What can patient-reported experience measures tell us about the variation in patients' experience of prostate cancer care? A cross-sectional study using survey data from the National Prostate Cancer Audit in England.

OBJECTIVES: A national survey aimed to measure how men with prostate cancer perceived their involvement in and decisions around their care immediately after diagnosis. This study aimed to describe any differences found by socio-demographic groups. DESIGN: Cross-sectional study of men who were diagnosed with and treated for prostate cancer. SETTING: The National Prostate Cancer Audit patient-reported experience measures (PREMs) survey in England. PARTICIPANTS: Men diagnosed in 2014-2016, with non-metastatic prostate cancer, were surveyed. Responses from 32 796 men were individually linked to records from a national clinical audit and to administrative hospital data. Age, ethnicity, deprivation and disease risk classification were used to explore variation in responses to selected questions. PRIMARY AND SECONDARY OUTCOME MEASURES: Responses to five questions from the PREMs survey: the proportion responding to the highest positive category was compared across the socio-demographic characteristics above. RESULTS: When adjusted for other factors, older men were less likely than men under the age of 60 to feel side effects had been explained in a way they could understand (men 80+: relative risk (RR)=0.92, 95% CI 0.84 to 1.00), that their views were considered (RR=0.79, 95% CI 0.73 to 0.87) or that they were involved in decisions (RR=0.92, 95% CI 0.85 to 1.00). The latter was also apparent for men who were not white (black men: RR=0.89, 95% CI 0.82 to 0.98; Asian men: RR=0.85, 95% CI 0.75 to 0.96) and, to a lesser extent, for more deprived men. CONCLUSIONS: The observed discrepancies highlight the need for more focus on initiatives to improve the experience of ethnic minority patients and those older than 60 years. The findings also argue for further validation of discriminatory instruments to help cancer care providers fully understand the variation in the experience of their patients.

Does Research from Clinical Trials in Metastatic Hormone-sensitive Prostate Cancer Treatment Translate into Access to Treatments for Patients in the "Real World"? A Systematic Review.

CONTEXT: Since 2015 there have been major advances in the management of primary metastatic hormone-sensitive prostate cancer (mHSPC) following the publication of key clinical trials that demonstrated significant clinical benefits with docetaxel chemotherapy or novel hormone therapy (NHT) in addition to androgen deprivation therapy (ADT). Despite these advances, there is evidence to show that these treatments are not being utilised for mHSPC in clinical practice. OBJECTIVE: To determine the utilisation of docetaxel and NHT in mHSPC in routine practice and the determinants of variation in their use. EVIDENCE ACQUISITION: MEDLINE and Embase were searched systematically for studies on utilisation of treatments for primary mHSPC that were based on regional or national data sets and published after January 2005. Study results were summarised using a narrative synthesis. EVIDENCE SYNTHESIS: Thirteen papers were included in the analysis, six full-text articles and seven abstracts, on studies that included a total of 166 876 patients. The utilisation rate of treatment intensification with either docetaxel or NHT (enzalutamide, apalutamide, or abiraterone) in addition to ADT ranged from 9.3% to 38.1% across the studies. Younger, White patients with fewer comorbidities and living in more urban settings were more likely to be prescribed treatment intensification. Patients treated in private academic institutions by oncologists were more likely to receive docetaxel or NHT. Socioeconomic status did not impact receipt of systemic therapy. NHT utilisation rates appear to have increased over time. CONCLUSIONS: These results highlight the need to change the approach to the treatment of primary mHSPC in the real world by harnessing the practice-changing results from recent trials in this setting to optimise upfront systemic therapy for this patient population. PATIENT SUMMARY: We reviewed the use of treatments for primary metastatic hormone-sensitive prostate cancer that showed a benefit in key clinical trials. We found that these treatments are underused, particularly among certain patient groups.

The Role of Multiparametric MRI and MRI-targeted Biopsy in the Diagnosis of Radiorecurrent Prostate Cancer: An Analysis from the FORECAST Trial.

BACKGROUND: The role of multiparametric magnetic resonance imaging (MRI) for detecting recurrent prostate cancer after radiotherapy is unclear. OBJECTIVE: To evaluate MRI and MRI-targeted biopsies for detecting intraprostatic cancer recurrence and planning for salvage focal ablation. DESIGN, SETTING, AND PARTICIPANTS: FOcal RECurrent Assessment and Salvage Treatment (FORECAST; NCT01883128) was a prospective cohort diagnostic study that recruited 181 patients with suspected radiorecurrence at six UK centres (2014 to 2018); 144 were included here. INTERVENTION: All patients underwent MRI with 5 mm transperineal template mapping biopsies; 84 had additional MRI-targeted biopsies. MRI scans with Likert scores of 3 to 5 were deemed suspicious. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: First, the diagnostic accuracy of MRI was calculated. Second, the pathological characteristics of MRI-detected and MRI-undetected tumours were compared using the Wilcoxon rank sum test and chi-square test for trend. Third, four biopsy strategies involving an MRI-targeted biopsy alone and with systematic biopsies of one to two other quadrants were studied. Fisher's exact test was used to compare MRI-targeted biopsy alone with the best other strategy for the number of patients with missed cancer and the number of patients with cancer harbouring additional tumours in unsampled quadrants. Analyses focused primarily on detecting cancer of any grade or length. Last, eligibility for focal therapy was evaluated for men with localised (≤T3bN0M0) radiorecurrent disease. RESULTS AND LIMITATIONS: Of 144 patients, 111 (77%) had cancer detected on biopsy. MRI sensitivity and specificity at the patient level were 0.95 (95% confidence interval [CI] 0.92 to 0.99) and 0.21 (95% CI 0.07 to 0.35), respectively. At the prostate quadrant level, 258/576 (45%) quadrants had cancer detected on biopsy. Sensitivity and specificity were 0.66 (95% CI 0.59 to 0.73) and 0.54 (95% CI 0.46 to 0.62), respectively. At the quadrant level, compared with MRI-undetected tumours, MRI-detected tumours had longer maximum cancer core length (median difference 3 mm [7 vs 4 mm]; 95% CI 1 to 4 mm, p < 0.001) and a higher grade group (p = 0.002). Of the 84 men who also underwent an MRI-targeted biopsy, 73 (87%) had recurrent cancer diagnosed. Performing an MRI-targeted biopsy alone missed cancer in 5/73 patients (7%; 95% CI 3 to 15%); with additional systematic sampling of the other ipsilateral and contralateral posterior quadrants (strategy 4), 2/73 patients (3%; 95% CI 0 to 10%) would have had cancer missed (difference 4%; 95% CI -3 to 11%, p = 0.4). If an MRI-targeted biopsy alone was performed, 43/73 (59%; 95% CI 47 to 69%) patients with cancer would have harboured undetected additional tumours in unsampled quadrants. This reduced but only to 7/73 patients (10%; 95% CI 4 to 19%) with strategy 4 (difference 49%; 95% CI 36 to 62%, p < 0.0001). Of 73 patients, 43 (59%; 95% CI 47 to 69%) had localised radiorecurrent cancer suitable for a form of focal ablation. CONCLUSIONS: For patients with recurrent prostate cancer after radiotherapy, MRI and MRI-targeted biopsy, with or without perilesional sampling, will diagnose cancer in the majority where present. MRI-undetected cancers, defined as Likert scores of 1 to 2, were found to be smaller and of lower grade. However, if salvage focal ablation is planned, an MRI-targeted biopsy alone is insufficient for prostate mapping; approximately three of five patients with recurrent cancer found on an MRI-targeted biopsy alone harboured further tumours in unsampled quadrants. Systematic sampling of the whole gland should be considered in addition to an MRI-targeted biopsy to capture both MRI-detected and MRI-undetected disease. PATIENT SUMMARY: After radiotherapy, magnetic resonance imaging (MRI) is accurate for detecting recurrent prostate cancer, with missed cancer being smaller and of lower grade. Targeting a biopsy to suspicious areas on MRI results in a diagnosis of cancer in most patients. However, for every five men who have recurrent cancer, this targeted approach would miss cancers elsewhere in the prostate in three of these men. If further focal treatment of the prostate is planned, random biopsies covering the whole prostate in addition to targeted biopsies should be considered so that tumours are not missed.

Organisation and delivery of supportive services for patients with prostate cancer in the National Health Service in England and Wales: a national cross-sectional hospital survey and latent class analysis.

OBJECTIVES: We assessed how often National Health Service (NHS) hospitals reported that they had specific supportive services for patients with prostate cancer available onsite, including nursing support, sexual function and urinary continence services, psychological and genetic counselling, and oncogeriatric services. We identified groups of hospitals with similar patterns of supportive services. DESIGN/SETTING: We conducted an organisational survey in 2021 of all NHS hospitals providing prostate cancer services in England and Wales. Latent class analysis grouped hospitals with similar patterns of supportive services. RESULTS: In 138 hospitals, an advanced prostate cancer nurse was available in 125 hospitals (90.6%), 107 (77.5%) had a clinical nurse specialist (CNS) attending all clinics, 103 (75.7%) had sexual function services, 111 (81.6%) had continence services and 93 (69.4%) psychological counselling. The availability of genetic counselling (41 hospitals, 30.6%) and oncogeriatric services (15 hospitals, 11.0%) was lower. The hospitals could be divided into three groups. The first and largest group of 85 hospitals provided the most comprehensive supportive services onsite: all hospitals had a CNS attending all clinics, 84 (98.8%) sexual function services and 73 (85.9%) continence services. A key characteristic of the second group of 31 hospitals was that none had a CNS attending all clinics. A key characteristic of the third group of 22 hospitals was that none had sexual function services available. The hospitals in the largest group were more likely to run joint clinics (p<0.001) and host the regional specialist multidisciplinary team (p=0.002). CONCLUSIONS: There is considerable variation in supportive services for prostate cancer available onsite in NHS hospitals in England and Wales. Availability of genetic counselling and oncogeriatric services is low. The different patterns of supportive services among hospitals demonstrate that initiatives to improve the availability of the entire range of supportive services to all patients should be carefully targeted.

Real-time, model-based magnetic field correction for moving, wearable MEG.

Most neuroimaging techniques require the participant to remain still for reliable recordings to be made. Optically pumped magnetometer (OPM) based magnetoencephalography (OP-MEG) however, is a neuroimaging technique which can be used to measure neural signals during large participant movement (approximately 1 m) within a magnetically shielded room (MSR) (Boto et al., 2018; Seymour et al., 2021). Nevertheless, environmental magnetic fields vary both spatially and temporally and OPMs can only operate within a limited magnetic field range, which constrains participant movement. Here we implement real-time updates to electromagnetic coils mounted on-board of the OPMs, to cancel out the changing background magnetic fields. The coil currents were chosen based on a continually updating harmonic model of the background magnetic field, effectively implementing homogeneous field correction (HFC) in real-time (Tierney et al., 2021). During a stationary, empty room recording, we show an improvement in very low frequency noise of 24 dB. In an auditory paradigm, during participant movement of up to 2 m within a magnetically shielded room, introduction of the real-time correction more than doubled the proportion of trials in which no sensor saturated recorded outside of a 50 cm radius from the optimally-shielded centre of the room. The main advantage of such model-based (rather than direct) feedback is that it could allow one to correct field components along unmeasured OPM axes, potentially mitigating sensor gain and calibration issues (Borna et al., 2022).

Prostate cancer outcomes following whole-gland and focal high-intensity focused ultrasound.

OBJECTIVE: To report the 5-year failure-free survival (FFS) following high-intensity focused ultrasound (HIFU). PATIENTS AND METHODS: This observational cohort study used linked National Cancer Registry data, radiotherapy data, administrative hospital data and mortality records of 1381 men treated with HIFU for clinically localised prostate cancer in England. The primary outcome, FFS, was defined as freedom from local salvage treatment and cancer-specific mortality. Secondary outcomes were freedom from repeat HIFU, prostate cancer-specific survival (CSS) and overall survival (OS). Cox regression was used to determine whether baseline characteristics, including age, treatment year, T stage and International Society of Urological Pathology (ISUP) Grade Group were associated with FFS. RESULTS: The median (interquartile range [IQR]) follow-up was 37 (20-62) months. The median (IQR) age was 65 (59-70) years and 81% had an ISUP Grade Group of 1-2. The FFS was 96.5% (95% confidence interval [CI] 95.4%-97.4%) at 1 year, 86.0% (95% CI 83.7%-87.9%) at 3 years and 77.5% (95% CI 74.4%-80.3%) at 5 years. The 5-year FFS for ISUP Grade Groups 1-5 was 82.9%, 76.6%, 72.2%, 52.3% and 30.8%, respectively (P < 0.001). Freedom from repeat HIFU was 79.1% (95% CI 75.7%-82.1%), CSS was 98.8% (95% CI 97.7%-99.4%) and OS was 95.9% (95% CI 94.2%-97.1%) at 5 years. CONCLUSION: Four in five men were free from local salvage treatment at 5 years but treatment failure varied significantly according to ISUP Grade Group. Patients should be appropriately informed with respect to salvage radical treatment following HIFU.

Influence of molecular imaging on patient selection for treatment intensification prior to salvage radiation therapy for prostate cancer: a post hoc analysis of the PROPS trial.

BACKGROUND: The impact of molecular imaging (MI) on patient management after biochemical recurrence (BCR) following radical prostatectomy has been described in many studies. However, it is not known if MI-induced management changes are appropriate. This study aimed to determine if androgen deprivation therapy (ADT) management plan is improved by MI in patients who are candidates for salvage radiation therapy. METHODS: Data were analyzed from the multicenter prospective PROPS trial evaluating PSMA/Choline PET in patients being considered for salvage radiotherapy (sRT) with BCR after prostatectomy. We compared the pre- and post-MI ADT management plans for each patient and cancer outcomes as predicted by the MSKCC nomogram. A higher percentage of predicted BCR associated with ADT treatment intensification after MI was considered as an improvement in a patient's management. RESULTS: Seventy-three patients with a median PSA of 0.38 ng/mL were included. In bivariate analysis, a positive finding on MI (local or metastatic) was associated with decision to use ADT with an odds ratio of 3.67 (95% CI, 1.25 to 10.71; p = 0.02). No factor included in the nomogram was associated with decision to use ADT. Also, MI improved selection of patients to receive ADT based on predicted BCR after sRT : the predicted nomogram 5-year biochemical-free survivals were 52.5% and 43.3%, (mean difference, 9.2%; 95% CI 0.8 to 17.6; p = 0.03) for sRT alone and ADT±sRT subgroups, while there was no statistically significant difference between subgroups before MI. CONCLUSIONS: PSMA and/or Choline PET/CT before sRT can potentially improve patient ADT management by directing clinicians towards more appropriate intensification.

External validation of a risk model predicting failure of salvage focal ablation for prostate cancer.

OBJECTIVES: To externally validate a published model predicting failure within 2 years after salvage focal ablation in men with localised radiorecurrent prostate cancer using a prospective, UK multicentre dataset. PATIENTS AND METHODS: Patients with biopsy-confirmed ≤T3bN0M0 cancer after previous external beam radiotherapy or brachytherapy were included from the FOcal RECurrent Assessment and Salvage Treatment (FORECAST) trial (NCT01883128; 2014-2018; six centres), and from the high-intensity focussed ultrasound (HIFU) Evaluation and Assessment of Treatment (HEAT) and International Cryotherapy Evaluation (ICE) UK-based registries (2006-2022; nine centres). Eligible patients underwent either salvage focal HIFU or cryotherapy, with the choice based predominantly on anatomical factors. Per the original multivariable Cox regression model, the predicted outcome was a composite failure outcome. Model performance was assessed at 2 years post-salvage with discrimination (concordance index [C-index]), calibration (calibration curve and slope), and decision curve analysis. For the latter, two clinically-reasonable risk threshold ranges of 0.14-0.52 and 0.26-0.36 were considered, corresponding to previously published pooled 2-year recurrence-free survival rates for salvage local treatments. RESULTS: A total of 168 patients were included, of whom 84/168 (50%) experienced the primary outcome in all follow-ups, and 72/168 (43%) within 2 years. The C-index was 0.65 (95% confidence interval 0.58-0.71). On graphical inspection, there was close agreement between predicted and observed failure. The calibration slope was 1.01. In decision curve analysis, there was incremental net benefit vs a 'treat all' strategy at risk thresholds of ≥0.23. The net benefit was therefore higher across the majority of the 0.14-0.52 risk threshold range, and all of the 0.26-0.36 range. CONCLUSION: In external validation using prospective, multicentre data, this model demonstrated modest discrimination but good calibration and clinical utility for predicting failure of salvage focal ablation within 2 years. This model could be reasonably used to improve selection of appropriate treatment candidates for salvage focal ablation, and its use should be considered when discussing salvage options with patients. Further validation in larger, international cohorts with longer follow-up is recommended.

Treatment-related toxicity using prostate bed versus prostate bed and pelvic lymph node radiation therapy following radical prostatectomy: A national population-based study.

Purpose There is debate about the effectiveness and toxicity of pelvic lymph node (PLN) irradiation in addition to prostate bed radiotherapy when used to treat disease recurrence following radical prostatectomy. We compared toxicity from radiation therapy (RT) to the prostate bed and pelvic lymph nodes (PBPLN-RT) with prostatebed only radiation therapy (PBO-RT) following radical prostatectomy. Methods and Materials Patients with prostate cancer who underwent post-prostatectomy RT between 2010 and 2016 were identified by using the National Prostate Cancer Audit (NPCA) database. Follow-up data was available up to December 31, 2018. Validated outcome measures, based on a framework of procedural and diagnostic codes, were used to capture ≥Grade 2 gastrointestinal (GI) and genitourinary (GU) toxicity. An adjusted competing-risks regression analysis estimated subdistribution hazard ratios (sHR). A sHR > 1 indicated a higher incidence of toxicity with PBPLN-RT than with PBO-RT. Results 5-year cumulative incidences in the PBO-RT (n = 5,087) and PBPLNRT (n = 593) groups was 18.2% and 15.9% for GI toxicity, respectively. For GU toxicity it was 19.1% and 20.7%, respectively. There was no evidence of difference in GI or GU toxicity after adjustment between PBO-RT and PBPLN-RT (GI: adjusted sHR, 0.90, 95% CI, 0.67-1.19; P = 0.45); (GU: adjusted sHR, 1.19, 95% CI, 0.99-1.44; P = 0.09). Conclusions This national population-based study found that including PLNs in the radiation field following radical prostatectomy is not associated with a significant increase in rates of ≥Grade 2 GI or GU toxicity at 5 years.

Salvage Radiation Therapy After Radical Prostatectomy: Analysis of Toxicity by Dose-Fractionation in the RADICALS-RT Trial.

PURPOSE: Emerging data indicate comparable disease control and toxicity of normal postoperative fractionation and moderate hypofractionation radiation therapy (RT) in prostate cancer. In RADICALS-RT, patients were planned for treatment with either 66 Gy in 33 fractions (f) over 6.5 weeks or 52.5 Gy in 20f over 4 weeks. This non-randomized, exploratory analysis explored the toxicity of these 2 schedules in patients who had adjuvant RT. METHODS AND MATERIALS: Information on RT dose was collected in all patients. The Radiation Therapy Oncology Group toxicity score was recorded every 4 months for 2 years, every 6 months until 5 years, then annually until 15 years. Patient-reported data were collected at baseline and at 1, 5, and 10 years using standard measures, including the Vaizey fecal incontinence score (bowel) and the International Continence Society Male Short-Form questionnaire (urinary incontinence). The highest event grade was recorded within the first 2 years and beyond 2 years and compared between treatment groups using the χ² test. RESULTS: Of 634 patients, 217 (34%) were planned for 52.5 Gy/20f and 417 (66%) for 66 Gy/33f. In the first 2 years, grade 1 to 2 cystitis was reported more frequently among the 66 Gy/33f group (52.5 Gy/20f: 20% vs 66 Gy/33f: 30%; P = .04). After 2 years, grade 1 to 2 cystitis was reported in 16% in the 66-Gy group and 9% in the 52.5-Gy group (P = .08). Other toxic effects were similar in the 2 groups, and very few patients had any grade 3 to 4 toxic effects. Patients reported slightly higher urinary and fecal incontinence scores at 1 year than at baseline, but no clinically meaningful differences were reported between the 52.5 Gy/20f and 66 Gy/33f groups. Patient-reported health was similar at baseline and at 1 year and similar between the 52.5 Gy/20f and 66 Gy/33f groups. CONCLUSIONS: Severe toxic effects were rare after prostate bed radiation therapy with either 52.5 Gy/20f or 66 Gy/33f. Only modest differences were recorded in toxic effects or in patient-reported outcomes between these 2 schedules.

A low prostate specific antigen predicts a worse outcome in high but not in low/intermediate-grade prostate cancer.

OBJECTIVE: The relationship between prostate-specific antigen (PSA) and prostate cancer (PCa) grade was traditionally thought to be linear but recent reports suggest this is not true in high-grade cancers. We aimed to compare the association between PSA and PCa-specific mortality (PCSM) in clinically localised low/intermediate and high-grade PCa. SUBJECTS/PATIENTS AND METHODS: Retrospective cohort study using the National Prostate Cancer Audit database in England of men treated with external beam radiotherapy (EBRT), EBRT and brachytherapy boost (EBRT + BT), radical prostatectomy or no radical local treatment between 2014 and 2018. Multivariable competing-risk regression was used to examine the association between PSA, Gleason, and PCSM. Multivariable restricted cubic spline regression was used to explore the non-linear associations of PSA and PCSM. RESULTS: 102,089 men were included, of whom 71,138 had low/intermediate-grade and 22,425 had high-grade PCa. In high-grade, 4-year PCSM was higher with PSA ≤5 than PSA 5.1-10 for men treated with EBRT (hazard ratio 1.96 (95% confidence interval 1.15-3.34) or no radical local treatment (hazard ratio 1.99 (95% confidence interval 1.33-2.98). Restricted cubic spline regression showed that PSA and PCSM have a non-linear association in high-grade but a linear association in low/intermediate-grade PCa. CONCLUSION: The low-PSA/high-grade combination in M0 PCa treated with EBRT has a higher PCSM than those with high-grade and intermediate PSA levels. In high-grade disease, the PSA association was non-linear; by contrast, low/intermediate-grade had a linear relationship. This confirms a more aggressive biology in low PSA secreting high-grade PCa and a worse outcome following treatment.

Hospital volume and outcomes after radical prostatectomy: a national population-based study using patient-reported urinary continence and sexual function.

BACKGROUND: Improvements in short-term outcomes have been reported for hospitals with higher radical prostatectomy (RP) volumes. However, the association with longer-term functional outcomes is unknown. METHODS: All patients diagnosed with non-metastatic prostate cancer in the English NHS between 2014 and 2016 who underwent RP (N = 10,089) were mailed a survey ≥18 months after diagnosis. Differences in patient-reported urinary continence and sexual function (EPIC-26 on scale from 0 to 100) by hospital volume group (≤60, 61-100, 101-140, >140 RPs/year) were estimated using multilevel linear regression. RESULTS: Overall, 7702 men (76.3%) responded. There were no statistically significant differences in urinary continence (p = 0.08) or sexual function scores with increasing volume group (p = 0.2). When modelled as a linear function, we found a non-significant increase of 0.70 (95% CI -0.41 to 1.80; p = 0.22) in urinary continence and a significant increase of 1.54 (0.62-2.45; p = 0.001) in sexual function scores for a 100-procedure increase in hospital volume, which did not meet the threshold for a minimal clinically important difference (10-12 points). The results were similar for robotic-assisted RP (5529 men [71.8%]). CONCLUSIONS: These results do not support further centralisation of RP services beyond levels in England where four in five hospitals perform >60 RPs/year.

Determinants of variation in radical local treatment for men with high-risk localised or locally advanced prostate cancer in England.

BACKGROUND: Many factors are implicated in the potential 'under-treatment' of prostate cancer but little is known about the between-hospital variation. METHODS: The National Prostate Cancer Audit (NPCA) database was used to identify high-risk localised or locally advanced prostate cancer patients in England, between January 2014 and December 2017, and the treatments received. Hospital-level variation in radical local treatment was explored visually using funnel plots. The intra-class correlation coefficient (ICC) quantified the between-hospital variation in a random-intercept multivariable logistic regression model. RESULTS: 53,888 men, from 128 hospitals, were included and 35,034 (65.0%) received radical local treatment. The likelihood of receiving radical local treatment was increased in men who were younger (the strongest predictor), more affluent, those with fewer comorbidities, and in those with a non-Black ethnic background. There was more between-hospital variation (P < 0.001) for patients aged ≥80 years (ICC: 0.235) compared to patients aged 75-79 years (ICC: 0.070), 70-74 years (ICC: 0.041), and <70 years (ICC: 0.048). Comorbidity and socioeconomic deprivation did not influence the between-hospital variation. CONCLUSIONS: Radical local treatment of high-risk localised or locally advanced prostate cancer depended strongly on age and comorbidity, but also on socioeconomic deprivation and ethnicity, with the between-hospital variation being highest in older patients.

Comparison of the treatment of men with prostate cancer between the US and England: an international population-based study.

INTRODUCTION: The treatment of prostate cancer varies between the United States (US) and England, however this has not been well characterised using recent data. We therefore investigated the extent of the differences between US and English patients with respect to initial treatment. METHODS: We used the Surveillance, Epidemiology, and End Results (SEER) database to identify men diagnosed with prostate cancer in the US and the treatments they received. We also used the National Prostate Cancer Audit (NPCA) database for the same purposes among men diagnosed with prostate cancer in England. Next, we used multivariable regression to estimate the adjusted risk ratio (aRR) of receiving radical local treatment for men with non-metastatic prostate cancer according to the country of diagnosis (US vs. England). The five-tiered Cambridge Prognostic Group (CPG) classification was included as an interaction term. RESULTS: We identified 109,697 patients from the SEER database, and 74,393 patients from the NPCA database, who were newly diagnosed with non-metastatic prostate cancer between April 1st 2014 and December 31st 2016 with sufficient information for risk stratification according to the CPG classification. Men in the US were more likely to receive radical local treatment across all prognostic groups compared to men in England (% radical treatment US vs. England, CPG1: 38.1% vs. 14.3% - aRR 2.57, 95% CI 2.47-2.68; CPG2: 68.6% vs. 52.6% - aRR 1.27, 95% CI 1.25-1.29; CPG3: 76.7% vs. 67.1% - aRR 1.12, 95% CI 1.10-1.13; CPG4: 82.6% vs. 72.4% - aRR 1.09, 95% CI 1.08-1.10; CPG5: 78.2% vs. 71.7% - aRR 1.06, 95% CI 1.04-1.07) CONCLUSIONS: Treatment rates were higher in the US compared to England raising potential over-treatment concerns for low-risk disease (CPG1) in the US and under-treatment of clinically significant disease (CPG3-5) in England.

Inconsistent language lateralisation - Testing the dissociable language laterality hypothesis using behaviour and lateralised cerebral blood flow.

BACKGROUND: Most people have strong left-brain lateralisation for language, with a minority showing right- or bilateral language representation. On some receptive language tasks, however, lateralisation appears to be reduced or absent. This contrasting pattern raises the question of whether and how language laterality may fractionate within individuals. Building on our prior work, we postulated (a) that there can be dissociations in lateralisation of different components of language, and (b) these would be more common in left-handers. A subsidiary hypothesis was that laterality indices will cluster according to two underlying factors corresponding to whether they involve generation of words or sentences, versus receptive language. METHODS: We tested these predictions in two stages: At Step 1 an online laterality battery (Dichotic listening, Rhyme Decision and Word Comprehension) was given to 621 individuals (56% left-handers); At Step 2, functional transcranial Doppler ultrasound (fTCD) was used with 230 of these individuals (51% left-handers). 108 left-handers and 101 right-handers gave useable data on a battery of three language generation and three receptive language tasks. RESULTS: Neither the online nor fTCD measures supported the notion of a single language laterality factor. In general, for both online and fTCD measures, tests of language generation were left-lateralised. In contrast, the receptive tasks were at best weakly left-lateralised or, in the case of Word Comprehension, slightly right-lateralised. The online measures were only weakly correlated, if at all, with fTCD measures. Most of the fTCD measures had split-half reliabilities of at least .7, and showed a distinctive pattern of intercorrelation, supporting a modified two-factor model in which Phonological Decision (generation) and Sentence Decision (reception) loaded on both factors. The same factor structure fitted data from left- and right-handers, but mean scores on the two factors were lower (less left-lateralised) in left-handers. CONCLUSIONS: There are at least two factors influencing language lateralization in individuals, but they do not correspond neatly to language generation and comprehension. Future fMRI studies could help clarify how far they reflect activity in specific brain regions.

Delphi study to identify consensus on patient selection for hydrogel rectal spacer use during radiation therapy for prostate cancer in the UK.

OBJECTIVES: To identify consensus on patient prioritisation for rectal hydrogel spacer use during radiation therapy for the treatment of prostate cancer in the UK. DESIGN: Delphi study consisting of two rounds of online questionnaires, two virtual advisory board meetings and a final online questionnaire. SETTING: Radical radiation therapy for localised and locally advanced prostate cancer in the UK. PARTICIPANTS: Six leading clinical oncologists and one urologist from across the UK. INTERVENTIONS: Rectal hydrogel spacer. PRIMARY AND SECONDARY OUTCOME MEASURES: None reported. RESULTS: The panel reached consensus on the importance of minimising toxicity for treatments with curative intent and that even low-grade toxicity-related adverse events can significantly impact quality of life. There was agreement that despite meeting rectal dose constraints, too many patients experience rectal toxicity and that rectal hydrogel spacers in eligible patients significantly reduces toxicity-related adverse events. However, as a consequence of funding limitations, patients need to be prioritised for spacer use. A higher benefit of spacers can be expected in patients on anticoagulation and in patients with diabetes or inflammatory bowel disease, but consensus could not be reached regarding patient groups expected to benefit less. While radiation therapy regimen is not a main factor determining prioritisation, higher benefit is expected in ultrahypofractionated regimens. CONCLUSION: There is a strong and general agreement that all patients with prostate cancer undergoing radical radiation therapy have the potential to benefit from hydrogel spacers. Currently, not all patients who could potentially benefit can access hydrogel spacers, and access is unequal. Implementation of the consensus recommendations would likely help prioritise and equalise access to rectal spacers for patients in the UK.

The future of PSMA PET and WB MRI as next-generation imaging tools in prostate cancer.

Radiolabelled prostate-specific membrane antigen (PSMA)-based PET-CT has been shown in numerous studies to be superior to conventional imaging in the detection of nodal or distant metastatic lesions. 68Ga-PSMA PET-CT is now recommended by many guidelines for the detection of biochemically relapsed disease after radical local therapy. PSMA radioligands can also function as radiotheranostics, and Lu-PSMA has been shown to be a potential new line of treatment for metastatic castration-resistant prostate cancer. Whole-body (WB) MRI has been shown to have a high diagnostic performance in the detection and monitoring of metastatic bone disease. Prospective, randomized, multicentre studies comparing 68Ga-PSMA PET-CT and WB MRI for pelvic nodal and metastatic disease detection are yet to be performed. Challenges for interpretation of PSMA include tracer trapping in non-target tissues and also urinary excretion of tracers, which confounds image interpretation at the vesicoureteral junction. Additionally, studies have shown how long-term androgen deprivation therapy (ADT) affects PSMA expression and could, therefore, reduce tracer uptake and visibility of PSMA+ lesions. Furthermore, ADT of short duration might increase PSMA expression, leading to the PSMA flare phenomenon, which makes the accurate monitoring of treatment response to ADT with PSMA PET challenging. Scan duration, detection of incidentalomas and presence of metallic implants are some of the major challenges with WB MRI. Emerging data support the wider adoption of PSMA PET and WB MRI for diagnosis, staging, disease burden evaluation and response monitoring, although their relative roles in the standard-of-care management of patients are yet to be fully defined.

Practicalities, challenges and solutions to delivering a national organisational survey of cancer service and processes: Lessons from the National Prostate Cancer Audit.

Organisational surveys are a critical process to assess the configuration and availability of services within health care systems. Cancer service organizational surveys enable understanding of variation in structure, processes and outcomes of cancer care according to the availability of facilities and their geographical organisation. This is critical for evaluating the delivery of cancer care services across a specified region. Furthermore, the organisational survey provides essential information about patient support services which can be used to inform patients where particular allied health services are available. The National Prostate Cancer Audit (NPCA) is an audit of all prostate cancer services in England and Wales. The NPCA encompasses all prostate cancer diagnostics, treatments (including surgery, radiotherapy and systemic therapy) and allied services. The NPCA conducted an organisational survey in 2021 via an online questionnaire sent to the prostate cancer clinical leads within each of the 138 NHS providers and we had a response rate of 93 %. There are many challenges to conducting an organisational survey and gaining a high completion rate is still difficult. The challenges that the NPCA faced included accuracy, completion, duplicates and discrepancies in responses. From this experience, we have developed some suggestions for the practical delivery and development of future organisational surveys. It was thanks to the use of many of these strategies, and the engagement of clinicians with the NPCA, that we were able to achieve such a high response rate. Despite these challenges, the importance of organisational surveys of cancer services is demonstrated by the better understanding of structure, processes and outcomes of cancer care according to the accessibility of facilities and their geographical organisation. This is essential for evaluating and improving the delivery of cancer care services across a region.