Background/Objectives: Late toxicity following radiotherapy is common and compromises patient quality of life. However, the impact of toxicity on patient-reported outcome measures (PROMs) five years after prostate external beam radiotherapy (EBRT) is poorly characterised. We describe PROMs using the Expanded Prostate Cancer Index Composite (EPIC-26) five years post-EBRT compared against radical prostatectomy (RP). Methods: A prospective cohort of patients with localised prostate cancer treated from 2000 to 2020 captured by a state-level cancer registry was analysed. Multivariable mixed-effects linear modelling was performed to compare differences between EPIC-26 domains over time between ERBT and RP patients. The percentage of patients recording a decline in EPIC-26 domains compared with baseline which exceeded the minimal clinically important difference (MCID) was calculated and compared between groups. Additionally, subgroup analysis was performed on patients treated using contemporary techniques. Results: There were 1720 patients (EBRT n = 1441 vs. RP n = 279) with evaluable EPIC-26 PROMS. Patients in the EBRT group had a higher median age (74 vs. 66, p < 0.001) and National comprehensive Cancer Network (NCCN) high-risk disease (61% vs. 24%, p < 0.001). Bowel domain scores were worse after EBRT compared to RP (beta −0.46, 95% CI −1.20–−0.28, p < 0.001), with a greater proportion of patients reporting a change in symptoms that exceeded the MICD at 12 months (22 vs. 11%, p = 0.009). Moderate/big bowel bother scores were significantly higher in the EBRT cohort at baseline and all follow-up periods compared to RP (beta −8.27, 95% CI −10.21–−6.34, p < 0.001). Pad use (i.e., ≥1) per day was significantly lower amongst the EBRT group (beta 16.56, 95% CI 14.35–18.76, p < 0.001). Despite contemporary techniques, EBRT was associated with worse bowel domain scores at 12 (75 vs. 80, p < 0.05) and 60 months (75 vs. 80, p < 0.05) compared to RP; however, EBRT was associated with less pad use at 12 (4% vs. 34%, p < 0.001), 24 (10% vs. 33%, p < 0.001) and 60 months (13% vs. 33%, p = 0.15) than RP. Conclusions: There are significant differences in PROMs after local curative treatment for prostate cancer which persist to five years post-treatment, despite contemporary techniques. Understanding the associated toxicity patterns helps inform shared decision-making during pre-treatment counselling.

Background In 2020, a research group published five linear longitudinal models, predict Expanded Prostate Cancer Index Composite-26 (EPIC-26) scores post-treatment for radical prostatectomy, external beam radiotherapy and active surveillance collectively in US patients with localized prostate cancer. Methods Our study externally validates the five prediction models for patient reported outcomes post-surgery for localised prostate cancer. The models’ calibration, fit, variance explained and discrimination (concordance-indices) were assessed. Two Australian validation cohorts 1 and 2 years post-prostatectomy were constructed, consisting of 669 and 439 subjects, respectively (750 in total). Patient reported function in five domains post-prostatectomy: sexual, bowel, hormonal, urinary incontinence and other urinary dysfunction (irritation/obstruction). Domain function was assessed using the EPIC-26 questionnaire. Results 1 year post-surgery, R 2 was highest for the sexual domain (35%, SD = 0.02), lower for the bowel (21%, SD = 0.03) and hormone (15%, SD = 0.03) domains, and close to zero for urinary incontinence (1%, SD = 0.01) and irritation/obstruction (− 5%, SD = 0.04). Calibration slopes for these five models were 1.04 (SD = 0.04), 0.84 (SD = 0.06), 0.85 (SD = 0.06), 1.16 (SD = 0.13) and 0.45 (SD = 0.04), respectively. Calibration-in-the-large values were − 2.2 (SD = 0.6), 2.1 (SD = 0.01), 5.1 (SD = 0.1), 9.6 (SD = 0.9) and 4.0 (SD = 0.2), respectively. Concordance-indices were 0.73, 0.70, 0.70, 0.58 and 0.62, respectively (all had SD = 0.01). Mean absolute error and root mean square error were similar across the validation and development cohorts. The validation measures were largely similar at 2 years post-surgery. Conclusions The sexual, bowel and hormone domain models validated well and show promise for accurately predicting patient reported outcomes in a non-US surgical population. The urinary domain models validated poorly and may require recalibration or revision.

In this critical review, we explore the study design, strengths, and limitations of landmark trial “Anticholinergic therapy vs. onabotulinumtoxinA for urgency urinary incontinence”. This trial was the first to directly compare two key treatment options for urge urinary incontinence – anticholinergic medication and intravesical botox, and still influences clinical guidelines a decade after publication. This non-inferiority, double-blinded, multi-centre randomised controlled trial administered Solifenacin or intra-detrusor botox to women, measuring outcomes six months post-treatment. Non-inferiority of the treatments was established, though Botox had a higher rate of retention and infection, with side effect profile rising as the key discriminator in selecting first-line therapy.

Objective: Positive surgical margins (PSMs) after radical prostatectomy (RP) indicate failure of surgery to completely clear cancer. PSMs confer an increased risk of biochemical recurrence (BCR), but how more robust outcomes are affected is unclear. This study investigated factors associated with PSMs following RP and determined their impact on clinical outcomes (BCR, second treatment [radiotherapy and/or androgen deprivation therapy], and prostate cancer-specific mortality [PCSM]). Methods: The study cohort included men diagnosed with prostate cancer (pT2-3b/N0/M0) be-tween January 1998 and June 2016 who underwent RP from the South Australian Prostate Cancer Clinical Outcomes Collaborative database. Factors associated with risk of PSMs were identified using Poisson regression. The impact of PSMs on clinical outcomes (BCR, second treatment, and PCSM) was assessed using competing risk regression. Results: Of the 2827 eligible participants, 28% had PSMs-10% apical, 6% bladder neck, 17% posterolateral, and 5% at multiple locations. Median follow-up was 9.6 years with 81 deaths from prostate cancer recorded. Likelihood of PSM increased with higher pathological grade and pathological tumor stage, and greater tumour volume, but decreased with increasing sur-geon volume (odds ratio [OR]: 0.93; 95% confidence interval [CI]: 0.88-0.98, per 100 previous prostatectomies). PSMs were associated with increased risk of BCR (adjusted sub-distribution hazard ratio [sHR] 2.5; 95% CI 2.1-3.1) and second treatment (sHR 2.9; 95% CI 2.4-3.5). Risk of BCR was increased similarly for each PSM location, but was higher for multiple margin sites. We found no association between PSMs and PCSM. Conclusion: Our findings support previous research suggesting that PSMs are not independently associated with PCSM despite strong association with BCR. Reducing PSM rates remains an important objective, given the higher likelihood of secondary treatment with associated co -morbidities. 2023 Editorial Office of Asian Journal of Urology. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/ licenses/by-nc-nd/4.0/).

Background: To describe changes in the use of prostate biopsy techniques among men diagnosed with prostate cancer in Australia and New Zealand and examine factors associated with these changes.Methods: We extracted data between 2015 and 2019 from 7 jurisdictions of the Australia and New Zealand Prostate Cancer Outcomes Registry (PCOR-ANZ). Distribution and time trend of transrectal (TR) vs. transperineal (TP) biopsy type, differences in the proportion of biopsy type by geographic jurisdiction, diagnosing institute characteristics (public vs. private, metropolitan vs. regional, case volume) and patient characteristics such as socio-economic status (SES), and location of residence were analyzed.Results: We analyzed data from 37,638 patients. The overall proportion of prostate cancer diagnosed by TP increased from 26% to 57% between 2015 and 2019. Patients living in a major city, a more socioeconomically advantaged area or who were diagnosed in a metropolitan or private hospital were more likely to have TP than TR. While all subgroups were observed to increase their use of TP over the study period, uptake grew faster for men from low SES areas and those diagnosed at a regional or low-volume hospital but slower for men living in outer regional/remote areas or treated at a public hospital.Conclusions: In this binational registry, prostate cancer is now more commonly diagnosed by TP than the TR approach. While the gap between uptakes of TP has diminished for patients with low vs. high SES, disparity has widened for patients from outer regional areas vs major cities and public vs. private hospitals. & COPY; 2023 Elsevier Inc. All rights reserved.

Background and objective: Radical prostatectomy (RP) is a common and widely used treatment for localized prostate cancer. Sequela following RP may include urinary incontinence and sexual dysfunction, outcomes which are recorded within a bi-national Prostate Cancer Outcomes Registry. The objective was to report population-wide urinary incontinence and sexual function outcomes recorded at 12 months following RP; and to quantify and explore factors associated with variation in outcome. Materials and methods: The Prostate Cancer Outcomes Registry of Australia and New Zealand (PCOR-ANZ) was used for this study. Participants were treated with radical prostatectomy between 2016 and 2020. Domain summary scores for urinary incontinence and sexual function from the EPIC-26 instrument were the main outcomes, taken at 12 months following surgery (6- 18 months). "Major" urinary and sexual function bother were also assessed. Variation in outcomes was investigated using linear and logistic multivariable regression models adjusted for covariates: age, socioeconomic status, PSA at diagnosis, surgical technique, surgical specimen grade group, margin status, and clinician surgical volume. Results and conclusions: The analytic cohort included 13,083 men with the mean urinary incontinence domain score being 76/ 100 (SD = 25) with 9.2% reporting major bother. For sexual function, the mean score was 29/100 (SD = 26) with 46% reporting major bother. Of the examined variables, age at surgery and surgical volume category were most predictive of function, with disparities exceeding minimally important differences, though large variation was observed between urologists within volume categories. There is considerable variation in 12-month postprostatectomy functional outcomes. Variation is explained by both patient and clinician factors, though some confounders are unmeasured in this cohort. (c) 2022 Elsevier Inc. All rights reserved.

Objective:Recent randomised controlled trials underestimated the incidence of genitourinary (GU) complications occurring more than 5 years following pelvic radiotherapy. This study aimed to determine the burden of treatment at a single institution from late GU complications after pelvic radiotherapy. Methods:A prospective study of all presentations for GU complications following pelvic radiotherapy at a tertiary urology department between November 2018 and November 2019 was performed. Subgroup analyses was performed on patients with prostate cancer (PCa) with late toxicity to compare patient demographics, radiotherapy, complications, and management factors. Results:There were 117 hospital encounters involving 46 patients with a 56.4% repeat encounter rate. Patients with PCa were the predominant group (n=39, 84.8%). External beam radiotherapy was the most common treatment modality (n=41, 89.1%). The median time from radiotherapy to encounter was 8 (range 0-23) years. Radiation-induced haemorrhagic cystitis was the most common presentation (n=70, 59.8%). Forty-four (42.7%) encounters for GU toxicity were managed operatively and 33 (32.0%) involved a non-operative procedure. Nine patients required packed red cell transfusion, with a total of 154 units transfused. Patients with PCa who presented with late GU toxicity had higher median Radiotherapy Oncology Group grades (p=0.020), proportion of emergency admissions (p=0.047), and frequency of clot urinary retention (p<0.001). Conclusion:There is a high burden of elective and emergency urology workload attributed to late pelvic radiation toxicity. Late GU toxicity occurring ≥5 years after radiotherapy is common and often more severe.

Background Recent studies have shown that radiation-induced pelvic toxicity often requires urological consultation. However, the 10-year incidence of genitourinary toxicity following intensity-modulated radiotherapy (IMRT) amongst patients with localised prostate cancer remains unclear. Hence, we conducted a systematic review and meta-analysis to determine the incidence of late genitourinary toxicity relying on Radiation Therapy Oncology Group (RTOG) and Common Terminology Criteria for Adverse Events (CTCAE) grade as well as the incidence of specific genitourinary toxicity. Secondary objectives involved quantifing the number of studies reporting 120-month follow-up endpoints, time to event analysis, predictive factors or economic evaluation. Methods Articles published from January 2008 to December 2021 describing prospective studies were systematically searched in MEDLINE, EMBASE and Cochrane (PROSPERO protocol CRD42019133320). Quality assessment was performed by use of the Cochrane Risk of Bias 2 Tool for RCTs and the Newcastle Ottowa Scale for non-RCTs. Meta-analysis was performed on the 60-month incidence of RTOG and CTCAE Grade ≥2 genitourinary toxicity, haematuria, urinary retention and urinary incontinence. Results We screened 4721 studies and six studies met our inclusion criteria. All included studies involved normofractionation, three included a hypofractionation comparator arm and none involved nodal irradiation. The pooled 60-month cumulative incidence of RTOG and CTCAE Grade ≥2 genitourinary toxicity were 17% (95% CI: 5–20%, n = 678) and 33% (95% CI: 27–38%, n = 153), respectively. The pooled 60-month cumulative incidence of Haematuria was 5% (95% CI: −4–14%, n = 48), Urinary incontinence 12% (95% CI: 6–18%, n = 194), Urinary retention 24% (95% CI: 9–40%, n = 10). One study reported time to event analyses, one reported predictive factors, no studies reported economic analysis or 120-month toxicity. There was considerable heterogeneity amongst the studies. Conclusion There are few high-quality studies reporting 60-month toxicity rates after IMRT. Conservative estimates of 60-month toxicity rates are high and there is need for longer follow-up and consistent toxicity reporting standards.

Studies of genitourinary toxicity following radiotherapy for prostate cancer are mainly from high volume single institutions and the incidence and burden of treatment remain uncertain. Hence we determine the cumulative incidence of treatment-related genitourinary toxicity in patients with localised prostate cancer treated with primary external beam radiotherapy (EBRT) at a state population level. We analysed data from a prospective population-based cohort, including hospital admission and cancer registry data, for men with localised prostate cancer who underwent primary EBRT without nodal irradiation between 1998 and 2019 in South Australia. The 10-year cumulative incidence of genitourinary toxicity requiring hospitalisation or procedures was determined. Clinical predictors of toxicity and the volume of admissions, non-operative, minor operative and major operative procedures were determined. All the included patients (n = 3350) had EBRT, with a median (IQR) of 74 Gy (70–78) in 37 fractions (35–39). The 10-year cumulative incidence of was 28.4% (95% CI 26.3–30.6) with a total of 2545 hospital admissions, including 1040 (41%) emergency and 1893 (74%) readmissions. The 10-year cumulative incidence of patients in this cohort requiring a urological operative procedure was 18% (95% CI 16.1–19.9), with a total of 106 (4.2%) non-operative, 1044 (41%) minor operative and 57 (2.2%) major operative urological procedures. Genitourinary toxicity after radiotherapy for prostate cancer is common. Although there continue to be advancements in radiotherapy techniques, patients and physicians should be aware of the risk of late toxicity when considering EBRT.

Purpose The risk of treatment-related toxicity is important for patients with localised prostate cancer to consider when deciding between treatment options. We developed a model to predict hospitalisation for radiation-induced genitourinary toxicity based on patient characteristics. Methods The prospective South Australian Prostate Cancer Clinical Outcomes registry was used to identify men with localised prostate cancer who underwent curative intent external beam radiotherapy (EBRT) between 1998 and 2019. Multivariable Cox proportional regression was performed. Model discrimination, calibration, internal validation and utility were assessed using C-statistics and area under ROC, calibration plots, bootstrapping, and decision curve analysis, respectively. Results There were 3,243 patients treated with EBRT included, of which 644 (20%) patients had a treated-related admission. In multivariable analysis, diabetes (HR 1.35, 95% CI 1.13–1.60, p < 0.001), smoking (HR 1.78, 95% CI 1.40–2.12, p < 0.001), and bladder outlet obstruction (BOO) without transurethral resection of prostate (TURP) (HR 7.49, 95% CI 6.18–9.08 p < 0.001) followed by BOO with TURP (HR 4.96, 95% CI 4.10–5.99 p < 0.001) were strong independent predictors of hospitalisation (censor-adjusted c-statistic = 0.80). The model was well-calibrated (AUC = 0.76). The global proportional hazards were met. In internal validation through bootstrapping, the model was reasonably discriminate at five (AUC 0.75) years after radiotherapy. Conclusions This is the first study to develop a predictive model for genitourinary toxicity requiring hospitalisation amongst men with prostate cancer treated with EBRT. Patients with localised prostate cancer and concurrent BOO may benefit from TURP before EBRT.

529 Background: Late relapses (LR) of non-seminomatous germ cell tumours (NSGCT), defined as those occurring after a disease free interval of 2 years, are increasingly recognised. We reviewed the features of LR in NSGCT within a tertiary referral testicular cancer service. Methods: 3,064 patients (pts) were referred to the testis multi-disciplinary team (January 2005 to Dec 2017). Pts who experienced a LR where initial pathology demonstrated NSGCT were identified. Data of their original and late presentation and management was reviewed from patient electronic records. Results: Of the 3,064 pts, 101 (3.3%) had a LR, with 43 pts (43%) relapsing after 10 years. 36 were symptomatic and 39 had raised markers (AFP 29, HCG 9, both 1). Table 1 shows stage at initial presentation and time to relapse. As regards treatment before late relapse, 13 CS1 patients had received prior chemotherapy (Cht) (8 as adjuvant and 5 Cht for early relapse). 59/60 CS2/3 patients received Cht as primary treatment and 41 had a post chemotherapy retroperitoneal lymph node dissection(PC-RPLND (bilateral template in 12). 20 of these 41 men who had a PC-RPLND experienced a LR in the retroperitoneum (6 after bilateral template) Patient management at relapse is summarised in table.Time to recurrence was longer in CS2/3 patients (p<0.001). 84 surgical procedures were [performed in 82 patients; histology was TD in 43, Yolk sac 14, De-differentiated in 7 and viable GCT in 12, benign 8. To date 22 patients have died, 13 of these patients relapsed at multiple sites. Conclusions: LR of NSGCT frequently occurs after an extended interval and typically occurs earlier in CS1 disease compared to higher stages. Aggressive surgery +/- chemotherapy can cure most patients. [Table: see text]

Background Antiandrogen withdrawal (AAW) response is the paradoxical decrease in prostate-specific antigen (PSA) following the withdrawal of antiandrogen in patients with advanced prostate cancer. Currently, the reported literature on the proportion of patients exhibiting AAW response and the differences in PSA response between the types of antiandrogens is unclear. Methods This review aimed to explore the PSA response to AAW and to identify if the response depends on the type of antiandrogens. A literature search was performed using databases PubMed, Cochrane and EMBASE with a cut-off date of 23rd of November 2020. Studies reporting on outcomes of AAW and prostate cancer were included. Studies were screened by two reviewers and relevant data extracted. Meta-analysis of outcomes was reported using random-effects and fixed-effects model. A subgroup analysis was performed for type of antiandrogen. Results From 450 studies, 23 were included with a total of 1474 patients with advanced prostate cancer were available for further analysis. Overall, 395 (26%) patients had any reduction in PSA levels (95% CI: 20–32%) and 183 (11%) patients had a ≥50% reduction in PSA levels (95% CI: 6–16%). Among the 1212 patients on first-generation antiandrogens, 30% (95% CI: 23–38%) had any PSA decline with 15% patients having a ≥50% PSA decline (95% CI: 8–22%). In contrast, among the 108 patients on second-generation antiandrogens, 7% (95% CI: 0–13%) had any PSA decline and only 1% (95% CI: 0–5%) had a ≥50% PSA decline. Also, among the 154 patients on androgen synthesis inhibitors, 26% (95% CI: 19–33%) had any PSA decline and only 4% (95% CI: 0–13%) had a ≥50% PSA decline. Conclusions One-fourth of patients treated with AAW show a PSA response. However, PSA response to AAW is uncommon with second-generation antiandrogens and androgen synthesis inhibitors. Further research is required to understand the differences in response between the types of antiandrogen.

Recent literature has reported that patients with prostate cancer treated with androgen deprivation therapy (ADT) have a lower incidence of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), an observation which has been widely reported by media outlets, together with speculation that ADT may be a potential treatment for coronavirus disease 2019 (COVID-19). The study by Montopoli et al.1Montopoli M. Zumerle S. Vettor R. et al.Androgen-deprivation therapies for prostate cancer and risk of infection by SARS-CoV-2: a population-based study (N = 4532).Ann Oncol. 2020; 31 (1040-1045): 1040-1045Abstract Full Text Full Text PDF PubMed Scopus (392) Google Scholar was conducted at a population level in Italy, a region experiencing a high level of COVID-19 cases. They observed in a cohort of men with prostate cancer that those prescribed ADT were less likely to report COVID-19 (4/5273 cases versus 114/37 161, odds ratio 4.05, 95% confidence interval 1.55–10.59, P = 0.00043). Benefits were also observed for classification of mild and severe disease and were used as a basis of the conclusion that 'ADT, based on luteinizing hormone-releasing hormone (LHRH) agonist/antagonists or AR inhibitors, may be considered to reduce SARS-CoV-2 infections or complications in high-risk male populations.' A useful metric to consider in this context is the number needed to treat, which is calculable from the data reported, but was not included by Montopoli et al.1Montopoli M. Zumerle S. Vettor R. et al.Androgen-deprivation therapies for prostate cancer and risk of infection by SARS-CoV-2: a population-based study (N = 4532).Ann Oncol. 2020; 31 (1040-1045): 1040-1045Abstract Full Text Full Text PDF PubMed Scopus (392) Google Scholar We calculate that the number needed to treat with ADT for the prevention of one COVID-19 case is 434. Treatment of these cases is not without risk and this is shown in Figure 1 with data extracted from Bagrodia et al.2Bagrodia A. Diblasio C.J. Wake R.W. Derweesh I.H. Adverse effects of androgen deprivation therapy in prostate cancer: current management issues.Indian J Urol. 2009; 25 (169-176): 169-176Crossref PubMed Scopus (13) Google Scholar In addition, diabetes mellitus, decreased libido, hot flashes and erectile dysfunction would be expected in a high proportion of men. These adverse events are calculated per person-year, a time frame which may be relevant to prevention of COVID-19. Montopoli et al.1Montopoli M. Zumerle S. Vettor R. et al.Androgen-deprivation therapies for prostate cancer and risk of infection by SARS-CoV-2: a population-based study (N = 4532).Ann Oncol. 2020; 31 (1040-1045): 1040-1045Abstract Full Text Full Text PDF PubMed Scopus (392) Google Scholar state that ADT could be administered transiently to minimise adverse events, though this hypothesis has not been tested in the data they present. Transient ADT treatment may be appropriate to reduce complications in those already infected with SARS-COV-2, although ADT adverse events are typically most common immediately after commencement.3O'Farrell S. Garmo H. Holmberg L. Adolfsson J. Stattin P. Van Hemelrijck M. Risk and timing of cardiovascular disease after androgen-deprivation therapy in men with prostate cancer.J Clin Oncol. 2015; 33 (1243-1251): 1243-1251Crossref PubMed Scopus (200) Google Scholar The mechanism of action which Montopoli et al.1Montopoli M. Zumerle S. Vettor R. et al.Androgen-deprivation therapies for prostate cancer and risk of infection by SARS-CoV-2: a population-based study (N = 4532).Ann Oncol. 2020; 31 (1040-1045): 1040-1045Abstract Full Text Full Text PDF PubMed Scopus (392) Google Scholar describe may provide a novel target for COVID-19 treatments, but it seems unlikely that existing ADTs will provide a viable treatment option. None declared.

AimThis paper describes the incidence and outcomes of childhood renal malignancies in Australia using national population‐based data from the Australian Childhood Cancer Registry.MethodsDe‐identified data for children (0–14 years) diagnosed with renal malignancies from 1983 to 2015 inclusive were extracted. Cause‐specific (CSS) and event‐free survival up to 20 years from diagnosis were estimated using the cohort method. Adjusted excess mortality hazard ratios were calculated using a multivariable flexible parametric survival model. Details relating to second primary malignancies (SPMs) were also examined.ResultsThere were 1046 children diagnosed with renal malignancies in Australia between 1983 and 2015 (91% nephroblastoma), generating an annual age‐standardised incidence rate of 8 per million children, which remained constant over the study period. CSS was 89% (95% confidence interval = 87–91%) and 88% (86–90%) at 5 and 20 years, respectively, and 5‐year event‐free survival was 82% (80–84%). Five‐year CSS did not change over the study period and was highest for nephroblastoma (91%). Of the 94% of patients achieving remission, 15% relapsed and subsequent 5‐year CSS was 49% (40%–58%). Eleven children were diagnosed with SPM (standardised incidence ratio = 2.9, 95% confidence interval = 1.6–5.3, P < 0.001), and five of them (45%) died within 5 years of the second diagnosis.ConclusionsChildren treated for renal malignancies in Australia have excellent long‐term survival, which is unchanged since 1983. SPMs are uncommon following treatment for childhood renal cancer but carry a poor prognosis. Relapse carries a similarly poor prognosis to SPM but is more common. These data are comparable to registry outcomes in similarly developed nations.

BackgroundTo investigate and validate previously published associations between time to prostate-specific antigen nadir and the time-to-nadir after radical prostatectomy with biochemical recurrence and to extend this analysis to overall survival and prostate cancer-specific mortality risk. MethodsThis is a retrospective analysis of 1796 men from the South Australian Prostate Cancer Clinical Outcomes Collaborative database treated with radical prostatectomy between 1998-2018 with available prostate-specific antigen nadir data within 1-6 months after surgery. Uni- and multivariable analyses of prostate-specific antigen nadir, time-to-nadir, biochemical recurrence and death were performed with Cox and competing risks models (adjusted for age, surgery year, tumour features and preoperative prostate-specific antigen).ResultsThe univariable analysis demonstrated those with shorter time-to-nadir <3 months had a decreased risk of biochemical recurrence (log-rank, p=0.0098) compared to those with longer time-to-nadir 3-6 months. For men with a time-to-nadir <3 months, a Log-rank test showed a decreased risk of prostate cancer-specific mortality (p=0.026) compared to time-to-nadir 3-6 months, without a difference in overall survival. Multivariable competing risk analyses indicated that biochemical recurrence was more likely when time-to-nadir was 3-6 months compared to <3 months (sHR=1.43, CI 1.01-2.02, p=0.04).ConclusionsAmong men undergoing radical prostatectomy, a shorter post-operative time-to-nadir <3 months is associated with decreased risk of biochemical recurrence compared to time-to-nadir 3-6 months. Following adjustment for confounders and competing risks, there was no significant difference in time-to-nadir for mortality outcomes.

PURPOSE This study aims to describe: (a) the proportion of prostate cancer patients satisfied with treatment, (b) how satisfaction changes after treatment, and (c) predictors of patient satisfaction including demographic, symptom-related and treatment variables. METHOD Self-reported quality of life and satisfaction questionnaire (UCLA Expanded Prostate Cancer Index Composite [EPIC] 26), and demographics were obtained from the South Australian Prostate Cancer Clinical Outcomes Collaborative (SA-PCCOC) database. Responses were obtained pre-treatment (radical prostatectomy or external beam radiation therapy) and 6, 12 and 24 months post-treatment, for patients diagnosed between 2009 and 2013. Mixed-effects models were used to estimate mean and change in satisfaction, and to identify predictive factors. RESULTS SA-PCCOC is a prospective, prostate cancer specific registry established in 1998, of which 1,713 patients were eligible for inclusion and 434 available for analysis. Overall, the majority of patients who completed questionnaires were satisfied with their treatment (82%). Satisfaction with care did not change over time post-treatment in multivariable analysis (p = 0.08). CONCLUSIONS Satisfaction with treatment is typically high among prostate cancer patients. Satisfaction did not change with time after treatment and appears to be associated with baseline hormonal scores and changes in hormonal scores post-treatment.

Purpose: The efficacy of pelvic floor muscle training (PFMT) for men with postprostatectomy incontinence (PPI) after robotic-assisted radical prostatectomy (RARP) is controversial and the mechanism for its possible effect remains unclear. The aim of this study was to investigate the relationship between bladder neck (BN) displacement, as a proxy for puborectal muscle activation, and continence outcomes after RARP. Methods: Data were extracted from the South Australian Prostate Cancer Clinical Outcomes Collaborative database for men undergoing RARP by high volume surgeons who attended preoperative pelvic floor physiotherapy for pelvic floor muscle (PFM) training between 2012 and 2015. Instructions were to contract the PFM as if stopping the flow of urine. BN displacement was measured with 2-dimensional transperineal ultrasound, without digital rectal examination. Urinary continence status was assessed preoperatively and at 3, 6, and 12 months using the Expanded Prostate Cancer index Composite 26. Data were analysed using logistic regression and mixed effects linear modelling. Confounding variables considered were baseline continence, age at diagnosis, margin status, nerve sparing procedures and pathological stage. Results: Of 671 eligible men, 358 met the inclusion criteria and were available for analysis, with 136 complete datasets at 12-month follow-up. While BN movement was associated with preoperative continence, there was no significant effect of BN displacement on the change in urinary continence at 12 months postprostatectomy (P =0.81) or on the influence of time on continence over 3-12 months. Conclusions: Continence outcomes were not associated with BN displacement, produced by activity of the puborectal portion of the levator ani muscle, at 3, 6, or 12 months after RARP. These results suggest that the puborectal muscle does not play a role in the recovery of continence after RARP and may help to explain the negative findings of many studies of PFMT for PPI.

Obese men have lower serum prostate-specific antigen (PSA) than comparably aged lean men, but the underlying mechanism remains unclear. The aim of this study was to determine the effect of obesity on PSA and the potential contributing mechanisms. A cohort of 1195 men aged 35 years and over at recruitment, with demographic, anthropometric (BMI, waist circumference (WC)) and serum hormone (serum testosterone, estradiol (E2)) PSA and hematology assessments obtained over two waves was assessed. Men with a history of prostate cancer or missing PSA were excluded, leaving 970 men for the final analysis. Mixed-effects regressions and mediation analyses adjusting for hormonal and volumetric factors explore the potential mechanisms relating obesity to PSA. After adjusting for age, PSA levels were lower in men with greater WC (P = 0.001). In a multivariable model including WC, age, E2/testosterone and PlasV as predictors, no statistically significant associations were observed between with PSA and either WC (P = 0.36) or PlasV (P = 0.49), while strong associations were observed with both E2/testosterone (P < 0.001) and age (P < 0.001). In the mediation analyses with PlasV as the mediator, the average causal mediation effect (ACME) explained roughly 20% of the total effect of WC on PSA (P = 0.31), while when E2/testosterone is a mediator, the ACME explained roughly 50% of the effect (P < 0.001). Our findings indicate that lower PSA levels in obese men, as compared to normal weight men, can be explained both by hormonal changes (elevated E2/testosterone ratio) and hemodilution. Hormonal factors therefore represent a substantial but underappreciated mediating pathway.