VHA) offers insights into olaparib use among a diverse population. We characterized the treatment patterns and outcomes of patients with mCRPC treated with olaparib. Methods: We identified all VHA patients with mCRPC who received olaparib between May 2020 and December 2023. We then performed a retrospective chart review of data from May 2018 to June 2025 to capture pre- and post-treatment data. Demographics, baseline characteristics, biomarker testing and treatment sequencing were summarized. We analyzed time to event outcomes: time to next therapy (TTNT), and overall survival (OS) via Kaplan-Meier methods, both starting from olaparib initiation. Results: We identified 477 mCRPC patients receiving olaparib. Median age at initiation was 75, older than subjects in PROfound (median age 69). Most patients were non-Hispanic White (69%), followed by Black/African American (20%) and Hispanic/Latino (6%). Between 2020 and 2023, olaparib was most commonly initiated in ≥5th line after prostate cancer diagnosis (46%), followed by 4 th (25%), 3 rd (22%), and 2 nd line (6.5%). All patients had received an androgen receptor pathway inhibitor prior to olaparib. Median time from HRR testing to olaparib initiation was 5 months. Median TTNT was 7 months; OS was 12 months. Use of olaparib in an earlier line post first NHA was associated with numerically longer OS (17 months for 1st line vs. 8 months for 4th or later). Conclusions: Within the VHA, olaparib showed favorable outcomes despite older age and late-line use, supporting effectiveness in routine practice and in a more diverse population with substantially higher representation of Black/African American and Hispanic/Latino individuals than in clinical trials. Understanding these treatment patterns provides insight into clinical practice and helps guide towards optimal integration of olaparib into management of mCRPC. Kaplan-Meier estimates for time to event outcomes. #Events/Total Median Time (95% CI) (months) Time to Next Treatment - All Patients 449/477 7 (6-8) - Olaparib Line of Treatment Post NHA 1st line 100/111 9 (7-10) 2nd line 151/162 8 (7-10) 3rd line 92/96 6 (5-8) 4th line or later 91/92 5 (4-6) Overall Survival - All Patients 395/477 12 (11-13) - Olaparib Line of Treatment Post NHA 1st line 79/111 17 (12-22) 2nd line 133/162 15 (12-17) 3rd line 85/96 10 (8-12) 4th line or later 88/92 8 (6-9)

BACKGROUND:We previously found that higher insulin resistance (IR) was associated with larger prostate size and greater risk of benign prostatic hyperplasia (BPH). Since BPH is the most common cause of lower urinary tract symptoms (LUTS), we investigated whether IR is also linked to incidence and progression of LUTS in the REDUCE study, a 4-year randomized trial of dutasteride vs. placebo for prostate cancer prevention. METHODS:Participants were required to complete the International Prostate Symptom Score (IPSS) questionnaire at recruitment and every subsequent 6 months. Fasting insulin and glucose levels were measured at study baseline, and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) was calculated based on these values. Multivariable Cox regression was used to assess associations between HOMA-IR and (1) LUTS incidence among asymptomatic patients (baseline IPSS < 8); or (2) LUTS progression among symptomatic patients (baseline IPSS ≥ 8) respectively. RESULTS:As previously reported within this cohort, at baseline, higher HOMA-IR quartiles were correlated with larger prostate volumes among both asymptomatic (N = 2745; p < 0.001) and symptomatic patients (N = 1942; p = 0.007). However, among asymptomatic patients, HOMA-IR whether analyzed as a continuous (p = 0.74) or categorized variable (all p ≥ 0.60) was not associated with LUTS incidence in multivariable analysis. Similarly, in symptomatic participants, no associations were found between HOMA-IR and LUTS progression in multivariable analyses, whether HOMA-IR was assessed as a categorical (all p ≥ 0.46) or continuous variable (p = 0.83). CONCLUSIONS:Although IR was linked to larger prostate volumes, it was not an independent risk factor of LUTS development or progression despite the known associations between BPH and LUTS.

QuestionDo disparities in cancer survival that are generally seen in the broader US population exist among Black veterans compared with veterans who are not Black receiving care through the Veterans Health Administration (VHA)?FindingsIn this systematic review of 39 studies representing 603 256 veterans, including a meta-analysis of 29 studies with sufficient outcome data, Black veterans with cancer receiving care through the VHA had similar or better overall survival and cancer-specific survival compared with those whose race was categorized as either White or non-Black.MeaningThese results suggest that equity in outcomes for Black veterans with cancer is being achieved for those receiving care through the VHA. This systematic review and meta-analysis of studies of US veterans receiving cancer care through the Veterans Health Administration compares outcomes for Black veterans compared with veterans from other racial groups. ImportanceIn the US, Black patients with cancer consistently experience worse survival compared to White patients, even after adjusting for age, sex, and disease stage. Whether these disparities exist among patients receiving care in the Veterans Health Administration (VHA), an integrated health system designed to provide near-equal access to care, remains uncertain.ObjectiveTo evaluate whether overall survival (OS) and cancer-specific survival (CSS) differ between Black veterans and those with other race receiving cancer care through VHA.Data SourcesPubMed was searched from January 2015 through April 2022. Reference lists from identified studies were also reviewed.Study SelectionStudies of US veterans receiving cancer care through the VHA were included if they reported OS or CSS by race and provided hazard ratios (HRs). Dual independent rating of titles and abstracts was conducted for inclusion.Data Extraction and SynthesisA random-effects model was used to pool effect sizes, the Paule-Mandel estimator was used to calculate the heterogeneity variance tau 2, and Knapp-Hartung adjustments were used to calculate the confidence interval of the pooled effect. Review and meta-analysis was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guideline.Main Outcomes and MeasuresOS and CSS were compared between Black veterans and those who were not Black using pooled HRs.ResultsOf 101 studies identified, 39 met inclusion criteria and 29 provided sufficient data for meta-analysis. The reported outcomes represented 603 256 veterans with cancer treated between 1983 and 2017, with a mean 29.0% (range, 8.9%-55.0%) of patients categorized as Black. All studies compared race by Black compared with White, except for 7 of 20 prostate cancer studies, which compared race by Black compared with non-Black. Black veterans were found to have better OS (HR, 0.93; 95% CI, 0.89-0.97) and CSS (HR, 0.94; 95% CI, 0.90-0.98). Survival advantages for Black veterans were observed across several cancer types, including bladder, laryngeal, lung, oropharyngeal, prostate, and plasma cell cancers. Between-study heterogeneity was low to moderate.Conclusions and RelevanceIn this systematic review and meta-analysis of peer-reviewed publications reporting the outcomes of veterans receiving cancer care through VHA, survival outcomes were generally similar or better for Black compared with White or non-Black veterans. These findings suggest that integrated health care systems providing near-equitable access to comprehensive cancer care can substantially reduce or eliminate disparities in cancer outcomes.

Purpose Social support, specifically marital status, has been shown as a significant prognostic factor for survival of multiple malignancies, including prostate cancer. However, this has not been investigated in an equal access Veterans Affairs (VA) cohort where other support systems exist that may minimize the potential benefit of social support from a partner. Methods We retrospectively reviewed data from 9,931 patients undergoing primary radical prostatectomy (RP) in the VA from 1988-2020 across 9 VA centers. Univariable and multivariable Cox proportional hazards models were used to test the association between marital status and biochemical recurrence (BCR), metastasis, castration-resistant PC (CRPC) and prostate cancer specific mortality (PCSM). Results 8,285 patients met the inclusion criteria: 54% were married, 30% were divorced/separated, 9% were single/never married, and 6% were widowed at the time of RP. Single/never married men were younger (median 61 vs 62-65 years), had surgery more recently (median 2009 vs 2003-2008), had higher PSA (median 6.9 ng/mL vs 6.4-6.8 ng/mL), and had lower BMI (median 27 vs 28) compared to other groups (all p < 0.05). The median time to BCR was significantly shorter for divorced/separated men (188.2 months) and single/never married men (154.8 months) compared to married men (243.0 months). Consistent with this finding, compared to married men, divorced/separated men had higher risk of BCR (HR = 1.12; 95% CI 1.03-1.21), as did single/never married men (HR = 1.13; 95% CI 1.00-1.28). However, these associations were insignificant in multivariable analyses (all p > 0.05). Conclusion Among men with localized prostate cancer undergoing RP within the VA, we found no association between marital status-defined as a demographic indicator of self-reported relationship category-and oncologic outcomes. Whether marital satisfaction or perceived partner support, which were not assessed in this study, influence post-RP outcomes remains to be investigated.

This cohort study compares magnetic resonance imaging with confirmatory biopsy for patients with favorable-risk prostate cancer undergoing active surveilance.

BACKGROUND:Multiple phase 3 metastatic castration-sensitive prostate cancer (mCSPC) studies consistently show a prostate-specific antigen (PSA) nadir of <0.2 ng/mL to be the preferred threshold for PSA response. However, in real-world practice, physicians often use other metrics such as percentage of PSA decline. METHODS:This retrospective analysis of Veterans Health Administration data (2006-2024) assessed the association between PSA response and overall survival (OS) in patients with mCSPC who initiated androgen deprivation therapy (ADT) ± other treatments, using landmark analyses with adjusted Cox regressions. PSA response metrics included ≥90% PSA decline and a PSA of <0.2 ng/mL within 9 months of starting therapy. RESULTS:Among 4890 patients, 44% reached a PSA of <0.2 ng/mL and 74% had ≥90% PSA decline. Patients with a PSA of <0.2 ng/mL within 9 months of ADT initiation had a reduced risk of death after this time point (adjusted hazard ratio [HR], 0.46; 95% confidence interval [CI], 0.40-0.54) versus patients who did not. OS improvements with a PSA of <0.2 ng/mL were similar, regardless of ≥90% (adjusted HR, 0.43; 95% CI, 0.35-0.52) or <90% PSA decline (adjusted HR, 0.36; 95% CI, 0.23-0.56). Achieving ≥90% PSA decline without a PSA of <0.2 ng/mL was unrelated to improved OS. Patients who initiated ADT plus androgen receptor pathway inhibitors versus ADT alone were more likely to achieve a PSA of <0.2 ng/mL during PSA follow-up (adjusted HR, 1.71; 95% CI, 1.55-1.88). CONCLUSIONS:In a real-world mCSPC setting, achieving a PSA of <0.2 ng/mL (whether or not a PSA decline of 90% was reached) within 9 months of initiating ADT ± other treatments was associated with improved OS, which supports a PSA nadir of <0.2 ng/mL for optimizing mCSPC outcomes.

BACKGROUND:This population-based study aimed to quantify fracture risk after androgen receptor pathway inhibitors in advanced prostate cancer patients by preexisting health conditions. METHODS:Patients were identified from the Surveillance, Epidemiology, and End Results-Medicare files who received abiraterone acetate with prednisone or enzalutamide between January 1, 2013, and December 31, 2020. Health and fracture history were based on claims 1 year before androgen receptor pathway inhibitor with follow-up through December 31, 2020. The main outcome of the study was the cumulative fracture risk after first date of androgen receptor pathway inhibitor. Fine and Gray subdistribution hazard model was used to obtain adjusted relative risks with confounding factors. RESULTS:This study included 10 463 patients (6037 treated with abiraterone acetate with prednisone; 4426 treated with enzalutamide). The 3-year fracture risk after androgen receptor pathway inhibitor was high, exceeding 25% among those without a prior fracture. Among 1445 men with a fracture the year before androgen receptor pathway inhibitor, 3-year fracture risk exceeded 50% and remained high (above 44%) despite using bone health agents. A recent history of fracture was associated with a 2.84-fold fracture risk (adjusted hazard ratio [HR] = 2.84, 95% confidence interval [CI] = 2.58 to 3.12). Preexisting osteoporosis and a comorbidity score of 2 or higher were associated with 15% (adjusted HR = 1.15, 95% CI = 1.03 to 1.29) and 11% (adjusted HR = 1.11, 95% CI = 1.00 to 1.24) higher fracture risks. Bone health agent use was associated with a 23% lower fracture risk (adjusted HR = 0.77, 95% CI = 0.70 to 0.83). CONCLUSIONS:Fracture risk after androgen receptor pathway inhibitor was high, exceeding 44% within 3 years in those with prior fractures despite bone health agents, suggesting limited benefit in patients with poor bone quality. Early identification and intervention for patients at high risk of fractures are critical.

5088 Background: The phase 3 EMBARK trial demonstrated significantly longer metastasis-free survival and overall survival for enzalutamide plus leuprolide (enzalutamide combination) vs leuprolide alone in patients with prostate cancer and high-risk biochemical recurrence (hrBCR). In EMBARK, patients with prostate-specific antigen (PSA) < 0.2 ng/mL at week 36 suspended treatment at week 37. Androgen deprivation-related testosterone suppression has been linked to adverse health outcomes, whereas testosterone recovery while off treatment has been associated with improved quality of life. The objective of this post hoc analysis was to assess testosterone recovery to > 250 ng/dL during treatment suspension in patients treated with enzalutamide combination. Methods: Eligible patients had hrBCR, with a PSA doubling time of ≤9 months. Patients were randomized 1:1:1 to enzalutamide + leuprolide, leuprolide alone, or enzalutamide monotherapy. Patients who suspended treatment at week 37 reinitiated treatment upon PSA increase to protocol-defined levels. Testosterone levels were assessed every 12 weeks. Results: In the enzalutamide combination group, 320 patients suspended treatment. During treatment suspension, testosterone recovery to > 250 ng/dL occurred in 108 patients (33.8%) (Table). Among those who recovered their testosterone, median and mean time to recovery was 5.6 months and 6.8 months, respectively, although some patients had delayed recovery (Table). Conclusions: Testosterone recovery to > 250 ng/dL during treatment suspension was observed in approximately one-third of patients treated with enzalutamide combination. While average time to testosterone recovery among those who recovered was ~6 months, recovery was delayed in some patients. Disclosure: Pfizer’s generative AI tool MAIA was used in developing this abstract; the authors reviewed, edited, and take full responsibility for the content. Clinical trial information: NCT02319837 . Enza combination(N=320) Patients who reached testosterone recovery, n (%) 108 (33.8) Time to testosterone recovery >250 ng/dL, months † Median (range) 5.6 (0.0–22.1) Mean (SD) 6.8 (2.87) The data cutoff date was January 31, 2023. † Time to testosterone recovery during treatment suspension is based on the number of patients who reached testosterone recovery, and was defined as the time from the date of the start of treatment suspension to the date of the first occurrence of testosterone >250 ng/dL. The summary is based on testosterone records during treatment suspension from patients who had treatment suspension and non-missing testosterone records after treatment suspension. For patients who reinitiated treatment, testosterone records after reinitiation were not considered.

5084 Background: Among patients with prostate cancer (PC), treatment with androgen deprivation therapy (ADT) is associated with reduced physical function, which can result in diminished quality of life and the occurrence of adverse medical events. The use of wearable activity monitors allows for remote monitoring of daily activity to potentially detect early functional decline and predict significant medical events such as hospitalization, serious adverse events, and premature death. This study evaluated whether wearable activity monitoring could serve as an early indicator of functional decline and impending adverse events in patients with PC undergoing ADT. Methods: PC patients receiving ADT at Cedars-Sinai and Durham VA who enrolled in the DigiPRO trial (NCT04575402) wore a Fitbit Charge over 12 weeks to track quantitative physical activity and sleep data for prediction of the occurrence of unexpected medical events (composite of hospitalization, premature death, or fall) and significant patient-reported physical function decline (> 5 NIH PROMIS T score points) within 6-months follow-up. Results: 40 patients were included in the analysis (median age 70, range 51-87, 37% Black and 63% White; 10% identified as Hispanic). On average, PC patients walked 5,189 steps/day, were sedentary 16 hours/day, and slept 5.8 hours/night. A clinically meaningful decline in daily steps (> 500 steps) within the first 3 months of initiating ADT was associated with higher odds of experiencing an unexpected medical event (hospitalization, death, fall) (OR = 3.03; 95% CI 1.6-5.9, p = 0.001 ) and clinically meaningful decline in patient-reported physical function (> 5 PROMIS T score points) occurring within 6 months from study completion (OR = 5.2, 95% CI; 1.3-11.7, p = 0.02 ). Conclusions: These findings suggest remote activity monitoring may serve as a novel early warning system to identify patients who are at increased risk of unexpected medical events and clinically meaningful physical function decline in PC patients undergoing ADT. Use of this early warning system could lead to targeted interventions in high-risk patients to reduce morbidity and perhaps even prolong survival in patients undergoing ADT. Clinical trial information: NCT04575402 .