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.

Population-based patient-reported quality of life outcomes following low-dose-rate versus high-dose-rate brachytherapy monotherapy for low-intermediate risk prostate cancer.

INTRODUCTION: To evaluate patient reported quality of life outcomes (QoL) following low-dose-rate brachytherapy (LDR-BT) and high-dose-rate brachytherapy (HDR-BT) monotherapy for prostate cancer at a population-based setting. METHODS: The study comprised men with low-intermediate risk prostate cancer in the Prostate Cancer Outcomes Registry Victoria (PCOR-Vic), who were treated with LDR-BT or HDR-BT monotherapy between 2015 and 2020 and completed the Expanded Prostate Cancer Index Composite (EPIC-26) questionnaire 12-month post-treatment. Men who had ADT were excluded (n = 12). Differences in substantial symptoms (i.e. 'moderate' or 'big' problem on a 5-point Likert scale) between LDR-BT and HDR-BT arms were evaluated using Pearson's chi-squared test. Multivariable linear regressions were used to estimate differences in EPIC-26 urinary, bowel and sexual functional domain scores between LDR-BT and HDR-BT arms. RESULTS: Overall, 198 men were included in this study, of which 167 (84%) had LDR-BT and 31 (16%) had HDR-BT. 9 (4.6%), 10 (5.1%) and 56 (28%) reported substantial symptoms for overall urinary, bowel and sexual function at 12-month post-treatment, with no significant difference between LDR-BT and HDR-BT arms. The adjusted mean differences in urinary incontinence, urinary obstructive, bowel and sexual function domain scores between LDR-BT and HDT-BT were: -3.53 (-8.21 to 1.14), -1.27 (-6.88 to 4.35), -0.01 (-5.63 to 5.63) and -8.68 (-21.44 to 4.07) respectively - these were not statistically significant and did not meet the minimal clinically important difference. CONCLUSION: This is the first Australian population-based study comparing QoL in men who had LDR-BT and HDR-BT, with no statistically or clinically significant differences in QoL observed at 12-month post-treatment.

Dissecting the spermatogonial stem cell niche using spatial transcriptomics.

Spermatogonial stem cells (SSCs) in the testis support the lifelong production of sperm. SSCs reside within specialized microenvironments called "niches," which are essential for SSC self-renewal and differentiation. However, our understanding of the molecular and cellular interactions between SSCs and niches remains incomplete. Here, we combine spatial transcriptomics, computational analyses, and functional assays to systematically dissect the molecular, cellular, and spatial composition of SSC niches. This allows us to spatially map the ligand-receptor (LR) interaction landscape in both mouse and human testes. Our data demonstrate that pleiotrophin regulates mouse SSC functions through syndecan receptors. We also identify ephrin-A1 as a potential niche factor that influences human SSC functions. Furthermore, we show that the spatial re-distribution of inflammation-related LR interactions underlies diabetes-induced testicular injury. Together, our study demonstrates a systems approach to dissect the complex organization of the stem cell microenvironment in health and disease.

Dissecting mammalian reproduction with spatial transcriptomics.

BACKGROUND: Mammalian reproduction requires the fusion of two specialized cells: an oocyte and a sperm. In addition to producing gametes, the reproductive system also provides the environment for the appropriate development of the embryo. Deciphering the reproductive system requires understanding the functions of each cell type and cell-cell interactions. Recent single-cell omics technologies have provided insights into the gene regulatory network in discrete cellular populations of both the male and female reproductive systems. However, these approaches cannot examine how the cellular states of the gametes or embryos are regulated through their interactions with neighboring somatic cells in the native tissue environment owing to tissue disassociations. Emerging spatial omics technologies address this challenge by preserving the spatial context of the cells to be profiled. These technologies hold the potential to revolutionize our understanding of mammalian reproduction. OBJECTIVE AND RATIONALE: We aim to review the state-of-the-art spatial transcriptomics (ST) technologies with a focus on highlighting the novel biological insights that they have helped to reveal about the mammalian reproductive systems in the context of gametogenesis, embryogenesis, and reproductive pathologies. We also aim to discuss the current challenges of applying ST technologies in reproductive research and provide a sneak peek at what the field of spatial omics can offer for the reproduction community in the years to come. SEARCH METHODS: The PubMed database was used in the search for peer-reviewed research articles and reviews using combinations of the following terms: 'spatial omics', 'fertility', 'reproduction', 'gametogenesis', 'embryogenesis', 'reproductive cancer', 'spatial transcriptomics', 'spermatogenesis', 'ovary', 'uterus', 'cervix', 'testis', and other keywords related to the subject area. All relevant publications until April 2023 were critically evaluated and discussed. OUTCOMES: First, an overview of the ST technologies that have been applied to studying the reproductive systems was provided. The basic design principles and the advantages and limitations of these technologies were discussed and tabulated to serve as a guide for researchers to choose the best-suited technologies for their own research. Second, novel biological insights into mammalian reproduction, especially human reproduction revealed by ST analyses, were comprehensively reviewed. Three major themes were discussed. The first theme focuses on genes with non-random spatial expression patterns with specialized functions in multiple reproductive systems; The second theme centers around functionally interacting cell types which are often found to be spatially clustered in the reproductive tissues; and the thrid theme discusses pathological states in reproductive systems which are often associated with unique cellular microenvironments. Finally, current experimental and computational challenges of applying ST technologies to studying mammalian reproduction were highlighted, and potential solutions to tackle these challenges were provided. Future directions in the development of spatial omics technologies and how they will benefit the field of human reproduction were discussed, including the capture of cellular and tissue dynamics, multi-modal molecular profiling, and spatial characterization of gene perturbations. WIDER IMPLICATIONS: Like single-cell technologies, spatial omics technologies hold tremendous potential for providing significant and novel insights into mammalian reproduction. Our review summarizes these novel biological insights that ST technologies have provided while shedding light on what is yet to come. Our review provides reproductive biologists and clinicians with a much-needed update on the state of art of ST technologies. It may also facilitate the adoption of cutting-edge spatial technologies in both basic and clinical reproductive research.

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.

Development of binational radiation therapy quality indicator reports for prostate cancer treatment using registry data.

INTRODUCTION: Quality indicators (QIs) are metrics which seek to allow comparison of clinicians' and institutes' practice to best evidence-based practice. The Australia and New Zealand Prostate Cancer Outcomes Registry (PCOR-ANZ) is a bi-national clinical quality registry with coverage estimated to be over 60% of the men newly diagnosed with prostate cancer. We outline the production and ambition of institute-level QI reports to benchmark performance for radiation therapy in the treatment of prostate cancer. METHODS: An expert clinician panel was assembled to create a list of candidate QIs based on a comprehensive literature review, and on modified Delphi-method and expert-consensus voting. A separate implementation group-including, clinicians, epidemiologists, data managers and data scientists-employed an evidence- and consensus- based approach to generate an effective QI report designed for automated production and regular distribution to participating institutes. Feedback from the recipient clinicians was sought to enable refinement of these reports. RESULTS: Seven QIs, including three related to post-treatment symptoms, were deemed feasible to analyse with the currently available data. Utilising an existing report template employed for benchmarking of surgical indicators, a novel radiation therapy report was generated using registry data in a secure analytical environment. The first, beta version of these reports have been produced and confidentially distributed. It is planned to automatically generate these reports biannually and iteratively refine them based on the clinician input. CONCLUSION: QI reports for the treatment of prostate cancer by radiation oncologists have been produced using data from Australia and New Zealand patients. These are being disseminated to institutes on a six-monthly basis allowing comparisons to de-identified peers. The reports aim to facilitate improving patient outcomes, deepen engagement with the radiation oncology community and increase the breadth of PCOR-ANZ coverage. Additional QIs will be included in future iterations of these reports as data matures.

Real-world utilisation of brachytherapy boost and patient-reported functional outcomes in men who had external beam radiation therapy for prostate cancer in Australia.

Background and purpose: We aimed to evaluate utilisation of brachytherapy (BT) boost in men who had external beam radiation therapy (EBRT) for prostate cancer, and to compare patient-reported functional outcomes (PRO) following each approach in a population-based setting in Australia. Materials and methods: This is a population-based cohort of men with localised prostate cancer enrolled in the Victorian Prostate Cancer Outcomes Registry, who had EBRT between 2015 and 2020. Primary outcomes were proportion who had BT-boost, and PRO (assessed using the EPIC-26 questionnaires) 12 months post-treatment. Multivariable logistic regressions were used to evaluate factors associated with BT-boost, and linear regressions were used to estimate differences in EPIC-26 domain scores between EBRT alone and EBRT + BT. Results: Of the 1,626 men in the study, 88 (5.4 %) had BT-boost. Factors independently associated with BT-boost were younger age, higher socioeconomic status, and treatment in public institutions. 1,555 men completed EPIC-26 questionnaires. No statistically or clinically significant differences in EPIC-26 urinary, sexual and bowel functional domain scores were observed between men who had EBRT + BT vs EBRT alone, with adjusted mean differences in urinary incontinence, urinary irritative/ obstruction, sexual, and bowel domain of 1.28 (95 %CI = -3.23 to 5.79), -2.87 (95 %CI = -6.46 to 0.73), 0.49 (95 %CI = -4.78 to 5.76), and 2.89 (95 %CI = -0.83 to 6.61) respectively. Conclusion: 1-in-20 men who had EBRT for prostate cancer had BT-boost. This is the first time that PRO following EBRT+/-BT is reported at a population-based level in Australia, with no evidence to suggest worse PRO with addition of BT-boost 12 months post-treatment.

A decade of declining prostatectomy margin positivity within a prostate cancer clinical quality registry.

CONTEXT: Positive surgical margin (PSM) on radical prostatectomy (RP) is associated with an increased risk of biochemical recurrence and use of salvage therapies. Given these adverse consequences, exploration of time trends and predictors of PSM will improve the patient outcomes following surgery for prostate cancer. METHODS: Pathological data from RP patients treated from 2011 to 2020 was extracted from the Victorian Prostate Cancer Outcomes Registry. This is a clinical quality registry that regularly benchmarks and reports back to individual clinicians the PSM percentage for their patients. Trends in PSM over time were visualized with separate running mean plots for both pT2 and pT3/4 disease. Predictors of PSM were explored with multivariable regression with date of surgery, surgical method, and hospital type, public or private, entered as covariates. RESULTS: In total, 12,394 patients formed the sample with PSM recorded in 25% (n = 3,141) of patients, 12% (777/6,640) in pT2 disease and 41% (2,364/5,754) in pT3/4 disease. Comparing 2011-12 to 2019-20, the pT3/4 PSM proportion declined from 50% to 38% while pT2 percentages were steady at 13%. In "high volume" institutions, pT2 PSM fell from 12% to 6.5%. Independent predictors of lower PSM were robotic vs. open method and being treated at a private vs. public institution. CONCLUSION: A clear decline in the proportion of pT3 PSM was observed in a large prostate cancer registry. Proposed explanatory factors include improved technical proficiency with robotic surgery and participation in a registry-based quality improvement initiative.

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.

Impact of delay from transperineal biopsy to radical prostatectomy upon objective measures of cancer control.

Objective: Treatment delays in prostate cancer have been characterised, although not explicitly in men undergoing transperineal prostate biopsies. We aimed to determine if delays to radical prostatectomy correlate with adverse outcomes using a contemporary population-based cohort of men diagnosed by transperineal biopsies. Methods: This study analysed men with prostate cancer of the International Society for Urological Pathology grade group ≥2, diagnosed by transperineal prostate biopsies who underwent prostatectomy, using the prospectively data from 1 January 2014 to 30 June 2018 Prostate Cancer Outcomes Registry-Victoria. Data were analysed according to stratified demographic and disease characteristics. Time intervals from biopsy (28, 60, 90, 120, and 270 days) were compared using odds ratios and regression analyses for proportion of upgrading, early biochemical recurrence, pT3 disease at prostatectomy, and positive surgical margins. Results: In total, 2008 men were analysed. There were 306 (16.7%) men with upgrading, 151 (8.4%) with biochemical recurrence, 1068 (54.1%) with pT3 disease, and 464 (23.1%) with positive surgical margins (percentages excluded patients with missing data). All adverse outcomes studied were significantly associated with higher prostate-specific antigen and grade at diagnosis. Delays of 120-270 days did not adversely alter the incidence of Gleason upgrading, pT3, or recurrence. Delays (most frequent 60-89 days, 28%) were associated with positive surgical margins but not monotonically. Regression modelling demonstrated no increased likelihood of most adverse outcomes for up to 270 days. Conclusion: Men with prostate cancer of grade group ≥2 diagnosed through transperineal biopsy may wait up to 270 days for a prostatectomy without a greater likelihood of upgrading, pT3 disease, positive surgical margins, or biochemical recurrence.

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.

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.

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.

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.

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.

Specialist physicians' referral behavior regarding preimplantation genetic testing for single-gene disorders: Is there room to grow?

OBJECTIVE: To assess whether primary care specialists' demographics, specialty, and knowledge of preimplantation genetic testing for monogenic disorders (PGT-M) influence their practice patterns. DESIGN: Cross-sectional survey study. SETTING: Academic medical center. PATIENTS: Not applicable. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Objective PGT-M knowledge, subjective comfort with PGT-related topics, PGT care practices (discussions/referrals), and PGT-M implementation barriers. RESULTS: Our survey had 145 respondents: 65 obstetrician/gynecologists, 36 internists, and 44 pediatricians. Overall, 88% believed that patients at a risk of passing on genetic disorders should be provided PGT-M information. However, few discussed PGT-M with their patients (24%) or referred them for testing (23%). Over half (63%) believed that the lack of physician knowledge was a barrier to PGT use. In terms of subjective comfort with PGT, only 1 in 5 physicians felt familiar enough with the topic to answer patient questions. There were higher odds of discussing (odds ratio, 3.21; 95% confidence interval, 1.75-5.87) or referring for PGT (odds ratio, 2.52; 95% confidence interval, 1.41-4.51) for each additional 0.5 correct answers to PGT knowledge-related questions. The odds of referring patients for PGT-M were the highest among obstetrician/gynecologists compared with those among the internists and pediatricians. CONCLUSIONS: Physician specialty and PGT knowledge were associated with PGT-M care delivery practices. Although most specialists believed in equipping at-risk patients with PGT-M information, <1 in 4 discussed or referred patients for PGT. The low levels of PGT-related care among providers may be owed to inadequate knowledge of and comfort with the topic. An opportunity to promote greater understanding of PGT-M among primary care specialists exists and can in turn improve the use of referrals to PGT-M services.

A multi-level spatio-temporal analysis on prostate cancer outcomes.

BACKGROUND: Geographic and temporal variation in positive surgical margins (PSM) for prostate cancer after radical prostatectomy (RP) has been observed. However, it is unclear how much of this variation could be attributed to patient, surgeon, institution, or socioeconomic-related factors and the impact of PSM on death among localized prostate cancer patients. METHODS: This study aimed to assess the independent and relative contribution of the patient, surgeon, institution and area-level risk factors on geographic and temporal variation of PSM and evaluate the impact of PSM on five-year all-cause and prostate cancer-specific mortality among localized prostate cancer patients. Within the hierarchical-related regression approach, we utilised Bayesian spatial-temporal multi-level models to study individual and area-level predictors with the outcomes, while accounting for geographically structured and unstructured correlation and non-linear trends. RESULTS: Individual-level data included 10,075 localized prostate cancer cases with RP reported to the Prostate Cancer Outcomes Registry Victoria between 2009 and 2018. Area-level data comprised socio-economic disadvantage and remoteness data at the local government area level in Victoria, Australia. 26 % of patients had PSM, and the rates varied across areas by years. This variation was mainly associated with NCCN risk, followed by RP techniques, surgical institution type, surgeon volume and socio-economic disadvantage. Intermediate (Odds ratio/OR = 1.21,95 % credible interval/Crl = 1.05-1.41), high/very-high risk groups (OR = 2.24,95 % Crl = 1.91-2.64) and public surgical institution (OR = 1.64, 95 % Crl = 1.46-1.84) were independently associated with a higher likelihood of PSM. Robot-assisted (OR = 0.61, 95 % Crl = 0.55-0.68), laparoscopic RP (OR = 0.76, 95 % Crl = 0.62-0.93), high-volume surgeon (OR = 0.84, 95 % Crl = 0.76-0.93) and socio-economically least disadvantaged status (OR = 0.78, 95 % Crl = 0.64-0.94) showed a lower likelihood of PSM. PSM was also independently associated with a higher five-year all-cause and prostate cancer-specific mortality. CONCLUSION: Aggressive tumour characteristics and RP techniques were the main contributors to the likelihood of PSM following RP. Reducing the prevalence of PSM will generally improve prostate cancer-specific and all-cause mortality.

Patterns of primary staging for newly diagnosed prostate cancer in the era of prostate specific membrane antigen positron emission tomography: A population-based analysis.

INTRODUCTION: There has been a growing body of evidence highlighting the improved sensitivity and specificity for prostate specific membrane antigen (PSMA) positron emission tomography (PET) in advanced prostate cancer imaging. We aimed to assess prostate cancer staging practice patterns in Australia using population-based data. SUBJECT AND METHODS: We extracted data on men diagnosed with prostate cancer between October 2016 and December 2018 from the Prostate Cancer Outcomes Registry-Victoria (PCOR-Vic). We evaluated trends and comparisons between patients receiving PET/CT (with or without conventional imaging (CImg)), and CImg alone, and analysed imaging modality as predictor of clinical regional node positive disease (cN1 vs cN0/X), metastatic disease (cM1 vs cM0/X), and treatment received. RESULTS: In total, 6139 patients in the registry had either a staging PET scan (n = 889, 14%), CImg without PET scan (n = 2464, 40%), or no recorded PET or CImg (n = 2786, 45%). The proportion of allimaged patients who received staging PET increased from 19% to 36% from the first to last three-month period, and in the high-risk category the increase was 23-43%. After adjustment for grade group, PET vs CImg-only patients were observed to have a higher proportion of cN1 disease (OR = 2.46, 95% CI: 1.90-3.20) but not cM1 disease (OR = 1.10, 95% CI: 0.84-1.44). CONCLUSIONS: Our registry data highlights the rapid uptake of PET imaging, particularly in high-risk disease. Based on this data, we highlight the increased diagnosis of nodal disease, thus potentially optimizing patient selection prior to definitive treatment for prostate cancer.

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.