Search

Men in whom external beam radiotherapy fails are usually placed on delayed hormone therapy. Some of these men have localized recurrence that might be suitable for further local therapy. We describe patterns of recurrence and suitability for focal ablative therapy in those undergoing transperineal template prostate mapping biopsies.The study included 145 consecutive patients (December 2007 to May 2014) referred with suspicion of recurrence due to rising prostate specific antigen after external beam radiotherapy or brachytherapy who underwent transperineal template prostate mapping biopsies. Suitability for focal ablative therapy required the cancer to be unifocal or unilateral, or bilateral/multifocal with 1 dominant index lesion and secondary lesions with Gleason score 3+3=6 with no more than 3 mm cancer core involvement.Mean patient age was 70.7 (SD 5.8) years. Median prostate specific antigen at time of transperineal template prostate mapping biopsy was 4.5 ng/ml (IQR 2.5-7.7). Overall 75.9% (110) were suitable for a form of focal salvage treatment, 40.7% (59) were suitable for quadrant ablation, 14.5% (21) hemiablation, 14.5% (21) bilateral focal ablation and 6.2% (9) for index lesion ablation.Three-quarters of patients who have localized radiorecurrent prostate cancer may be suitable for focal ablative therapy to the prostate based on transperineal template prostate mapping biopsies.

Purpose Little is known about the toxicity of additional pelvic lymph node irradiation in men receiving intensity modulated radiation therapy (IMRT) for prostate cancer. The aim of this study was to compare patient-reported outcomes after IMRT to the prostate only (PO-IMRT) versus the prostate and pelvic lymph nodes (PPLN-IMRT). Methods and Materials Patients who received a diagnosis of high-risk or locally advanced prostate cancer in the English National Health Service between April 2014 and September 2016 who were treated with IMRT were mailed a questionnaire at least 18 months after diagnosis. Patient-reported urinary, sexual, bowel, and hormonal functional domains on a scale from 0 to 100, with higher scores indicating better outcomes, and generic health-related quality of life were collected using the Expanded Prostate Cancer Index Composite 26-item version and EQ-5D-5L. We used linear regression to compare PPLN-IMRT versus PO-IMRT with adjustment for patient, tumor, and treatment characteristics. Results Of the 7017 men who received a questionnaire, 5468 (77.9%) responded; 4196 (76.7%) had received PO-IMRT and 1272 (23.3%) PPLN-IMRT. Adjusted differences in the Expanded Prostate Cancer Index Composite 26-item version domain scores were smaller than 1 (P always >.2), except for sexual function, with men who had PPNL-IMRT reporting a lower mean score (adjusted difference, 2.3; 95% confidence interval, 0.9-3.7; P = .002). This did not represent a clinically relevant difference. There was no significant difference in health-related quality of life (P = .5). Conclusions Additional pelvic lymph node irradiation does not lead to clinically meaningful increases in the toxicity of IMRT for prostate cancer according to patient-reported functional outcomes and health-related quality of life.

Summary Background The optimal timing of radiotherapy after radical prostatectomy for prostate cancer is uncertain. We aimed to compare the efficacy and safety of adjuvant radiotherapy versus an observation policy with salvage radiotherapy for prostate-specific antigen (PSA) biochemical progression. Methods We did a randomised controlled trial enrolling patients with at least one risk factor (pathological T-stage 3 or 4, Gleason score of 7–10, positive margins, or preoperative PSA ≥10 ng/mL) for biochemical progression after radical prostatectomy (RADICALS-RT). The study took place in trial-accredited centres in Canada, Denmark, Ireland, and the UK. Patients were randomly assigned in a 1:1 ratio to adjuvant radiotherapy or an observation policy with salvage radiotherapy for PSA biochemical progression (PSA ≥0·1 ng/mL or three consecutive rises). Masking was not deemed feasible. Stratification factors were Gleason score, margin status, planned radiotherapy schedule (52·5 Gy in 20 fractions or 66 Gy in 33 fractions), and centre. The primary outcome measure was freedom from distant metastases, designed with 80% power to detect an improvement from 90% with salvage radiotherapy (control) to 95% at 10 years with adjuvant radiotherapy. We report on biochemical progression-free survival, freedom from non-protocol hormone therapy, safety, and patient-reported outcomes. Standard survival analysis methods were used. A hazard ratio (HR) of less than 1 favoured adjuvant radiotherapy. This study is registered with ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and Dec 30, 2016, 1396 patients were randomly assigned, 699 (50%) to salvage radiotherapy and 697 (50%) to adjuvant radiotherapy. Allocated groups were balanced with a median age of 65 years (IQR 60–68). Median follow-up was 4·9 years (IQR 3·0–6·1). 649 (93%) of 697 participants in the adjuvant radiotherapy group reported radiotherapy within 6 months; 228 (33%) of 699 in the salvage radiotherapy group reported radiotherapy within 8 years after randomisation. With 169 events, 5-year biochemical progression-free survival was 85% for those in the adjuvant radiotherapy group and 88% for those in the salvage radiotherapy group (HR 1·10, 95% CI 0·81–1·49; p=0·56). Freedom from non-protocol hormone therapy at 5 years was 93% for those in the adjuvant radiotherapy group versus 92% for those in the salvage radiotherapy group (HR 0·88, 95% CI 0·58–1·33; p=0·53). Self-reported urinary incontinence was worse at 1 year for those in the adjuvant radiotherapy group (mean score 4·8 vs 4·0; p=0·0023). Grade 3–4 urethral stricture within 2 years was reported in 6% of individuals in the adjuvant radiotherapy group versus 4% in the salvage radiotherapy group (p=0·020). Interpretation These initial results do not support routine administration of adjuvant radiotherapy after radical prostatectomy. Adjuvant radiotherapy increases the risk of urinary morbidity. An observation policy with salvage radiotherapy for PSA biochemical progression should be the current standard after radical prostatectomy. Funding Cancer Research UK, MRC Clinical Trials Unit, and Canadian Cancer Society.

Background and purpose In the post-prostatectomy setting the value of Intensity-modulated (IMRT) relative to 3D-conformal radiotherapy (3D-CRT) in reducing toxicity remains unclear. We compared genitourinary (GU) and gastrointestinal (GI) toxicity after post-prostatectomy IMRT or 3D-CRT. Materials and methods A population-based study of all patients treated with post-prostatectomy 3D-CRT (n = 2422) and IMRT (n = 603) was conducted between January 1 2010 and December 31 2013 in the English National Health Service. We identified severe GI and GU toxicity using a validated coding-framework and compared IMRT and 3D-CRT using a competing-risks proportional hazards regression analysis. Results There was no difference in GI toxicity between patients who received IMRT and 3D-CRT (3D-CRT: 5.8 events/100 person-years; IMRT: 5.5 events/100 person-years; adjusted HR: 0.85, 95%CI: 0.63–1.13; p = 0.26). The GU toxicity rate was lower with IMRT but this effect was not statistically significant (3D-CRT: 5.4 events/100 person-years; IMRT: 3.8 events/100 person-years; adjusted HR: 0.76, 95%CI: 0.55–1.03; p = 0.08). Conclusions The use of post-prostatectomy IMRT compared to 3D-CRT is not associated with a statistically significant reduction in rates of severe GU and GI toxicity, although there is some evidence that GU toxicity is lower with IMRT. We would caution against rapid transition to post-prostatectomy IMRT until further evidence is available supporting its superiority.

Background: Lateralised language processing is a well-established finding in monolinguals. In bilinguals, studies using fMRI have typically found substantial regional overlap between the two languages, though results may be influenced by factors such as proficiency, age of acquisition and exposure to the second language. Few studies have focused specifically on individual differences in brain lateralisation, and those that have suggested reduced lateralisation may characterise representation of the second language (L2) in some bilingual individuals. Methods: In Study 1, we used functional transcranial Doppler sonography (FTCD) to measure cerebral lateralisation in both languages in high proficiency bilinguals who varied in age of acquisition (AoA) of L2. They had German (N = 14) or French (N = 10) as their first language (L1) and English as their second language. FTCD was used to measure task-dependent blood flow velocity changes in the left and right middle cerebral arteries during phonological word generation cued by single letters. Language history measures and handedness were assessed through self-report. Study 2 followed a similar format with 25 Japanese (L1) /English (L2) bilinguals, with proficiency in their second language ranging from basic to advanced, using phonological and semantic word generation tasks with overt speech production. Results: In Study 1, participants were significantly left lateralised for both L1 and L2, with a high correlation (r = .70) in the size of laterality indices for L1 and L2. In Study 2, again there was good agreement between LIs for the two languages (r = .77 for both word generation tasks). There was no evidence in either study of an effect of age of acquisition, though the sample sizes were too small to detect any but large effects. Conclusion: In proficient bilinguals, there is strong concordance for cerebral lateralisation of first and second language as assessed by a verbal fluency task.

Purpose To compare, in a national population-based study, severe genitourinary (GU) and gastrointestinal (GI) toxicity in patients with prostate cancer who were treated with radical intensity modulated radiation therapy (IMRT) or 3-dimensional conformal radiation therapy (3D-CRT). Methods and Materials Patients treated with IMRT (n=6933) or 3D-CRT (n=16,289) between January 1, 2010 and December 31, 2013 in the English National Health Service were identified using cancer registry data, the National Radiotherapy Dataset, and Hospital Episodes Statistics, the administrative database of care episodes in National Health Service hospitals. We developed a coding system that identifies severe toxicity (at least grade 3 according to the National Cancer Institute Common Terminology Criteria for Adverse Events scoring system) according to the presence of a procedure and a corresponding diagnostic code in patients' Hospital Episodes Statistics records after radiation therapy. A competing risks regression analysis was used to estimate hazard ratios (HRs), comparing the incidence of severe GI and GU complications after IMRT and 3D-CRT, adjusting for patient, disease, and treatment characteristics. Results The use of IMRT, as opposed to 3D-CRT, increased from 3.1% in 2010 to 64.7% in 2013. Patients who received IMRT were less likely than those receiving 3D-CRT to experience severe GI toxicity (4.9 vs 6.5 per 100 person-years; adjusted HR 0.66; 95% confidence interval 0.61-0.72) but had similar levels of GU toxicity (2.3 vs 2.4 per 100 person-years; adjusted HR 0.94; 95% confidence interval 0.84-1.06). Conclusions Prostate cancer patients who received radical radiation therapy using IMRT were less likely to experience severe GI toxicity, and they had similar GU toxicity compared with those who received 3D-CRT. These findings in an unselected “real-world” population support the use of IMRT, but further cost-effectiveness studies are urgently required.

Objectives Despite the rapid adoption of robot-assisted radical prostatectomy (RARP), there is little evidence about the occurrence of medium-term urinary complications with this type of surgery compared to laparoscopic (LRP) or retropubic open radical prostatectomy (ORP). The aim of this study was to evaluate the occurrence of severe urinary complications within two years of surgery in men undergoing RARP, LRP or ORP. Patients and Methods Population-based cohort study of men who underwent RARP (n=4,947), LRP (n= 5,479), or ORP (n=6,873) between 2008 and 2012 in the English National Health Service (NHS) using national cancer registry records linked to Hospital Episodes Statistics – an administrative database of admissions to NHS hospitals. We identified the occurrence of any severe urinary or severe stricture-related complication within two years of surgery using a validated tool. Multi-level regression modelling was used to determine the association between the type of surgery and occurrence of complications with adjustment for patient and surgical factors. Results Men undergoing RARP were least likely to experience any urinary complication (10.5%) or a stricture-related complication (3.3%) compared to those who had LRP (15.8% any or 5.7% stricture-related) or ORP (19.1% any or 6.9% stricture-related). The impact of the type of surgery on the occurrence of any urinary or stricture-related complications remained statistically significant with adjustment for patient and surgical factors (p < 0.01). Conclusion Men who underwent RARP have the lowest risk of developing severe urinary complications within two years of surgery. This article is protected by copyright. All rights reserved.

The increased number of treatment options for prostate cancer has raised questions over who should be taking responsibility for initiating and ongoing management of patients. In this article the authors report on the findings of a survey seeking the views of UK oncologists and urologists on where they think responsibilities lie.

Locally advanced prostate cancer is defined as primary tumours extending outside the prostate gland to the surrounding tissues or seminal vesicles but without spread beyond the pelvic region. With radical treatment there is good prospect of cure. Radiotherapy in combination with hormone therapy is well established, but specific NICE guidelines have only recently been published. The guidelines recommend offering either radical prostatectomy (RP), possibly with adjuvant radiotherapy, or radical radiotherapy (RT) with neo-adjuvant hormone therapy as treatment for men with locally advanced prostate cancer. Given that guidelines on managing locally advanced prostate cancer have recently changed, we wanted to quantify the baseline variation in use of radical treatments for this patient group. Methods: Men with T3/T4 N0 M0 prostate cancer who were diagnosed in 2010–2012 were identified using data from the National Cancer Registration and Analysis Service (NCRAS). Data on age, ethnicity, deprivation, Charlson comorbidity score, Strategic Clinical Network (SCN) of residence, and treatments delivered were extracted. A multivariable logistic regression was undertaken to identify important variables. Results: Overall, 1692 (14%) of men in the cohort had a record of radical prostatectomy. A total of 6212 (52%) had a record of curative RT. In a regression model each decade increase in age yielded odds of 0.39 ( p < 0.001) for receiving radical treatment. Black men were only half as likely as white men to receive radical treatment (OR = 0.54; p < 0.001). Deprivation, comorbidity and SCN of residence had smaller effects. The variation observed in radical treatment between SCNs largely disappeared once the multiple variables were accounted for. Conclusion: Radical treatments vary by 71% to 85% between networks for men aged 60–69 years. Given that men >80 years made up 12% of the study population and only 6% had a Charlson comorbidity score >0, there is a possibility that some men with ‘clinically significant’ disease are undertreated.

Objective\ud Documentations of the experiences of patients with advanced prostate cancer and their partners are sparse. Views of care and treatment received for metastatic castrate resistant prostate cancer (mCRPC) are presented here.\ud \ud Methods\ud Structured interviews conducted within 14 days of a systemic therapy for mCRPC starting and 3 months later explored: treatment decisions, information provision, perceived benefits and harms of treatment, and effects of these on patients’ and partners’ lives.\ud \ud Results\ud Thirty-seven patients and 33 partners recruited from UK cancer centres participated. The majority of patients (46%) reported pain was their worst symptom and many wanted to discuss its management (baseline-50%; 3 months-33%). Patients and partners believed treatment would: delay progression (>75%), improve wellbeing (33%), alleviate pain (≈12%) and extend life (15% -patients, 36% -partners). At 3 months most men (42%) said fatigue was the worst treatment-related side effect (SE), 27% experienced unexpected SEs, and 54% needed help with SEs. Most patients received SE information (85% written; 75% verbally); many additionally searched the internet (33%-patients; 55%-partners). Only 54% of patients said nurse support was accessible. \ud \ud Conclusion\ud Pain and other symptom management is not optimal. Increased specialist nurse provision and earlier palliative care links are needed. Dedicated clinics may be justified.

Early and accurate localization of lesions in patients with biochemical recurrence (BCR) of prostate cancer may guide salvage therapy decisions. The present study,Men with a first episode of BCR after curative-intent primary therapy were enrolled at 6 UK sites. Patients underwent

AIM To explore the practice and views of uro-oncologists in the UK regarding their use of bone supportive agents in patients with prostate cancer. METHODS An expert-devised online questionnaire was completed by members of the British Uro-oncology Group (BUG). RESULTS Of 160 uro-oncologists invited, 81 completed the questionnaire. Approximately 70% of respondents never use a bone supportive agent in patients with metastatic hormone-naive prostate cancer on androgen deprivation therapy (ADT). However, use was more frequent in men with metastatic castration-resistant prostate cancer, from first-line treatment onwards. The majority of uro-oncologists do not use a bone supportive agent to prevent skeletal-related events in men with non-metastatic disease unless the individual patient is at an increased risk of osteoporosis. In men with more advanced disease, respondents would use an oral or intravenous (IV) bisphosphonate in 41% and 61% of patients, respectively. Zoledronic acid is the first-choice bone supportive treatment in 77% of cases, with the lack of clinical data cited as a barrier to use for other IV bisphosphonates. Local guidelines also have a significant influence on the use of bone supportive agents, especially with respect to denosumab. Bone mineral density measurement is conducted in approximately 40% of men with ADT exposure of 2 years or longer, or those with metastatic prostate cancer. CONCLUSION Uro-oncologists in the UK generally do not use bone supportive agents for men with metastatic hormone-naive prostate cancer or those with non-metastatic disease. However, increasing the duration of ADT and the presence of castration-resistant metastatic prostate cancer increases use.

Aim\ud \ud To explore the practice and attitudes of uro‐oncologists in the UK regarding monitoring testosterone levels and the use of testosterone replacement therapy (TRT) in their prostate cancer patients treated with androgen deprivation therapy (ADT).\ud \ud \ud Methods\ud \ud An expert‐devised online questionnaire was completed by the members of the British Uro‐oncology Group (BUG).\ud \ud \ud Results\ud \ud Of 160 uro‐oncologists invited, 84 completed the questionnaire. Before initiating ADT in patients with non‐metastatic prostate cancer, only 45% of respondents measured testosterone levels and 61% did not measure testosterone at all during ADT in the adjuvant or neoadjuvant setting. However, in men with metastatic prostate cancer, 71% of the uro‐oncologists measured testosterone before starting ADT and the majority continued testing during treatment. Approximately two‐thirds of respondents did not prescribe TRT for their patients who were in remission following neo(adjuvant) ADT and who had castration levels of testosterone.\ud \ud \ud Discussion\ud \ud Among UK uro‐oncologists, the measurement of testosterone levels before and during ADT was not typically part of routine practice in the management of patients with prostate cancer. However, testosterone levels were checked more frequently for patients with metastatic disease than disease at an earlier stage. Testing could be conducted in parallel with PSA measurement as testosterone levels are linked to biochemical failure. The majority of specialists participating in the survey did not prescribe TRT for their patients in remission following ADT.\ud \ud \ud Conclusion\ud \ud Uro‐oncologists in the UK do not generally measure testosterone as part of their patient management and they remain cautious about the possible benefits of TRT in men with prostate cancer.

Background Accurate whole-body staging following biochemical relapse in prostate cancer is vital in determining the optimum disease management. Current imaging guidelines recommend various imaging platforms such as computed tomography (CT), Technetium 99 m (99mTc) bone scan and 18F-choline and recently 68Ga-PSMA positron emission tomography (PET) for the evaluation of the extent of disease. Such approach requires multiple hospital attendances and can be time and resource intensive. Recently, whole-body magnetic resonance imaging (WB-MRI) has been used in a single visit scanning session for several malignancies, including prostate cancer, with promising results, providing similar accuracy compared to the combined conventional imaging techniques. The LOCATE trial aims to investigate the application of WB-MRI for re-staging of patients with biochemical relapse (BCR) following external beam radiotherapy and brachytherapy in patients with prostate cancer. Methods/design The LOCATE trial is a prospective cohort, multi-centre, non-randomised, diagnostic accuracy study comparing WB-MRI and conventional imaging. Eligible patients will undergo WB-MRI in addition to conventional imaging investigations at the time of BCR and will be asked to attend a second WB-MRI exam, 12-months following the initial scan. WB-MRI results will be compared to an enhanced reference standard comprising all the initial, follow-up imaging and non-imaging investigations. The diagnostic performance (sensitivity and specificity analysis) of WB-MRI for re-staging of BCR will be investigated against the enhanced reference standard on a per-patient basis. An economic analysis of WB-MRI compared to conventional imaging pathways will be performed to inform the cost-effectiveness of the WB-MRI imaging pathway. Additionally, an exploratory sub-study will be performed on blood samples and exosome-derived human epidermal growth factor receptor (HER) dimer measurements will be taken to investigate its significance in this cohort. Discussion The LOCATE trial will compare WB-MRI versus the conventional imaging pathway including its cost-effectiveness, therefore informing the most accurate and efficient imaging pathway. Trial registration LOCATE trial was registered on ClinicalTrial.gov on 18th of October 2016 with registration reference number NCT02935816.

PURPOSE There is a debate about the effectiveness and toxicity of pelvic lymph node (PLN) irradiation for the treatment of men with high-risk prostate cancer. This study compared the toxicity of intensity-modulated radiation therapy (IMRT) to the prostate and the pelvic lymph nodes (PPLN-IMRT) with prostate-only IMRT (PO-IMRT). MATERIALS AND METHODS Patients with high-risk localized or locally advanced prostate cancer treated with IMRT in the English National Health Service between 2010 and 2013 were identified by using data from the Cancer Registry, the National Radiotherapy Dataset, and Hospital Episode Statistics, an administrative database of all hospital admissions. Follow-up was available up to December 31, 2015. Validated indicators were used to identify patients with severe toxicity according to the presence of both a procedure code and diagnostic code in patient Hospital Episode Statistics records. A competing risks regression analysis, with adjustment for patient and tumor characteristics, estimated subdistribution hazard ratios (sHRs) by comparing GI and genitourinary (GU) complications for PPLN-IMRT versus PO-IMRT. RESULTS Three-year cumulative incidence in the PPLN-IMRT (n = 780) and PO-IMRT (n = 3,065) groups was 14% for both groups for GI toxicity, and 9% and 8% for GU toxicity, respectively. Patients receiving PPLN-IMRT and PO-IMRT had similar levels of severe GI (adjusted sHR, 1.00; 95% CI, 0.80 to 1.24; P = .97) and GU (adjusted sHR, 1.10; 95% CI, 0.83 to 1.46; P = .50) toxicity rates. CONCLUSION Including PLNs in radiation fields for high-risk or locally advanced prostate cancer is not associated with increased GI or GU toxicity at 3 years. Additional follow-up is required to answer questions about its impact on late GU toxicity. Results from ongoing trials will provide insight into the anticancer effectiveness of PLN irradiation.

In South Carolina, sea level rise and sinking land surface means that the coastal areas of the state will experience a relative sea level rise ranging between approximately 0.5 to 1.5 feet in 2030, 0.75 to 3.2 feet in 2050, and 1.75 and 10.8 feet by 2100. These ranges are based on scenarios that encompass uncertainties about physical processes and about future levels of greenhouse gas emissions. They cover low rates of sea level rise and low greenhouse gas emissions to high rates of sea level rise and high greenhouse gas emissions to convey the future risks for the purpose of long-term decision making. Many communities are already experiencing impacts of recurrent flooding, sometimes called nuisance flooding, associated with “king tides” and meteorological events. For the state and county and local governments, sea level rise and increased flooding pose a significant, costly, and persistent threat to roads and highways. These natural disasters and chronic flood damages will inevitably encourage South Carolinians to reconsider the status quo of road maintenance and repair. Under projected sea level rise, repetitive or severe damages will lead to tough decisions about whether to decrease routine maintenance, transfer control of the roads to different government authorities, or abandon existing roads. Although the South Carolina Department of Transportation (SCDOT) owns more than 50% of the roads and highways across the state, adaptation efforts related to road maintenance and abandonment can be expected to occur at both the state and local levels. The state, towns, cities, and counties have legal responsibilities to maintain roads, and they all certainly have an interest in ensuring that roads are safe and maintained. This white paper discusses how South Carolina law may impact local governments that are facing the effects of coastal flooding on their public roadways. The paper first outlines the statutory basis for road ownership and the duties that flow from such ownership. It then reviews potential causes of actions resulting from the breach of duties of maintenance and good repair. Finally, it addresses the procedural requirements for formal road abandonment and takings liability from loss of road access.

During October 2012, Superstorm Sandy became the largest Atlantic hurricane on record, ravaging the US Eastern Seaboard. While the storm caused billions of dollars in property damage and clean-up costs, it also provided a wake-up call to the risks faced by our historic national treasures. Ellis Island, the gateway to the American dream for millions of immigrants, was completely submerged under the massive storm surge caused by the hurricane. Liberty Island, home to the iconic Statute of Liberty, was 75% submerged and faced tens of millions of dollars of damage. The intensity of Superstorm Sandy and its aftermath revealed that rising sea levels and aberrant weather events are increasingly placing our nation’s historic landmarks and sites of cultural heritage at risk. While the impacts of climate change may potentially devastate historical sites, hope is not lost. As oceanographer John Englander points out, we are given a “blessing” in some ways because, “unlike a storm, rising sea level does give us time to prepare.” To protect precious historic resources in the face of climate change, the first thing that must be “adapted” is our nation’s overall preservation approach. The importance of preserving historic and archeological sites has long been recognized in the nation, with a comprehensive preservation scheme codified with the passing of the 1966 National Historic Preservation Act. This landmark piece of legislation embodied the traditional concepts of preservation: that historic buildings and their cultural landscapes should remain intact, in their original locations, with their original features. However, a changing climate will challenge the traditional approach. Treasured historic properties are becoming increasingly vulnerable in their current conditions and locations. Many of the sites crucial to the development of the nation are located along the coasts and are at most risk from rising sea levels. Flood-proofing measures and adaptation plans will be critical strategies for withstanding sea level rise in the decades to come, but many of these strategies are incompatible with federal, state, and local historic preservation laws. Raising the elevation of a historic home or refurbishing it with modern materials may make the property more resilient, for example, but will fundamentally change its look and be inconsistent with the character of a historic district. To promote adaptation and protect precious resources, preservationists therefore should re-evaluate what it means to “save” a historic building or cultural landmark. Given rising sea levels, maintaining a structure as is, in its historical location, could end up being a death sentence for the structure in its entirety; introducing flexibility into the standards for gaining and retaining historical designations will be needed. This white paper maintains that both the federal government and local governments will have large but different roles to play in adaptation efforts designed to conserve the nation’s history and culture under the existing national preservation framework. Section I examines the statutory schemes behind two major federal laws that impact decision-making regarding historic structures: the National Historic Preservation Act and the National Flood Insurance Program. The section then highlights the relationships between the regulatory schemes promulgated under these federal laws and suggests how new adaptive measures and incentives can be built in to encourage resiliency planning and action for vulnerable buildings. Section II moves away from individual historic property decision making and suggests how climate change resiliency strategies can be incorporated into the review procedures required by the National Historic Preservation Act when federal agency actions affect historic properties. Section III maintains that while changes to federal regulations will be important for a long-term and cohesive preservation response to climate change, local governments will be on the frontline of identifying and protecting their most vulnerable and cherished historic assets. This section highlights important local work being done to preserve cultural heritage and suggests a model for other susceptible coastal cities to undertake while waiting for policy change on a national scale.

e14050 Background: Historically, metastatic spinal cord compression (MSCC) referrals trend towards a Friday peak in incidence (Koiter E, Radioth Onc 2013). However, data from a single, tertiary centre in the UK showed a reversal in the Friday peak (Adeleke S, Annals of Oncology 2020). This was attributed to early case referrals and quicker treatment decisions. In this new study, we explored whether a similar pattern was apparent in multiple district general hospital (DGH) settings and attempt to identify underlying causes. DGHs manage a larger proportion of cancer patients in the UK. Methods: 1,069 patients between 1 Jan 2015 and 31 Dec 2020 were identified across 4 hospitals in Kent, UK with a population of 1.6 million people. 220, 181, 182, 159, 134 and 193 MSCC patients were identified annually (2015-2020). Commonest cancers were prostate (24.1%), lung (19.3%) and breast (12.3%). Thoracic and lumbar regions constituted 80% of MSCC sites. Kruskal Wallis was used to compare differences in referrals across weekdays. Data was then dichotomised to Fridays only vs. other days of the week combined, as previously reported (De Bono B, Acta Neurochir 2019). Chi squared was used to compare frequency of referrals between the two groups. Chi squared goodness of fit test was conducted to detect if Friday reflected the day with highest referrals across the week. Results: Across the region, 2015 saw the highest number of Friday referrals relative to other days, p= 0.002. Friday referrals continued to drop, year on year, until 2018 with a corresponding increase in mid-week referrals. After 2018, there was a return in trend to a further Friday peak across the region, though p= 0.836. On an individual hospital basis, the persistent Friday peak in the region was driven by two hospitals. Having a 7-day acute oncology service (AOS), 7-day radiology reporting and single referral point of contact in the department, were factors identified that kept the referrals across the week uniform. On another note, a substantial shift towards a single 8Gy fraction vs. 20Gy in 5 fractions was observed across the region. This change coincided with SCORAD III data (Hoskin P, ASCO 2017) and demonstrates adherence to evidence-based practice in the region. Conclusions: This large multi-centre retrospective study shows a differential referral pattern in the region, with hospitals with 7-day AOS/Radiology reporting and single point of referral (e.g, similar to MSCC coordinator role) having a quicker treatment turnaround and uniform referrals across the week. The MSCC coordinator has been shown to streamline service, ensure timely decision-making and improved survival outcomes (Richards L, Spine J 2017). The role is recommended by NICE UK. DGHs should consider appointing an MSCC coordinator when designing/auditing their service. The shift towards single 8Gy fraction can provide a ‘one-stop’ service where patients are scanned, planned and treated on the same day.

5009 Background: Radiotherapy is a common and effective treatment for localised prostate cancer. However, recurrence of cancer can occur in 10-15% of men in the following 5 years. Most patients with recurrence are managed using hormonal therapy with associated systemic side-effects and subsequent development of castrate resistance. Salvage prostatectomy confers a high risk of urine incontinence and rectal injury. Accurately localising and ablating only areas of recurrence within the prostate might be effective with fewer side-effects. The FOcal RECurrent Assessment and Salvage Treatment (FORECAST) trial assessed this diagnostic and treatment pathway for men with radiorecurrent cancer (NCT01883128). Methods: We first compared the accuracy of multi-parametric MRI (mp-MRI) and MRI-targeted biopsy in identifying areas of recurrent cancer to a transperineal template prostate mapping (TTPM) biopsy (Apr/2014-Jan/2018) in 181 patients from 6 UK centres. We then assessed the functional and cancer control outcomes of focally ablating areas of intraprostatic recurrence in 93 patients with localised or metastatic cancer (using cryotherapy or HIFU). Primary outcomes were sensitivity of mpMRI and MRI-targeted biopsies and urinary continence after focal ablation. A key secondary outcome was progression free survival (PFS) defined as no new metastases or hormone use (localised group only), or chemotherapy or further local treatment. Results: Of 181 men with suspicion of recurrence following radiotherapy, re-staging whole-body imaging (Choline PET and Bone Scan) showed localised disease in 128 (71%), nodal disease only in 13 (7%) and 38 (21%) metastatic. The sensitivity of MRI-targeted biopsy was 92% (95%CI 83-97%). Specificity, and positive and negative predictive values, were 75% (95%CI 45-92%), 94% (95%CI 86-98%) and 65% (95%CI 38-86%). 4/72 (6%) cancers were missed on TTPM biopsies alone and 6/72 (8%) were missed on MRI-targeted biopsies alone. Overall sensitivity of mpMRI was 81% (95%CI 73-88%) using Likert score 4-5 to denote a positive test. Specificity, and positive and negative predictive values, were 88% (95%CI 73-98%), 96% (95%CI 90-99%) and 57% (95%CI 42-70%). In the 93 men undergoing focal ablation, urinary continence was preserved in 78/93 (84%); 5/93 (5%) had a CTCAE grade 3+ adverse events. There were no rectal injuries. With a median follow-up of 27.8 [SD 1.3] months, PFS was 66% [54-75] at 24-months. Metastases-free survival in the 73 men with localised disease was 80% [95%CI 68–88] at 24-months. There were no cancer specific deaths. Conclusions: Prostate mpMRI and MRI-targeted biopsies can accurately detect and localise recurrent prostate cancer following radiotherapy. Focal ablation to areas of intra-prostatic recurrence preserves continence in the majority of men with good cancer control. Clinical trial information: NCT01883128.

216 Background: Prostate cancer is a common condition with varied pathologies based on stage, grade and presenting PSA allowing non-metastatic cases to be risk stratified at presentation. There is an evidence base for the use of Androgen Deprivation Therapy (ADT) combined with radical radiation showing a survival benefit but with an increase in patient morbidity. Prostate cancer risk stratification can be used to guide ADT therapy duration to reduce toxicity but it is unknown how closely these guidelines are followed internationally. Methods: A cross sectional survey collecting data on 15,255 patients with prostate cancer was conducted across 5 European countries and Japan. Data was interrogated to provide real-world evidence for ADT prescribing in combination with radical radiotherapy treatment and compared against the available evidence base and international best practice guidelines. Results: 3,393 patients were included in data analysis; 53% were high risk, 35% intermediate, and 12% low risk cases. 48% of patients were ages 71-80yrs with 10% being aged over 80. Data, including proposed length of hormone treatment was available for 2,832 patients. Concordance to the evidence base was good for high- and low-risk prostate cancer patients (64% and 96% respectively) but there was more disparity in the intermediate risk group with a concordance rate of only 28%. Conclusions: The data was robust enough to be interrogated and produce meaningful results. Concordance to the evidence base was high in both high and low risk disease although there was a tendency towards over-treatment in both these groups in some of the countries included. There was significant disparity in the intermediate risk group with evidence of both over- and potential under-treatment across all countries. Any potential over treatment with ADT needs to take account of the known evidence base and the potential for bone and metabolic toxicities. The data suggests that guidelines offering greater clarity on the role of ADT in intermediate risk prostate cancer may be beneficial.

Aims Multi-parametric magnetic resonance imaging (mpMRI) may identify radio-recurrent intra-prostatic cancer accurately. We aimed to compare visually directed MRI-targeted biopsies (MRI-TB) to an accurate reference standard – transperineal prostate mapping (TPM) biopsies with 5 mm sampling – in the detection of clinically significant cancer in men with biochemical failure after radiotherapy. Materials and methods A retrospective registry analysis between 2006 and 2014 identified 77 men who had undergone mpMRI followed by MRI-TB and TPM. Clinical significance was set at two definitions of disease. Definition 1 was Gleason ≥ 4+3 and/or maximum cancer core length ≥ 6 mm. Definition 2 was Gleason ≥ 3+4 and/or maximum cancer core length ≥ 4 mm. Results Of the 77 patients included, the mean age was 70 years (range 61–82; standard deviation 5.03). The median prostate-specific antigen (PSA) at the time of external beam radiotherapy (EBRT) was 14 ng/ml (interquartile range 7.83–32.50). The most frequent EBRT dose given was 74 Gy over 37 fractions. Eight patients had iodine-seed implant brachytherapy or high dose rate brachytherapy. Neoadjuvant/adjuvant hormonal therapy use was reported in 38. The time from EBRT to biochemical recurrence was a median of 60 months (interquartile range 36.75–85.00). The median PSA at the time of mpMRI was 4.68 ng/ml (interquartile range 2.68–7.60). The median time between mpMRI and biopsy was 2.76 months (interquartile range 1.58–4.34). In total, 2392 TPM and 381 MRI-TB cores were taken with 18% and 50% cancer detection, respectively. Detection rates of definition 1 clinically significant cancer were 52/77 (68%) versus 55/77 (71%) for MRI-TB and TPM, respectively. MRI-TB was more efficient requiring 1 core versus 2.8 cores to detect definition 2 cancer. Conclusion MRI-TB seems to have encouraging detection rates for clinically significant cancer with fewer cores compared with TPM, although TPM had higher detection rates for smaller lower grade lesions.

Survival remains a primary aim of treatment in prostate cancer, but quality of life is also an essential benefit of any therapy. Patient-reported outcome measures, which record quality of life as perceived by the patient, are now widely used in cancer trials and, as discussed in this article, have a place in everyday practice.

IMPORTANCE: Perirectal spacers are intended to lower the risk of rectal toxic effects associated with prostate radiotherapy. A quantitative synthesis of typical clinical results with specific perirectal spacers is limited. OBJECTIVE: To evaluate the association between perirectal hydrogel spacer placement and clinical outcomes of men receiving radiotherapy for prostate cancer. DATA SOURCES: A systematic search was performed of the Cochrane Central Register of Controlled Trials, MEDLINE, and Embase for articles published through September 2019. STUDY SELECTION: Studies comparing men who received a hydrogel spacer vs men who did not receive a spacer (controls) prior to prostate radiotherapy. DATA EXTRACTION AND SYNTHESIS: Via random-effects meta-analysis, group comparisons were reported using the weighted mean difference for continuous measures and the risk ratio for binary measures. MAIN OUTCOMES AND MEASURES: Procedural results, the percentage volume of rectum receiving at least 70 Gy radiation (v70), early (≤3 months) and late (>3 months) rectal toxic effects, and early and late changes in bowel-related quality of life on the Expanded Prostate Cancer Index Composite (minimal clinically important difference, 4 points). RESULTS: The review included 7 studies (1 randomized clinical trial and 6 cohort studies) involving 1011 men (486 who received a hydrogel spacer and 525 controls), with a median duration of patient follow-up of 26 months (range, 3-63 months). The success rate of hydrogel spacer placement was 97.0% (95% CI, 94.4%-98.8% [5 studies]), and the weighted mean perirectal separation distance was 11.2 mm (95% CI, 10.1-12.3 mm [5 studies]). Procedural complications were mild and transient, occurring in 0% to 10% of patients within the studies. The hydrogel spacer group received 66% less v70 rectal irradiation compared with controls (3.5% vs 10.4%; mean difference, −6.5%; 95% CI, –10.5% to –2.5%; P = .001 [6 studies]). The risk of grade 2 or higher rectal toxic effects was comparable between groups in early follow-up (4.5% in hydrogel spacer group vs 4.1% in control group; risk ratio, 0.82; 95% CI, 0.52-1.28; P = .38 [6 studies]) but was 77% lower in the hydrogel spacer group in late follow-up (1.5% vs 5.7%; risk ratio, 0.23; 95% CI, 0.06-0.99; P = .05 [4 studies]). Changes in bowel-related quality of life were comparable between groups in early follow-up (mean difference, 0.2; 95% CI, –3.1 to 3.4; P = .92 [2 studies]) but were greater in the hydrogel spacer group in late follow-up (mean difference, 5.4; 95% CI, 2.8-8.0; P

19 Background: Imaging options to localize lesions in men with biochemical recurrence (BCR) of prostate cancer after radical prostatectomy (RP) are limited, especially at low PSA levels. Consequently, radiation oncologists typically target the prostate bed (PB) with or without pelvic lymph nodes (LN) based on clinical or pathologic features. The FALCON study (NCT02578940) evaluated the clinical benefit of 18F-fluciclovine PET through its impact on management plans for men with BCR. Here, we report the impact on salvage radiotherapy (RT) decisions in men post-RP. Methods: Men with a first BCR episode following curative-intent therapy who were being considered for salvage therapy underwent 18F-fluciclovine PET at one of 6 UK sites. Physicians documented patients’ treatment plans pre- and post-scan. Imaging results and management plans were stratified by prior treatment as determined from patient records. Results: Sixty-five (63%) of the 104 FALCON patients had undergone RP. Of these, 62 (median PSA, 0.32 ng/mL) had a pre-scan plan for salvage RT. Lesions were found in 21 (34%) patients (median PSA, 0.32 ng/mL), of whom 10 (16%; median PSA, 0.54 ng/mL) had extraprostatic findings (Table). Post-scan, 25 (40%) men had a management change, 17 (68%) due to a positive scan. Of the 25 post-scan revisions, 17 (68%) were changes to the treatment modality: 8 to systemic therapy, 8 to watchful waiting, 1 other. A further 8 (32%) men had RT fields modified: PB alone modified to include a boost to a 18F-fluciclovine-avid lesion (n = 7) or whole pelvis field refocused on a smaller area (n = 1). Conclusions: Two fifths of men scheduled to undergo salvage RT after RP had their management plan revised following 18F-fluciclovine PET. The majority of changes involved a completely new treatment modality. Future studies to evaluate the clinical outcomes of such changes are warranted. Clinical trial information: NCT02578940. [Table: see text]

Aims\ud Delaying progression, ameliorating symptoms and maintaining quality of life (QoL) are primary aims of treatment for metastatic castrate-resistant prostate cancer (mCRPC). Real-world rather than clinical trial data about symptoms and side-effects are sparse. In EXTREQOL, patients' QoL, pain and information needs were recorded during treatment.\ud \ud Material and methods\ud Men with mCRPC from 20 UK cancer centres starting various systemic mCRPC treatments completed QoL, pain and information needs questionnaires at baseline, 3 and 6 months.\ud \ud Results\ud In total, 132 patients were recruited. Overall QoL declined significantly by 6 months (Functional Assessment of Cancer Therapy-Prostate [FACT-P] mean = –3.89, 95% confidence interval –6.7 to –1.05, P = 0.007; Trial Outcome Index [TOI] analysis mean = –3.10, 95% confidence interval –5.34 to –0.83, P = 0.007). Those who came off novel therapy and remained on luteinising hormone-releasing hormone agonist therapy alone had worse scores than patients receiving concomitant chemotherapy (Prostate Concerns Subscale mean difference = –4.45, 95% confidence interval –7.06 to –1.83, P = 0.001; TOI mean difference = –5.62, 95% confidence interval –10.97 to –0.26, P = 0.040). At 3 and 6 months, men who reported pain at baseline improved (43%, 40%), but for others pain levels remained the same (45%, 42%) or worsened (13%, 18%). Information regarding supportive care was lacking throughout the period of time on the study.\ud \ud Conclusion\ud Most mCRPC treated patients experience reduced QoL and inadequate pain control. More help with pain management and better information provision regarding supportive care is warranted.

In many countries, specialist cancer services are centralised to improve outcomes. We explored how centralisation affects the radical treatment of high‐risk and locally advanced prostate cancer in the English NHS. 79,085 patients diagnosed with high‐risk and locally advanced prostate cancer in England (April 2014 to March 2016) were identified in the National Prostate Cancer Audit database. Poisson models were used to estimate risk ratios (RR) for undergoing radical treatment by whether men were diagnosed at a regional co‐ordinating centre (‘hub’), for having surgery by the presence of surgical services on‐site, and for receiving high dose‐rate brachytherapy (HDR‐BT) in addition to external beam radiotherapy by its regional availability. Men were equally likely to receive radical treatment, irrespective of whether they were diagnosed in a hub (RR 0.99, 95% CI 0.91–1.08). Men were more likely to have surgery if they were diagnosed at a hospital with surgical services on site (RR 1.24, 1.10–1.40), and more likely to receive additional HDR‐BT if they were diagnosed at a hospital with direct regional access to this service (RR 6.16, 2.94–12.92). Centralisation of specialist cancer services does not affect whether men receive radical treatment, but it does affect treatment modality. Centralisation may have a negative impact on access to specific treatment modalities., What's new? More than one‐quarter of men with high‐risk or locally advanced prostate cancer in England do not receive radical treatment with radiotherapy or surgery, potentially owing to differences in treatment access. Here, prostate cancer service centralisation in England was investigated for potential impacts on treatment access. Among English patients in the National Prostate Cancer Audit database, centralisation had no impact on decisions to use radical treatment. It did, however, affect treatment option availability, with potential consequences for patient outcome. Patients were more likely to undergo surgery or high dose‐rate brachytherapy when diagnosed at hospitals with direct links to these services.

Aims There is limited evidence about how patients respond to hospital choice policies, the factors that inform and influence patient choices or how relevant these policies are to cancer patients. This study sought to evaluate hospital choice policies from the perspective of men who received treatment for prostate cancer in the English National Health Service. Materials and methods Semi-structured interviews were undertaken with a purposive sample of 25 men across England. Fourteen men had chosen to receive treatment at a cancer centre other than their nearest. Interviews were recorded and analysed concurrently with data collection. Results Men highlight that the geographical configuration of specialist services, the perceived urgency of the condition and the protocolisation of treatment pathways all limit their choice of a specialist treatment centre. Diseases such as cancer appear not to be well suited to the patient choice model, given the lack of hospital-level outcome data. Men instead use proxy measures of quality, leaving them vulnerable to influence by marketing and media reports. Men wishing to consider other treatment centres need to independently collect and appraise complex treatment-related information, which creates socioeconomic inequities in access to treatments. A positive impact of the choice agenda is that it enables patients to ‘exit care' not meeting their expectations. Discussion Policy makers have failed to consider the organisational, disease-specific and socio-cognitive factors that influence a patient's ability to choose their cancer treatment provider. Valid comparative hospital-level performance information is required to guide patients' choices, otherwise patients will continue to depend on informal sources, which will not necessarily improve their health care outcomes.

Background: Robot-assisted radical prostatectomy (RARP) has been rapidly adopted without robust evidence comparing its functional outcomes against laparoscopic radical prostatectomy (LRP) or open retropubic radical prostatectomy (ORP) approaches. This study compared patient-reported functional outcomes following RARP, LRP or ORP. Methods: All men diagnosed with prostate cancer in England during April – October 2014 who underwent radical prostatectomy were identified from the National Prostate Cancer Audit and mailed a questionnaire 18 months after diagnosis. Group differences in patient-reported sexual, urinary, bowel and hormonal function (EPIC-26 domain scores) and generic health-related quality of life (HRQoL; EQ-5D-5L scores), with adjustment for patient and tumour characteristics, were estimated using linear regression. Results: In all, 2219 men (77.0%) responded; 1310 (59.0%) had RARP, 487 (21.9%) LRP and 422 (19.0%) ORP. RARP was associated with slightly higher adjusted mean EPIC-26 sexual function scores compared with LRP (3·5 point difference; 95% CI: 1.1–5.9, P=0.004) or ORP (4.0 point difference; 95% CI: 1.5–6.5, P=0.002), which did not meet the threshold for a minimal clinically important difference (10–12 points). There were no significant differences in other EPIC-26 domain scores or HRQoL. Conclusions: It is unlikely that the rapid adoption of RARP in the English NHS has produced substantial improvements in functional outcomes for patients.