The impact of genomic biomarkers on a clinical risk prediction model for upgrading/upstaging among men with favorable-risk prostate cancer.

BACKGROUND: The challenge of distinguishing indolent from aggressive prostate cancer (PCa) complicates decision-making for men considering active surveillance (AS). Genomic classifiers (GCs) may improve risk stratification by predicting end points such as upgrading or upstaging (UG/US). The aim of this study was to assess the impact of GCs on UG/US risk prediction in a clinicopathologic model. METHODS: Participants had favorable-risk PCa (cT1-2, prostate-specific antigen [PSA] ≤15 ng/mL, and Gleason grade group 1 [GG1]/low-volume GG2). A prediction model was developed for 864 men at the University of California, San Francisco, with standard clinical variables (cohort 1), and the model was validated for 2267 participants from the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) registry (cohort 2). Logistic regression was used to compute the area under the receiver operating characteristic curve (AUC) to develop a prediction model for UG/US at prostatectomy. A GC (Oncotype Dx Genomic Prostate Score [GPS] or Prolaris) was then assessed to improve risk prediction. RESULTS: The prediction model included biopsy GG1 versus GG2 (odds ratio [OR], 5.83; 95% confidence interval [CI], 3.73-9.10); PSA (OR, 1.10; 95% CI, 1.01-1.20; per 1 ng/mL), percent positive cores (OR, 1.01; 95% CI, 1.01-1.02; per 1%), prostate volume (OR, 0.98; 95% CI, 0.97-0.99; per mL), and age (OR, 1.05; 95% CI, 1.02-1.07; per year), with AUC 0.70 (cohort 1) and AUC 0.69 (cohort 2). GPS was associated with UG/US (OR, 1.03; 95% CI, 1.01-1.06; p < .01) and AUC 0.72, which indicates a comparable performance to the prediction model. CONCLUSIONS: GCs did not substantially improve a clinical prediction model for UG/US, a short-term and imperfect surrogate for clinically relevant disease outcomes.

Long-term Prostate Cancer-specific Mortality After Prostatectomy, Brachytherapy, External Beam Radiation Therapy, Hormonal Therapy, or Monitoring for Localized Prostate Cancer.

BACKGROUND: The optimal treatment of localized prostate cancer (PCa) remains controversial. OBJECTIVE: To compare long-term survival among men who underwent radical prostatectomy (RP), brachytherapy (BT), external beam radiation therapy (EBRT), primary androgen deprivation therapy (PADT), or monitoring (active surveillance [AS]/watchful waiting [WW]) for PCa. DESIGN, SETTING, AND PARTICIPANTS: This is a cohort study with long-term follow-up from the multicenter, prospective, largely community-based Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) registry. Men with biopsy-proven, clinical T1-3aN0M0, localized PCa were consecutively accrued within 6 mo of diagnosis and had clinical risk data and at least 12 mo of follow-up after diagnosis available. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: PCa risk was assessed, and multivariable analyses were performed to compare PCa-specific mortality (PCSM) and all-cause mortality by primary treatment, with extensive adjustment for age and case mix using the Cancer of the Prostate Risk Assessment (CAPRA) score and a well-validated nomogram. RESULTS AND LIMITATIONS: Among 11 864 men, 6227 (53%) underwent RP, 1645 (14%) received BT, 1462 (12%) received EBRT, 1510 (13%) received PADT, and 1020 (9%) were managed with AS/WW. At a median of 9.4 yr (interquartile range 5.8-13.7) after treatment, 764 men had died from PCa. After adjusting for CAPRA score, the hazard ratios for PCSM with RP as the reference were 1.57 (95% confidence interval [CI] 1.24-1.98; p < 0.001) for BT, 1.55 (95% CI 1.26-1.91; p < 0.001) for EBRT, 2.36 (95% CI 1.94-2.87; p < 0.001) for PADT, and 1.76 (95% CI 1.30-2.40; p < 0.001) for AS/WW. In models for long-term outcomes, PCSM differences were negligible for low-risk disease and increased progressively with risk. Limitations include the evolution of diagnostic and therapeutic strategies for PCa over time. In this nonrandomized study, the possibility of residual confounding remains salient. CONCLUSIONS: In a large, prospective cohort of men with localized PCa, after adjustment for age and comorbidity, PCSM was lower after local therapy for those with higher-risk disease, and in particular after RP. Confirmation of these results via long-term follow-up of ongoing trials is awaited. PATIENT SUMMARY: We evaluated different treatment options for localized prostate cancer in a large group of patients who were treated mostly in nonacademic medical centers. Results from nonrandomized trials should be interpret with caution, but even after careful risk adjustment, survival rates for men with higher-risk cancer appeared to be highest for patients whose first treatment was surgery rather than radiotherapy, hormones, or monitoring.

Ten-year work burden after prostate cancer treatment.

INTRODUCTION: We aim to characterize the magnitude of the work burden (weeks off from work) associated with prostate cancer (PCa) treatment over a 10-year period after PCa diagnosis and identify those at greatest risk. MATERIALS AND METHODS: We identified men diagnosed with PCa treated with radical prostatectomy, radiation therapy, or active surveillance/watchful waiting within CaPSURE. Patients self-reported work burden and SF36 general health scores via surveys before and 1,3,5, and 10 years after treatment. Using multivariate repeated measures generalized estimating equation modeling we examined the association between primary treatment with risk of any work weeks lost due to care. RESULTS: In total, 6693 men were included. The majority were White (81%, 5% Black, and 14% Other) with CAPRA low- (60%) or intermediate-risk (32%) disease and underwent surgery (62%) compared to 29% radiation and 9% active surveillance. Compared to other treatments, surgical patients were more likely to report greater than 7 days off work in the first year, with relatively less time off over time. Black men (RR 0.64, 95% CI 0.54-0.77) and those undergoing radiation (vs. surgery, RR 0.46, 95% CI 0.41-0.51) were less likely to report time off from work over time. Mean baseline GH score (73 [SD 18]) was similar between race and treatment groups, and stable over time. CONCLUSIONS: The work burden of cancer care continued up to 10 years after treatment and varied across racial groups and primary treatment groups, highlighting the multifactorial nature of this issue and the call to leverage greater resources for those at greatest risk.

Long-term complications and health-related quality of life outcomes after radical prostatectomy with or without subsequent radiation treatment for prostate cancer.

BACKGROUND: To report objective long-term complications and health related quality of life (HRQOL) outcomes after radical prostatectomy (RP) with and without radiation therapy (RT) for prostate cancer (CaP). METHODS: We analyzed patients diagnosed with CaP who underwent RP from the UCSF Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) registry between 1995 and 2020. Cox proportional hazards were used to assess risk of postoperative complications which included cystitis, gastrointestinal (GI) toxicity, incontinence requiring a surgical procedure, ureteral injury and urinary stricture. Repeated measures mixed models were used to assess the effects of radiation and complications on patient-reported urinary, bowel, and sexual function after surgery. RESULTS: Of 6,258 men who underwent RP, cumulative incidence of EBRT was 9.1% at 5 years after surgery. Patients who received postoperative radiation were at increased risk for onset of cystitis (HR 5.60, 95% CI 3.40-9.22, P < 0.01). Receipt of RT was not associated with other complications. In repeated measures analysis, postoperative RT was associated with worsening general health scores, adjusting for complications of incontinence, urinary stricture, GI toxicity or ureteral injury, independent of whether patients had those complications. CONCLUSIONS: RT after RP was associated with an increase in the risk of cystitis and worse general health in the long term. Other complications and HRQOL outcomes did not demonstrate differences by whether patients had RT or not. While post-operative RT is the only curative option for CaP after RP, patients and providers should be aware of the increased risks when making treatment decisions.

Post-diagnostic health behaviour scores and risk of prostate cancer progression and mortality.

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.

The Long-term Incidence and Quality of Life Outcomes Associated With Treatment-Related Toxicities of External Beam Radiotherapy for Prostate Cancer.

OBJECTIVE: To assess the long-term incidence of treatment-related toxicities and quality of life (QOL) outcomes associated with toxicity after external beam radiotherapy (EBRT) for prostate cancer. METHODS: We identified all men who had EBRT between 1994 and 2017 from Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE), a longitudinal, nationwide prostate cancer registry. CaPSURE was queried for patient-reported and International Classification of Diseases-9/10 and Current Procedural Terminology codes. The Medical Outcomes Studies Short Form 36 and the University of California, Los Angeles Prostate Cancer Index were used to provide measures of general health, sexual, urinary, and bowel function. Repeated measures mixed models were used to determine QOL change after onset of toxicity. RESULTS: From a total of 15,332, 1744 (11.4%) men had EBRT. The median follow-up was 7.9years (interquartile range [IQR] 4.3-12.7). The median time to onset of any toxicity including urinary pad usage in 265 (15.4% at 8years) men was 4.3years (IQR 1.8-8.0). The most frequent toxicity was hemorrhagic cystitis (104, 5.9% at 8years) after a median of 3.7years (1.3-7.8), gastrointestinal (48, 2.7% at 8years) after a median of 4.2years (IQR 1.3-7.8), followed by urethral stricture (47, 2.4% at 8years) after a median of 3.7years (IQR 1.9-9.1). Repeated measures mixed models found that onset of hemorrhagic cystitis was associated with change in general health over time. CONCLUSION: EBRT for prostate cancer is associated with distinct treatment-related toxicities which can occur many years after treatment and can affect QOL. These results may help men understand the long-term implications of treatment decisions.

Emulation of a target trial with sustained treatment strategies: an application to prostate cancer using both inverse probability weighting and the g-formula.

As with many chronic illnesses, recurrent prostate cancer generally requires sustained treatment to prolong survival. However, initiating treatment immediately after recurrence may negatively impact quality of life without any survival gains. Therefore, we consider sustained strategies for initiating treatment based on specific characteristics of prostate-specific antigen (PSA), which can indicate disease progression. We define the protocol for a target trial comparing treatment strategies based on PSA doubling time, in which androgen deprivation therapy is initiated only after doubling time decreases below a certain threshold. Such a treatment strategy means the timing of treatment initiation (if ever) is not known at baseline, and the target trial protocol must explicitly specify the frequency of PSA monitoring until the threshold is met, as well as the duration of treatment. We describe these and other components of a target trial that need to be specified in order for such a trial to be emulated in observational data. We then use the parametric g-formula and inverse-probability weighted dynamic marginal structural models to emulate our target trial in a cohort of prostate cancer patients from clinics across the United States.

Postdiagnostic Inflammatory, Hyperinsulinemic, and Insulin-Resistant Diets and Lifestyles and the Risk of Prostate Cancer Progression and Mortality.

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.

Androgen Deprivation Therapy and the Risk of Dementia after Treatment for Prostate Cancer.

PURPOSE: The association between androgen deprivation therapy (ADT) and dementia in men with prostate cancer remains inconclusive. We assessed the association between cumulative ADT exposure and the onset of dementia in a nationwide longitudinal registry of men with prostate cancer. MATERIALS AND METHODS: A retrospective analysis of men aged ≥50 years from the CaPSURE (Cancer of the Prostate Strategic Urologic Research Endeavor) registry was performed. The primary outcome was onset of dementia after primary treatment. ADT exposure was expressed as a time-varying independent variable of total ADT exposure. The probability of receiving ADT was estimated using a propensity score. Cox proportional hazards regression was performed to determine the association between ADT exposure and dementia with competing risk of death, adjusted for propensity score and clinical covariates among men receiving various treatments. RESULTS: Of 13,570 men 317 (2.3%) were diagnosed with dementia after a median of 7.0 years (IQR 3.0-12.0) of followup. Cumulative ADT use was significantly associated with dementia (HR 2.02; 95% CI 1.40-2.91; p <0.01) after adjustment. In a subset of 8,506 men, where propensity score matched by whether or not they received ADT, there was also an association between ADT use and dementia (HR 1.59; 95% CI 1.03-2.44; p=0.04). There was no association between primary treatment type and onset of dementia in the 8,489 men in the cohort who did not receive ADT. CONCLUSIONS: Cumulative ADT exposure was associated with dementia. This increased risk should be accompanied by a careful discussion of the needs and benefits of ADT in those being considered for treatment.

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

PURPOSE: Post-diagnostic coffee and tea consumption and prostate cancer progression is understudied. METHODS: We examined 1,557 men from the Cancer of the Prostate Strategic Urologic Research Endeavor who completed a food frequency questionnaire a median of 28 months post-diagnosis. We estimated associations between post-diagnostic coffee (total, caffeinated, decaffeinated) and tea (total, non-herbal, herbal) and risk of prostate cancer progression (recurrence, secondary treatment, bone metastases, or prostate cancer death) using Cox proportional hazards regression. We also examined whether smoking (current, former, never) modified these associations. RESULTS: We observed 167 progression events (median follow-up 9 years). Higher coffee intake was associated with higher risk of progression among current smokers (n = 95). The hazard ratio (HR) [95% confidence interval (CI)] for 5 vs 0 cups/day of coffee was 0.5 (CI 0.2, 1.7) among never smokers, but 4.5 (CI 1.1, 19.4) among current smokers (p-interaction: 0.001). There was no association between total coffee intake and prostate cancer progression among never and former smokers. However, we observed an inverse association between decaffeinated coffee (cups/days) and risk of prostate cancer progression in these men (HR > 0 to < 1 vs 0: 1.1 (CI 0.7, 1.8); HR1 to <2 vs 0: 0.7 (CI 0.3, 1.4); HR≥2 vs 0: 0.6 (CI 0.3, 1.1); p-trend = 0.03). There was no association between tea and prostate cancer progression, overall or by smoking status. CONCLUSION: Among non-smoking men diagnosed with localized prostate cancer, moderate coffee and tea consumption was not associated with risk of cancer progression. However, post-diagnostic coffee intake was associated with increased risk of progression among current smokers.

Patient Perceptions on Barriers and Facilitators to Accessing Low-acuity Surgery During COVID-19 Pandemic.

BACKGROUND: The onset of the COVID-19 pandemic led to the postponement of low-acuity surgical procedures in an effort to conserve resources and ensure patient safety. This study aimed to characterize patient-reported concerns about undergoing surgical procedures during the pandemic. METHODS: We administered a cross-sectional survey to patients who had their general and plastic surgical procedures postponed at the onset of the pandemic, asking about barriers to accessing surgical care. Questions addressed dependent care, transportation, employment and insurance status, as well as perceptions of and concerns about COVID-19. Mixed methods and inductive thematic analyses were conducted. RESULTS: One hundred thirty-five patients were interviewed. We identified the following patient concerns: contracting COVID-19 in the hospital (46%), being alone during hospitalization (40%), facing financial stressors (29%), organizing transportation (28%), experiencing changes to health insurance coverage (25%), and arranging care for dependents (18%). Nonwhite participants were 5 and 2.5 times more likely to have concerns about childcare and transportation, respectively. Perceptions of decreased hospital safety and the consequences of possible COVID-19 infection led to delay in rescheduling. Education about safety measures and communication about scheduling partially mitigated concerns about COVID-19. However, uncertainty about timeline for rescheduling and resolution of the pandemic contributed to ongoing concerns. CONCLUSIONS: Providing effective surgical care during this unprecedented time requires both awareness of societal shifts impacting surgical patients and system-level change to address new barriers to care. Eliciting patients' perspectives, adapting processes to address potential barriers, and effectively educating patients about institutional measures to minimize in-hospital transmission of COVID-19 should be integrated into surgical care.

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

BACKGROUND: Diet and exercise may be associated with quality of life and survival in men with prostate cancer. OBJECTIVE: This study aimed to determine the feasibility and acceptability of a remotely delivered web-based behavioral intervention among men with prostate cancer. METHODS: We conducted a multi-site 4-arm pilot randomized controlled trial of a 3-month intervention (TrueNTH Community of Wellness). Eligibility included self-reported prostate cancer diagnosis, having a personal device that connected to the internet, age ≥18 years, and ability to read English and receive text messages and emails. Men receiving chemotherapy or radiation, or those who reported contraindications to exercise, could participate with physician clearance. Participants were randomized (1:1:1:1) to additive intervention levels: website; website and personalized diet and exercise prescription; website, personalized prescription, Fitbit, and text messages; and website, personalized prescription, Fitbit, text messages, and 2 30-minute phone calls-one with an exercise trainer and one with a registered dietician. Primary outcomes were feasibility (accrual and attrition) and acceptability (survey data and website use). We described self-reported diet and exercise behavior at the time of enrollment, 3 months, and 6 months as secondary outcomes. RESULTS: In total, 202 men consented and were randomized between August 2017 and September 2018 (level 1: 49, level 2: 51, level 3: 50, level 4: 52). A total of 160 men completed the onboarding process and were exposed to their randomly assigned intervention (38, 38, 42, and 42 in levels 1, 2, 3, and 4, respectively). The follow-up rate was 82.7% (167/202) at 3 months and 77.2% (156/202) at 6 months. Participants had a median age of 70 years and were primarily White and college educated. Website visit frequency over the 3-month intervention period increased across levels (median: 2, 9, 11, and 16 visits for levels 1, 2, 3, and 4, respectively). Most were satisfied or very satisfied with the intervention (20/39, 51%; 27/42, 64%; 23/44, 52%; and 27/42, 64% for levels 1, 2, 3, and 4, respectively). The percentage of men who reported being very satisfied was highest among level 4 participants (10/42, 24% vs 4/39, 10%; 5/42, 12%; and 5/44, 11% for levels 1, 2, and 3, respectively). Dissatisfaction was highest in level 1 (5/39, 13% vs 1/42, 2%; 3/44, 7%; and 2/42, 5% for levels 2, 3, and 4, respectively). We observed small improvements in diet and physical activity at 3 months among men in level 4 versus those in level 1. CONCLUSIONS: A web-based, remotely delivered, tailored behavioral intervention for men with prostate cancer is feasible. Future studies are warranted to increase the effect of the intervention on patient behavior while maintaining sustainability and scalability as well as to design and implement interventions for more diverse populations. TRIAL REGISTRATION: ClinicalTrials.gov NCT03406013; http://clinicaltrials.gov/ct2/show/NCT03406013.

The Relative Impact of Urinary and Sexual Function vs Bother on Health Utility for Men With Prostate Cancer.

Function and bother are related but distinct aspects of health-related quality of life. The objective of this study was to compare quantitatively the relative impacts of function and bother in urinary, sexual, and bowel outcomes on health utility as a reflection of health-related quality of life in men with prostate cancer. Our analysis included participants in the Cancer of the Prostate Strategic Urologic Research Endeavor utility supplementary study, with a final cohort of 1617 men. Linear regression on the patients' function and bother summary scores (0-100) from the University of California, Los Angeles Prostate Cancer Index was performed to predict bias-corrected health utilities. Urinary and sexual bother were associated with each health utility, and their coefficients were 3.7 and 20.8 times greater, respectively, than those of the corresponding function. To our knowledge, our study provides the first quantitative and direct comparison of the impacts of function vs bother on health utility.

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

BACKGROUND: Exercise and a healthy diet can improve the quality of life and prognosis of prostate cancer survivors, but there have been limited studies on the feasibility of web-based lifestyle interventions in this population. OBJECTIVE: This study aims to develop a data-driven grounded theory of web-based engagement by prostate cancer survivors based on their experience in the Community of Wellness, a 12-week randomized clinical trial designed to support healthy diet and exercise habits. METHODS: TrueNTH's Community of Wellness was a four-arm pilot study of men with prostate cancer (N=202) who received progressive levels of behavioral support (level 1: website; level 2: website with individualized diet and exercise recommendations; level 3: website with individualized diet and exercise recommendations, Fitbit, and text messages; and level 4: website with individualized diet and exercise recommendations, Fitbit and text messages, and separate phone calls with an exercise trainer and a registered dietitian). The primary aim of the study is to determine the feasibility and estimate the effects on behaviors (results reported in a separate paper). Following the 12-week intervention, we invited participants to participate in 4 focus groups, one for each intervention level. In this report, we used grounded theory analyses including open, axial, and selective coding to generate codes and themes from the focus group transcripts. Categories were refined across levels using embodied categorization and constant comparative methods. RESULTS: In total, 20 men with prostate cancer participated in the focus groups: 5, 4, 5, and 6 men in levels 1, 2, 3, and 4, respectively. Participants converged on 5 common factors influencing engagement with the intervention: environment (home environment, competing priorities, and other lifestyle programs), motivation (accountability and discordance experienced within the health care system), preparedness (technology literacy, health literacy, trust, and readiness to change), program design (communication, materials, and customization), and program support (education, ally, and community). Each of these factors influenced the survivors' long-term impressions and habits. We proposed a grounded theory associating these constructs to describe the components contributing to the intuitiveness of a web-based lifestyle intervention. CONCLUSIONS: These analyses suggest that web-based lifestyle interventions are more intuitive when we optimize participants' technology and health literacy; tailor interface design, content, and feedback; and leverage key motivators (ie, health care providers, family members, web-based coach) and environmental factors (ie, familiarity with other lifestyle programs). Together, these grounded theory-based efforts may improve engagement with web-based interventions designed to support prostate cancer survivorship.

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

BACKGROUND: New data is emerging to guide initial treatment of patients with metastatic prostate cancer (CaP). This study utilizes the Cancer of the Prostate Strategic Urologic Research Endeavor registry to evaluate variations in survival based on initial treatment received by men with metastatic disease at diagnosis or after progression. MATERIALS AND METHODS: Cancer of the Prostate Strategic Urologic Research Endeavor is a national registry of men diagnosed with CaP and managed at 43 community, academic, and Veteran's centers. We examined socio-demographic factors, disease biology, initial and subsequent therapy received, and survival among patients who presented with de novo or recurrent metastatic disease stratified by receipt of initial local therapy vs. combined local and hormonal therapy. The outcome was prostate cancer specific mortality (PCSM). We performed Fine and Gray competing risks regression analysis to evaluate the association between timing of metastasis and PCSM, adjusted for age, initial treatment, and subsequent therapy. RESULTS: Of the 14,753 patients diagnosed with CaP from 1990 to 2016, 669 (5%) had metastatic disease. Among the examined patients, 303 (45%) had metastatic disease at diagnosis and 366 (55%) progressed to metastatic disease. Overall, 461 (69%) were ≥65 years old, 582 (87%) had Medicare, and 227 (34%) had an annual income < $30,000. Prostate-specific antigen at diagnosis was >20 ng/ml for 342 (51%) patients and biopsy Gleason grade was ≥4 + 3 for 386 (58%) patients. Among patients with metastatic disease at diagnosis, 31 (10%) received initial local therapy and 272 (90%) received initial hormonal therapy. Among patients who progressed to metastatic disease, 239 (65%) received initial local therapy and 127 (35%) received initial systemic hormonal therapy. Among patients with metastatic disease, the multivariate competing risks model, after adjusting for sociodemographics, marital status, diagnosis year, and comorbidities, revealed a significantly lower risk of PCSM among patients with de novo vs. recurrent metastatic disease (Hazard Ratio 0.66 (95% Confidence Interval 0.51, 0.85) P = 0.002). In the stratified analysis, no difference was seen for patients treated with initial hormonal vs. combined local and hormonal therapy. CONCLUSIONS: In this analysis of a nationwide cohort of men treated for CaP with all types of therapy over 25 years, we observed that among men with metastatic CaP, the risk of PCSM was lower for de novo vs. recurrent metastatic disease. Additionally, no difference was observed based on initial treatment with combined local and hormonal therapy vs. hormonal therapy alone.

Understanding the Major Factors Affecting Response Shift Effects on Health-Related Quality of Life: What the Then-Test Measures in a Longitudinal Prostate Cancer Registry.

BACKGROUND: Localized prostate cancer (PCa) treatments provide high survival rates, with patients often surviving a decade or longer after treatment. Therefore, treatment options are progressively based on quality of life. The objective of this research was to investigate magnitude of response shift (RS) in health-related quality of life (HRQOL) responses in men with clinically localized PCa using a generic questionnaire and a disease-specific questionnaire in an observational longitudinal patient registry study. PATIENTS AND METHODS: A cohort study was conducted using the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) database. Patients were annually surveyed using the Medical Outcomes Study Questionnaire Short Form 36 (SF-36) and the UCLA Prostate Cancer Index (PCI) HRQOL measures. A total of 3161 active patients were eligible for a one-off supplemental study asking retrospective HRQOL scores (then-test). We calculated RS, observed change, and RS adjusted change. Statistical difference was determined by t test. RESULTS: Patients consistently reported higher recalled pretreatment HRQOL compared to baseline scores for SF-36 and PCI, confirming the existence of a RS (P < .05). On average, PCI demonstrated larger RS by a factor of 2 than SF-36. More specific, RS was greater especially in SF-36 physical domains compared to mental health items. PCI measured PCa-specific physical adverse effects only. Patients whose cancer had recurred reported slightly lower SF-36 RS than those whose cancer had not recurred. CONCLUSION: RS occurrence was measured in both the disease-specific questionnaire and the generic HRQOL questionnaire, demonstrating continued low health and symptom scores after RS adjustment. Therefore, health professionals should adjust for this phenomenon when assessing patient's HRQOL treatment responses, and clinicians should address their continued sexual and urinary functional loss.

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

OBJECTIVES: Development and pilot evaluation of a personalized decision support intervention to help men with early-stage prostate cancer choose among active surveillance, surgery, and radiation. METHODS: We developed a decision aid featuring long-term survival and side effects data, based on focus group input and stakeholder endorsement. We trained premedical students to administer the intervention to newly diagnosed men with low-risk prostate cancer seen at the University of California, San Francisco. Before the intervention, and after the consultation with a urologist, we administered the Decision Quality Instrument for Prostate Cancer (DQI-PC). We hypothesized increases in two knowledge items from the DQI-PC: How many men diagnosed with early-stage prostate cancer will eventually die of prostate cancer? How much would waiting 3 months to make a treatment decision affect chances of survival? Correct answers were: "Most will die of something else" and "A little or not at all." RESULTS: The development phase involved 6 patients, 1 family member, 2 physicians, and 5 other health care providers. In our pilot test, 57 men consented, and 44 received the decision support intervention and completed knowledge surveys at both timepoints. Regarding the two knowledge items of interest, before the intervention, 35/56 (63%) answered both correctly, compared to 36/44 (82%) after the medical consultation (P = .04 by chi-square test). CONCLUSIONS: The intervention was associated with increased patient knowledge. Data from this pilot have guided the development of a larger scale randomized clinical trial to improve decision quality in men with prostate cancer being treated in community settings.

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

BACKGROUND: The association of obesity at diagnosis with prostate cancer progression is uncertain. This study aimed to examine the relationship between body mass index (BMI; 18.5-<25, 25-<30, 30-<35, ≥35 kg/m2) and prognostic risk at diagnosis, compare the concordance between prognostic risk assessed at diagnostic biopsy versus pathologic risk assessed at surgery across BMI categories, and investigate the association between obesity and prostate cancer recurrence and all-cause death. METHODS: We examined men enrolled in CaPSURE who underwent radical prostatectomy between 1995 and 2017. Multiple imputation methods were used to handle missing data and reported along with complete case findings. RESULTS: Participants (n = 5,200) were followed for a median of 4.5 years; 685 experienced recurrence. Obesity was associated with higher prognostic risk at time of diagnosis (ORobese = 1.5; ORvery obese = 1.7) and upward reclassification of disease between biopsy and surgery, driven by change in tumor stage (ORobese = 1.3; ORvery obese = 1.6). We observed an association between BMI and recurrence with adjustment for disease severity using diagnostic factors (HRvery obese = 1.7); this association disappeared when adjusting for disease severity factors obtained at surgery. CONCLUSIONS: Our findings suggest that residual confounding may partially explain the conflicting evidence regarding obesity's influence on prostate cancer progression. Assessing T-stage via digital rectal exam may be complicated in larger men, potentially affecting clinical treatment decisions. A strong association with all-cause mortality demonstrates healthier BMI at diagnosis may still improve overall survival. IMPACT: Patients with greater BMI are prone to more advanced disease at diagnosis and may be more likely to have their tumor stage underestimated at diagnosis.

What Matters? The Valued Life Activities of Older Adults Undergoing Elective Surgery.

OBJECTIVES: Valued life activities are those activities an individual deems particularly important or meaningful. Surgery in older adults can affect their ability to perform valued activities, but data are lacking. We characterized these activities and assessed performance of them following surgery. DESIGN: Retrospective observational study. SETTING: Preoperative program for older adults undergoing elective surgery at an academic hospital. PARTICIPANTS: Older adults (N = 194) in the program from February 2015 to February 2018. MEASUREMENTS: A preoperative written questionnaire asked, "What are the activities that are most important to you to be able to do when you return home from surgery?" Participants could list up to three activities. Content analysis was used to develop domains of valued life activities and categorize responses. Postoperative questionnaires and medical records were used to determine ability to perform activities 6 months after surgery. RESULTS: Of 194 participants (mean age = 74.9 ± 9.1 y), 57.7% were female; 33.5% had more than two comorbid conditions. We elicited 510 valued activities, with a mean of 2.6 (± .7) activities per participant. Content analysis revealed five categories: (1) recreational activities (28.9%); (2) mobility (24.9%); (3) activities of daily living (ADLs; 17.5%); (4) instrumental activities of daily living (IADLs; 16.9%); and (5) social activities (12.0%). Ultimately, 154 participants had surgery, of which 27.3% were unable to perform one of their valued activities at 6 months. Performance varied between activity categories; 91.9% of mobility activities, 90.8% of ADLs, 80.3% of IADLs, 77.3% of social activities, and 65.5% of recreational activities were able to be performed after surgery. CONCLUSION: Older adults expressed a wide range of valued life activities. More than one-quarter were unable to engage in at least one valued life activity after surgery, with recreation the most commonly affected. Assessment of valued life activities should be incorporated into the perioperative management of older adults. J Am Geriatr Soc 67:2305-2310, 2019.

Robust Health Utility Assessment Among Long-term Survivors of Prostate Cancer: Results from the Cancer of the Prostate Strategic Urologic Research Endeavor Registry.

BACKGROUND: Valid health utility values are essential for comparative effectiveness analyses. However, subjective utilities in long-term survivors of prostate cancer (PCa) with various oncological and functional outcomes have not been well described. OBJECTIVE: To quantify utilities in long-term survivors of PCa using the standard gamble method, generally regarded as the approach best grounded in economic theory. DESIGN, SETTING, AND PARTICIPANTS: We performed a cross-sectional study nested within a prospective cohort-Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE). Overall, 1884 (59.7%) of 3155 active participants across all disease states returned the questionnaire. INTERVENTION: Various primary treatments for PCa. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Utility values for PCa health, sexual function, urinary function, bowel function, and overall health were measured, based on patients' conditions at the time of the survey. Bias correction methods were employed. RESULTS AND LIMITATIONS: After exclusion of incomplete or disqualified data, 1740 (92.3% of responding) patients were included in the final analysis. The mean age was 73.1 ±â€¯8.2 yr at a median of 9 yr (interquartile range: 6-11) since diagnosis. Mean utilities for PCa health and overall health were 0.934 ±â€¯0.120 and 0.960 ±â€¯0.100, respectively. After bias correction by probability weighting function, utilities were 0.866 ±â€¯0.154 and 0.897 ±â€¯0.142, and by mixed model correction, 0.845 ±â€¯0.186 and 0.884 ±â€¯0.176, respectively. Measured utilities were similarly high for specific functional outcomes, even with bias corrections. Survivorship bias and skewed proportion of disease status due to natural history of PCa were potential limitations. CONCLUSIONS: Standard gamble-based utilities in long-term survivors of PCa were much higher than those determined previously. The results indicate substantial human resilience: most PCa patients adapt to their health status over time even if they experience incomplete functional recovery and would not take risk in pursuit of better quality of life. PATIENT SUMMARY: We elicited health utilities (measures of quality of life) among long-term survivors of prostate cancer using the most robust method. These were much higher than previously reported values that were based on theoretical scenarios or indirect methods. Long-term survivors of prostate cancer may adapt well to their health conditions over time even if they experience disease-specific or functional problems.