Benefits and harms of prostate specific antigen testing according to Australian guidelines.

Guidelines for prostate specific antigen (PSA) testing in Australia recommend that men at average risk of prostate cancer who have been informed of the benefits and harms, and who decide to undergo regular testing, should be offered testing every 2 years from 50 to 69 years. This study aimed to estimate the benefits and harms of regular testing in this context. We constructed Policy1-Prostate, a discrete event microsimulation platform of the natural history of prostate cancer and prostate cancer survival, and PSA testing patterns and subsequent management in Australia. The model was calibrated to pre-PSA (before 1985) prostate cancer incidence and mortality and validated against incidence and mortality trends from 1985 to 2011 and international trials. The model predictions were concordant with trials and Australian observed incidence and mortality data from 1985 to 2011. Out of 1000 men who choose to test according to the guidelines, 36 [21-41] men will die from prostate cancer and 126 [119-133] men will be diagnosed with prostate cancer, compared with 50 [47-54] and 94 [90-98] men who do not test, respectively. During the 20 years of active PSA testing, 32.3% [25.6%-38.8%] of all PSA-test detected cancers are overdiagnosed cases that is, 30 [21-42] out of 94 [83-107] PSA-test detected cancers. Australian men choosing to test with PSA every two years from 50 to 69 will reduce their risk of ever dying from prostate cancer and incur a risk of overdiagnosis: for every man who avoids dying from prostate cancer, two will be overdiagnosed with prostate cancer between 50 and 69 years of age. Australian men, with health professionals, can use these results to inform decision-making about PSA testing.

Descriptive analysis of prostate cancer pathology data from diagnosis and surgery in men from the 45 and Up Study.

Information available from the New South Wales Cancer Registry (NSWCR) about the aggressiveness of prostate cancer is limited to the summary stage variable 'degree of spread', which contains a high proportion of cases defined as 'unknown'. In this study we demonstrate the feasibility of obtaining and analysing prostate cancer pathology data from stored pathology records. Pathology data were extracted from stored pathology records of incident prostate cancer cases in men participating in the 45 and Up Study, a large Australian prospective cohort study, who were diagnosed between January 2006 and December 2013. Baseline questionnaires from the 45 and Up Study were linked to the NSWCR. Demographic and pathology items were tabulated and associations described. We evaluated the completeness of pathological characteristics by degree of spread of cancer at diagnosis. Among the 123,921 men enrolled in the 45 and Up Study, 5,091 had incident prostate cancer and 5,085 were linked to a pathology record. The most complete variables included grade group of diagnostic (85.8%) and surgical (99.8%) specimens, margin status (98.1%), extraprostatic extension (95.1%) and seminal vesicle invasion (96.8%). Most diagnostic specimens were grade group 1 (26.6%) or 2 (23.5%). Of the 5,085 cases, 30.8% were classified by the NSWCR with unknown degree of spread; a pathology record could be extracted for 99.4% of these. The unknown degree of spread cases had similar levels of completeness and distribution of diagnostic and surgical pathology features to those with a localised degree of spread. This study demonstrated the feasibility of obtaining and analysing data derived from pathology reports from centralised state-based cancer registry notifications. Supplementing degree of spread information with pathology data from diagnosis and surgery will improve both the quality of research and policy aimed at improving the lives of men with prostate cancer.

Alcohol consumption and socioeconomic status associated with the risk of kidney cancer in a large Australian cohort study.

PURPOSE: Studies have shown an inverse association between alcohol consumption and kidney cancer risk. We postulate that this inverse association may be further influenced by other risk factors. METHODS: We used an Australian cohort, the 45 and Up Study, recruited between 2005 and 2009 to investigate the association between alcohol consumption, and other potential risk factors and kidney cancer incidence. The median follow-up was 5.4 years. RESULTS: Of the 267,357 participants aged ≤45 years living in New South Wales, 497 were diagnosed with kidney cancer. There was a significant inverse association between alcohol consumption and risk of kidney cancer (P = .027), and a significant inverse dose-response relationship (P = .011). There was a significant interaction between alcohol consumption and socioeconomic status (P interaction = .001). Participants residing in higher socioeconomic areas (the two most advantaged quintiles) who consumed 8-10 drinks or greater than 10 drinks per week, respectively, had a lower risk of kidney cancer compared to the group who consumed 1-4 drinks per week (hazard ratio (HR) 0.34, 95% confidence interval (CI) 0.15-0.76, HR 0.51, 95% CI 0.31-0.83) with a dose-response trend of HR 0.62 (95% CI 0.42-0.93) per 7 drink increase in weekly alcohol consumption. CONCLUSIONS: There could be an inverse association between alcohol consumption and risk in those residents in higher socioeconomic areas.

Family history, obesity, urological factors and diabetic medications and their associations with risk of prostate cancer diagnosis in a large prospective study.

BACKGROUND: Prostate cancer (PC) aetiology is unclear. PC risk was examined in relation to several factors in a large population-based prospective study. METHODS: Male participants were from Sax Institute's 45 and Up Study (Australia) recruited between 2006 and 2009. Questionnaire and linked administrative health data from the Centre for Health Record Linkage and Services Australia were used to identify incident PC, healthcare utilisations, Prostate Specific Antigen (PSA) testing reimbursements and dispensing of metformin and benign prostatic hyperplasia (BPH) prescriptions. Multivariable Cox and Joint Cox regression analyses were used to examine associations by cancer spread, adjusting for various confounders. RESULTS: Of 107,706 eligible men, 4257 developed incident PC up to end 2013. Risk of PC diagnosis increased with: PC family history (versus no family history of cancer; HRadjusted = 1.36; 95% CI:1.21-1.52); father and brother(s) diagnosed with PC (versus cancer-free family history; HRadjusted = 2.20; 95% CI:1.61-2.99); severe lower-urinary-tract symptoms (versus mild; HRadjusted = 1.77; 95% CI:1.53-2.04) and vasectomy (versus none; HRadjusted = 1.08; 95% CI:1.00-1.16). PC risk decreased with dispensed prescriptions (versus none) for BPH (HRadjusted = 0.76; 95% CI:0.69-0.85) and metformin (HRadjusted = 0.57; 95% CI:0.48-0.68). Advanced PC risk increased with vasectomy (HRadjusted = 1.28; 95% CI:1.06-1.55) and being obese (versus normal weight; HRadjusted = 1.31; 95% CI:1.01-1.69). CONCLUSION: Vasectomy and obesity are associated with an increased risk of advanced PC. The reduced risk of localised and advanced PC associated with BPH, and diabetes prescriptions warrants investigation.

Characteristics Associated with the Use of Diagnostic Prostate Biopsy and Biopsy Outcomes in Australian Men.

BACKGROUND: Population characteristics associated with the use of prostate biopsy are poorly understood. We described the use of diagnostic prostate biopsy and subsequent biopsy outcomes in a population-based Australian cohort. METHODS: A total of 91,764 men from the Sax Institute's 45 and Up Study (New South Wales, Australia) recruited during 2006 to 2009 were included. Self-completed baseline questionnaires and linked administrative health data were used. Study period was from the date of recruitment to December 2013. Cox regression and logistic regression identified factors associated with receipt of biopsy and subsequent prostate cancer diagnosis. RESULTS: During the study period, 5,089 participants had a diagnostic prostate biopsy, and 2,805 men (55.1% of those biopsied) received a cancer diagnosis. Men with a family history of prostate cancer (HR 1.55; 95% confidence interval (CI), 1.43-1.68), severe lower urinary tract symptoms (HR 1.62; 95% CI, 1.41-1.86), or a record of medication for benign prostatic hyperplasia (HR 1.34; 95% CI, 1.23-1.47) had increased risks of receiving a biopsy. Men with a family history of prostate cancer had increased odds of a positive biopsy (OR 1.21; 95% CI, 1.01-1.43). High alcohol consumption (≥21 drinks per week compared with 1-6 drinks per week) was associated with decreased risk of biopsy (HR 0.88; 95% CI, 0.80-0.96) but increased odds of a positive biopsy (OR 1.63; 95% CI, 1.32-2.02). CONCLUSIONS: Certain characteristics are associated with both undertaking diagnostic prostate biopsy and positive biopsy outcomes. IMPACT: This highlights the need to improve management of specific groups of men, especially those with clinical symptoms that overlap with prostate cancer, in their investigation for prostate cancer.

Post-treatment levels of plasma 25- and 1,25-dihydroxy vitamin D and mortality in men with aggressive prostate cancer.

Vitamin D may reduce mortality from prostate cancer (PC). We examined the associations of post-treatment plasma 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D concentrations with PC mortality. Participants were PC cases from the New South Wales Prostate Cancer Care. All contactable and consenting participants, at 4.9 to 8.6 years after diagnosis, were interviewed and had plasma 25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D (1,25(OH)2D) measured in blood specimens. Cox regression allowing for left-truncation was used to calculate adjusted mortality hazards ratios (HR) and 95% confidence intervals (95% CI) for all-cause and PC-specific mortality in relation to vitamin D levels and other potentially-predictive variables. Of the participants (n = 111; 75·9% response rate), there were 198 deaths from any cause and 41 from PC in the study period. Plasma 25(OH)D was not associated with all-cause or PC-specific mortality (p-values > 0·10). Plasma 1,25(OH)2D was inversely associated with all-cause mortality (HR for highest relative to lowest quartile = 0·45; 95% CI: 0·29-0·69), and PC-specific mortality (HR = 0·40; 95% CI: 0·14-1·19). These associations were apparent only in men with aggressive PC: all-cause mortality HR = 0·28 (95% CI·0·15-0·52; p-interaction = 0·07) and PC-specific mortality HR = 0·26 (95% CI: 0·07-1.00). Time spent outdoors was also associated with lower all-cause (HR for 4th relative to 1st exposure quartile = 0·42; 95% CI: 0·24-0·75) and PC-specific (HR = 0·48; 95% CI: 0·14-1·64) mortality, although the 95% CI for the latter was wide. The inverse association between post-treatment plasma 1,25(OH)2D levels and all-cause and PC-specific mortality in men with aggressive PC, suggest a possible beneficial effect of vitamin D supplementation in these men.

Patterns of prostate-specific antigen testing by remoteness of residence and socio-economic status: An Australian population-based study.

OBJECTIVE: Describes the variation in prostate cancer testing by the remoteness of residence and socio-economic status groups in Australia. DESIGN: A national population-based descriptive study using Medicare data extracted by the Department of Health (formerly the Department of Health and Ageing). SETTING: Australia. PARTICIPANTS: All men, with a Medicare-reimbursed prostate-specific antigen test conducted in Australia between 2002 and 2017, were included. We focused on "screening and case finding" tests (Medicare Benefits Schedule item number 66655) from 1 April 2005 to 31 December 2009, to describe testing differences in subgroups. Groups were categorised into State and Territory, socio-economic status and region of residence. A negative binomial regression model was fitted to measure the incidence rate ratios of those who had a screening prostate-specific antigen test by group. MAIN OUTCOME MEASURES: Age-standardised testing rates and incidence rate ratios. RESULTS: Between 2002 and 2017, 11 588 775 screening prostate-specific antigen tests were reimbursed by the Department of Human Services. During 2005-2009, 52% of all Australian men, aged 40 years and over, had a screening test. The incidence rate ratios differed by State and Territory. Men aged 40 years and over, living in very remote areas, were 43% less likely to have had a screening test than residents of major cities. Prostate-specific antigen testing rates fell in all age groups between 2007 and 2009 and 2017. CONCLUSIONS: The prostate-specific antigen testing behaviour differs between community groups in Australia. Men were less likely to have had a screening prostate-specific antigen test the farther they lived from the major cities. This highlights the need for a more targeted approach to achieve an equitable and evidence-based prostate cancer care across all sectors of the community.

Increased risk of suicide in New South Wales men with prostate cancer: Analysis of linked population-wide data.

BACKGROUND: An elevated risk of suicide after a diagnosis of prostate cancer has been reported previously in the USA and Sweden. We aimed to identify whether prostate cancer survivors resident in New South Wales Australia are at higher risk of suicide and if so, who is most at risk. METHODS: Data were obtained from the New South Wales (NSW) Cancer Registry for all men diagnosed with prostate cancer in NSW during 1997 to 2007. These were linked by the Centre for Health Record Linkage (CHeReL) to Australian Bureau of Statistics Mortality Data to the end of 2007 to determine vital status and cause of death. We compared the number of suicides observed for prostate cancer survivors with the expected number of suicides based on age- and calendar year- specific rates for the NSW male population using standardised mortality ratios (SMRs). Suicide rate ratios (RR) by disease and patients' characteristics were estimated using multivariable negative binomial regression to determine the most at risk groups. RESULTS: During the study period 51,924 NSW men were diagnosed with prostate cancer. Forty nine of these men were subsequently recorded as committing suicide up to 10 years after diagnosis with an SMR of 1.70 (95% CI:1.26-2.25). Twenty six (53%) of these suicides occurred within 12 months after diagnosis. Risk diminished over time since diagnosis (RR in 1-2 years after diagnosis = 0.29, 95% CI: 0.12-0.71, 2-4 years RR = 0.30, 95% CI: 0.14-0.16 and 4+ years RR = 0.26, 95% CI: 0.11-0.60 compared with <1 year since diagnosis). Men with non-localised disease had a higher risk of suicide compared to men with localised disease (RR = 2.68, 95% CI: 1.15-6.23). Men living outside major cities had lower risk of suicide compared to those resident in major cities (rate ratio = 0.42, 95% CI: 0.20-0.87). Single, divorced, widowed or separated men were more likely to commit suicide than married men (RR = 4.18, 95% CI: 2.36-7.42). CONCLUSION: Risk of suicide is higher for NSW men diagnosed with prostate cancer than the general age matched male population. Vulnerable or lonely men and those with pre-existing depression or suicidal ideation who are diagnosed with prostate cancer should be offered additional psychological support.

Factors associated with prostate specific antigen testing in Australians: Analysis of the New South Wales 45 and Up Study.

Australia has one of the highest incidence rates of prostate cancer (PC) worldwide, due in part to widespread prostate specific antigen (PSA) testing. We aimed to identify factors associated with PSA testing in Australian men without a diagnosis of prostate cancer or prior prostate disease. Participants were men joining the 45 and Up Study in 2006-2009, aged ≥45 years at recruitment. Self-completed questionnaires were linked to cancer registrations, hospitalisations, health services data and deaths. Men with a history of PC, radical prostatectomy or a "monitoring" PSA test for prostate disease were excluded. We identified Medicare reimbursed PSA tests during 2012-2014. Multivariable logistic regression was used to estimate adjusted odds ratios (OR) for the association between having PSA tests and factors of interest. Of the 62,765 eligible men, 51.8% had at least one screening PSA test during 2012-2014. Factors strongly associated with having a PSA test included having 27+ general practitioner consultations (versus 3-9 consultations; OR = 2.00; 95%CI = 1.90-2.11), benign prostatic hyperplasia treatment (versus none; OR = 1.59(95%CI = 1.49-1.70), aged 60-69 years (versus 50-59 years; OR = 1.54; 95%CI = 1.48-1.60). These results emphasise the important role of primary care in decision making about PSA testing.

Cytoreductive nephrectomy for metastatic renal cell carcinoma: inequities in access exist despite improved survival.

The use of cytoreductive nephrectomy (CRN) in the targeted therapy era is still debated. We aimed to determine factors associated with reduced use of CRN and determine the effect of CRN on overall survival in patients with metastatic renal cell carcinoma (RCC). All advanced RCC diagnosed between 2001 and 2009 in New South Wales, Australia, were identified from the Central Cancer Registry. Records of treatment and death were electronically linked. Follow-up was to the end of 2011. Multivariable logistic regression analysis was used to determine factors associated with the receipt of CRN. Cox proportional hazards model was used to determine factors associated with survival. A total of 1062 patients were identified with metastatic RCC of whom 289 (27%) received CRN. There was no difference in the use of CRN over the time period of the study. Females (OR 0.68 (95% CI: 0.48-0.96)), unmarried individuals (OR 0.68 (95% CI: 0.48-0.96)), treatment in a nonteaching hospital (OR 0.26 (95% CI: 0.18-0.36)) and individuals without private insurance (OR 0.29 (95% CI: 0.20-0.41)) all had reduced likelihood of receiving CRN. On multivariable analysis, not receiving CRN resulted in a 90% increase in death (HR 1.90 (95% CI: 1.61-2.25)). In addition, increasing age (P < 0.001), increasing Charlson comorbidity status (P = 0.002) and female gender also had a significant independent association with death. Despite a strong association with improved survival, individuals who are elderly, female, have treatment in a nonteaching facility or have no private insurance have a reduced likelihood of receiving CRN.

Predictors of surgical approach for the management of renal cell carcinoma: a population-based study from New South Wales.

BACKGROUND: The simultaneous adoption of laparoscopy and partial nephrectomy (PN) has been reported to result in unintended consequences. We aim to examine the contemporary (2001-2009) trends in use of PN and laparoscopy within a population-wide database. METHODS: All renal cell carcinomas diagnosed between 2001 and 2009 in New South Wales, Australia, were identified from the Central Cancer Registry. Records of treatment were electronically linked. All patients with localized renal cell carcinoma who underwent surgical treatment were selected for this study (3771 patients). Follow-up was to the end of 2010. Multivariable logistic regression analysis was used to determine predictors of PN and laparoscopy. RESULTS: In the entire cohort, 150 (4%), 495 (13%), 1516 (40%) and 1610 (43%) received laparoscopic PN, open PN, laparoscopic radical nephrectomy (RN) and open RN, respectively. Between the years 2001 and 2009, there was a gradual increase in the use of PN except between 2005 and 2007. Between 2001 and 2009, a rapid uptake of laparoscopy was observed. Multivariable analysis demonstrated that age (OR: 0.99 (0.98-0.99)), year of surgery (OR: 1.15 (1.11-1.19)), comorbidity (OR: 1.40 (1.12-1.76)) and hospital case load >8/year (OR: 2.39 (1.49-3.81)) predicted use of PN. Year of surgery (OR: 1.19 (1.15-1.21)), comorbidity (OR: 0.70 (0.58-0.85)), non-teaching hospital (OR: 0.70 (0.53-0.93)), private hospital (OR: 1.86 (1.45-2.38)) and hospital case load > 8/year (OR: 3.36 (2.22-5.09)) predicted use of laparoscopy. CONCLUSION: The unintended decrease in PN associated with increased use of laparoscopic RN had reversed by 2009. Hospital case load predicts the use of PN and laparoscopy.

Long-term health care costs for patients with prostate cancer: a population-wide longitudinal study in New South Wales, Australia.

AIM: Prostate cancer (PCa) is the most commonly diagnosed cancer in Australian males. There are limited data on the long-term health system costs associated with PCa. The aim of this study is to estimate long-term health care costs of PCa. METHODS: We estimated the health system costs for a cohort of 1873 males diagnosed with PCa between 2000 and 2002, using linked medical, pharmaceutical and hospital data. Treatment was defined by an initial phase, measuring health care costs up to 6 months following diagnosis and a continuing phase (including metastatic treatment), measuring treatments to 9.5 years. Nonparametric models were used to calculate average health care costs by PCa risk groups at diagnosis (low to metastatic) and treatment pathways. RESULTS: Health system costs increased with increasing PCa risk category, from $16 923 (low risk) to $39 101 (metastatic risk group). For men with initial localized risk, costs were $8 454 for the active surveillance treatment pathway, $9621 for external beam radiation therapy/brachytherapy, $19 210 for androgen deprivation therapy, $20 636 for radical prostatectomy, $21 161 for radical prostatectomy + external beam radiation therapy/brachytherapy, $21 388 for any of the treatments previously listed + androgen deprivation therapy, with an additional cost of $55 370 if metastatic treatment was undertaken. CONCLUSIONS: Treatment costs are highest during two phases over the natural cycle of the disease, the initial diagnosis phase and the metastatic treatment phase. Both the initial phase costs and low-risk category costs are driven largely by the rates of radical prostatectomy. Our study provides comprehensive long-term estimates of PCa costs.

Volume-outcome relationship in penile cancer treatment: a population based patterns of care and outcomes study from Australia.

OBJECTIVES: To study the patterns of care of penile cancer diagnosed in the state of New South Wales (NSW) over a 10 year period and determine factors that are associated with differences in survival. PATIENTS AND METHODS: All invasive penile cancer diagnosed between 2001 and 2009 in NSW, Australia, were identified from the Central Cancer Registry. Records of treatment from the Admitted Patient Data Collection and deaths from the Registry of Births Deaths and Marriages were electronically linked. Predictors of receiving an inguinal lymph node dissection (ILND) were analysed using multivariable logistic regression. Survival analyses were performed with Kaplan-Meier and Cox proportional hazards models. RESULTS: A total of 220 men were diagnosed with penile cancer over the 10 years from 69 centres. The median number of penile operations performed over 10 years was <4. Radical penile surgery (partial or total penectomy) was performed in 70% of the cases and the proportion of patients receiving radical surgery increased over time (P = 0.015). Only 53/220 men with invasive penile cancer received an ILND. Younger age and higher stage were the only factors that predicted whether ILND was performed. Overall survival (OS) was predicted by age, stage, marital status and co-morbidity status. Low centre volume decreased OS by 37% (HR 0.63 [95% CI: 0.40-0.97]). For men who received ILND, low centre volume decreased OS by 60% (HR 0.40 [95% CI: 0.19-0.85]). CONCLUSIONS: There is a decreasing trend for the use of conservative penile surgery and median centre volumes for penile cancer surgery in NSW are low. A decrease in overall survival is observed in men treated in lower volume surgery centres.

Contemporary radical cystectomy outcomes in patients with invasive bladder cancer: a population-based study.

OBJECTIVE: To determine the contemporary survival outcomes from a whole population and identify significant predictors of survival, as contemporary population-based survival outcomes after radical cystectomy (RC) for the treatment of bladder cancer (BC) are sparse. Reports suggest a large disparity between population outcomes and those of centres of excellence. PATIENTS AND METHODS: All invasive BC cases diagnosed between 2001 and 2007 in New South Wales, Australia, were identified from the Central Cancer Registry. Records of treatment and death were electronically linked. All patients who underwent RC between 2001 and 2009 were selected for this study (804 patients). Follow-up was to the end of 2009. Outcomes assessed were disease-specific survival (DSS) and overall survival (OS). Multivariable Cox regression and log-rank analysis were used to model and compare survival within groups. RESULTS: Of 804 patients diagnosed during the study period 420 (52.2%) died during follow-up. The 5-year DSS and OS for all patients was 59.6% and 53.2%, respectively. The 5-year DSS for patients with localised, regional and distant disease, undergoing RC was 72%, 51% and 10%, respectively. Age (P < 0.001) and stage (P < 0.001) were associated with 5-year DSS and OS after adjusting for all other variables. High-volume centres had significantly better 5-year DSS compared with low-volume centres (P < 0.05). The 30-day mortality for high- vs low-volume centres was 1.8% and 3.6%, respectively. Perioperative mortality improved over time for high- and moderate-volume centres but not for low-volume centres. CONCLUSION: Contemporary survival outcomes after RC are much improved compared with older studies and appear close to results from academic centres of excellence. High-volume centres report better 5-year DSS outcomes than lower volume centres.

Poor survival of females with bladder cancer is limited to those aged 70 years or over: a population-wide linkage study, New South Wales, Australia.

Although men are diagnosed with bladder cancer (BC) with a rate three times higher than women, women experience poorer survival. The cause of this gender difference is not clear. The aim of this study was to investigate the discrepancy in survival from BC by gender and explore potential explanations for the difference using a population-wide linkage study. Using the New South Wales (NSW) Central Cancer Registry, all invasive BC cases diagnosed between 2001 and 2009 were identified. Records were linked to the NSW Admitted Patient Data Collection (APDC), to retrieve treatment details, and to the Registry of Births Deaths and Marriages and Australian Bureau of Statistics to obtain death details. A total of 5377 new cases of BC were identified. No differences were identified in the proportions of patients presenting at different stages between genders. However, disease-specific survival (DSS) was worse for females compared to males with localized and regional disease (P < 0.05). This difference was only apparent in individuals aged ≥ 70 years and no difference was identified in those younger. Multivariable Cox-regression analysis of the cohort of individuals aged ≥ 70 years revealed that stage, age, comorbidity, and sex remained independent variables (P < 0.05) predicting DSS. In a population wide analysis, females aged 70 years or more suffer worse DSS compared to males. The differences are not accounted for by stage at presentation or comorbidity and are independent of age. BC in postmenopausal females may be biologically more aggressive.