Preference Elicitation and Treatment Decision-Making Among Men Diagnosed With Prostate Cancer: Randomized Controlled Trial Results of Healium.

BACKGROUND: Elicitation of patients' preferences is an integral part of shared decision-making, the recommended approach for prostate cancer decision-making. Existing decision aids for this population often do not specifically focus on patients' preferences. Healium is a brief interactive web-based decision aid that aims to elicit patients' treatment preferences and is designed for a low health literate population. OBJECTIVE: This study used a randomized controlled trial to evaluate whether Healium, designed to target preference elicitation, is as efficacious as Healing Choices, a comprehensive education and decision tool, in improving outcomes for decision-making and emotional quality of life. METHODS: Patients diagnosed with localized prostate cancer who had not yet made a treatment decision were randomly assigned to the brief Healium intervention or Healing Choices, a decision aid previously developed by our group that serves as a virtual information center on prostate cancer diagnosis and treatment. Assessments were completed at baseline, 6 weeks, and 3 months post baseline, and included decisional outcomes (decisional conflict, satisfaction with decision, and preparation for decision-making), and emotional quality of life (anxiety/tension and depression), along with demographics, comorbidities, and health literacy. RESULTS: A total of 327 individuals consented to participate in the study (171 were randomized to the Healium intervention arm and 156 were randomized to Healing Choices). The majority of the sample was non-Hispanic (272/282, 96%), White (239/314, 76%), married (251/320, 78.4%), and was on average 62.4 (SD 6.9) years old. Within both arms, there was a significant decrease in decisional conflict from baseline to 6 weeks postbaseline (Healium, P≤.001; Healing Choices, P≤.001), and a significant increase in satisfaction with one's decision from 6 weeks to 3 months (Healium, P=.04; Healing Choices, P=.01). Within both arms, anxiety/tension (Healium, P=.23; Healing Choices, P=.27) and depression (Healium, P=.001; Healing Choices, P≤.001) decreased from baseline to 6 weeks, but only in the case of depression was the decrease statistically significant. CONCLUSIONS: Healium, our brief decision aid focusing on treatment preference elicitation, is as successful in reducing decisional conflict as our previously tested comprehensive decision aid, Healing Choices, and has the added benefit of brevity, making it the ideal tool for integration into the physician consultation and electronic medical record. TRIAL REGISTRATION: ClinicalTrials.gov NCT05800483; https://clinicaltrials.gov/study/NCT05800483.

Improved cancer coping from a web-based intervention for prostate cancer survivors: A randomized controlled trial.

OBJECTIVES: Prostate cancer (PCa) survivors report poor physical functioning alongside negative psychological outcomes as they cope with treatment side effects and practical concerns after treatment completion. This study evaluated PROGRESS, a web-based intervention designed to improve adaptive coping among PCa survivors. METHODS: Localized PCa patients (N = 431) within one year of treatment completion were randomized to receive educational booklets or PROGRESS + educational booklets. Surveys completed at baseline, 1-, 3-, and 6-months assessed patient characteristics; functional quality of life and coping (primary outcomes); and psychosocial outcomes (e.g., self-efficacy, marital communication; secondary outcomes). Intent-to-treat and as-treated analyses were completed to assess change in outcomes from baseline to 6 months using linear mixed effects regression models. RESULTS: In the intent-to-treat analyses, participants randomized to the intervention group had improved diversion coping (i.e., healthy redirection of worrying thoughts about their cancer), but more difficulties in marital communication (ps < 0.05). However, PROGRESS usage was low among those randomized to the intervention group (38.7%). The as-treated analyses found PROGRESS users reported fewer practical concerns but had worse positive coping compared to PROGRESS non-users (ps < 0.05). CONCLUSIONS: The findings suggest PROGRESS may improve certain aspects of adaptive coping among PCa survivors that use the website, but does not adequately address the remaining coping and psychosocial domains. Additional research is needed to better understand the gaps in intervention delivery contributing to low engagement and poor improvement across all domains of functional quality of life and adaptive coping.

Extracapsular extension on multiparametric magnetic resonance imaging better predicts pT3 disease at radical prostatectomy compared to perineural invasion on biopsy.

INTRODUCTION: Risk assessment for non-organ-confined prostate cancer (PCa) is important in the surgical planning for radical prostatectomy (RP). Perineural invasion (PNI) on prostate biopsy has been associated with adverse pathological outcomes at prostatectomy. Similarly, the identification of suspected extracapsular extension (ECE) on multiparametric magnetic resonance imaging (mpMRI) has been shown to predict non-organ-confined disease. However, no prior study has compared these factors in predicting adverse pathology at prostatectomy. We evaluated mpMRI ECE and prostate biopsy PNI on multivariable analysis to determine their ability to predict pathological stage at time of RP. METHODS: We retrospectively investigated the prostatectomy database at our institution to identify men who underwent prostate biopsy with pre-biopsy mpMRI and subsequent RP from 2013-2017. Multivariable regression analysis was performed to compare the association of mpMRI ECE (mECE) and PNI on prostate biopsy on the likelihood of finding pT3 disease on pathology post-prostatectomy. RESULTS: Of a total 454 RP between 2013 and 2017, 191 patients met our inclusion criteria. Stage pT2 and pT3+ were found in 120 (62.8%) and 71 (37.2%) patients, respectively. Patients with mECE had 4.84 cumulative odds of worse pathological stage on RP (p=0.045) compared to PNI on biopsy, which showed cumulative odds of 2.25 (p=0.048). When controlling only for those patients without PNI, mECE was still found to be a significant predictor of pT3 disease at RP (p=0.030); however, in patients without mECE, PNI was not significant (p=0.062). CONCLUSIONS: While mECE and biopsy PNI were both associated with worse pathological stage on RP, mECE had significantly higher cumulative odds compared to PNI. The significant predictive ability of mECE adds further clinical value to the use of mpMRI in PCa management. While validation in a larger cohort is required, these factors have important clinical implications with regards to early diagnosis of advanced disease and surgical planning.

Incidence of Significant Findings of Microhematuria Workup in Women-What Guidelines Work Best?

OBJECTIVE: To apply the American Urogynecological Society (AUGS)/American College of Obstetricians and Gynecologists (ACOG) recommendations of foregoing workup in patients under 50 years of age with less than 25 red cells per high-powered field, to a cohort of asymptomatic microscopic hematuria (AMH) patients, and assess diagnostic accuracy, sensitivity, specificity, positive, and negative predictive value compared to the American Urologic Association (AUA) guidelines. METHODS: Retrospective review of female patients who underwent AMH evaluation from 2012 to 2015. The number of patients who would have avoided workup following the AUGS/ACOG recommendations was determined. Sensitivity, specificity, positive- and negative-predictive value and accuracy of the AUGS/ACOG recommendations compared to AUA guidelines were determined. RESULTS: Six hundred twenty women underwent AMH workup with 265 women undergoing full workup as per the AUA guidelines. Applying the AUGS/ACOG recommendations to this cohort would not have resulted in missed malignant diagnoses. Two tumors were found, both in patients who had undergone complete workup, and for whom AUGS/ACOG recommends workup. Following the AUGS/ACOG recommendations would have avoided workup in 126/620 of all women and 44/265 women who underwent the full AUA workup. In looking at findings of malignancy, the AUGS/ACOG workup had a sensitivity of 100% and a negative predictive value of 100% as compared to the AUA guidelines. CONCLUSION: AUA guidelines may over screen female low risk AMH patients. Extensive workup in a low risk group of female patients does not result in increased cancer diagnoses. Perhaps a more nuanced approach could result in fewer workups without compromising cancer detection.

Development and evaluation of a bladder Cancer specific survivorship care plan by patients and clinical care providers: a multi-methods approach.

BACKGROUND, CONTEXT AND PURPOSE: In spite of the mixed evidence for their impact, survivorship Care Plans (SCPs) are recommended to enhance quality of care for cancer survivors. Data on the feasibility of SCPs in bladder cancer (BC) is sparse. Using a mixed-methods approach, this study describes the iterative development, acceptability and feasibility of BC specific SCP (BC-SCP) in clinical settings. METHODS: In Phase I, we developed the BC-SCP. In Phase II, we conducted four focus groups with 19 patients and 15 providers to examine its acceptability and usability challenges. Data analyses using the Atlas.ti program, informed refinement of the BC-SCP. In Phase III, we conducted feasibility testing of the refined BC-SCP with 18 providers from 12 health-centers. An encounter survey was completed after each assessment to examine the feasibility of the BC-SCP. Chi-square and Fisher Exact tests were used for comparative analyses. RESULTS: During phase I, we observed high patient and provider acceptability of the BC-SCP and substantial engagement in improving its content, design, and structure. In Phase II, providers completed 59 BC-SCPs. Mean time for BC-SCP completion was 12.3 min. Providers reported that BC-SCP content was clear, did not hamper clinic flow and was readily completed with easy-to-access information. Comparative analyses to examine differences in SCP completion time by patient clinico-demographic characteristics and provider type revealed no significant differences. CONCLUSIONS: Our BC-SCP has clinical relevance, and can be used in an active practice setting. However, considerable progress will be necessary to achieve implementation of and sharing the BC-SCP with patients and care providers, particularly within the electronic medical record. In summary, BC-SCPs are essential to improve the follow up care of BC survivors. Clinical resources are required to ensure appropriate implementation of BC-SCPs. TRIAL REGISTRATION: Study HUM00056082.

Use of a Risk Stratification Tool to Guide Evaluation of Patients With Asymptomatic Microscopic Hematuria.

OBJECTIVE: To determine if use of the hematuria risk index can reduce testing and cost, while maintaining equivalent lesion detection in patients with asymptomatic microscopic hematuria. MATERIALS AND METHODS: Retrospective cohort study of 1049 patients at single institution. Hematuria risk index score was calculated based on clinical factors including age, sex, smoking history, and degree of hematuria for each patient along with evaluation studies performed and total number of tumors discovered. Cost benefit analysis was performed based on published Medicare averages. RESULTS: Tumor detection rate in overall, low-risk, and moderate-risk groups were 1.2%, 0%, and 2.96% at a total cost of $408,376. When low-risk group is not screened cost decreases to $166,252 with no lesions missed. The cost to discover one lesion/cancer in the overall group was $34,031.3, the cost to find one high-grade clinically significant lesion/cancer was $136,125.3 for the overall group. When the low-risk group was removed, the cost to find a high-grade clinically significant lesion/cancer decreased to $55,417.3 without missing any significant lesions. Ultrasound may be utilized instead of computed tomography with minimal loss of lesion detection in select moderate risk patients. CONCLUSION: None of the low-risk hematuria risk patients were diagnosed with any lesions, as such these patients may not need an evaluation. Furthermore, by utilizing a risk-stratified approach to the assessment of asymptomatic microscopic hematuria health care costs can be significantly decreased with limited negative consequences in terms of lesion detection.

Examining the impact of a multimedia intervention on treatment decision-making among newly diagnosed prostate cancer patients: results from a nationwide RCT.

Men diagnosed with early stage prostate cancer face multiple treatment options, each with distinctive side effects that have significant implications for post-treatment quality of life. Healing Choices for Men with Prostate Cancer is a multimedia educational and decision aid program. This nation-wide randomized controlled trial evaluated the impact of Healing Choices on reducing decisional conflict and distress. Eligible prostate cancer patients who called the National Cancer Institute's Cancer Information Service (CIS) were invited to participate. After a baseline interview, participants were randomized to usual personalized consultation with a CIS specialist (comparison condition) or CIS personalized consultation plus the Healing Choices program (intervention condition). The Decision Conflict Scale and Impact of Event Scale assessed decisional conflict about prostate cancer treatment and cancer-related distress, respectively. Analyses evaluated group differences at 2 months postenrollment. Hypothesized moderation of intervention effects by demographic and clinical characteristics were evaluated. The final sample consisted of N = 349 participants (intervention: n = 181; comparison n = 168). Men were on average 64 years old, primarily White, and well educated. The difference in total decisional conflict was not significant (DCS total score; F[1,311] = .99, p = .32). The difference in cancer-related distress at 2 months between the intervention and the comparison groups was not significant (F[1,337] = .01, p = .93). Evaluation of specific decision processes indicated a significant effect on levels of perceived decisional support (intervention, M = 34.8, SD = 15.7; comparison, M = 38.3, SD = 16.1; F[1,337] = 3.74, p = .05). The intervention effect was greatest for nonwhite minority participants (b = -9.65, SE = 4.67) and those with lower educational attainment (b = 3.87, SE = 2.21). This interactive, comprehensive education and decision aid program may be most effective for a subset of prostate cancer patients in need of educational and decisional support.

Racial Disparities in Clinically Significant Prostate Cancer Treatment: The Potential Health Information Technology Offers.

PURPOSE: Black men are more likely to die as a result of prostate cancer than white men, despite effective treatments that improve survival for clinically significant prostate cancer. We undertook this study to identify gaps in prostate cancer care quality, racial disparities in care, and underlying reasons for poorer quality care. METHODS: We identified all black men and random age-matched white men with Gleason scores ≥ 7 diagnosed between 2006 and 2013 at two urban hospitals to determine rates of treatment underuse. Underuse was defined as not receiving primary surgery, cryotherapy, or radiotherapy. We then interviewed treating physicians about the reasons for underuse. RESULTS: Of 359 black and 282 white men, only 25 (4%) experienced treatment underuse, and 23 (92%) of these were black. Most (78%) cases of underuse were due to system failures, where treatment was recommended but not received; 38% of these men continued receiving care at the hospitals. All men with treatment underuse due to system failures were black. CONCLUSION: Treatment rates of prostate cancer are high. Yet, racial disparities in rates and causes of underuse remain. Only black men experienced system failures, a type of underuse amenable to health information technology-based solutions. Institutions are missing opportunities to use their health information technology capabilities to reduce disparities in cancer care.

Computerized cognitive training in prostate cancer patients on androgen deprivation therapy: a pilot study.

PURPOSE: Prostate cancer patients who have undergone androgen deprivation therapy (ADT) may experience cognitive impairment, yet there is an unmet need for nonpharmacological interventions to address cognitive impairment in this population. This study examines the feasibility, acceptability, and preliminary efficacy of a home-based computerized cognitive training (CCT) program to treat cancer-related cognitive impairment. METHODS: Sixty men who had received ≥ 3 months of ADT were screened for at least mild cognitive or neurobehavioral impairment and randomized to 8 weeks of CCT or usual care. Follow-up assessments occurred immediately post-intervention or equivalent (T2) and 8 weeks later (T3). The acceptability of CCT was also assessed. RESULTS: Feasibility:A priori feasibility thresholds were partially met (i.e., randomization rate > 50%, retention rate > 70% excluding CCT drop-outs, but < 70% for intent-to-treat). Acceptability: Participants were mostly satisfied with CCT and found it somewhat enjoyable, though barriers to uptake existed. Preliminary efficacy: Linear mixed models indicated significant time by group effects favorable to CCT in reaction time (p = .01), but unfavorable to CCT in verbal and visual memory (ps < .05). Memory was temporarily suppressed in the CCT group at T2, but normalized by T3. There was no effect of CCT on self-reported cognitive functioning, neurobehavioral functioning, nor quality of life. CONCLUSIONS: This study provides tentative support for the feasibility and acceptability of CCT to treat mild cognitive impairment in ADT patients. CCT had a beneficial effect on reaction time, but temporarily suppressed memory. CCT's benefits may be limited to a narrow area of functioning. Larger-scale studies are needed.

Cost-effectiveness analysis of treatments for metastatic castration resistant prostate cancer.

OBJECTIVE: Treatment options for metastatic castration resistant prostate cancer (mCRPC) have expanded rapidly in recent years. Given the significant economic burden, we sought perform a cost-effectiveness analysis (CEA) of the contemporary treatment paradigm for mCRPC. METHODS: We devised a treatment protocol consisting of sipuleucel-T, enzalutamide, abiraterone, docetaxel, radium-223, and cabazitaxel. We estimated number and length of treatments for each therapy using dosing schedules or progression free survival data from published clinical trials. We estimated treatment cost using billing data and Medicare reimbursement values and performed a CEA. Our analysis assumed US$100,000 per life year saved (LYS) as the threshold societal willingness to pay. RESULTS: Incremental cost-effectiveness ratios (ICER) for strategies incorporating sipuleucel-T that were not eliminated by extended dominance exceeded the societal threshold willingness-to-pay of US$100,000 per LYS, the lowest of which was sipuleucel-T + enzalutamide + abiraterone + docetaxel at US$207,714 per LYS. Enzalutamide + abiraterone + docetaxel exhibited the most favorable ICER among strategies without sipuleucel-T at US$165,460 per LYS. CONCLUSION: Based on the available survival data and current costs of treatment, all treatment strategies greatly exceed a commonly assumed societal willingness-to-pay threshold of US$100,000 per LYS. Improvements in this regard can only come with a reduction in pricing, better tailoring of treatment or significant enhancements in survival with clinical use of treatment combinations or sequences.

Role of multi-parametric MRI of the prostate for screening and staging: Experience with over 1500 cases.

OBJECTIVE: Contemporary prostate cancer (PCa) screening modalities such as prostate specific antigen (PSA) and digital rectal examination (DRE) are limited in their ability to predict the detection of clinically significant disease. Multi-parametric magnetic resonance imaging (mpMRI) of the prostate has been explored as a staging modality for PCa. Less is known regarding its utility as a primary screening modality. We examined our experience with mpMRI as both a screening and staging instrument. METHODS: mpMRI studies performed between 2012 and 2014 in patients without PCa were cross-referenced with transrectal ultrasonography (TRUS) biopsy findings. Statistical analyses were performed to determine association of mpMRI findings with overall cancer diagnoses and clinically significant (Gleason score ≥7) disease. Subgroup analyses were then performed on patients with a history of prior negative biopsy and those without a history of TRUS biopsy. mpMRI studies were also cross-referenced with RP specimens. Statistical analyses determined predictive ability of extracapsular extension (ECE), seminal vesicle involvement (SVI), and pathologic evidence of clinically significant disease (Gleason score ≥7). RESULTS: Four hundred biopsy naïve or prior negative biopsy patients had positive mpMRI studies. Overall sensitivity, specificity, positive and negative predictive values were 94%, 37%, 58%, and 87%, respectively and 95%, 31%, 42%, and 93%, respectively for overall cancer detection and Gleason score ≥7 disease. In patients with no prior biopsy history, mpMRI sensitivity, specificity, positive and negative predictive values were 94%, 36%, 65%, and 82%, for all cancers, and 95%, 30%, 50%, and 89% for Gleason score≥7 lesions, respectively. In those with prior negative biopsy sensitivity, specificity, positive and negative predictive values were 94%, 37%, 52%, and 90% for all cancers, and 96%, 32%, 36%, and 96% for Gleason score ≥7 lesions, respectively. Seventy-four patients underwent radical prostatectomy (RP) after mpMRI. Lesion size on mpMRI correlated with the presence of Gleason score ≥7 cancers (p = 0.005). mpMRI sensitivity, specificity, positive and negative predictive values were 84%, 39%, 81%, and 44% respectively, for Gleason ≥7 cancer. For ECE and SVI, sensitivity and specificity were 58% and 98% and 44% and 97%, respectively. CONCLUSION: mpMRI is an accurate predictor of TRUS biopsy and RP outcomes. mpMRI has significant potential to change PCa management, particularly in the screening population, in whom a significant proportion may avoid TRUS biopsy. Further studies are necessary to determine how mpMRI should be incorporated into the current PCa screening and staging paradigms.

Heterogeneity of Outcomes in D'Amico Intermediate-Risk Prostate Cancer Patients after Radical Prostatectomy: Influence of Primary and Secondary Gleason Score.

AIM: The aim of this study was to clarify and examine the outcomes of prostate cancer patients classified as intermediate risk (IR) using the D'Amico risk classification system, specifically focusing on the influence of primary and secondary biopsy Gleason score (BGS). PATIENTS AND METHODS: An institutional review board-approved database of robotic-assisted radical prostatectomies performed after 2006 was stratified by standard D'Amico criteria. IR patients were then sub-stratified by BGS. Pathologic and intermediate-term biochemical disease-free survival (BDFS) outcomes were analyzed. RESULTS: Overall, 1,090 patients were classified as D'Amico low-risk, 896 as IR, and 240 as high-risk. Of the 896 IR patients, 63 had BGS 6, 630 were 3 + 4 = 7, and 203 4 + 3 = 7. Among IR patients, as the BGS increased, there was an increasing likelihood of extracapsular extension (21, 28, and 38%, respectively; p = 0.005), positive surgical margins (14, 26, 31%; p = 0.048), and worse 3-year BDFS (96, 94, 88%; p = 0.01). Multivariable logistic regression and Cox regression analyses confirmed differences among IR groups. CONCLUSION: D'Amico IR patients demonstrate significant heterogeneity in both pathologic outcomes and BDFS. IR patients with a BGS of 6 appear to have similar intermediate-term BDFS as low-risk patients. An increasing BGS from 3 + 3 to 3 + 4 to 4 + 3 results in a higher likelihood of locally-advanced disease and intermediate-term biochemical failure.

Partial Nephrectomy is Associated with Higher Risk of Relapse Compared with Radical Nephrectomy for Clinical Stage T1 Renal Cell Carcinoma Pathologically Up Staged to T3a.

PURPOSE: We studied recurrence-free survival after partial vs radical nephrectomy for clinical stage T1 renal cell carcinoma in all patients and in those up staged to pathological stage T3a. MATERIALS AND METHODS: We retrospectively reviewed the records of 1,250 patients who underwent partial or radical nephrectomy for clinically localized T1 renal cell carcinoma between 2006 and 2014. Recurrence-free survival was estimated using the Kaplan-Meier method and evaluated as a function of nephrectomy type with the log rank test and Cox models, adjusting for clinical, radiological and pathological characteristics. RESULTS: A total of 86 recurrences (7%) were observed during a median followup of 37 months. No difference in recurrence-free survival between partial and radical nephrectomy was found among all clinical stage T1 renal cell carcinomas. T3a up staging was noted in 140 patients (11%) and recurrent disease was observed in 44 (31.4%) during a median followup of 38 months. Among up staged T3a cases partial nephrectomy was associated with shorter recurrence-free survival compared to radical nephrectomy on univariable analysis (recurrence HR 2.04, 95% CI 1.12-3.68, p = 0.019) and multivariable analysis (recurrence HR 5.39, 95% CI 1.94-14.9, p = 0.001). CONCLUSIONS: In a subgroup of patients clinically staged T1 renal cell carcinoma will be pathologically up staged to T3a. Among these patients those who undergo partial nephrectomy appear to have inferior recurrence-free survival relative to those who undergo radical nephrectomy.

Are magnetic resonance imaging undetectable prostate tumours clinically significant? Results of histopathological analyses.

OBJECTIVE: To investigate whether tumours at threshold values for detection on magnetic resonance imaging (MRI) represent clinically significant tumours or not, and therefore the utility of MRI in active surveillance (AS) protocols. PATIENTS AND METHODS: A retrospective analysis of a single institution database was performed after Institutional Review Board approval. Between 2010 and 2013, 1633 patients underwent robot-assisted laparoscopic prostatectomy (RALP) at a single institution by a single surgeon. Of these, 1361 had complete clinical data and were included in analysis. Multivariate logistic regression was used to assess histopathological grade compared to tumour size whilst controlling for biopsy Gleason score, prostate-specific antigen level, body mass index, race, and age. RESULTS: Of 120 tumours <5 mm in size, four were Gleason score 4 + 3. Of 276 tumours of 5-10 mm, 22 (8.1%) were Gleason score 4 + 3 and one (0.2%) was Gleason score 8. On multivariate regression analyses, tumours of <5 mm were much less likely to be high grade (Gleason score >3 + 4) at RALP compared to larger tumours (3.3% vs 25.1%, P < 0.001), or Gleason score ⩾8 (0.0% vs 7.6%, P < 0.001). Size was further shown to significantly correlate with grade on multivariate regression (P < 0.001). CONCLUSIONS: Prostate tumours below the detection threshold for MRI (5 mm) most probably represent clinically insignificant tumours, which alone would not necessitate leaving AS in favour of more aggressive therapy. These findings point to a possible role of MRI in modern AS protocols.

Unmet informational and supportive care needs of patients following cystectomy for bladder cancer based on age, sex, and treatment choices.

PURPOSE: Assessing the unmet needs of cancer patients can help providers tailor health care services to patients' specific needs. This study examines whether the unmet informational and supportive care needs of the patients with muscle-invasive bladder cancer vary by the patients' age, sex, or individual treatment choices. METHODS AND MATERIALS: Participants (N = 30 survivors; 73.3% men) were recruited from the Mount Sinai Medical Center and through advertisements posted on a national Bladder Cancer Advocacy Network website between December 2011 and September 2012. Data were collected through individual interviews and electronic medical record review. A prior qualitative study of this cohort, using immersion/crystallization approach, confirmed the prevalence of unmet needs across the disease trajectory. This is a secondary quantitative analysis of the initial interview data we collected (i.e., quantitative analyses of transformed qualitative data using Chi-square and Fisher exact tests) to examine differences in unmet needs based on the patient's age, sex, and treatment choices. RESULTS: Younger patients (<60y) were less satisfied with the treatment information received presurgery and more likely to report posttreatment complications, choose a neobladder, and seek and receive professional support regarding sexual function, than were older patients (P<0.05). More women than men reported difficulties with self-care and relied on themselves in disease self-management as opposed to relying on spousal support (P<0.05). Patients with neobladder were more likely to report difficulties with urinary incontinence and deterioration in sexual function, whereas patients with ileal conduit were more likely to require spousal help with self-care. Patients who received chemotherapy were significantly more likely to report changes in everyday life (P<0.05). Lastly, regardless of age, sex, or treatment choice, up to 50% of patients reported feeling depressed before or after treatment. CONCLUSIONS: Unmet informational and supportive needs of patients with muscle-invasive bladder cancer during survivorship, and vary by age, sex, and treatment choices. Educational and psychological assessments as well as clinical interventions should be tailored to a patient's specific unmet needs, and to specific clinical and demographic characteristics.

Urinary Incontinence Following Prostate Brachytherapy.

OBJECTIVE: To define the incidence, time course, and risk factors associated with the development of urinary incontinence (UI) following prostate brachytherapy. MATERIALS AND METHODS: A total of 2461 men were identified who underwent permanent interstitial prostate brachytherapy with or without external beam radiation therapy. We examined the relationship between clinical- and treatment-related variables with the onset of UI, defined as leakage requiring pad usage, and further classified as stress (SUI) or urge (UUI) predominant, using univariate and Cox proportional hazards regression models. The changes in International Prostate Symptom Score and quality of life domains were assessed from baseline to last follow, and examined by UI status. RESULTS: Patients were followed for a median of 6.4 years (interquartile range 4.1-9.3). UI was reported in 108 individuals (4.4%), at a median of 1.8 years (interquartile range 5 months-4.4 years): 30 with SUI and 78 with UUI. Seventy-two men (66.7%) reported using 1, 24 (22.2%) using 2, and 12 (11%) using ≥3 pads per day. On multivariate analysis, post-implantation transurethral resection of the prostate, urinary retention, external beam radiation therapy, and higher pretreatment International Prostate Symptom Score were significantly associated with the development of SUI, although transurethral resection of the prostate was the only significant risk factor associated with SUI. Men experiencing UI reported greater declines in urinary quality of life; however, no significant difference was observed between SUI and UUI. CONCLUSION: UI occurred in 4.4% of patients following prostate brachytherapy and is more commonly urge-predominant in character. Distinct risk factors exist for the development of UUI vs SUI. Urinary leakage requiring pad usage was associated with declines in urinary QOL.

Cognitive and neurobehavioral symptoms in patients with non-metastatic prostate cancer treated with androgen deprivation therapy or observation: A mixed methods study.

BACKGROUND: Few studies have investigated prostate cancer patients' experiences of cognitive functioning or neurobehavioral symptoms (i.e., behavioral changes associated with neurological dysfunction) following androgen deprivation therapy (ADT). METHODS: Semi-structured interviews conducted from the US by phone and in-person were used to explore and characterize the: 1) experience of cognitive and neurobehavioral functioning in non-metastatic prostate cancer patients undergoing ADT (n = 19) compared with patients who had not undergone ADT (n = 20); 2) perceived causes of cognitive and neurobehavioral symptoms; 3) impact of these symptoms on quality of life; and 4) strategies used to cope with or compensate for these symptoms. Neuropsychological performance was assessed to characterize the sample. RESULTS: Overall, ADT patients experienced marginally more cognitive problems than non-ADT (nADT) patients even though there were no significant differences between groups in neuropsychological performance. ADT patients also experienced more declines in prospective memory and multi-tasking than nADT patients. Significant proportions of participants in both groups also experienced retrospective memory, attention and concentration, and information processing difficulties. With respect to neurobehavioral symptoms, more ADT patients experienced emotional lability and impulsivity (both aspects of disinhibition) than nADT patients. Among the causes to which participants attributed declines, both groups attributed them primarily to aging. A majority of ADT patients also attributed declines to ADT. For both groups, increased cognitive and neurobehavioral symptoms negatively impacted quality of life, and most participants developed strategies to ameliorate these problems. CONCLUSION: ADT patients are more vulnerable to experiencing specific cognitive and neurobehavioral symptoms than nADT patients. This study highlights the importance of capturing: a) cognitive symptoms not easily detected using neuropsychological tests; b) neurobehavioral symptoms that can be confused with psychological symptoms, and c) causal beliefs that may affect how people cope with these symptoms. Effective interventions are needed to assist prostate cancer patients in managing these symptoms.

Humoral Immune Response against Nontargeted Tumor Antigens after Treatment with Sipuleucel-T and Its Association with Improved Clinical Outcome.

PURPOSE: Antitumor activity of cancer immunotherapies may elicit immune responses to nontargeted (secondary) tumor antigens, or antigen spread. We evaluated humoral antigen spread after treatment with sipuleucel-T, an immunotherapy for asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC), designed to target prostatic acid phosphatase (PAP; primary antigen). EXPERIMENTAL DESIGN: Serum samples from patients with mCRPC enrolled in the placebo-controlled phase III IMPACT study (evaluable n = 142) were used to assess humoral antigen spread after treatment with sipuleucel-T. Immunoglobulin G (IgG) responses to self-antigens (including tumor antigens) were surveyed using protein microarrays and confirmed using Luminex xMAP. IgG responses were subsequently validated in ProACT (n = 33), an independent phase II study of sipuleucel-T. Association of IgG responses with overall survival (OS) was assessed using multivariate Cox models adjusted for baseline prostate-specific antigen (PSA) and lactate dehydrogenase levels. RESULTS: In patients from IMPACT and ProACT, levels of IgG against multiple secondary antigens, including PSA, KLK2/hK2, K-Ras, E-Ras, LGALS8/PCTA-1/galectin-8, and LGALS3/galectin-3, were elevated after treatment with sipuleucel-T (P < 0.01), but not control. IgG responses (≥ 2-fold elevation posttreatment) occurred in ≥ 25% of patients, appeared by 2 weeks after sipuleucel-T treatment, and persisted for up to 6 months. IgG responses to PSA and LGALS3 were associated with improved OS in sipuleucel-T-treated patients from IMPACT (P ≤ 0.05). CONCLUSIONS: Sipuleucel-T induced humoral antigen spread in patients with mCRPC. IgG responses were associated with improved OS in IMPACT. The methods and results reported may identify pharmacodynamic biomarkers of clinical outcome after sipuleucel-T treatment, and help in clinical assessments of other cancer immunotherapies. See related commentary by Hellstrom and Hellstrom, p. 3581.

Decision-making Processes among Prostate Cancer Survivors with Rising PSA Levels: Results from a Qualitative Analysis.

BACKGROUND: Prostate cancer survivors with a rising prostate-specific antigen (PSA) level have few treatment options, experience a heightened state of uncertainty about their disease trajectory that might include the possibility of cancer metastasis and death, and often experience elevated levels of distress as they have to deal with a disease they thought they had conquered. Guided by self-regulation theory, the present study examined the cognitive and affective processes involved in shared decision making between physicians and patients who experience a rising PSA after definitive treatment for prostate cancer. METHODS: In-depth interviews were conducted with 34 prostate cancer survivors who had been diagnosed with a rising PSA (i.e., biochemical failure) within the past 12 months. Survivors were asked about their experiences and affective responses after being diagnosed with a rising PSA and while weighing potential treatment options. In addition, patients were asked about their decision-making process for the initial prostate cancer treatment. RESULTS: Compared with the initial diagnosis, survivors with a rising PSA reported increased negative affect following their diagnosis, concern about the treatability of their disease, increased planning and health behavior change, heightened levels of worry preceding doctor appointments (especially prior to the discussion of PSA testing results), and a strong reliance on physicians' treatment recommendations. CONCLUSIONS: Prostate cancer survivors' decision-making processes for the treatment of a rising PSA are markedly different from those of the initial diagnosis of prostate cancer. Because patients experience heightened distress and rely more heavily on their physicians' recommendations with a rising PSA, interactions with the health care provider provide an excellent opportunity to address and assist patients with managing the uncertainty and distress inherent with rising PSA levels.

Adult cancer clinical trials that fail to complete: an epidemic?

The number and diversity of cancer therapeutics in the pipeline has increased over the past decade due to an enhanced understanding of cancer biology and the identification of novel therapeutic targets. At the same time, the cost of bringing new drugs to market and the regulatory burdens associated with clinical drug development have progressively increased. The finite number of eligible patients and limited financial resources available to evaluate promising new therapeutics represent rate-limiting factors in the effort to translate preclinical discoveries into the next generation of standard therapeutic approaches. Optimal use of resources requires understanding and ultimately addressing inefficiencies in the cancer clinical trials system. Prior analyses have demonstrated that a large proportion of trials initiated by the National Cancer Institute (NCI) Cooperative Group system are never completed. While NCI Cooperative Group trials are important, they represent only a small proportion of all cancer clinical trials performed. Herein, we explore the problem of cancer clinical trials that fail to complete within the broader cancer clinical trials enterprise. Among 7776 phase II-III adult cancer clinical trials initiated between 2005-2011, we found a seven-year cumulative incidence of failure to complete of approximately 20% (95% confidence interval = 18% to 22%). Nearly 48000 patients were enrolled in trials that failed to complete. These trials likely contribute little to the scientific knowledge base, divert resources and patients from answering other critical questions, and represent a barrier to progress.