Application of deep learning in cancer epigenetics through DNA methylation analysis.

DNA methylation is a fundamental epigenetic modification involved in various biological processes and diseases. Analysis of DNA methylation data at a genome-wide and high-throughput level can provide insights into diseases influenced by epigenetics, such as cancer. Recent technological advances have led to the development of high-throughput approaches, such as genome-scale profiling, that allow for computational analysis of epigenetics. Deep learning (DL) methods are essential in facilitating computational studies in epigenetics for DNA methylation analysis. In this systematic review, we assessed the various applications of DL applied to DNA methylation data or multi-omics data to discover cancer biomarkers, perform classification, imputation and survival analysis. The review first introduces state-of-the-art DL architectures and highlights their usefulness in addressing challenges related to cancer epigenetics. Finally, the review discusses potential limitations and future research directions in this field.

Polarization Engineering of Entangled Photons from a Lithium Niobate Nonlinear Metasurface.

Complex polarization states of photon pairs are indispensable in various quantum technologies. Conventional methods for preparing desired two-photon polarization states are realized through bulky nonlinear crystals, which can restrict the versatility and tunability of the generated quantum states due to the fixed crystal nonlinear susceptibility. Here we present a solution using a nonlinear metasurface incorporating multiplexed silica metagratings on a lithium niobate film of 300 nm thickness. We fabricate two orthogonal metagratings on a single substrate with an identical resonant wavelength, thereby enabling the spectral indistinguishability of the emitted photons, and we demonstrate in experiments that the two-photon polarization states can be shaped by the metagrating orientation. Leveraging this essential property, we formulate a theoretical approach for generating arbitrary polarization-entangled qutrit states by combining three metagratings on a single metasurface, allowing the encoding of the desired quantum states or information. Our findings enable miniaturized optically controlled quantum devices by using ultrathin metasurfaces as polarization-entangled photon sources.

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.

Patient "No-Show" Increases the Risk of 90-Day Complications Following Primary Total Knee Arthroplasty: A Retrospective Cohort Study of 6,776 Patients.

BACKGROUND: Patients who "no-show" (NS) clinical appointments are at a high risk of adverse health outcomes. The objective of this study was to evaluate and characterize the relationship between NS visits prior to primary total knee arthroplasty (TKA) and 90-day complications after TKA. METHODS: We retrospectively reviewed 6,776 consecutive patients undergoing primary TKA. Study groups were separated based on whether patients who NS versus always attended their appointment. A NS was defined as an intended appointment that was not canceled or rescheduled ≤2 hours before the appointment in which the patient did not show. Data collected included total number of follow-up appointments prior to surgery, patient demographics, comorbidities, and 90-day postoperative complications. RESULTS: Patients who have ≥3 NS appointments had 1.5 times increased odds of a surgical site infection (odds ratio (OR) 1.54, P = .002) compared to always attended patients. Patients who were ≤65 years old (OR: 1.41, P < .001), smokers (OR: 2.01, P < .001), and had a Charlson comorbidity index ≥3 (OR: 4.48, P < .001) were more likely to miss clinical appointments. CONCLUSION: Patients who have ≥3 NS appointments prior to TKA had an increased risk for surgical site infection. Sociodemographic factors were associated with higher odds of missing a scheduled clinical appointment. These data suggest that orthopaedic surgeons should consider NS data as an important clinical decision-making tool to assess risk for postoperative complications to minimize complications following TKA.

Patterns of Misdiagnosis and Discordance in Detecting Osteoporosis: A Comparison of Dual-energy X-ray Absorptiometry and Lumbar Computed Tomography Hounsfield Units.

STUDY DESIGN: This was a retrospective chart review. OBJECTIVE: This study aims to identify the prevalence of osteoporosis (OP) by lumbar computed tomography (CT) Hounsfield units (HUs) in patients who have normal or osteopenic bone determined by dual-energy x-ray absorptiometry (DEXA). SUMMARY OF BACKGROUND DATA: OP is a critical issue in the postmenopausal and aging population. Bone mineral density assessment by DEXA has been described as insensitive for diagnosing OP in the lumbar spine. Improving the detection of OP can bring more patients to treatment and reduce the risks associated with low bone mineral density. PATIENTS AND METHODS: We retrospectively reviewed all patients with DEXA scans and noncontrast CTs of the lumbar spine over a 15-year period. Patients were diagnosed as non-OP if they had a normal DEXA T -score (≥ -1) or osteopenic DEXA T -score (between -1.1 and -2.4). Patients in this cohort were considered osteoporotic by CT if L1-HU ≤110. Demographics and lumbar HUs were compared between these stratified groups. RESULTS: A total of 74 patients were included for analysis. All patients were demographically, similar, and the average patient age was 70 years. The prevalence of OP determined by CT L1-HU ≤110 was 46% (normal DEXA: 9%, osteopenic DEXA: 63%). A significant number of males in our study were considered osteoporotic by L1-HU ≤110 (74%, P = 0.03). All individual axial and sagittal lumbar HU measurements including L1-L5 average lumbar HUs were statistically significant among non-OP and OP groups except for the lower lumbar levels ( P > 0.05 for L4 axial HUs, and L4-L5 sagittal HUs). CONCLUSIONS: The prevalence of OP in patients with normal or osteopenic T -scores is high. Among those with osteopenia by DEXA, more than 50% may lack appropriate medical treatment. The DEXA scan may be particularly insensitive to male bone quality making the CT HU the diagnostic method of choice for detecting OP. LEVEL OF EVIDENCE: Level III.

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.

Patient Perspectives on Artificial Intelligence in Healthcare Decision Making: A Multi-Center Comparative Study.

Objective: Investigate the patient opinion on the use of Artificial Intelligence (AI) in Orthopaedics. Methods: 397 orthopaedic patients from a large urban academic center and a rural health system completed a 37-component survey querying patient demographics and perspectives on clinical scenarios involving AI. An average comfort score was calculated from thirteen Likert-scale questions (1, not comfortable; 10, very comfortable). Secondary outcomes requested a binary opinion on whether it is acceptable for patient healthcare data to be used to create AI (yes/no) and the impact of AI on: orthopaedic care (positive/negative); healthcare cost (increase/decrease); and their decision to refuse healthcare if cost increased (yes/no). Bivariate and multivariable analyses were employed to identify characteristics that impacted patient perspectives. Results: The average comfort score across the population was 6.4, with significant bivariate differences between age (p = 0.0086), gender (p = 0.0001), education (p = 0.0029), experience with AI/ML (p < 0.0001), survey format (p < 0.0001), and four binary outcomes (p < 0.05). When controlling for age and education, multivariable regression identified significant relationships between comfort score and experience with AI/ML (p = 0.0018) and each of the four binary outcomes (p < 0.05). In the final multivariable model gender, survey format, perceived impact of AI on orthopaedic care, and the decision to refuse care if it were to increase cost remained significantly associated with the average AI comfort score (p < 0.05). Additionally, patients were not comfortable undergoing surgery entirely by a robot with distant physician supervision compared to close supervision. Conclusion: The orthopaedic patient appears comfortable with AI joining the care team.

Physician Perspectives on Telemedicine at an Integrated Health System During the COVID-19 Pandemic.

Introduction: The use of telemedicine (TM) for patient care greatly increased during the COVID pandemic. This study presents data from a single health system regarding physician's perspectives on TM, which could ultimately determine how it is used in the future. Methods: A questionnaire was distributed to physicians throughout the health system. Physicians were divided based on the standard level of patient interaction in each specialty, as well as practice locations and years in practice. Physician perspectives were categorized by their opinions on different aspects of telehealth visits. Results: Of 1,794 physicians, 379 (20.7%) responded to the survey. Psychiatrists used TM significantly more than other groups and project the most future use. Surgeons were least likely to incorporate TM in the future. Ability to perform a physical examination via TM differed significantly by specialty and practice environment, but not by years in practice. Frequency of being able to complete a treatment plan via TM differed significantly by specialty, but not by years in practice or practice environment. Overall, 76.3% of physicians reported feeling "satisfied" with performing TM visits. Satisfaction with TM varied significantly by specialty and practice environment, but not by years in practice. There were no significant differences regarding physician expectations on reimbursement or billing for TM visits based on specialty, age, or practice environment. Conclusions: Discrepancies exist among physicians with respect to their satisfaction and expected future use of TM. Consensus may be difficult to reach regarding reimbursement for these visits, and further work is needed to clarify the optimal practice setting for TM.

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.

Spatially entangled photon pairs from lithium niobate nonlocal metasurfaces.

Metasurfaces consisting of nanoscale structures are underpinning new physical principles for the creation and shaping of quantum states of light. Multiphoton states that are entangled in spatial or angular domains are an essential resource for many quantum applications; however, their production traditionally relies on bulky nonlinear crystals. We predict and demonstrate experimentally the generation of spatially entangled photon pairs through spontaneous parametric down-conversion from a metasurface incorporating a nonlinear thin film of lithium niobate covered by a silica meta-grating. We measure the correlations of photon pairs and identify their spatial antibunching through violation of the classical Cauchy-Schwarz inequality, witnessing the presence of multimode entanglement. Simultaneously, the photon-pair rate is strongly enhanced by 450 times as compared to unpatterned films because of high-quality-factor resonances. These results pave the way to miniaturization of various quantum devices by incorporating ultrathin metasurfaces functioning as room temperature sources of quantum-entangled photons.

Sensitivity of Reverse Transcription Polymerase Chain Reaction Tests for Severe Acute Respiratory Syndrome Coronavirus 2 Through Time.

BACKGROUND: Reverse transcription polymerase chain reaction (RT-PCR) tests are the gold standard for detecting recent infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Reverse transcription PCR sensitivity varies over the course of an individual's infection, related to changes in viral load. Differences in testing methods, and individual-level variables such as age, may also affect sensitivity. METHODS: Using data from New Zealand, we estimate the time-varying sensitivity of SARS-CoV-2 RT-PCR under varying temporal, biological, and demographic factors. RESULTS: Sensitivity peaks 4-5 days postinfection at 92.7% (91.4%-94.0%) and remains over 88% between 5 and 14 days postinfection. After the peak, sensitivity declined more rapidly in vaccinated cases compared with unvaccinated, females compared with males, those aged under 40 compared with over 40s, and Pacific peoples compared with other ethnicities. CONCLUSIONS: Reverse transcription PCR remains a sensitive technique and has been an effective tool in New Zealand's border and postborder measures to control coronavirus disease 2019. Our results inform model parameters and decisions concerning routine testing frequency.

Interventions for obstructive uropathy in advanced prostate cancer: a population-based study.

OBJECTIVES: To develop and validate a coding framework to identify interventions for upper tract obstructive uropathy (UTOU) in men with locally advanced and metastatic prostate cancer (PCa) using administrative hospital data to assess clinical outcomes. There are no population-based studies on the incidence, treatment, and outcomes of this complication. PATIENTS AND METHODS: Patients newly diagnosed with PCa between April 2014 and March 2019 were identified in the English cancer registry. A coding framework based on procedure (Office of Population Censuses and Surveys Classification of Surgical Operations and Procedures fourth edition) and diagnostic (International Classification of Diseases, 10th edition) codes was developed and validated. Subsequent clinical outcomes were determined using Hospital Episodes Statistics to determine the utility of the intervention. RESULTS: A total of 77 010 patients newly diagnosed with locally advanced, and 30 083 patients with metastatic PCa were identified. Of these, 1951 (1.8%) patients underwent an intervention for UTOU according to our coding framework: 830 (42.5%) had locally advanced disease and 1121 (57.5%) had metastatic disease. In all, 844 (43.3%) had a percutaneous nephrostomy (PCN), 473 (24.2%) had a PCN with antegrade stent, and 634 (32.5%) had a retrograde stent. The mean follow-up was 43.2 months. The cumulative incidence of the use of these interventions at 1, 3, and 5 years was 2.5%, 3.6% and 4.2% in men with metastases compared to 0.5%, 0.9% and 1.4% in men with locally advanced disease. CONCLUSION: A new coding framework, developed to identify procedures for UTOU was applied in the largest study to date of UTOU in men with primary locally advanced and metastatic PCa. Results demonstrated that 2% of men with locally advanced PCa and 4% of men with metastatic PCa require an intervention to resolve UTOU within 5 years of their PCa diagnosis.

Gender diversity in UK surgical specialties: a national observational study.

OBJECTIVES: To compare gender diversity between UK surgical specialties, assess trends over time, and estimate when gender parity might be achieved. DESIGN: Observational study. SETTING: National Health Service, UK. PARTICIPANTS: NHS Hospital & Community Health Service workforce statistics for 2011 to 2020 MAIN OUTCOME MEASURES: Logistic regression was used to compare female representation in 2020 between surgical specialties, and to examine for any significant trends between 2011 and 2020. The method of least squares was used to estimate when female representation of specialty registrars would reach 50% ('gender parity') for specialties with <40% female representation. RESULTS: In 2020, female consultant and specialty registrar representation was significantly different between surgical specialties (both p<0.001). Female representation for each specialty were as follows (from highest to lowest): Specialty Registrars-Ophthalmology 49.7%, Otolaryngology 48.2%, Paediatric Surgery 45.5%, Plastic Surgery 42.2%, General Surgery 39.8%, Urology 31.6%, Vascular Surgery 25.0%, Neurosurgery 24.7%, Cardiothoracic Surgery 21.3%, and Trauma and Orthopaedics 20.6%; Consultants-Ophthalmology 32.4%, Paediatric Surgery 31.7%, Plastic Surgery 20.9%, General Surgery 17.5%, Otolaryngology 17%, Vascular Surgery 13.7%, Urology 11.7%, Cardiothoracic Surgery 10.8%, Neurosurgery 8.2%, and Trauma and Orthopaedics 7.3%. There was a significant positive trend in female representation of specialty registrars between 2011 and 2020 for all specialties except for Paediatric Surgery (representation consistently >45%) and Vascular Surgery (representation consistently <30%). General Surgery was estimated to achieve gender parity of their specialty registrars by 2028, Urology by 2033, Neurosurgery by 2064, Trauma and Orthopaedics by 2070, and Cardiothoracic Surgery by 2082. CONCLUSIONS: Despite improvements over the last decade, gender disparity persists in the UK surgical workforce and there are significant differences between surgical specialties. Further work is necessary to establish the reasons for these observed differences with a specific focus on Vascular Surgery, Cardiothoracic Surgery, Neurosurgery, and Trauma and Orthopaedics.

Implementation of patient-reported outcome measures into health care for men with localized prostate cancer.

Measuring treatment-related quality of life (QOL) has become an increasingly requisite component of delivering high-quality care for patients with prostate cancer. Patient-reported outcome measures (PROMs) have, therefore, become an important tool for understanding the adverse effects of radical prostate cancer treatment and have been widely integrated into clinical practice. By providing real-time symptom monitoring and improved clinical feedback to patients and providers, PRO assessment has led to meaningful gains in prostate cancer care delivery and quality improvement worldwide. By providing an avenue for benchmarking, collaboration and population health monitoring, PROMs have delivered substantial improvements beyond providing individual symptom feedback. However, multilevel barriers exist that need to be addressed before the routine implementation of PROMs is achieved. Improvements in collection, interpretation, standardization and reporting will be crucial for the continued implementation of PROM instruments in prostate cancer pathways.

Impact of the COVID-19 pandemic on the diagnosis and treatment of men with prostate cancer.

OBJECTIVE: To determine the impact of the COVID-19 pandemic on diagnostic and treatment activity in 2020 across hospital providers of prostate cancer (PCa) care in the English National Health Service. METHODS: Diagnostic and treatment activity between 23 March (start of first national lockdown in England) and 31 December 2020 was compared with the same calendar period in 2019. Patients newly diagnosed with PCa were identified from national rapid cancer registration data linked to other electronic healthcare datasets. RESULTS: There was a 30.8% reduction (22 419 vs 32 409) in the number of men with newly diagnosed PCa in 2020 after the start of the first lockdown, compared with the corresponding period in 2019. Men diagnosed in 2020 were typically at a more advanced stage (Stage IV: 21.2% vs 17.4%) and slightly older (57.9% vs 55.9% ≥ 70 years; P < 0.001). Prostate biopsies in 2020 were more often performed using transperineal (TP) routes (64.0% vs 38.2%). The number of radical prostatectomies in 2020 was reduced by 26.9% (3896 vs 5331) and the number treated by external beam radiotherapy (EBRT) by 14.1% (9719 vs 11 309). Other changes included an increased use of EBRT with hypofractionation and reduced use of docetaxel chemotherapy in men with hormone-sensitive metastatic PCa (413 vs 1519) with related increase in the use of enzalutamide. CONCLUSION: We found substantial deficits in the number of diagnostic and treatment procedures for men with newly diagnosed PCa after the start of the first lockdown in 2020. The number of men diagnosed with PCa decreased by about one-third and those diagnosed had more advanced disease. Treatment patterns shifted towards those that limit the risk of COVID-19 exposure including increased use of TP biopsy, hypofractionated radiation, and enzalutamide. Urgent concerted action is required to address the COVID-19-related deficits in PCa services to mitigate their impact on long-term outcomes.

Urinary incontinence and use of incontinence surgery after radical prostatectomy: a national study using patient-reported outcomes.

OBJECTIVES: To investigate whether patient-reported urinary incontinence (UI) and bother scores after radical prostatectomy (RP) result in subsequent intervention with UI surgery. PATIENTS AND METHODS: Men diagnosed with prostate cancer in the English National Health Service between April 2014 and January 2016 were identified. Administrative data were used to identify men who had undergone a RP and those who subsequently underwent a UI procedure. The National Prostate Cancer Audit database was used to identify men who had also completed a post-treatment survey. These surveys included the Expanded Prostate Cancer Composite Index (EPIC-26). The frequency of subsequent UI procedures, within 6 months of the survey, was explored according to EPIC-26 UI scores. The relationship between 'good' (≥75) or 'bad' (≤25) EPIC-26 UI scores and perceptions of urinary bother was also explored (responses ranging from 'no problem' to 'big problem' with respect to their urinary function). RESULTS: We identified 11 290 men who had undergone a RP. The 3-year cumulative incidence of UI surgery was 2.5%. After exclusions, we identified 5165 men who had also completed a post-treatment survey after a median time of 19 months (response rate 74%). A total of 481 men (9.3%) reported a 'bad' UI score and 207 men (4.0%) also reported that they had a big problem with their urinary function. In all, 47 men went on to have UI surgery within 6 months of survey completion (0.9%), of whom 93.6% had a bad UI score. Of the 71 men with the worst UI score (zero), only 11 men (15.5%) subsequently had UI surgery. CONCLUSION: In England, there is a significant number of men living with severe, bothersome UI after RP, and an unmet clinical need for UI surgery. The systematic collection of patient-reported outcomes could be used to identify men who may benefit from UI surgery.