Medication-based Comorbidity Measures and Prostate Cancer Treatment Selection.

INTRODUCTION: We aimed to assess the association between comorbidities and prostate cancer management. PATIENTS AND METHODS: We studied 12,603 South Australian men diagnosed with prostate cancer between 2003 and 2019. Comorbidity was measured one year prior to prostate cancer diagnosis using a medication-based comorbidity index (Rx-Risk). Binomial logistic regression analyses were used to assess the association between comorbidities and primary treatment selection (active surveillance, radical prostatectomy (RP), external beam radiotherapy (EBRT) with or without androgen deprivation therapy (ADT), brachytherapy, ADT alone, and watchful waiting (WW)). Certain common comorbidities within Rx-Risk (cardiac disorders, diabetes, chronic airway diseases, depression and anxiety, thrombosis, and chronic pain) were also assessed. All models were adjusted for sociodemographic and tumor characteristics. RESULTS: Likelihood of receiving RP was lower among men with Rx-Risk score ≥3 (odds ratio (OR) 0.62, 95%CI:0.56-0.69) and Rx-Risk 2 (OR 0.80, 95%CI:0.70-0.92) compared with no comorbidity (Rx-Risk ≤0). Men with high comorbidity (Rx-Risk ≥3) were more likely to have received ADT alone (OR 1.76, 95%CI:1.40-2.21), EBRT (OR 1.30, 95%CI:1.17-1.45) or WW (OR 1.49, 95%CI:1.19-1.88) compared with Rx-Risk ≤0. Pre-existing cardiac and respiratory disorders, thrombosis, diabetes, depression and anxiety, and chronic pain were associated with lower likelihood of selecting RP and higher likelihood of EBRT (except chronic airway disease) or WW (except diabetes and depression and anxiety). Cardiac disorders and thrombosis were associated with higher likelihood of selecting ADT alone. Furthermore, age had greater effect on treatment choice than the level of comorbidity. CONCLUSION: High comorbidity burden was associated with primary treatment choice, with significantly less RP and more EBRT, WW and ADT alone among men with higher levels of comorbidity. Each of the individual comorbid conditions also influenced treatment selection.

Clinical and functional outcomes for risk-appropriate treatments for prostate cancer.

Objectives: To describe real-world clinical and functional outcomes in an Australian cohort of men with localised prostate cancer according to treatment type and risk category. Subjects and methods: Men diagnosed from 2008 to 2018 who were enrolled in South Australian Prostate Cancer Clinical Outcomes Collaborative registry-a multi-institutional prospective clinical registry-were studied. The main outcome measures were overall survival, cancer-specific survival, decline in functional outcomes, biochemical recurrence and transition to active treatment following active surveillance. Multivariable adjusted models were applied to estimate outcomes. Results: Of the 8513 eligible men, majority of men (46%) underwent radical prostatectomy (RP) followed by external beam radiation therapy with or without androgen deprivation therapy (EBRT +/- ADT) in 22% of the cohort. Five-year overall survival was above 91%, and 5-year prostate cancer-specific survival was above 97% in the low- and intermediate-risk categories across all treatments. Five-year prostate cancer-specific survival in the active surveillance group was 100%. About 37% of men with high-risk disease treated with RP and 17% of men treated with EBRT +/- ADT experienced biochemical recurrence within 5 years of treatment. Of men on active surveillance, 15% of those with low risk and 20% with intermediate risk converted to active treatment within 2 years. The decline in urinary continence and sexual function 12 months after treatment was greatest among men who underwent RP while the decline in bowel function was greatest for men who received EBRT +/- ADT. Conclusion: This contemporary real-world evidence on risk-appropriate treatment outcomes helps inform treatment decision-making for clinicians and patients.

Factors impacting on sexual function among men on active surveillance for prostate cancer.

BACKGROUND: Active surveillance (AS) aims to reduce overtreatment and minimize the negative side effects of radical therapies (i.e., prostatectomy or radiotherapy) while preserving quality of life. However, a substantial proportion of men can experience a decline in sexual function during AS follow-up. The aim of this study was to identify predictors of declining sexual function among men on AS. METHODS: Men enrolled from 2008 to 2018 in the South Australian Prostate Cancer Clinical Outcomes Collaborative registry-a prospective clinical registry-were studied. Sexual function outcomes were measured using expanded prostate cancer index composite (EPIC-26) at baseline and 12-months postdiagnosis. Multivariable regression models adjusted for baseline score and other sociodemographic and clinical factors were applied to identify predictors of sexual function score at 12-months. RESULTS: A total of 554 men were included. Variables that showed significant association with decline in sexual function score at 12-months were: having two or more biopsies after diagnosis (mean change score (MCS): -16.3, p < 0.001) compared with no biopsy, higher number of positive biopsy cores (MCS: -1.6, p = 0.004), being in older age category (above 70 vs. below 60: MCS: -16.7, p < 0.001; 65-70 vs. below 60: MCS: -9.7, p = 0.024), having had depression (MCS: -9.0, p = 0.020), and impaired physical function (MCS: -10.0, p = 0.031). Greater socioeconomic advantage (highest vs. lowest quintile: MCS: 15.7, p = 0.022) and year of diagnosis (MCS: 2.6 for every year, p < 0.001) were positively associated with 12-months sexual function score. Neither biopsy type, biopsy timing nor PSA velocity were associated with declines in sexual function. CONCLUSIONS: Our findings suggest that multiple factors affected sexual function during AS. Interventions toward reducing the number of biopsies through less invasive monitory approaches, screening for physical and mental well-being, and targeted emotional support and counseling services may be helpful for men on AS.

Patient-reported functional outcome measures and treatment choice for prostate cancer.

BACKGROUND: The aim of this study was to describe changes in patient-reported functional outcome measures (PROMs) comparing pre-treatment and 12 months after radical prostatectomy (RP), external beam radiation therapy (EBRT), brachytherapy and active surveillance (AS). METHODS: Men enrolled from 2010 to 2019 in the South Australian Prostate Cancer Clinical Outcomes Collaborative registry a prospective clinical registry were studied. Urinary, bowel, and sexual functions were measured using Expanded Prostate Cancer Index Composite (EPIC-26) at baseline and 12 months post-treatment. Higher scores on the EPIC-26 indicate better function. Multivariable regression models were applied to compare differences in function and extent of bother by treatment. RESULTS: Of the 4926 eligible men, 57.0% underwent RP, 20.5% EBRT, 7.0% brachytherapy and 15.5% AS. While baseline urinary and bowel function varied little across treatment groups, sexual function differed greatly (adjusted mean scores: RP = 56.3, EBRT = 45.8, brachytherapy = 61.4, AS = 52.8; p < 0.001). Post-treatment urinary continence and sexual function declined in all treatment groups, with the greatest decline for sexual function after RP (adjusted mean score change - 28.9). After adjustment for baseline differences, post-treatment sexual function scores after EBRT (6.4; 95%CI, 0.9-12.0) and brachytherapy (17.4; 95%CI, 9.4-25.5) were higher than after RP. Likewise, urinary continence after EBRT (13.6; 95%CI, 9.0-18.2), brachytherapy (10.6; 95%CI, 3.9-17.3) and AS (10.6; 95%CI, 5.9-15.3) were higher than after RP. Conversely, EBRT was associated with lower bowel function (- 7.9; 95%CI, - 12.4 to - 3.5) than RP. EBRT and AS were associated with lower odds of sexual bother (OR 0.51; 95%CI, 0.29-0.89 and OR 0.60; 95%CI, 0.38-0.96, respectively), and EBRT with higher odds of bowel bother (OR 2.01; 95%CI, 1.23-3.29) compared with RP. CONCLUSION: The four common treatment approaches for prostate cancer were associated with different patterns of patient-reported functional outcomes, both pre- and 12 months post-treatment. However, after adjustment, RP was associated with a greater decline in urinary continence and sexual function than other treatments. This study underscores the importance of collecting baseline PROMs to interpret post-treatment functional outcomes.

Protocol for the Flinders Kidney Health Registry: patient outcomes of kidney cancers and nephrectomies.

BACKGROUND: Kidney cancer accounts for 2% of new cancers diagnosed in Australia annually. Partial and radical nephrectomy are the treatment of choice for kidney cancer. Nephrectomy is also performed for living donor kidney transplantation. Nephrectomy is a risk factor for new-onset chronic kidney disease (CKD) or deterioration of pre-existing CKD. Understanding the risk factors for new-onset or deterioration of existing CKD after nephrectomy is important in developing preventive measures to provide better care for these patients. There is also a need to understand the incidence, natural history, management trends, and sequelae of radiofrequency ablation as well as surveillance of small renal cancers or small renal masses (SRMs). Clinical registries are critical in providing excellent patient-centre care and clinical research as well as basic science research. Registries evaluate current practice and guide future practice. The Flinders Kidney Health Registry will provide the key information needed to assess various treatment outcomes of patients with kidney cancer and patients who underwent nephrectomy for other reasons. The registry aims to provide clinical decision makers with longitudinal data on patient outcomes, health systems performance, and the effect of evolving clinical practice. The registry will also provide a platform for large-scale prospective clinical studies and research. METHODS: Patients above the age of 18 undergoing nephrectomy or radiofrequency ablation for any indication and patients with SRMs will be included in the registry. Demographic, clinical and quality of life data will be collected from hospital information systems and directly from the patient and/or caregiver. DISCUSSION: The Registry will report a summary of patient characteristics including indication for treatment, clinical risk profiles, surgical and oncological outcomes, the proportion of patients who progress to CKD and end stage kidney disease, quality of life post treatment as well as other relevant outcomes for all patients who have undergone nephrectomy for any indication, ablation or surveillance for SRMs. The registry will record the follow-up practice after nephrectomy and patient on active surveillance, which will help to develop and enhance a best practice protocol. The collected prospective data will provide a platform for ongoing patient-orientated research and improve patient-centred healthcare delivery.

Evaluation of selective bone scan staging in prostate cancer - external validation of current strategies and decision-curve analysis.

BACKGROUND: Recommendations for staging newly diagnosed prostate cancer patients vary between guidelines and literature. METHODS: Our objective was to validate and compare prediction models selecting newly diagnosed prostate cancer patients for bone scan staging. To achieve this, we validated eleven models in a population-based cohort of 10,721 patients diagnosed with prostate cancer between 2005 and 2019. The primary outcome was net-benefit. This was assessed at different balances of conservatism and tolerance, represented by preference ratio and number-willing-to-test (NWT). Secondary outcomes included calibration slope, calibration-in-the-large (intercept), and discrimination measured by Area-under-the-receiver-operator-characteristics curve (AUC). RESULTS: For preference ratios less than 1:39 (NWT greater than 40), scanning everyone provided greater net-benefit than selective staging. For preference ratios 1:39 to 3:97 (NWT 33-40), the European Association of Urology (EAU) 2020 guideline recommendation was the best approach. For preference ratios 3:97-7:93 (NWT 14-33), scanning EAU high-risk patients only was preferable. For preference ratios 7:93-1:9 (NWT 10-13), scanning only Gnanapragasam Group 5 patients was best. All models had similar fair discrimination (AUCs 0.68-0.80), but most had poor calibration. CONCLUSIONS: We identified three selective staging strategies that outperformed all other approaches but did so over different ranges of conservatism and tolerance. Scanning only EAU high-risk patients provided the greatest net-benefit over the greatest range of preference ratios and scenarios, but other options may be preferable depending upon the local healthcare system's degree of conservatism and tolerance.

The bidirectional association between depression and lower urinary tract symptoms (LUTS) in men: A systematic review and meta-analysis of observational studies.

BACKGROUND: Recent evidence from observational studies suggests a bidirectional association between lower urinary tract symptoms (LUTS) and depression in men. We sought to systematically quantify the effect of the presence of LUTS on depression symptoms, compared to those without LUTS, in adult males, and vice versa. METHODS: Electronic databases (MEDLINE, PsycINFO, SCOPUS, Embase) were examined for articles in English before March 2021. Observational studies of men aged over 18 years; reporting an association between LUTS and depression; including a validated scale for LUTS and depression symptoms were eligible for study inclusion. RESULTS: Seventeen studies out of 1787 records identified 163 466 men with reported depression symptoms by LUTS status, while 10 studies reported 72 363 men with LUTS by depression symptoms. Pooled estimates showed a strong effect of LUTS presence on depression risk (OR: 2.89, 95% CI: 2.50-3.33), with a high degree of heterogeneity among the examined studies (I2 = 83%; τ2 = 0,06; p < 0.001). Subgroup analyses demonstrated differences by study region (Q value:13.7, df:4, p = 0.003), setting (7.8(2), p = 0.020), design (7.2(1), p = 0.003), quality (6.2(1), p = 0.013), and LUTS measure (40.9(3), p < 0.001). Pooled estimates also showed a strong effect of depression presence on LUTS risk in men (OR: 3.13, 95% CI: 2.72-3.60), with only moderate heterogeneity between studies (I2 = 58%; τ2 = 0,02; p = 0.001). CONCLUSIONS: The strong relationship observed between LUTS and depression implies shared risk factors that cannot be solely attributed to the prostate. This has immediate implications for future studies and the assessment and management of patients with either condition.

Cancer cell detection device for the diagnosis of bladder cancer from urine.

Bladder cancer is common and has one of the highest recurrence rates. Cystoscopy, the current gold standard diagnosis approach, has recently benefited from the introduction of blue light assisted photodynamic diagnostic (PDD). While blue light cystoscopy improves diagnostic sensitivity, it remains a costly and invasive approach. Here, we present a microfluidic-based platform for non-invasive diagnosis which combines the principle of PDD with whole cell immunocapture technology to detect bladder cancer cells shed in patient urine ex vivo. Initially, we demonstrate with model cell lines that our non-invasive approach achieves highly specific capture rates of bladder cancer cells based on their Epithelial Cell Adhesion Molecule expression (>90%) and detection by the intensity levels of Hexaminolevulinic Acid-induced Protoporphyrin IX fluorescence. Then, we show in a pilot study that the biosensor platform successfully discriminates histopathologically diagnosed cancer patients (n = 10) from non-cancer controls (n = 25). Our platform can support the development of a novel non-invasive diagnostic device for post treatment surveillance in patients with bladder cancer and cancer detection in patients with suspected bladder cancer.

Prognostic Differences in ISUP Grade Group 4: a Systematic Review and Meta-Analysis.

The ISUP (Internal Society of Urologic Pathology) recently adopted a five-tiered prognostication system. There is evidence to suggest that the ISUP grade group 4 is a heterogeneous entity regarding prognosis. Our aim was to systematically examine the existing evidence to determine if outcome differences exist within the ISUP grade group 4. A systematic search of the literature for all studies examining the heterogeneity of the ISUP grade group 4 was conducted. Available studies were combined with meta-analysis to evaluate prognostic differences within the ISUP grade group 4 measured by all-cause mortality (ACM) and the prostate cancer-specific mortality (PCSM). Eight studies were identified and utilised a variety of outcome measures to answer the question of heterogeneity within the ISUP grade group 4. Four of these studies examined prognosis using both ACM and PCSM. These were combined into a meta-analysis. The combined group of 5 + 3/3 + 5 had statistically significant higher ACM (hazard ratio [HR] 1.23, 95% confidence internal [Cl] 1.08-1.41) when compared to the 4 + 4 group. There was no difference in the PCSM between the two groups (HR 1.34, 95% CI 0.89-2.01). However, heterogeneity was high for this analysis secondary to a range of methodological differences. Our meta-analysis showed that Gleason grade 3 + 5/5 + 3 had higher ACM than Gleason grade group 4 + 4. Measures of PCSM were statistically insignificant, although heterogeneity was high. Evidence suggests that heterogeneity is likely, although inconclusive. Further studies with consistent methodologies are required to answer this question.