The effect of COVID-19 on prostate cancer testing in Australia.

AIM: The effects of the COVID-19 pandemic on healthcare in Australia have yet to be fully determined. There are well documented decreases in the rates of screening and diagnostic testing for many cancers in 2020, with commensurate stage migration of cancers when they are eventually detected. We aimed to determine whether there was a decrease in the rate of prostate cancer (PC) screening and testing in Australia in 2020. METHOD: Data was extracted from the Department of Human Services (DHS) website for Medicare Benefits Schedule (MBS) item numbers for tests pertinent to detection of Prostate Cancer. This data is de-identified and publicly available. Data was analysed at both a national, and a state level. RESULTS: For 2020 nationwide the percentage change for prostate cancer testing was minor with 97% as many PSA tests, 99% as many prostate MRIs, and 105% as many prostate biopsies as the average for the preceding years. The differences were not significant (PSA tests p = 0.059 and prostate biopsies p = 0.109). The predicted values are fairly similar to both the average values for the preceding 5 years and the actual number of tests done in 2020. With exception of PSA tests in Victoria the actual number of tests performed was within the 95% Prediction Interval (performed: 167,426; predicted 171,194-196,699; p = 0.015). CONCLUSION: The current pandemic has had a widespread reach across Australia, with varying impact across each state and territory. Contrary to the trends across the world, our data suggest that during 2020 in Australia most areas remained unaffected in terms of prostate cancer testing excluding Victoria, which had statistically significant decrease in the number of PSA tests correlating with the extended lockdown that occurred in the state.

Changes in prostate cancer incidence, mortality and survival in relation to prostate specific antigen testing in New South Wales, Australia.

BACKGROUND: To examine changes in prostate cancer incidence and mortality rates, and 5-year relative survival, in relation to changes in the rate of prostate specific antigen (PSA) screening tests and the use of radical prostatectomy (RP) in the Australian population. METHODS: Prostate cancer stage-specific incidence rates, 5-year relative survival and mortality rates were estimated using New South Wales Cancer Registry data. PSA screening test rates and RP/Incidence ratios were estimated from Medicare Benefits Schedule claims data. We used multiple imputation to impute stage for cases with "unknown" stage at diagnosis. Annual percentage changes (APC) in rates were estimated using Joinpoint regression. RESULTS: Trends in the age-standardized incidence rates for localized disease largely mirrored the trends in PSA screening test rates, with a substantial 'spike' in the rates occurring in 1994, followed by a second 'spike' in 2008, and then a significant decrease from 2008 to 2015 (APC -6.7, 95% CI -8.2, -5.1). Increasing trends in incidence rates were observed for regional stage from the early 2000s, while decreasing or stable trends were observed for distant stage since 1993. The overall RP/Incidence ratio increased from 1998 to 2003 (APC 9.6, 95% CI 3.8, 15.6), then remained relatively stable to 2015. The overall 5-year relative survival for prostate cancer increased from 58.4% (95% CI: 55.0-61.7%) in 1981-1985 to 91.3% (95% CI: 90.5-92.1%) in 2011-2015. Prostate cancer mortality rates decreased from 1990 onwards (1990-2006: APC -1.7, 95% CI -2.1, -1.2; 2006-2017: APC -3.8, 95% CI -4.4, -3.1). CONCLUSIONS: Overall, there was a decrease in the incidence rate of localized prostate cancer after 2008, an increase in survival over time and a decrease in the mortality rate since the 1990s. This seems to indicate that the more conservative use of PSA screening tests in clinical practice since 2008 has not had a negative impact on population-wide prostate cancer outcomes.

'Pain-free TRUS B': a phase 3 double-blind placebo-controlled randomized trial of methoxyflurane with periprostatic local anaesthesia to reduce the discomfort of transrectal ultrasonography-guided prostate biopsy (ANZUP 1501).

OBJECTIVE: To determine whether the addition of inhaled methoxyflurane to periprostatic infiltration of local anaesthetic (PILA) during transrectal ultrasonography-guided prostate biopsies (TRUSBs) improved pain and other aspects of the experience. PATIENTS AND METHODS: We conducted a multicentre, placebo-controlled, double-blind, randomized phase 3 trial, involving 420 men undergoing their first TRUSB. The intervention was PILA plus a patient-controlled device containing either 3 mL methoxyflurane, or 3 mL 0.9% saline plus one drop of methoxyflurane to preserve blinding. The primary outcome was the pain score (0-10) reported by the participant after 15 min. Secondary outcomes included ratings of other aspects of the biopsy experience, willingness to undergo future biopsies, urologists' ratings, biopsy completion, and adverse events. RESULTS: The mean (SE) pain scores 15 min after TRUSB were 2.51 (0.22) in those assigned methoxyflurane vs 2.82 (0.22) for placebo (difference 0.31, 95% confidence interval [CI] -0.75 to 0.14; P = 0.18). Methoxyflurane was associated with better scores for discomfort (difference -0.48, 95% CI -0.92 to -0.03; P = 0.035, adjusted [adj.] P = 0.076), whole experience (difference -0.50, 95% CI -0.92 to -0.08; P = 0.021, adj. P = 0.053), and willingness to undergo repeat biopsies (odds ratio 1.67, 95% CI 1.12-2.49; P = 0.01) than placebo. Methoxyflurane resulted in higher scores for drowsiness (difference +1.64, 95% CI 1.21-2.07; P < 0.001, adj. P < 0.001) and dizziness (difference +1.78, 95% CI 1.31-2.24; P < 0.001, adj. P < 0.001) than placebo. There was no significant difference in the number of ≥ grade 3 adverse events. CONCLUSIONS: We found no evidence that methoxyflurane improved pain scores at 15 min, however, improvements were seen in patient-reported discomfort, overall experience, and willingness to undergo repeat biopsies.

High-dose vitamin D supplementation to prevent prostate cancer progression in localised cases with low-to-intermediate risk of progression on active surveillance (ProsD): protocol of a phase II randomised controlled trial.

INTRODUCTION: Active surveillance (AS) for patients with prostate cancer (PC) with low risk of PC death is an alternative to radical treatment. A major drawback of AS is the uncertainty whether a patient truly has low risk PC based on biopsy alone. Multiparametric MRI scan together with biopsy, appears useful in separating patients who need curative therapy from those for whom AS may be safe. Two small clinical trials have shown short-term high-dose vitamin D supplementation may prevent PC progression. There is no substantial evidence for its long-term safety and efficacy, hence its use in the care of men with PC on AS needs assessment. This protocol describes the ProsD clinical trial which aims to determine if oral high-dose vitamin D supplementation taken monthly for 2 years can prevent PC progression in cases with low-to-intermediate risk of progression. METHOD AND ANALYSIS: This is an Australian national multicentre, 2:1 double-blinded placebo-controlled phase II randomised controlled trial of monthly oral high-dose vitamin D supplementation (50 000 IU cholecalciferol), in men diagnosed with localised PC who have low-to-intermediate risk of disease progression and are being managed by AS. This trial will assess the feasibility, efficacy and safety of supplementing men with an initial oral loading dose of 500 000 IU cholecalciferol, followed by a monthly oral dose of 50 000 IU during the 24 months of AS. The primary trial outcome is the commencement of active therapy for clinical or non-clinical reason, within 2 years of AS. ETHICS AND DISSEMINATION: This trial is approved by Bellberry Ethics Committee (2016-06-459). All results will be reported in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ACTRN12616001707459.

Preventing Osteoporosis in Men Taking Androgen Deprivation Therapy for Prostate Cancer: A Systematic Review and Meta-Analysis.

CONTEXT: Advanced prostate cancer (PCa) is treated with androgen deprivation therapy (ADT) which results in loss of bone mineral density (BMD) and osteoporosis. OBJECTIVE: To perform a systematic review and meta-analysis of evidence to determine the most effective methods of preventing BMD loss in patients with PCa treated with ADT. EVIDENCE ACQUISITION: A systematic search of the Medline, Embase, and EBM Reviews databases was conducted on July 20, 2016 to identify studies on men who received an intervention to prevent osteoporosis after diagnosis of PCa and treatment with ADT. The Preferred Reporting Items for Systematic Reviews and Meta-analyses statement was followed and the studies found were critically appraised. EVIDENCE SYNTHESIS: Twenty-five studies were included in the review and 13 had quantitative data sufficient for meta-analysis of BMD loss. Bisphosphonates led to a significant improvement in areas assessed: the mean difference was 7.09% (95% confidence interval [CI] 5.05-9.13%; p<0.00001) for lumbar BMD, 4.63% (95% CI 0.87-8.4; p=0.02) for femoral neck BMD, and 3.16% (95% CI 0.09-6.23%; p=0.04) for total hip BMD. Selective estrogen receptor modulators (SERMs) were less effective, exercise studies had inconsistent effects, and denosumab could not be quantitatively analyzed. CONCLUSIONS: Bisphosphonates and denosumab are effective treatments in preventing BMD loss in men with PCa taking ADT. SERMs are a less effective alternative. Exercise programs are insufficient in isolation but have a role as an adjunct for holistic care. PATIENT SUMMARY: In this review we determined the best option for preventing osteoporosis in men with prostate cancer being treated with androgen deprivation therapy. We found that bisphosphonates, denosumab, and selective estrogen receptor modulators (SERMs) were effective, but exercise was not useful in isolation. We conclude that bisphosphonates, denosumab, or SERMs should be used and exercise encouraged.

Factors related to receipt of non-cancer-related transurethral prostatectomy: findings from a large prospective study of 106†769 middle-aged and older Australian men.

BACKGROUND: Transurethral prostatectomy (TURP) is a common surgical intervention for chronic lower urinary tract symptoms (LUTS). Little large-scale evidence exists on factors related to receipt of non-cancer-related TURP. METHODS: A prospective study of men aged ≥45 years participating in the 45 and Up Study, a large Australian cohort study, without prior prostatectomy and/or bowel/genital/urinary-tract cancer; questionnaire data were linked to hospitalisations and deaths. HRs for TURP were estimated in relation to multiple factors, adjusting for confounders. RESULTS: There were 3416 incident TURPs among 106 769 men (median follow-up 5.8 years), with rates of 1.8, 5.3, 9.1 and 11.4/1000 person-years for ages 45-54, 55-64, 65-74 and ≥75 years, respectively. Age-adjusted rates of TURP varied markedly according to baseline LUTS from 2.2/1000 person-years with no/mild symptoms to 30.7/1000 person-years with severe symptoms. Annual household income ≥$70 000 versus <$20 000, having private health insurance and living in major cities were associated with higher TURP rates; there were no significant differences according to baseline diabetes, stroke, high blood pressure or cardiovascular disease. Men reporting severe versus no physical functioning limitation, high versus low psychological distress or poor versus excellent self-rated health were 36-51% more likely to undergo procedures overall, but were 24-37% less likely to undergo procedures following additional adjustment for need (baseline LUTS). CONCLUSIONS: TURP rates were most strongly related to baseline LUTS and age, consistent with appropriate health services targeting. Lower TURP rates in men experiencing socioeconomic disadvantage and with poor health/disability, after accounting for baseline LUTS, suggest inequity and factors such as frailty and risks related to surgery.