Decade-long trends in prostate cancer biopsy grade groups and treatment within a population-based registry.

OBJECTIVE: To assess changes in diagnosis prostate cancer (PCa) grade, biopsy and treatment approach over a decade (2011-2020) at a population level within a clinical quality cancer registry. PATIENTS AND METHODS: Patients diagnosed by prostate biopsy between 2011 and 2020 were retrieved from the Victorian Prostate Cancer Outcomes Registry, a prospective, state-wide clinical quality registry in Australia. Distributions of each grade group (GG) proportion over time were modelled with restricted cubic splines, separately by biopsy technique, age group and subsequent treatment method. RESULTS: From 2011 to 2020, 24 308 men were diagnosed with PCa in the registry. The proportion of GG 1 disease declined from 36-23%, with commensurate rises in GG 2 (31-36%), GG 3 (14-17%) and GG 5 (9.3-14%) disease. This pattern was similar for men diagnosed by transrectal ultrasonography or transperineal biopsy. Patients aged <55 years had the largest absolute reduction in GG 1 PCa, from 56-35%, compared to patients aged 55-64 (41-31%), 65-74 (31-21%), and ≥75 years (12-10%). The proportion of prostatectomies performed for patients with GG 1 disease fell from 28% to 7.1% and, for primary radiation therapy, the proportion fell from 22% to 3.5%. CONCLUSION: From 2011 to 2020, there has been a substantial decrease in the proportion of GG 1 PCa diagnosed, particularly in younger men. The percentage of interventional management performed in GG 1 disease has fallen to very low levels. These results reflect the implementation of major changes to diagnostic and treatment guidelines and inform the future allocation of treatment methods.

How Does Age Affect Urinary Continence following Robot-Assisted Radical Prostatectomy? A Prospective Multi-Institutional Study Using Independently Collected, Validated Questionnaires.

PURPOSE: Robot-assisted radical prostatectomy (RARP) is associated with poorer postoperative urinary continence in older men. However, published studies reporting conflicting results have design limitations with insufficient data at the extremes of age. The purpose of this study was to assess the effect of age on post-RARP urinary continence. MATERIALS AND METHODS: This study included 5,648 patients from 2 prospective Australian databases who underwent a primary RARP for prostate cancer between 2008 and 2019. Significant urinary bother and pad-usage were evaluated 12 months post-RARP by EPIC-26 (Expanded Prostate Cancer Index Composite) questionnaires, independently collected by third parties. Multivariable logistic regression was used to investigate the relationship between continence and age. RESULTS: Percentages of significant bother increased with age: 4.2%, 6.8% 9.1% and 12.9% at age groups <55, 55-64, 65-74 and ≥75 years, respectively. Compared with men aged 65-69 years, the odds of significant bother in patients <55 years was significantly lower (odds ratio [OR] 0.49, 95% confidence interval [CI] 0.32-0.75, p=0.001). Corresponding OR found no significant difference in bother in patients ≥70 (OR 1.24, 95% CI 0.94-1.63, p=0.13) or ≥75 years (OR 1.41, 95% CI 0.88-2.25, p=0.16). Pad-free rates markedly decreased with age: 86%, 79%, 68% and 50% at ages, <55, 55-64, 65-74 and ≥75 years, respectively. Corresponding social continence (0-1 pads/day) rates also decreased with age: 98%, 96%, 92% and 85%. CONCLUSIONS: Urinary bother and pad-usage post-RARP are excellent in young men but worsen with age. Older patients were only slightly more likely to be "significantly bothered" by incontinence despite higher pad-usage.

Mapping disadvantage: identifying inequities in functional outcomes for prostate cancer survivors based on geography.

BACKGROUND: Prostate cancer is the most common internal malignancy in Australian men, and although most patients have good survival outcomes, treatment toxicities can impair function, leading to diminished quality of life for prostate cancer survivors. Socioeconomic disadvantage and geographical remoteness have been shown to be related to worse oncologic outcomes, and it is expected that they would similarly influence functional outcomes in prostate cancer. METHODS: Using data from the Victorian Prostate Cancer Outcomes Registry (n = 10,924), we investigated functional outcomes as measured by the Expanded Prostate Cancer Index Composite-26 (EPIC-26) following prostate cancer treatment, focusing on associations with socioeconomic status and geographical remoteness and controlling for clinicopathologic characteristics. A single composite score was developed from the five separate EPIC-26 domains for use in geo-mapping. RESULTS: A total of 7690 patients had complete EPIC-26 data, allowing mapping hotspots of poor function using our composite score. These hotspots were observed to relate to areas of socioeconomic disadvantage. Significant heterogeneity in outcomes was seen in urban areas, with hotspots of good and poor function. Both socioeconomic disadvantage and geographical remoteness were found to predict for worse functional outcomes, although only the former is significant on multivariate analysis. CONCLUSIONS: Geo-mapping of functional outcomes in prostate cancer has the potential to guide health care service provision and planning. A nuanced policy approach is required so as not to miss disadvantaged patients who live in urban areas. We have demonstrated the potential of geo-mapping to visualise population-level outcomes, potentially allowing targeted interventions to address inequities in quality of care.

How Prostate Cancer Patients are Surveyed may Influence Self-Reported Sexual Function Responses.

BACKGROUND: The side effects of prostate cancer treatment include decreases in sexual function, hence, the way patient reported outcomes are collected may affect the quantity and quality of responses. AIM: To determine the effect that different survey modes (email, telephone, or mail) had on the quantity of missing data and self-reported function following treatment. METHODS: Men newly diagnosed with prostate cancer and enrolled in the Victorian Prostate Cancer Outcomes Registry formed the study population. The Expanded Prostate Cancer Index Composite (EPIC-26) survey instrument was administered approximately 1 year after their initial treatment. EPIC-26 measures self-reported function in the sexual, urinary, bowel, and hormonal domains. Multivariable regression models were used to examine effects of survey mode, adjusting for age, residence, socioeconomic status, diagnosing institute type, risk group and primary treatment modality. OUTCOMES: The percentage of patients for whom a domain score could not be calculated due to missing responses and the functional score within each domain. RESULTS: Registry staff attempted to reach 8,586 men eligible to complete the EPIC-26. Of these, 4,301 (50%) returned the survey via email, 1,882 (22%) completed by telephone, and 197 (2.3%) by mail. 2,206 (26%) were uncontactable or did not respond. Email responders had the highest proportion answering all 26 questions (95% vs 87% by phone and 67% by mail). The sexual function score was unable to be calculated due to missing responses for 1.3% of email responders, 8.8% by phone, and 8.1% by mail. After adjustment for patient and disease factors, phone responders were almost 6 times more likely than email responders to have a missing score in this domain, odds ratio = 5.84 (95% confidence interval: 4.06-8.40). The adjusted mean functional score (out of 100) was higher for those responding by phone than email or mail across all domains. The largest adjusted difference between phone and email was observed in the hormonal domain (mean difference 4.5, 95% confidence interval: 3.5-5.4), exceeding the published minimally important difference for this score. CLINICAL IMPLICATIONS: Studies that ask questions regarding sexual health and use multi-modal data collection methods should be aware that this potentially affects their data and consider adjusting for this factor in their analyses. STRENGTHS AND LIMITATIONS: A large study sample utilizing a widely available survey instrument. Patient specific reasons for non-response were not explored. CONCLUSION: Completion mode effects should be considered when analyzing responses to sexual function questions in an older, male population. Papa N, Bensley JG, Perera M, et al. How Prostate Cancer Patients are Surveyed may Influence Self-Reported Sexual Function Responses. J Sex Med 2022;19:1442-1450.

Self-reported lack of energy or feeling depressed 12 months after treatment in men diagnosed with prostate cancer within a population-based registry.

OBJECTIVE: Feeling depressed and lethargic are common side effects of prostate cancer (PCa) and its treatments. We examined the incidence and severity of feeling depressed and lack of energy in patients in a population based PCa registry. METHODS: We included men diagnosed with PCa between 2015 and 2019 in Victoria, Australia, and enrolled in the Prostate Cancer Outcomes Registry. The primary outcome measures were responses to two questions on the Expanded Prostate Cancer Index Composite (EPIC-26) patient reported instrument: problems with feeling depressed and problems with lack of energy 12 months following treatment. We evaluated associations between these and age, cancer risk category, treatment type, and urinary, bowel, and sexual function. RESULTS: Both outcome questions were answered by 9712 out of 12,628 (77%) men. 981 patients (10%) reported at least moderate problems with feeling depressed; 1563 (16%) had at least moderate problems with lack of energy and 586 (6.0%) with both. Younger men reported feeling depressed more frequently than older men. Lack of energy was more common for treatments that included androgen deprivation therapy than not (moderate/big problems: 31% vs. 13%), irrespective of disease risk category. Both outcomes were associated with poorer urinary, bowel, and sexual functional domain scores. CONCLUSIONS: Self-reported depressive feelings and lack of energy were frequent in this population-based registry. Problems with feeling depressed were more common in younger men and lack of energy more common in men having hormonal treatment. Clinicians should be aware of the incidence of these symptoms in these at-risk groups and be able to screen for them.

Comparison of urinary and sexual patient-reported outcomes between open radical prostatectomy and robot-assisted radical prostatectomy: a propensity score matched, population-based study in Victoria.

BACKGROUND: Robot-assisted radical prostatectomy (RARP) rates have been increasing worldwide despite a lack of evidence of superior patient-reported outcomes (PROs) compared to open radical prostatectomy (ORP). METHODS: This retrospective study included men who contributed data to the Prostate Cancer Outcomes Registry-Victoria (PCOR-Vic), underwent ORP or RARP between January 2014 and May 2018, and completed the EPIC-26 questionnaire 12 months post-surgery. Urinary and sexual bother items, the urinary incontinence domain score, the urinary irritative/obstructive domain score, the sexual domain score and the pad usage item from the EPIC-26 questionnaire were compared between the two cohorts. Unmatched and propensity score matched cohorts were used to determine if there were differences in urinary and sexual PROs between ORP and RARP after accounting for the patient case-mix and surgeon characteristics. RESULTS: Of 3826 patients undergoing radical prostatectomy (RP), 1047 received ORP and 2779 received RARP. Propensity score matching reduced the magnitude of the observed differences in four out of six outcomes (urinary bother, urinary incontinence domain, pad usage and sexual domain). Using a propensity score matched cohort, there were no statistically significant differences for RARP patients, compared to ORP patients, in terms of urinary bother (Rd = 0.47%, P = 0.707), urinary incontinence domain scores (Coeff = - 0.84, P = 0.506), urinary irritative/obstructive domain scores (Coeff = 1.03, P = 0.105), pad usage (Rd = - 0.75%, P = 0.771) and sexual bother (Rd = - 0.89%, P = 0.731). RARP patients had slightly higher sexual domain scores (Coeff = 3.65, P = 0.005). CONCLUSION: There were no differences in urinary PROs between ORP and RARP when assessed 12 months post-surgery. The sexual domain slightly favoured RARP, however this was not deemed clinically significant.

Predictors of real-world utilisation of docetaxel combined with androgen deprivation therapy in metastatic hormone-sensitive prostate cancer.

BACKGROUND: Docetaxel has emerged as a standard-of-care for metastatic hormone-sensitive prostate cancer (mHSPC). Uptake of docetaxel for mHSPC in Australia has not previously been reported. AIMS: To investigate the real-world uptake of docetaxel in mHSPC and to identify predictors of utilisation of docetaxel in mHSPC. METHODS: Men diagnosed from June 2014 to December 2018 and enrolled in the Prostate Cancer Outcomes Registry-Victoria (PCOR-Vic) were included. Data collected include demographics, diagnosis method and institution, staging investigations and treatments within 12 months of diagnosis. Wilcoxon rank-sum, Chi-squared and trend tests were used to identify predictors of docetaxel utilisation. All predictors were entered as covariates simultaneously into a multivariable logistic regression model. Statistical significance was set at 0.05 (two sided). RESULTS: In all, 1014 men with mHSPC were analysed, 25% of whom received docetaxel with androgen deprivation therapy. Uptake of docetaxel increased from 20% in 2014 to 33% in 2018. Predictors of higher usage of docetaxel were younger age and treatment in a private hospital, with both remaining significant on multivariable analysis. Notably, the proportion of men aged <70 years receiving docetaxel increased from 54% in 2014-2015 to 64% in 2016-2018, while in men aged ≥70 years the comparative figures were 15% and 22% respectively. CONCLUSIONS: Although docetaxel was not used in the majority of cases, there was a clear increase in docetaxel uptake, especially in younger men following publication of the CHAARTED and STAMPEDE trials. Identifying barriers to real-world implementation of pivotal clinical trial data is critical to improving outcomes in mHSPC.

Geospatial and temporal variation of prostate cancer incidence.

OBJECTIVES: The objective of this study was to evaluate geographical and temporal variations in prostate cancer incidence in Victoria, Australia. STUDY DESIGN & METHODS: This study analysed 105,349 cases of incident prostate cancer between 1982 and 2016 from the population-based Victorian Cancer Registry. We performed Poisson regression analyses to identify an association between an annual number of prostate cancer counts, prostate-specific antigen (PSA) tests and the elderly male population (≥65) after adjusting for population at risk and years. We also applied Bayesian spatial-temporal models to determine any association with prostate cancer incidence and area-level factors. RESULTS: The overall trend of the age-standardized prostate cancer incidence was increasing. The highest age-specific incidence was observed among people aged 65-74 years in the pre- and post-PSA periods. Every increase in 1000 PSA tests per 100,000 population, prostate cancer incidence increased by 17% (relative risk [RR] = 1.17, 95% confidence interval [CI] = 1.13-1.22). A 1% increase in the proportion of the male population (≥65) correlated with a 7% increase in prostate cancer cases (RR = 1.07, 95% CI = 1.06-1.10). Compared with early PSA periods, decreasing trends of low-grade cases and growing trends of high- and intermediate-grade cases were observed after a decline in PSA test usage in late PSA periods. Men living in the most socioeconomically advantaged postal areas had a decreased risk of prostate cancer (RR = 0.914, 95% CI = 0.858-0.976). CONCLUSIONS: Age-specific risk of developing biological prostate cancer, temporal changes in PSA testing and an increasingly elderly population contributed to an increasing trend of prostate cancer incidence. When incidence trends were investigated at a more granular geographic level, socioeconomically advantaged status was associated with decreased prostate cancer risk.

A randomised controlled trial comparing completeness of responses of three methods of collecting patient-reported outcome measures in men diagnosed with prostate cancer.

PURPOSE: The purpose of the study was to compare completeness, timeliness and cost of patient-reported outcome measures (PROMs) collection using telephone, email and post in men with prostate cancer. METHODS: A parallel, three-arm randomised controlled equivalence trial. 1168 patients were randomised to telephone (n = 295), postal (n = 388) and email (n = 385) arms. Participants were asked to provide self-reported responses for 26 items of Expanded Prostate Cancer Index Composite. Cost and resource data were collected from a provider perspective. RESULTS: Equivalence tests showed no difference in completeness in the three arms within a 10% equivalence margin. Men diagnosed in public hospitals were less likely to complete the survey compared to those in private hospitals, OR = 0.19 (95% CI 0.04-0.89) (p = 0.035). The email survey required significantly less time to complete than telephone and postal methods [median time of 2 min (IQR 1,8) vs. 7 min (IQR 6,9) vs. 10 min (IQR 9,12), respectively (p < 0.001)]. The incremental cost effectiveness ratio for email compared to telephone was AUD$1.90, cost-effective if users valued an additional 1% improvement in survey completion greater than AUD$1.90. CONCLUSION: Email method took less time and cost and should be used as the primary PROMs collection, with telephone if men without email or do not respond to email.

Active surveillance of men with low risk prostate cancer: evidence from the Prostate Cancer Outcomes Registry-Victoria.

OBJECTIVE: To characterise the practice of active surveillance (AS) for men with low risk prostate cancer by examining the characteristics of those who commence AS, the rate of adherence to accepted AS follow-up protocols over 2 years, and factors associated with good adherence. Design, setting: Retrospective cohort study; analysis of data collected from 38 sites participating in the Prostate Cancer Outcomes Registry-Victoria. PARTICIPANTS: Men diagnosed with prostate cancer between August 2008 and December 2014 aged 75 years or less at diagnosis, managed by AS for at least 2 years, and with an ISUP grade group of 3 or less (Gleason score no worse than 4 + 3 = 7). MAIN OUTCOME MEASURES: Adherence to an AS schedule consisting of at least three PSA measurements and at least one biopsy in the 2 years following diagnosis. RESULTS: Of 1635 men eligible for inclusion in the analysis, 433 (26.5%) adhered to the AS protocol. The significant predictor of adherence in the multivariate model was being diagnosed in a private hospital (v public hospital: adjusted odds ratio [aOR], 1.83; 95% CI, 1.42-2.37; P < 0.001). Significant predictors of non-adherence included being diagnosed by transurethral resection of the prostate (v transrectal ultrasound biopsy [TRUS]: OR, 0.54; 95% CI, 0.39-0.77; P < 0.001) or transperineal biopsy (v TRUS: OR, 0.32; 95% CI, 0.19-0.52; P < 0.001), and being 66 years of age or more at diagnosis (v < 55 years: OR, 0.65; 95% CI, 0.45-0.92; P = 0.015). CONCLUSION: Almost three-quarters of men who had prostate cancer with low risk of disease progression did not have follow-up investigations consistent with standard AS protocols. The clinical consequences of this shortcoming are unknown.

A synthetic luciferin improves bioluminescence imaging in live mice.

Firefly luciferase is the most widely used optical reporter for noninvasive bioluminescence imaging (BLI) in rodents. BLI relies on the ability of the injected luciferase substrate D-luciferin to access luciferase-expressing cells and tissues within the animal. Here we show that injection of mice with a synthetic luciferin, CycLuc1, improves BLI with existing luciferase reporters and enables imaging in the brain that could not be achieved with D-luciferin.

A Department of Motor Vehicle-Based Intervention to Promote Organ Donor Registrations in New York State.

CONTEXT: Examination of efficacy of motor vehicle representative educational training and dissemination of promotional materials as a means to promote organ donation enrollments in New York State. OBJECTIVE: To increase the number of New York State residents who consent to donation through the department of motor vehicle transactions during project period. SETTING: County-run motor vehicle offices across New York State. PARTICIPANTS: Customers who present to New York Department of Motor Vehicle offices and the representative who work at designated bureaus. INTERVENTIONS: point-of-decision materials including promotional posters, brochures, website, and the motor vehicle representative training sessions. MAIN OUTCOME MEASURES: Reasons for enrollment decision, knowledge/experience with donation, monthly consent rates, enrollment in state organ, and tissue registry. RESULTS: Customers who elected not to register reported no reason or uncertainty surrounding enrollment. The representatives reported experience with donation, discussion with customers, and need for additional education on organ donation. Enrollment cards were mailed to 799 project staff; counties where offices participated in intervention did not indicate significantly higher monthly enrollments when comparing pre- to postenrollment rates. CONCLUSIONS: Use of point-of-decision materials and enrollment cards proved inexpensive method to register customers with a 3.6% return rate. Customers report low (27%) enrollment rate and reticence to consent to donation. Educational training sessions with representatives did not yield significant enrollment increases when evaluating data at county-level enrollment.

Position-dependent splicing activation and repression by SR and hnRNP proteins rely on common mechanisms.

Alternative splicing is regulated by splicing factors that modulate splice site selection. In some cases, however, splicing factors show antagonistic activities by either activating or repressing splicing. Here, we show that these opposing outcomes are based on their binding location relative to regulated 5' splice sites. SR proteins enhance splicing only when they are recruited to the exon. However, they interfere with splicing by simply relocating them to the opposite intronic side of the splice site. hnRNP splicing factors display analogous opposing activities, but in a reversed position dependence. Activation by SR or hnRNP proteins increases splice site recognition at the earliest steps of exon definition, whereas splicing repression promotes the assembly of nonproductive complexes that arrest spliceosome assembly prior to splice site pairing. Thus, SR and hnRNP splicing factors exploit similar mechanisms to positively or negatively influence splice site selection.

Reasons for (not) signing the state registry: surveying Department of Motor Vehicles customers in New York state.

CONTEXT: Prior research examining rationales for enrolling as an organ donor is biased because of its reliance on college student samples and retrospective recall. OBJECTIVE: To characterize New York state residents' registry enrollment decisions in close proximity to a registration opportunity. DESIGN: -Surveys were conducted with customers exiting Department of Motor Vehicle offices. PARTICIPANTS: A total of 1325 customers were surveyed upon exiting 1 of 18 Department of Motor Vehicle offices spanning 9 counties. MAIN OUTCOME MEASURE: Customers making donation-relevant transactions (ie, license renewal/registration) reported whether they had registered as a donor that day, and all other customers reported whether they had registered as a donor in the past. Customers reported reasons to justify their enrollment decision through short interview questions. RESULTS: Among current donation-relevant transactions (n = 299), 27% reported enrolling in the registry. Of remaining customers, 39% reported enrolling in the state registry in the past. For those who elected not to enroll, many failed to communicate a reason for their decision, or reported a lack of opportunity to sign or decisional uncertainty. Among enrollees, reasons for registration included the altruistic benefits of donation, prior registration, personal experience with donation, and rational arguments for donation. CONCLUSION: The value of point-of-decision survey data are discussed in relation to strategic efforts to promote organ donor registration.

Progesterone Hypersensitivity: The Utility of a Janus Kinase Inhibitor for Recurrent Erythema Multiforme.

BACKGROUND: Progestogen hypersensitivity (PH) is a rare phenomenon reported in women with an immunologic response to rising progesterone levels in the luteal phase. This disease's rarity and clinical spectrum make it challenging to diagnose. CASE: In this case report, we will discuss a 14-year-old female with monthly oral mucositis and palmar lesions consistent with erythema multiforme. Over 2 years, she underwent an extensive multidisciplinary workup and was trialed on many different medical therapies. SUMMARY AND CONCLUSION: The prevalence of PH has grown in the literature over the past decade. Due to progesterone's role in many biochemical pathways, the pathophysiology is complex. Although many modalities are efficacious for treating PH's cyclical eruptions, we propose treatment with a Janus kinase inhibitor when hormonal management alone is insufficient.

Price pressure. As the number of costly specialty drugs grows, insurers and providers push for more reasonable alternatives.

Faced with a rising tide of specialty drugs with eyebrow-raising prices, hospitals and insurers are pushing back. That means looking for less-costly alternatives, though options are limited. "Our goal is, as more patients come along, we get them on Elelyso and not on more expensive Cerezyme," says Eric Cannon, chief of pharmacy for insurer SelectHealth. Elelyso entered the market in 2012 and costs about $150,000 per year for a patient, versus the more costly rival drug Cerezyme.

The charity offering. Despite disparity in margins, rich and poor hospitals offer similar levels of subsidized care.

Despite large variations in margins among hospitals, there is a much smaller difference in how much goes toward free and subsidized spending. But hospital officials say focusing on free care unfairly excludes other subsidized spending and community services. Poudre Valley Health System's Rulon Stacey, left, says the system has increased subsidized health spending to $26.1 million, not all of which is reflected as charity care.

Still finding their way. Pioneer ACOs see modest savings in first year, with nearly one-third dropping out.

The Medicare AC0 program realized modest savings during its first year, but not everyone wants to stay, with nine out of 32 dropping out. Some fear the financial risks. "Everybody wants to fix the healthcare problems now, but if you push it too fast it blows up in your face," says Dr. David Spahlinger, of the University of Michigan Health System, which is switching its ACO to the Shared Savings Program from the Pioneer model.

Package deals. Despite increased scrutiny, executive pay at not-for-profit hospitals still on the rise.

Scrutiny of the compensation of executives at not-for-profit healthcare organizations may be growing, but the highest-paid such executives saw their median total pay grow 12% annually, a review of 2011 and 2010 data shows. Leading the pack for actively employed executives was George Halvorson, left, of Kaiser Permanente. "Compensation paid to senior management is substantially less than that of many for-profit health" insurers, a Kaiser spokesman said.

Push in the right direction. ACOs increasingly see insurance benefits as opportunity to offer incentives promoting value-based decisions.

The movement for accountable care has hospitals and physicians looking to tweak benefits to push patients toward making better choices. Banner Health sees a big opportunity to influence patients covered by private insurance because employers have more flexibility to modify benefit design. "Half of the equation is the patient taking on accountability," says Dr. Tricia Nguyen, chief medical officer of Banner's ACO.